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t100 | Deep vein thrombosis (DVT) occurs when a blood clot forms in a leg vein. The clot can break up and move to the lungs, leading to a potentially serious blockage in blood flow (pulmonary embolism or PE). Because of the damage to the leg vein, post‐thrombotic syndrome (PTS) may develop any time over the next couple of years. Symptoms include leg pain, swelling, skin pigmentation and leg ulcers, leading to loss of mobility. Anticoagulants are the standard treatment for DVT or a clot in a calf vein. These thin the blood to reduce further clots from forming and prevent PE; yet PTS can still develop. Thrombolysis breaks down the blood clot. For DVT, drugs such as streptokinase, urokinase and tissue plasminogen activator are infused into a vein in the arm or foot or, in some cases, directly at the site of the clot using a catheter and X‐ray control. Bleeding complications, stroke or intracerebral haemorrhage are potential harmful events for both treatments. and The review results are based on 17 controlled trials that randomised a total of 1103 people with acute DVT (within 21 days of onset of symptoms) to receive thrombolysis or anticoagulant treatment. Trials were carried out principally in the USA, Scandinavia, Germany and the UK. All trials included men and women ranging in age from 18 to 75 years with a preponderance of older adults. The present review (current until February 2016) showed that thrombolysis may have advantages over standard anticoagulation treatment. Thrombolysis effectively dissolved the clot so that complete clot breakdown occurred more often with thrombolysis than with standard anticoagulant therapy. Blood flow in the affected vein (venous patency) was also better maintained. Three trials (306 participants) continued for over six months and found that fewer people developed PTS when treated with thrombolysis, 45% compared with 66% in the standard anticoagulation treatment group. Two trials (211 participants) which continued for over five years also showed that fewer people developed PTS when treated with thrombolysis. Those receiving thrombolysis had more bleeding complications than with standard anticoagulation (10% versus 8%). Most bleeding episodes and deaths occurred in the older studies. Use of strict eligibility criteria appears to have improved the safety of this treatment, which is effective delivered directly to the clot by catheter or via bloodstream from another vein. | Standard treatment for deep vein thrombosis aims to reduce immediate complications. Use of thrombolysis or clot dissolving drugs could reduce the long‐term complications of post‐thrombotic syndrome (PTS) including pain, swelling, skin discolouration, or venous ulceration in the affected leg. This is the third update of a review first published in 2004. Objectives To assess the effects of thrombolytic therapy and anticoagulation compared to anticoagulation alone for the management of people with acute deep vein thrombosis (DVT) of the lower limb as determined by the effects on pulmonary embolism, recurrent venous thromboembolism, major bleeding, post‐thrombotic complications, venous patency and venous function. Search methods For this update the Cochrane Vascular Information Specialist (CIS) searched the Specialised Register (February 2016). In addition the CIS searched the Cochrane Register of Studies (CENTRAL (2016, Issue 1)). Trial registries were searched for details of ongoing or unpublished studies. Selection criteria Randomised controlled trials (RCTs) examining thrombolysis and anticoagulation versus anticoagulation for acute DVT were considered. Data collection and analysis For this update (2016), LW and CB selected trials, extracted data independently, and sought advice from MPA where necessary. We assessed study quality with the Cochrane risk of bias tool. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (CI). Data were pooled using a fixed‐effect model unless significant heterogeneity was identified in which case a random‐effects model was used. Seventeen RCTs with 1103 participants were included. These studies differed in the both thrombolytic agent used and in the technique used to deliver it. Systemic, loco‐regional and catheter‐directed thrombolysis (CDT) were all included. Fourteen studies were rated as low risk of bias and three studies were rated as high risk of bias. We combined the results as any (all) thrombolysis compared to standard anticoagulation. Complete clot lysis occurred significantly more often in the treatment group at early follow‐up (RR 4.91; 95% CI 1.66 to 14.53, P = 0.004) and at intermediate follow‐up (RR 2.44; 95% CI 1.40 to 4.27, P = 0.002; moderate quality evidence). A similar effect was seen for any degree of improvement in venous patency. Up to five years after treatment significantly less PTS occurred in those receiving thrombolysis (RR 0.66, 95% CI 0.53 to 0.81; P < 0.0001; moderate quality evidence). This reduction in PTS was still observed at late follow‐up (beyond five years), in two studies (RR 0.58, 95% CI 0.45 to 0.77; P < 0.0001; moderate quality evidence). Leg ulceration was reduced although the data were limited by small numbers (RR 0.87; 95% CI 0.16 to 4.73, P = 0.87). Those receiving thrombolysis had increased bleeding complications (RR 2.23; 95% CI 1.41 to 3.52, P = 0.0006; moderate quality evidence). Three strokes occurred in the treatment group, all in trials conducted pre‐1990, and none in the control group. There was no significant effect on mortality detected at either early or intermediate follow‐up. Data on the occurrence of pulmonary embolism (PE) and recurrent DVT were inconclusive. Systemic thrombolysis and CDT had similar levels of effectiveness. Studies of CDT included two trials in femoral and iliofemoral DVT, and results from these are consistent with those from trials of systemic thrombolysis in DVT at other levels of occlusion. Thrombolysis increases the patency of veins and reduces the incidence of PTS following proximal DVT by a third. Evidence suggests that systemic administration and CDT have similar effectiveness. Strict eligibility criteria appears to improve safety in recent studies and may be necessary to reduce the risk of bleeding complications. This may limit the applicability of this treatment. In those who are treated there is a small increased risk of bleeding. Using GRADE assessment, the evidence was judged to be of moderate quality due to many trials having low numbers of participants. However, the results across studies were consistent and we have reasonable confidence in these results. |
t101 | Varicose veins (varices) are enlarged veins occurring below the skin's surface, usually in the legs. One‐third of the UK population may be affected. They can be painful and itchy, the surrounding skin may change colour, and occasionally they may bleed; in some people, untreated varicose veins may lead to ulceration. Varicose veins occur due to leaky valves within the veins. Traditionally, they were treated with surgery to remove the veins. Newer techniques require neither vein removal, nor a general anaesthetic; they may involve less pain after the procedure and have a lower risk of complications, resulting in quicker recovery and return to normal activities. Endovenous laser ablation (EVLA) and radiofrequency ablation (RFA) are methods that seal the main leaking vein. They are performed using a local anaesthetic; a probe is passed into the vein: either a tiny laser or radiofrequency makes the wall of the vein heat up causing the vein to clot off and seal. With ultrasound‐guided foam sclerotherapy (UGFS), a foam is injected into the veins; the foam pushes the blood away, causing thickening and scarring of the inside of the vein so that it becomes blocked. We searched for all randomised controlled trials to March 2016 that compared at least one of the newer techniques with surgery, when treating short saphenous vein (SSVs; found in the lower leg) varices. We found three trials comparing EVLA with surgery; one trial compared UGFS with surgery, but none reported RFA. The main measures (outcomes) were recanalisation (blood flowing in the veins again) or persistence of reflux (due to failure of treatment) at six weeks; recurrence of reflux at one year; clinical evidence of recurrence (presence of new varicose veins) at one year; repeat treatment due to failure; quality of life (QoL) at six weeks and one year after the treatment; and complications after treatment. The EVLA versus surgery comparison included 311 participants: 185 received EVLA and 126 received surgery. In the UGFS comparison, each treatment group contained 21 people. For several outcomes in the EVLA comparison, only one study provided data; consequently, this review has limited ability to demonstrate meaningful results for some planned outcomes. EVLA versus surgery: there was less recanalisation or persistence of reflux at six weeks and less recurrence of reflux at one year in the EVLA group; however, there were insufficient data to report clear differences in clinical recurrence at one year. One trial reported four participants in each group required further treatment. There was no difference between treatments in QoL. Although some participants had postoperative complications (e.g., sural nerve injury (the sural nerve is in the calf), infection, deep venous thrombosis (DVT; blood clots in veins), inflammation of the wall of the vein), most complications improved without treatment and the two cases of DVT resolved after treatment with medicines. UGFS versus surgery: there were insufficient data to detect clear differences between treatment groups for recanalisation or persistence of reflux at six weeks and recurrence of reflux at one year. | Short (or small) saphenous vein (SSV) varices occur as a result of an incompetent sapheno‐popliteal junction, where the SSV joins the popliteal vein, resulting in reflux in the SSV; they account for about 15% of varicose veins. Untreated varicose veins may sometimes lead to ulceration of the leg, which is difficult to manage. Traditionally, treatment was restricted to surgery or conservative management. Since the 1990s, however, a number of minimally invasive techniques have been developed; these do not normally require a general anaesthetic, are day‐case procedures with a quicker return to normal activities and avoid the risk of wound infection which may occur following surgery. Nerve injury remains a risk with thermal ablation, but in cases where it does occur, the injury tends to be transient. Objectives To compare the effectiveness of endovenous laser ablation (EVLA), radiofrequency ablation (RFA) and ultrasound‐guided foam sclerotherapy (UGFS) versus conventional surgery in the treatment of SSV varices. Search methods The Cochrane Vascular Information Specialist searched the Specialised Register (last searched 17 March 2016) and the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 2). We searched clinical trials databases for details of ongoing or unpublished studies. Selection criteria We considered all randomised controlled trials (RCTs) comparing EVLA, endovenous RFA or UGFS with conventional surgery in the treatment of SSV varices for inclusion. Data collection and analysis We independently reviewed, assessed and selected trials that met the inclusion criteria; any disagreements were resolved by discussion. We extracted data and used the Cochrane's tool for assessing risk of bias. When the data permitted, we performed either fixed‐effect meta‐analyses with odds ratios (ORs) and 95% confidence intervals (CIs) or random‐effects meta‐analyses where there was moderate to significant heterogeneity. We identified three RCTs, all of which compared EVLA with surgery; one also compared UGFS with surgery. There were no trials comparing RFA with surgery . The EVLA versus surgery comparison included 311 participants: 185 received EVLA and 126 received surgery. In the UGFS comparison, each treatment group contained 21 people. For several outcomes in the EVLA comparison, only a single study provided relevant data; as a result, the current review is limited in its ability to demonstrate meaningful results for some planned outcomes. The quality of evidence according to GRADE was moderate to low for the outcome measures in the EVLA versus surgery comparison, but low for the UGFS versus surgery comparison. Reasons for downgrading in the EVLA versus surgery comparison were risk of bias (for some outcomes, the outcome assessors were not blinded; and in one study the EVLA‐surgery allocation of 2:1 did not appear to be prespecified); imprecision (data were only available from a single small study and the CIs were relatively wide); indirectness (one trial reported results at six months rather than one year and was inadequately powered for SSV varices‐only analysis). Reasons for downgrading in the UGFS versus surgery comparison were imprecision (only one trial offered UGFS and several participants were missing from the analysis) and a limitation in design (the study was inadequately powered for SSV participants alone). For the EVLA versus surgery comparison, recanalisation or persistence of reflux at six weeks occurred less frequently in the EVLA group than in the surgery group (OR 0.07, 95% CI 0.02 to 0.22; I 2 = 51%; 289 participants, 3 studies, moderate‐quality evidence). Recurrence of reflux at one year was also less frequent in the EVLA group than in the surgery group (OR 0.24, 95% CI 0.07 to 0.77; I 2 = 0%; 119 participants, 2 studies, low‐quality evidence). For the outcome clinical evidence of recurrence (i.e. presence of new visible varicose veins) at one year, there was no difference between the two treatment groups (OR 0.54, 95% CI 0.17 to 1.75; 99 participants, 1 study, low‐quality evidence). Four participants each in the EVLA and surgery groups required reintervention due to technical failure (99 participants, 1 study, moderate‐quality evidence). There was no difference between the two treatment groups for disease‐specific quality of life (QoL) (Aberdeen Varicose Veins Questionnaire) either at six weeks (mean difference (MD) 0.15, 95% CI ‐1.65 to 1.95; I 2 = 0%; 265 participants, 2 studies, moderate‐quality evidence), or at one year (MD ‐1.08, 95% CI ‐3.39 to 1.23; 99 participants, 1 study, low‐quality evidence). Main complications reported at six weeks were sural nerve injury, wound infection and deep venous thrombosis (DVT) (one DVT case in each treatment group; EVLA: 1/161, 0.6%; surgery 1/104, 1%; 265 participants, 2 studies, moderate‐quality evidence). For the UGFS versus surgery comparison, there were insufficient data to detect clear differences between the two treatment groups for the two outcomes recanalisation or persistence of reflux at six weeks (OR 0.34, 95% CI 0.06 to 2.10; 33 participants, 1 study, low‐quality evidence), and recurrence of reflux at one year (OR 1.19, 95% CI 0.29 to 4.92; 31 participants, 1 study, low‐quality evidence). No other outcomes could be reported for this comparison because the study data were not stratified according to saphenous vein. Moderate‐ to low‐quality evidence exists to suggest that recanalisation or persistence of reflux at six weeks and recurrence of reflux at one year are less frequent when EVLA is performed, compared with conventional surgery. For the UGFS versus conventional surgery comparison, the quality of evidence is assessed to be low; consequently, the effectiveness of UGFS compared with conventional surgery in the treatment of SSV varices is uncertain. Further RCTs for all comparisons are required with longer follow‐up (at least five years). In addition, measurement of outcomes such as recurrence of reflux, time taken to return to work, duration of procedure, pain, etc., and choice of time points during follow‐up should be standardised such that future trials evaluating newer technologies can be compared efficiently. |
t102 | Central venous access (CVA) involves a large bore catheter inserted in a vein in the neck, upper chest or groin (femoral) area to give drugs that cannot be given by mouth or via a conventional needle (cannula or tube in the arm). CVA is widely used. However, its thrombotic (causing a blood clot) and infectious complications can be life‐threatening and involve high‐cost therapy. Research has revealed that the risk of catheter‐related complications varies according to the sites of central venous catheter (CVC) insertion. It would be helpful to find the preferred site of insertion to minimize the risk of catheter‐related complications. This review examined whether there was any evidence to show that CVA through any one site (neck, upper chest, or femoral area) is better than the other. Four studies were identified comparing data from 1513 participants. For the purpose of this review, three comparisons were evaluated: 1) internal jugular versus subclavian CVA routes; 2) femoral versus subclavian CVA routes; and 3) femoral versus internal jugular CVA routes. We compared short‐term and long‐term catheter insertion. We defined long‐term as for more than one month and short‐term as for less than one month, according to the Food and Drug Administration (FDA). No randomized controlled trial was found comparing all three CVA routes and reporting the complications of venous stenosis. Subclavian and internal jugular CVA routes had similar risks for catheter‐related complications in long‐term catheter insertion in cancer patients. Subclavian CVA was preferable to femoral CVA in short‐term catheter insertion because of lower risks of catheter colonization and thrombotic complications. In catheter insertion for short‐term haemodialysis, femoral and internal jugular CVA routes had similar risks for catheter‐related complications except internal jugular CVA routes were associated with higher risks of mechanical complications. | Central venous access (CVA) is widely used. However, its thrombotic, stenotic and infectious complications can be life‐threatening and involve high‐cost therapy. Research revealed that the risk of catheter‐related complications varied according to the site of CVA. It would be helpful to find the preferred site of insertion to minimize the risk of catheter‐related complications. This review was originally published in 2007 and was updated in 2011. Objectives 1. Our primary objective was to establish whether the jugular, subclavian or femoral CVA routes resulted in a lower incidence of venous thrombosis, venous stenosis or infections related to CVA devices in adult patients. 2. Our secondary objective was to assess whether the jugular, subclavian or femoral CVA routes influenced the incidence of catheter‐related mechanical complications in adult patients; and the reasons why patients left the studies early. Search methods We searched CENTRAL ( The Cochrane Library 2011, Issue 9), MEDLINE, CINAHL, EMBASE (from inception to September 2011), four Chinese databases (CBM, WANFANG DATA, CAJD, VIP Database) (from inception to November 2011), Google Scholar and bibliographies of published reviews. The original search was performed in December 2006. We also contacted researchers in the field. There were no language restrictions. Selection criteria We included randomized controlled trials comparing central venous catheter insertion routes. Data collection and analysis Three authors assessed potentially relevant studies independently. We resolved disagreements by discussion. Dichotomous data on catheter‐related complications were analysed. We calculated relative risks (RR) and their 95% confidence intervals (CI) based on a random‐effects model. We identified 5854 citations from the initial search strategy; 28 references were then identified as potentially relevant. Of these, we Included four studies with data from 1513 participants. We undertook a priori subgroup analysis according to the duration of catheterization, short‐term (< one month) and long‐term (> one month) defined according to the Food and Drug Administration (FDA). No randomized controlled trial (RCT) was found comparing all three CVA routes and reporting the complications of venous stenosis. Regarding internal jugular versus subclavian CVA routes, the evidence was moderate and applicable for long‐term catheterization in cancer patients. Subclavian and internal jugular CVA routes had similar risks for catheter‐related complications. Regarding femoral versus subclavian CVA routes, the evidence was high and applicable for short‐term catheterization in critically ill patients. Subclavian CVA routes were preferable to femoral CVA routes in short‐term catheterization because femoral CVA routes were associated with higher risks of catheter colonization (14.18% or 19/134 versus 2.21% or 3/136) (n = 270, one RCT, RR 6.43, 95% CI 1.95 to 21.21) and thrombotic complications (21.55% or 25/116 versus 1.87% or 2/107) (n = 223, one RCT, RR 11.53, 95% CI 2.80 to 47.52) than with subclavian CVA routes. Regarding femoral versus internal jugular routes, the evidence was moderate and applicable for short‐term haemodialysis catheterization in critically ill patients. No significant differences were found between femoral and internal jugular CVA routes in catheter colonization, catheter‐related bloodstream infection (CRBSI) and thrombotic complications, but fewer mechanical complications occurred in femoral CVA routes (4.86% or 18/370 versus 9.56% or 35/366) (n = 736, one RCT, RR 0.51, 95% CI 0.29 to 0.88). Subclavian and internal jugular CVA routes have similar risks for catheter‐related complications in long‐term catheterization in cancer patients. Subclavian CVA is preferable to femoral CVA in short‐term catheterization because of lower risks of catheter colonization and thrombotic complications. In short‐term haemodialysis catheterization, femoral and internal jugular CVA routes have similar risks for catheter‐related complications except internal jugular CVA routes are associated with higher risks of mechanical complications. |
t103 | We reviewed the evidence about the effect of antidepressants on depression in people with dementia. Depression can be hard to recognise in people with dementia, but there is evidence that it is common and associated with increased disability, poorer quality of life, and shorter life expectancy. Many people with dementia are prescribed antidepressants to treat depression, but there is uncertainty about how effective this is. Each of them used a set of formal criteria to diagnose both depression and dementia and compared an antidepressant against a dummy pill (placebo). The older studies used more old‐fashioned antidepressants (imipramine, clomipramine, and moclobemide) and the newer studies used more modern ones, such as venlafaxine, mirtazapine and so‐called SSRI antidepressants (sertraline, fluoxetine, citalopram and escitalopram). The people taking part in the studies had an average age of 75 and they had mild or moderate dementia. We found that there was little or no difference in scores on depression rating scales between people treated with antidepressants and those treated with placebo for 12 weeks. The evidence to support this finding was of high quality, which suggests that further research is unlikely to find a different result. Another way to assess the effect of antidepressants is to count the number of people in the antidepressant and placebo groups who show significant clinical improvement (response) or who recover from depression (remission). There was low‐quality evidence on the number of people showing a significant clinical improvement and the result was imprecise so we were unable to be sure of any effect on this measure. People taking an antidepressant were probably more likely to recover from depression than were those taking placebo (antidepressant: 40%, placebo: 21.7%). There was moderate‐quality evidence for this finding, so it is possible that further research could find a different result. We found that antidepressants did not affect the ability to manage daily activities and probably had little or no effect on a test of cognitive function (which includes attention, memory, and language). | The use of antidepressants in dementia accompanied by depressive symptoms is widespread, but their clinical efficacy is uncertain. This review updates an earlier version, first published in 2002. Objectives To determine the efficacy and safety of any type of antidepressant for patients who have been diagnosed as having dementia of any type and depression as defined by recognised criteria. Search methods We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group’s Specialised Register, on 16 August 2017. ALOIS contains information on trials retrieved from databases and from a number of trial registers and grey literature sources. Selection criteria We included all relevant double‐blind, randomised trials comparing any antidepressant drug with placebo, for patients diagnosed as having dementia and depression. Data collection and analysis Two review authors selected studies for inclusion and extracted data independently. We assessed risk of bias in the included studies using the Cochrane 'Risk of bias' tool. Where clinically appropriate, we pooled data for treatment periods up to three months and from three to nine months. We included ten studies with a total of 1592 patients. Eight included studies reported sufficiently detailed results to enter into analyses related to antidepressant efficacy. We split one study which included two different antidepressants and therefore had nine groups of patients treated with antidepressants compared with nine groups receiving placebo treatment. Information needed to make 'Risk of bias' judgements was often missing. We found high‐quality evidence of little or no difference in scores on depression symptom rating scales between the antidepressant and placebo treated groups after 6 to 13 weeks (standardised mean difference (SMD) ‐0.10, 95% confidence interval (CI) ‐0.26 to 0.06; 614 participants; 8 studies). There was probably also little or no difference between groups after six to nine months (mean difference (MD) 0.59 point, 95% CI ‐1.12 to 2.3, 357 participants; 2 studies; moderate‐quality evidence). The evidence on response rates at 12 weeks was of low quality, and imprecision in the result meant we were uncertain of any effect of antidepressants (antidepressant: 49.1%, placebo: 37.7%; odds ratio (OR) 1.71, 95% CI 0.80 to 3.67; 116 participants; 3 studies). However, the remission rate was probably higher in the antidepressant group than the placebo group (antidepressant: 40%, placebo: 21.7%; OR 2.57, 95% CI 1.44 to 4.59; 240 participants; 4 studies; moderate‐quality evidence). The largest of these studies continued for another 12 weeks, but because of imprecision of the result we could not be sure of any effect of antidepressants on remission rates after 24 weeks. There was evidence of no effect of antidepressants on performance of activities of daily living at weeks 6 to 13 (SMD ‐0.05, 95% CI ‐0.36 to 0.25; 173 participants; 4 studies; high‐quality evidence) and probably also little or no effect on cognition (MD 0.33 point on the Mini‐Mental State Examination, 95% CI ‐1.31 to 1.96; 194 participants; 6 studies; moderate‐quality evidence). Participants on antidepressants were probably more likely to drop out of treatment than those on placebo over 6 to 13 weeks (OR 1.51, 95% CI 1.07 to 2.14; 836 participants; 9 studies). The meta‐analysis of the number of participants suffering at least one adverse event showed a significant difference in favour of placebo (antidepressant: 49.2%, placebo: 38.4%; OR 1.55, 95% CI 1.21 to 1.98, 1073 participants; 3 studies), as did the analyses for participants suffering one event of dry mouth (antidepressant: 19.6%, placebo: 13.3%; OR 1.80, 95% CI 1.23 to 2.63, 1044 participants; 5 studies), and one event of dizziness (antidepressant: 19.2%, placebo: 12.5%; OR 2.00, 95% CI 1.34 to 2.98, 1044 participants; 5 studies). Heterogeneity in the way adverse events were reported in studies presented a major difficulty for meta‐analysis, but there was some evidence that antidepressant treatment causes more adverse effects than placebo treatment does. The available evidence is of variable quality and does not provide strong support for the efficacy of antidepressants for treating depression in dementia, especially beyond 12 weeks. On the only measure of efficacy for which we had high‐quality evidence (depression rating scale scores), antidepressants showed little or no effect. The evidence on remission rates favoured antidepressants but was of moderate quality, so future research may find a different result. There was insufficient evidence to draw conclusions about individual antidepressant drugs or about subtypes of dementia or depression. There is some evidence that antidepressant treatment may cause adverse events. |
t104 | Colorectal (large bowel) cancer including rectal cancer is the third most common cause of cancer deaths in the western world. The risk of developing rectal cancer increases with age and is most common in people around 70 years of age. The treatment consists of complete surgical resection of the tumour and surrounding tissue by a technique called total mesorectal excision (TME), sometimes combined with chemotherapy and radiotherapy. This surgery can be performed by either normal open abdominal surgery with a large incision or by keyhole laparoscopic surgery with several small incisions for the instruments and camera. For colon cancer, laparoscopic surgery is proven to result in faster postoperative recovery, fewer complications and better cosmetic results. These results are expected to be equal for rectal surgery. However, surgery for rectal cancer is technically more difficult than for colon cancer due to the location deeper in the pelvis and close to important nerves. Therefore a complete and safe resection of the tumour should be guaranteed, this is important to reduce the risk of recurrence of the tumour and could be tested by assessing recurrence rates and patient survival in the long term. In this updated review, we have assessed all randomised studies of laparoscopic and open TME for rectal cancer, to compare and combine their results. We included 14 trials reporting on a total of 3528 patients undergoing rectal cancer surgery. In 14.5% of those having laparoscopic surgery needed conversion to open surgery by a large incision in the abdomen due to difficulties or problems during the procedure. There is currently moderate quality evidence that laparoscopic total mesorectal excision (LTME) has similar effects to open TME (OTME) on long term survival outcomes for the treatment of rectal cancer. The estimated effect was imprecise and further research could impact on our confidence int this result. There is moderate quality evidence that it leads to better short‐term post‐surgical outcomes in terms of length of hospital stay. We found that pain was lower in the LTME group and that resumption of diet was better. We did not find clear evidence of a difference in quality of life between the two groups, but costs were higher for LTME. We await long‐term data from a number of ongoing and recently completed studies to contribute to our understanding of the effects of these surgical approaches on long‐term disease free, overall survival and local recurrence. | Colorectal cancer including rectal cancer is the third most common cause of cancer deaths in the western world. For colon carcinoma, laparoscopic surgery is proven to result in faster postoperative recovery, fewer complications and better cosmetic results with equal oncologic results. These short‐term benefits are expected to be similar for laparoscopic rectal cancer surgery. However, the oncological safety of laparoscopic surgery for rectal cancer remained controversial due to the lack of definitive long‐term results. Thus, the expected short‐term benefits can only be of interest when oncological results are at least equal. Objectives To evaluate the differences in short‐ and long‐term results after elective laparoscopic total mesorectal excision (LTME) for the resection of rectal cancer compared with open total mesorectal excision (OTME). Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2013, Issue 2), MEDLINE (January 1990 to February 2013), EMBASE (January 1990 to February 2013), ClinicalTrials.gov (February 2013) and Current Controlled Trials (February 2013). We handsearched the reference lists of the included articles for missed studies. Selection criteria Only randomised controlled trials (RCTs) comparing LTME and OTME, reporting at least one of our outcome measures, was considered for inclusion. Data collection and analysis Two authors independently assessed study quality according to the CONSORT statement, and resolved disagreements by discussion. We identified 45 references out of 953 search results, of which 14 studies met the inclusion criteria involving 3528 rectal cancer patients. We did not consider the risk of bias of the included studies to have impacted on the quality of the evidence. Data were analysed according to an intention‐to‐treat principle with a mean conversion rate of 14.5% (range 0% to 35%) in the laparoscopic group. There was moderate quality evidence that laparoscopic and open TME had similar effects on five‐year disease‐free survival (OR 1.02; 95% CI 0.76 to1.38, 4 studies, N = 943). The estimated effects of laparoscopic and open TME on local recurrence and overall survival were similar, although confidence intervals were wide, both with moderate quality evidence (local recurrence: OR 0.89; 95% CI 0.57 to1.39 and overall survival rate: OR 1.15; 95% CI 0.87 to1.52). There was moderate to high quality evidence that the number of resected lymph nodes and surgical margins were similar between the two groups. For the short‐term results, length of hospital stay was reduced by two days (95% CI ‐3.22 to ‐1.10), moderate quality evidence), and the time to first defecation was shorter in the LTME group (‐0.86 days; 95% CI ‐1.17 to ‐0.54). There was moderate quality evidence that 30 days morbidity were similar in both groups (OR 0.94; 95% CI 0.8 to 1.1). There were fewer wound infections (OR 0.68; 95% CI 0.50 to 0.93) and fewer bleeding complications (OR 0.30; 95% CI 0.10 to 0.93) in the LTME group. There was no clear evidence of any differences in quality of life after LTME or OTME regarding functional recovery, bladder and sexual function. The costs were higher for LTME with differences up to GBP 2000 for direct costs only. We have found moderate quality evidence that laparoscopic total mesorectal excision (TME) has similar effects to open TME on long term survival outcomes for the treatment of rectal cancer. The quality of the evidence was downgraded due to imprecision and further research could impact on our confidence in this result. There is moderate quality evidence that it leads to better short‐term post‐surgical outcomes in terms of recovery for non‐locally advanced rectal cancer. Currently results are consistent in showing a similar disease‐free survival and overall survival, and for recurrences after at least three years and up to 10 years, although due to imprecision we cannot rule out superiority of either approach. We await long‐term data from a number of ongoing and recently completed studies to contribute to a more robust analysis of long‐term disease free, overall survival and local recurrence. |
t105 | We reviewed the evidence regarding the effect of any type of chest physiotherapy for children with pneumonia. Pneumonia is a type of lung infection and the biggest cause of worldwide deaths among children aged up to five years. Chest physiotherapy may contribute to children's recovery because it can help to open airways and assist breathing. We included six studies involving 559 children with pneumonia aged from 29 days to 12 years. This is an update of a review published in 2013 and includes three new studies. Studies were conducted in hospitals in Bangladesh, Brazil, China, Egypt, and South Africa. Pneumonia was described as moderate to severe in three studies, but severity was not described in three studies. All studies included children who received physiotherapy and others who did not. All children also received standard medical treatment for pneumonia. The studies assessed deaths, length of hospital stay, time taken to attain normal test results (no signs of pneumonia), and adverse events. Study funding sources Four studies reported sources of funding (a child health agency, university, government research grants), and two did not report study funding sources. One study reported fewer deaths in children who received bubble continuous positive airway pressure (bCPAP). Physiotherapy techniques (bCPAP, assisted autogenic drainage, and conventional chest physiotherapy) were not associated with shorter hospital stays. Two studies reported improvements in blood oxygen levels after chest physiotherapy (CPAP and conventional chest physiotherapy). No clear improvement in respiratory rate was observed after conventional chest physiotherapy. Based on the available evidence, we could not confirm if chest physiotherapy is beneficial or not for children with pneumonia. | Pneumonia is a lung infection that causes more deaths in children aged under five years than any other single cause. Chest physiotherapy is widely used as adjuvant treatment for pneumonia. Physiotherapy is thought to help remove inflammatory exudates, tracheobronchial secretions, and airway obstructions, and reduce airway resistance to improve breathing and enhance gas exchange. This is an update of a review published in 2013. Objectives To assess the effectiveness of chest physiotherapy with regard to time until clinical resolution in children (from birth to 18 years) of either gender with any type of pneumonia. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 1), which includes the Cochrane Acute Respiratory Infections Group Specialised Register, MEDLINE (22 February 2018), Embase (22 February 2018), CINAHL (22 February 2018), LILACS (22 February 2018), Web of Science (22 February 2018), and PEDro (22 February 2018). We also searched clinical trials registers (ClinicalTrials.gov and WHO ICTRP) to identify planned, ongoing, and unpublished trials. Selection criteria We included randomised controlled trials (RCTs) that compared any type of chest physiotherapy with no chest physiotherapy for children with pneumonia. Data collection and analysis We used standard Cochrane methodological procedures. The primary outcomes of interest were mortality, duration of hospital stay, and time to clinical resolution. We included three new RCTs for this update, for a total of six included RCTs involving 559 children aged from 29 days to 12 years with pneumonia who were treated as inpatients. Pneumonia severity was described as moderate in one trial, severe in two trials, and was not stated in three trials . The studies assessed five different interventions: effects of conventional chest physiotherapy (3 studies, 211 children), positive expiratory pressure (1 study, 72 children), continuous positive airway pressure (CPAP) (1 study, 94 children), bubble CPAP (bCPAP) (1 study, 225 children), and assisted autogenic drainage (1 studies, 29 children). The included studies were conducted in Bangladesh, Brazil, China, Egypt, and South Africa. The studies were overall at low risk of bias. Blinding of participants was not possible in most studies, but we considered that the outcomes were unlikely to be influenced by the lack of blinding. One study of bCPAP reported that three deaths occurred in children in the physiotherapy group (N = 79), and 20 deaths in the control group (N = 146) (risk ratio (RR) 0.28, 95% confidence interval (CI) 0.08 to 0.90; 225 children; low‐quality evidence). One study of assisted autogenic drainage (N = 29), and one study of conventional chest physiotherapy (N = 72) reported no deaths occurred. It is uncertain whether chest physiotherapy techniques (bCPAP, assisted autogenic drainage, and conventional chest physiotherapy) reduced hospital stay duration (days) (mean difference (MD) 0.10, 95% CI ‐0.56 to 0.76; 4 studies; low‐quality evidence). There was variation among clinical parameters used to define clinical resolution. Two small studies found no difference in resolution of fever between children in the physiotherapy (conventional chest physiotherapy and assisted autogenic drainage) and control groups. Of five studies that considered peripheral oxygen saturation levels, only two reported that use of chest physiotherapy (CPAP and conventional chest physiotherapy) showed a greater improvement in peripheral oxygen saturation levels. However, it was unclear whether respiratory rate (breaths/min) improved after conventional chest physiotherapy (MD ‐2.25, 95% CI ‐5.17 to 0.68; 2 studies, 122 children; low‐quality evidence). Two studies assessed adverse events (number of events), but only one study reported any events (RR 1.28, 95% CI 0.98 to 1.67; 2 studies, 254 children; low‐quality evidence). We could draw no reliable conclusions concerning the use of chest physiotherapy for children with pneumonia due to the small number of included trials with differing and statistical presentation of data. Future studies should consider the following key points: appropriate sample size with adequate power to detect expected differences, standardisation of chest physiotherapy techniques, appropriate outcomes (such as duration of leukocytosis, and airway clearance), and adverse effects. |
t106 | Speech and language therapy for children with cerebral palsy might improve their communication skills, but more research is needed. Cerebral palsy (CP) is a movement disorder caused by damage to the brain before, during or soon after birth. The ability for people with CP to communicate effectively is often impaired by problems with speech and also gestures usually used in communication. Speech and language therapy aims to help people with CP maximise their communication skills. This can include ways of enhancing natural forms of communication, introducing aids such as symbol charts or devices with synthetic speech, and training communication partners. The review found some weak evidence that speech and language therapy might help children with CP, but more research is needed. | The production of speech, language and gesture for communication is often affected by cerebral palsy. Communication difficulties associated with cerebral palsy can be multifactorial, arising from motor, intellectual and sensory impairments. Children with this diagnosis can experience mild to severe difficulties in expressing themselves. They are often referred to speech and language therapy (SLT) services to maximise their communication skills and help them to take as independent a role as possible in interaction activities. Therapy can include introducing augmentative and alternative communication (AAC) systems, such as symbol charts or communication aids with synthetic speech, as well as treating children's natural forms of communication. Various strategies have been used to treat the communication disorders associated with cerebral palsy, but evidence of their effectiveness is limited. Objectives To determine the effectiveness of SLT that focuses on the child or their familiar communication partners, as measured by change in interaction patterns. To determine if individual types of SLT intervention are more effective than others in changing interaction patterns. Search methods Searches were conducted of MEDLINE, CINAHL, EMBASE, PsycINFO, LLBA, ERIC, WEB of SCIENCE, Scopus, NRR, BEI, SIGLE (to January 2011). A previous version of this review included studies up to the end of 2002. References from identified studies were examined and relevant journals and conference reports were handsearched. Selection criteria Any experimental study containing an element of a control was included in this review. This includes non‐randomised group studies and single case experimental designs in which two interventions were compared or two communication processes were examined. Data collection and analysis All authors searched for and selected studies for inclusion. L Pennington (LP) assessed all papers for inclusion, J Goldbart (JG) and J Marshall (JM) independently assessed separate random samples, each comprising 25% of all identified studies. Two review authors independently abstracted data from each selected study. Disagreements were settled by discussion between the three review authors. Sixteen studies were included in the review. Nine studies evaluated treatment given directly to children, seven investigated the effects of training for communication partners. Participants in the studies varied widely in age, type and severity of cerebral palsy, cognitive and linguistic skills. Studies focusing directly on children suggest that this model of therapy delivery has been associated with increases in treated speech and communication skills by individual children. However, methodological flaws and small sample sizes prevent firm conclusions being made about the effectiveness of the therapy. In addition, maintenance of these skills was not investigated thoroughly. The studies targeting communication partners used small exploratory group designs which often contained insufficient detail to allow replication, although more recent studies have improved in this area. Overall, the studies of indirect intervention have very low power and cannot provide evidence of effectiveness of this type of treatment. Firm evidence of the positive effects of SLT for children with cerebral palsy has not been demonstrated by this review. However, positive trends in communication change were shown. No change in practice is recommended from this updated review. Further research is needed to describe this client group, and its possible clinical subgroups, and the methods of treatment currently used in SLT. Research is also needed to investigate the effectiveness of new and established interventions and their acceptability to families. Rigour in research practice needs to be extended to enable firm associations between therapy and the communication change to be made. There are now sufficient data to develop randomised controlled studies of dysarthria interventions and group parent training programmes. Such research is urgently needed to ensure clinically effective provision for this group of children, who are at severe risk of social and educational exclusion. |
t107 | We reviewed the evidence on the effects of corticosteroids given by mouth or injection for acute middle ear infection (acute otitis media (AOM)) in children, particularly in improving symptoms such as ear pain, fever, irritability, lack of sleep, and lack of appetite. We also looked at the side effects of corticosteroids. Acute otitis media is common in children and causes ear pain and non‐specific symptoms such as fever, irritability, and deafness. It is often treated with antibiotics, although ear pain generally resolves within two days, and antibiotics help symptoms only slightly. Other treatments (such as over‐the‐counter antihistamines and decongestants) do not help very much. Corticosteroids are often prescribed to reduce inflammation in children for other illnesses, and so may also help symptoms of AOM, which is an inflammatory process. We investigated whether using corticosteroids was better or worse than nothing in improving AOM‐related symptoms. We included two studies involving 252 children with AOM, aged from three months to six years, receiving hospital ambulatory care. Children were treated with an antibiotic injection and either oral corticosteroid or a placebo (treatment with no effect). In one study, fluid from the middle ear was collected by inserting a needle through the eardrum to measure the level of inflammation. Study funding sources The National Institutes of Health (NIH) and the National Center for Research Resources, NIH, US Public Health Service funded both studies. Pharmaceutical companies provided the drug but did not contribute any other scientific or financial support. Corticosteroids did not make a significant difference in improving the symptoms and inflammation of the eardrum(s) at Day 5 and Day 14, but we are unsure of this effect due to the small numbers of children in the studies. There were no significant differences between the corticosteroid and placebo groups in terms of resolving fluid in children's middle ears (at 1, 2, and 3 months) and experiencing new episodes of AOM (at 1, 2, 3 months, and 4 and 6 months). Neither study reported a reduction in the duration of overall or specific symptoms, rupture of eardrum(s), the occurrence of middle ear inflammation in the other ear following the current ear infection, or serious complications. We could not draw any conclusions regarding the effects of corticosteroids for AOM in children. | Acute otitis media (AOM) is a common acute infection in children. Pain is its most prominent and distressing symptom. Antibiotics are commonly prescribed for AOM, although they have only a modest effect in reducing pain at two to three days. There is insufficient evidence for benefits of other treatment options, including systemic corticosteroids. However, systemic corticosteroids are potent anti‐inflammatory drugs, and so theoretically could be effective, either alone or as an addition to antibiotics. Objectives To assess the effects of systemic corticosteroids (oral or parenteral), with or without antibiotics, for AOM in children. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) which contains the Cochrane ARI Group's Specialised Register, MEDLINE (Ovid), Embase (Elsevier), CINAHL (EBSCO), Web of Science (Thomson Reuters), and LILACS (BIREME) for published studies, and ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) for completed and ongoing studies, to 20 February 2018. We checked the reference lists of all primary studies and review articles for additional references and contacted experts in the field to identify additional unpublished materials. Selection criteria We included randomised controlled trials of children with AOM that compared any systemic corticosteroid (oral or parenteral) with placebo, either with antibiotics (corticosteroid plus antibiotic versus placebo plus antibiotic) or without antibiotics (corticosteroid versus placebo). Data collection and analysis Three review authors (EDS, RR, YP) independently screened the titles and abstracts and retrieved the full texts of potentially relevant studies. We independently extracted and outcome data from the included studies, and assessed the risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We assessed study quality using the GRADE method. We included two studies involving 252 children with AOM aged from three months to six years receiving hospital ambulatory care who were treated with intramuscular ceftriaxone, and who were then randomised to the corticosteroid group (corticosteroid and corticosteroid plus antihistamine) or the placebo group (antihistamine and double placebo). In one study, children also had a needle aspiration of middle ear fluid. Both studies were at unclear risk of bias for allocation concealment, and unclear to high risk of bias for selective reporting. One study (N = 179) included pain as an outcome, but we were unable to derive the proportion of children with persistent pain at Day 5 and Day 14. Reduction of overall or specific symptoms was presented as improvement in clinical symptoms and resolution of inflamed tympanic membranes without the need for additional antibiotic treatment: at Day 5 (94% of children in the treatment group (N = 89) versus 89% in the placebo group (N = 90); risk ratio (RR) 1.06, 95% confidence interval (CI) 0.97 to 1.16) and Day 14 (91% versus 87%; RR 1.05, 95% CI 0.95 to 1.17). Low‐quality evidence meant that we are uncertain of the effectiveness of corticosteroids for this outcome. The second study (N = 73) reported a reduction of overall or specific symptoms without additional antibiotic treatment during the first two weeks as a favourable outcome. Children in the treatment group had more favourable outcomes (adjusted odds ratio 65.9, 95% CI 1.28 to 1000; P = 0.037), although the numbers were small. We were unable to pool the results with the other study because it did not report the proportion of children with this outcome by treatment group. Only one study reported adverse effects of corticosteroids (e.g. drowsiness, nappy rash), but did not quantify incidence, so we were unable to draw conclusions about adverse effects. Neither study reported a reduction in overall or specific symptom duration. The evidence for the effect of systemic corticosteroids on AOM is of low to very low quality, meaning the effect of systemic corticosteroids on important clinical outcomes in AOM remains uncertain. Large, high‐quality studies are required to resolve the question . |
t108 | We reviewed the evidence about the effects of exercise rehabilitation on functional exercise capacity and health‐related quality of life for patients who have been critically unwell in the intensive care unit (ICU). Functional exercise capacity is a term used to express how well individuals perform activities such as walking or climbing the stairs. Adults often develop muscle wasting and weakness during ICU admission. This may occur as a result of the illness itself, and because patients tend to be less mobile and physically active whilst they are receiving treatment. As they recover, this muscle weakness can cause difficulty in their ability to exercise and carry out normal activities of daily living. Adult patients can become depressed or low in mood as a result of the illness and the effects of their reduced strength, which can last for many years. We wanted to measure health‐related quality of life to determine whether exercise programmes can help patients recover from critical illness‐related physical deconditioning and muscle weakness after they have been discharged from the ICU, and can help them to feel better about themselves. We included six studies that involved 483 participants (298 male, 185 female) over the age of 18 years. Participants had received breathing support from a machine (been mechanically ventilated) for longer than 24 hours whilst in the ICU and had begun an exercise programme after leaving the ICU. Studies were carried out in the UK, Australia, the USA and Italy. Exercise programmes were delivered on the ward in two studies; on the ward and in the community in one study; and in the community in three studies. The duration of the intervention varied according to length of hospital stay after ICU discharge up to a fixed time of 12 weeks. Exercises included arm or leg cycling, walking and general muscle strengthening at home, provision of self help manuals and hospital‐based multi‐exercise programmes carried out in physiotherapist‐led gymnasiums. Three of the six studies were funded by government health research funding agencies. One study was supported by combined funding from an independent charity and a commercial company (with no interest in the results of the study). One study did not report a funding source, and another was funded by an academic health research agency. Three studies reported improvement in functional exercise capacity following completion of the exercise programme, and the other three found no effects of treatment. Only two studies measured patient‐reported health‐related quality of life, and both of these studies showed no effects related to treatment. No study included an evaluation of acceptance of the treatment by patients or the experience of patient participation in an exercise‐based programme. We found considerable differences across included studies regarding types of exercise, how measurements of functional exercise capacity were collected, ways by which results were presented and people who had been critically ill. Exercise programmes were compared with usual care, with lack of acknowledgement of the standard level of rehabilitation and exercise in usual practice. | Skeletal muscle wasting and weakness are significant complications of critical illness, associated with degree of illness severity and periods of reduced mobility during mechanical ventilation. They contribute to the profound physical and functional deficits observed in survivors. These impairments may persist for many years following discharge from the intensive care unit (ICU) and can markedly influence health‐related quality of life. Rehabilitation is a key strategy in the recovery of patients after critical illness. Exercise‐based interventions are aimed at targeting this muscle wasting and weakness. Physical rehabilitation delivered during ICU admission has been systematically evaluated and shown to be beneficial. However, its effectiveness when initiated after ICU discharge has yet to be established. Objectives To assess the effectiveness of exercise rehabilitation programmes, initiated after ICU discharge, for functional exercise capacity and health‐related quality of life in adult ICU survivors who have been mechanically ventilated longer than 24 hours. Search methods We searched the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid SP MEDLINE, Ovid SP EMBASE and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) via EBSCO host to 15 May 2014. We used a specific search strategy for each database. This included synonyms for ICU and critical illness, exercise training and rehabilitation. We searched the reference lists of included studies and contacted primary authors to obtain further information regarding potentially eligible studies. We also searched major clinical trials registries (Clinical Trials and Current Controlled Trials) and the personal libraries of the review authors. We applied no language or publication restriction. We reran the search in February 2015 and will deal with the three studies of interest when we update the review. Selection criteria We included randomized controlled trials (RCTs), quasi‐RCTs and controlled clinical trials (CCTs) that compared an exercise intervention initiated after ICU discharge versus any other intervention or a control or ‘usual care’ programme in adult (≥ 18 years) survivors of critical illness. Data collection and analysis We used standard methodological procedures as expected by the Cochrane Collaboration. We included six trials (483 adult ICU participants). Exercise‐based interventions were delivered on the ward in two studies; both on the ward and in the community in one study; and in the community in three studies. The duration of the intervention varied according to length of hospital stay following ICU discharge (up to a fixed duration of 12 weeks). Risk of bias was variable for all domains across all trials. High risk of bias was evident in all studies for performance bias, although blinding of participants and personnel in therapeutic rehabilitation trials can be pragmatically challenging. For other domains, at least half of the studies were at low risk of bias. One study was at high risk of selection bias, attrition bias and other sources of bias. Risk of bias was unclear for the remaining studies across domains. We decided not to undertake a meta‐analysis because of variation in study design, types of interventions and outcome measurements. We present a narrative description of individual studies for each outcome. All six studies assessed functional exercise capacity, although we noted wide variability in the nature of interventions, outcome measures and associated metrics and data reporting. Individually, three studies reported positive results in favour of the intervention. One study found a small short‐term benefit in anaerobic threshold (mean difference (MD) 1.8 mL O 2 /kg/min, 95% confidence interval (CI) 0.4 to 3.2; P value = 0.02). In a second study, both incremental (MD 4.7, 95% CI 1.69 to 7.75 watts; P value = 0.003) and endurance (MD 4.12, 95% CI 0.68 to 7.56 minutes; P value = 0.021) exercise testing results were improved with intervention. Finally self reported physical function increased significantly following use of a rehabilitation manual (P value = 0.006). Remaining studies found no effect of the intervention. Similar variability was evident with regard to findings for the primary outcome of health‐related quality of life. Only two studies evaluated this outcome. Individually, neither study reported differences between intervention and control groups for health‐related quality of life due to the intervention. Four studies reported rates of withdrawal, which ranged from 0% to 26.5% in control groups, and from 8.2% to 27.6% in intervention groups. The quality of evidence for the effect of the intervention on withdrawal was low. Very low‐quality evidence showed rates of adherence with the intervention. Mortality ranging from 0% to 18.8% was reported by all studies. The quality of evidence for the effect of the intervention on mortality was low. Loss to follow‐up, as reported in all studies, ranged from 0% to 14% in control groups, and from 0% to 12.5% in intervention groups, with low quality of evidence. Only one non‐mortality adverse event was reported across all participants in all studies (a minor musculoskeletal injury). At this time, we are unable to determine an overall effect on functional exercise capacity, or on health‐related quality of life, of an exercise‐based intervention initiated after ICU discharge for survivors of critical illness. Meta‐analysis of findings was not appropriate because the number of studies and the quantity of data were insufficient. Individual study findings were inconsistent. Some studies reported a beneficial effect of the intervention on functional exercise capacity, and others did not. No effect on health‐related quality of life was reported. Methodological rigour was lacking across several domains, influencing the quality of the evidence. Wide variability was noted in the characteristics of interventions, outcome measures and associated metrics and data reporting. If further trials are identified, we may be able to determine the effects of exercise‐based intervention following ICU discharge on functional exercise capacity and health‐related quality of life among survivors of critical illness. |
t109 | Waterpipe smoking is a traditional method of tobacco use, especially in the Eastern Mediterranean Region, but its use is now spreading worldwide. It is smoked socially and often shared between friends or family at home, or in bars and cafes that provide waterpipes to patrons. In the absence of relevant data, many waterpipe tobacco smokers believe this form of tobacco use is less lethal and addictive than other methods of tobacco smoking, because the smoke passes through water on its way to the user. At least in some cultures, women and girls are more likely to use a waterpipe than other forms of tobacco, and it is popular among younger smokers. Current evidence suggests that waterpipe smoking may be as addictive as other forms of tobacco use, that some users have difficulty quitting on their own and that they may experience similar risks to health as cigarette smokers. We also searched a number of electronic databases, including MEDLINE, EMBASE, PsycINFO and CINAHL, using a variety of names and spellings for waterpipe use ('waterpipe' or 'narghile' or 'arghile' or 'shisha' or 'goza' or 'narkeela' or 'hookah' or 'hubble bubble'). We searched for published and unpublished trials in any language, and especially in areas where waterpipe use is widespread. We identified three studies that tested behavioural methods to help waterpipe smokers to quit. Two were waterpipe‐specific interventions and one was a non‐specific tobacco intervention.One small, pilot study was set in the USA, and delivered a Powerpoint presentation online to 91 college students who were using waterpipe. One study was a secondary analysis of data from 264 waterpipe smokers who were part of a trial that enrolled people suspected of having tuberculosis from 33 healthcare clinics in Pakistan. Clinics were randomly assigned to deliver a behavioural intervention versus control (usual care), or a behavioural intervention plus medication (bupropion) versus control (usual care). The third study, set in Egypt, targeted both cigarette and waterpipe smokers, and was a community‐based programme. In all three trials, the percentage of participants who stopped smoking waterpipe was higher in the intervention groups than in the control groups, although this was a statistically significant finding in only two of the trials. People who received either behavioural treatment or behavioural treatment plus buproprion were more likely to quit waterpipe smoking at six months follow‐up than those who received usual care. Men smoking waterpipe in the Egyptian study were more likely to have quit at one year follow‐up in the intervention villages than in the control villages. | Waterpipe tobacco smoking is a traditional method of tobacco use, especially in the Eastern Mediterranean Region (EMR), but its use is now spreading worldwide. Recent epidemiological data, for example, show that waterpipe smoking has become the most prevalent tobacco use method among adolescents in the EMR, and the second most prevalent in the US. Waterpipes are used socially, often being shared between friends or family at home, or in dedicated bars and cafes that provide waterpipes to patrons. Because the smoke passes through a reservoir of water, waterpipe tobacco smoking is perceived as being less harmful than other methods of tobacco use. At least in some cultures, women and girls are more likely to use a waterpipe than to use other forms of tobacco, and it is popular among younger smokers. Accumulating evidence suggests that some waterpipe smokers become addicted, have difficulty quitting, and experience similar health risks as cigarette smokers. Objectives To evaluate the effectiveness of tobacco cessation interventions for waterpipe users. Search methods We searched the Cochrane Tobacco Addiction Review Group specialized register in June 2015. We also searched MEDLINE, EMBASE, PsycINFO and CINAHL , using variant terms and spellings ('waterpipe' or 'narghile' or 'arghile' or 'shisha' or 'goza' or 'narkeela' or 'hookah' or 'hubble bubble'). We searched for trials, published or unpublished, in any language, and especially in regions where waterpipe use is widespread. Selection criteria We sought randomized, quasi‐randomized or cluster‐randomized controlled trials of smoking cessation interventions for waterpipe smokers of any age or gender. The primary outcome of interest was abstinence from tobacco use, measured at six months post‐cessation or longer, regardless of whether abstinence was biochemically verified. We included interventions that were pharmacological (for example, nicotine replacement therapy (NRT) or bupropion) or behavioural, or both, and could be directed at individual waterpipe users or at groups of users. We only included tobacco cessation interventions, and did not consider trials of prevention of uptake. Data collection and analysis Two review authors assessed abstracts of the studies retrieved by the search strategy, for possible inclusion in the review. We retrieved full‐text articles for all abstracts that any of the authors believed might be suitable. Two review authors then extracted data and assessed trial quality independently in accordance with standard Cochrane Collaboration methodologies. We aimed to pool groups of studies that we considered to be sufficiently similar, provided there was no evidence of substantial statistical heterogeneity, and aimed to estimate a pooled risk ratio (RR) using the Mantel‐Haenszel fixed‐effect method. Where meta‐analysis was not possible, we presented summary and descriptive statistics. Our search retrieved 1311 unique citations, of which 1289 were excluded after title and abstract screening. Of the remaining 22, we excluded 19 because they were empirical studies that were not randomized, quasi‐randomized or cluster‐randomized controlled trials (n = 12), because they were review articles (n = 3), because they described protocols only (n = 2), they were conducted among cigarette smokers only (n = 1), or they had only a three‐month follow‐up (n = 1). We identified three controlled trials which tested cessation interventions for waterpipe smokers. Studies were carried out in Egypt (Mohlman 2013), Pakistan (Dogar 2014), and the US (Lipkus 2011). One was a randomized controlled trial and two were cluster‐randomized trials. Two studies tested individual‐level interventions, and one tested a community‐level intervention. Two studies included only behavioural interventions, and one study (Dogar 2014) included two intervention groups: one behavioural, and the other behavioural with bupropion. The Lipkus and Mohlman studies delivered waterpipe‐specific interventions, and the Dogar study delivered a non‐specific tobacco intervention. Due to study variation we did not pool results, and intervention effects are reported descriptively. Compared to control groups, waterpipe smoking cessation rates were higher in the intervention groups in all three studies, with a significant difference in two studies. For the Dogar study, the RRs for waterpipe smoking abstinence at 25 weeks among waterpipe‐only smokers were 2.2 (95% confidence interval (CI) 1.3 to 3.8; 180 participants) in the behavioural group, and 2.5 (95% CI 1.3 to 4.7; 84 participants) in the behavioural plus bupropion group. In our analysis we have combined both groups, to give a RR of 2.28 (95% CI 1.36 to 3.83; 200 participants). The Mohlman study delivered a RR in male waterpipe‐smokers at one year in favour of the intervention of 3.25 (95% CI 1.19 to 8.89). Although the literature on waterpipe cessation interventions remains sparse, the reviewed studies provide a basis for developing interventions in this area. The lack of statistically significant effects in one of the three studies is not unexpected, given the small and pilot nature of the studies. The studies highlight important design and content issues that need to be considered for future cessation trials in waterpipe smokers. These include building on the vast experience developed in the study of smoking cessation interventions in cigarette smokers, whilst including components and assessment tools that address the specific aspects of waterpipe smoking, such as its social dimension, unique experiences, and cues. |
t110 | Medications that target the body's immune system have been used for a long time to treat urothelial cancer. When the cancer has spread to other organs outside the urinary tract, patients are often treated with chemotherapy using medicines called cisplatin or carboplatin (platinum‐containing chemotherapy). However, often the cancer comes back or becomes worse despite treatment. This review considers the evidence for pembrolizumab, which is a member of a new class of medications that work through the immune sytem, and compares it to chemotherapy. We considered only randomised controlled trials in this Cochrane Rapid Review, as they offer the most reliable results. Participants included in this trial had metastatic (cancer that has spread to other parts of the body) or advanced cancer that could not be removed by surgery, that had come back or worsened with other chemotherapy. We found that pembrolizumab probably improves overall survival a little (evidence of moderate certainty). Pembrolizumab may have little or not effect on the time for the cancer to worsen or advance (low certainty evidence). It probably improves treatment response as seen on X‐ray scans such as computer tomography (moderate certainty of evidence). Pembrolizumab may have little or no effect on deaths resulting from the treatment itself (low certainty evidence) but may result in fewer patients stopping treatment due to unwanted side effects (low certainty evidence). It may also cause less serious side effects. These conclusions are based on a single trial paid for by the company that makes pembrolizumab. | The use of systemic immunotherapy targets is emerging as an important treatment option for metastatic urothelial carcinoma, particularly for patients who cannot tolerate or who fail cisplatin‐based chemotherapy. One such target is the inhibition of the checkpoint protein programmed cell death‐1 (PD‐1) receptor and its ligand (PD‐L1) by monoclonal antibodies. Objectives To assess the effects of pembrolizumab monotherapy versus chemotherapy for treatment of advanced urothelial carcinoma with disease progression during or following platinum‐containing chemotherapy. Search methods We performed a Cochrane Rapid Review, limiting our search to published studies in the English language. We searched databases of the medical literature, including the Cochrane Central Register of Controlled Trials and MEDLINE, as well as trial registries including ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP). Our search extended from January 2000 to June 2018. Selection criteria We included randomised controlled trials except cross‐over trials and cluster randomised trials. We excluded all other study designs. Participants included had locally advanced or metastatic urothelial carcinoma of the bladder, with disease progression during or following platinum‐containing chemotherapy (synonymous with second‐/third‐/fourth‐line therapy). This review focused on pembrolizumab (synonyms: MK‐3475, lambrolizumab, Keytruda). Data collection and analysis Two review authors independently classified and abstracted data from the included study. The certainty of evidence was rated according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We identified one randomised controlled trial that included 542 participants, which compared the use of pembrolizumab monotherapy versus chemotherapy for the treatment of advanced urothelial carcinoma with disease progression during or following platinum‐containing chemotherapy. Results were reported after a median follow‐up of 14.1 months (range 9.9 to 22.1 months). Primary outcomes Pembrolizumab probably reduces the risk of death from any cause (hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.59 to 0.90; moderate certainty evidence). This corresponds to 115 fewer deaths (191 fewer to 38 fewer) per 1000 participants with pembrolizumab at 12 months. We downgraded the certainty of evidence one level for imprecision. Pembrolizumab may slightly improve quality of life (change from baseline to week 15 assessed with the Core Quality of Life Questionnaire; higher value reflects better quality of life; scale 0 to 100) with a mean difference (MD) of 9.05, 95% CI 4.61 to 13.50; low certainty evidence). We downgraded the certainty of evidence two levels for study limitations and imprecision. Secondary outcomes Pembrolizumab may have little or no effect on disease progression (HR 0.98, 95% CI 0.81 to 1.19; low certainty evidence). This corresponds to three fewer patients (42 fewer to 24 more) whose disease progressed per 1000 participants at 12 months. We downgraded the certainty of evidence two levels for study limitations and imprecision. Pembrolizumab probably improves treatment response (based on complete or partial radiologic response) with a risk ratio (RR) of 1.85, 95% CI 1.24 to 2.77; moderate certainty evidence). This corresponds to 97 more respondents (27 more to 202 more) per 1000 participants with pembrolizumab. We downgraded the certainty of evidence one level for imprecision. Pembrolizumab may have little or no effect on treatment‐related mortality (RR 0.96, 95% CI 0.24 to 3.79; low certainty evidence). This corresponds to one fewer (12 fewer to 44 more) treatment‐related deaths per 1000 participants with pembrolizumab. We downgraded the certainty of evidence two levels for study limitations and imprecision. Pembrolizumab may have little or no effect on discontinuations due to adverse events (RR 0.66, 95% CI 0.39 to 1.10). This corresponds to 54 fewer discontinuations per 1000 participants (95% CI 79 fewer to 7 more). We downgraded the certainty of evidence for study limitations and imprecision. Pembrolizumab may reduce serious adverse events (RR 0.83, 95 CI 0.72 to 0.97; low certainty evidence). This corresponds to 107 fewer serious averse events per 1000 participants (95% CI 19 fewer to 176 fewer). We downgraded two levels for study limitations and imprecision. The use of pembrolizumab in men with advanced urothelial carcinoma with disease progression during or following platinum‐containing chemotherapy probably improves overall survival when compared with chemotherapy alone. At 12 months follow‐up about 70% of those in the chemotherapy group had died, compared with 59% of those treated with pembrolizumab. We are very uncertain about the effects of pembolizumab on quality of life. Pembolizumab may also improve treatment response rates, and reduce the risk of serious adverse events, but may make little or no difference to discontinuations of treatment due to adverse events. These conclusions are based on a single trial that was sponsored by the producer of pembrolizumab. |
t111 | There is little doubt that women should be encouraged to utilise positions which give them the greatest comfort, control and benefit during first stage labour. As women in most western societies now lie in bed for the entire duration of their labour, it is important that they understand the risks and benefits of the positions they choose. This review included 25 studies (involving 5218 women). Although many studies were not of high quality, and most of the women were low risk, they did show that the first stage of labour may be approximately one hour and twenty minutes shorter for women who are upright or walk around. As every contraction is potentially painful, and prolonged labour can be an overwhelming and exhausting process resulting in an increased need for medical intervention, this is a meaningful outcome for women. Indeed other important outcomes for women who were upright and mobile compared with lying down in bed included a reduction in the risk of caesarean birth, less use of epidural as a method of pain relief, and less chance of their babies being admitted to the neonatal unit. However, based on the results of this review we recommend that wherever possible, women should be encouraged and supported to use upright and mobile positions of their choice during first stage labour, as this may enhance the progress of their labour and may lead to better outcomes for themselves and their babies. | It is more common for women in both high‐ and low‐income countries giving birth in health facilities, to labour in bed. There is no evidence that this is associated with any advantage for women or babies, although it may be more convenient for staff. Observational studies have suggested that if women lie on their backs during labour this may have adverse effects on uterine contractions and impede progress in labour, and in some women reduce placental blood flow. Objectives To assess the effects of encouraging women to assume different upright positions (including walking, sitting, standing and kneeling) versus recumbent positions (supine, semi‐recumbent and lateral) for women in the first stage of labour on duration of labour, type of birth and other important outcomes for mothers and babies. Search methods We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (31 January 2013). Selection criteria Randomised and quasi‐randomised trials comparing women randomised to upright versus recumbent positions in the first stage of labour. Data collection and analysis We used methods described in the Cochrane Handbook for Systematic Reviews of Interventions for carrying out data collection, assessing study quality and analysing results. Two review authors independently evaluated methodological quality and extracted data for each study. We sought additional information from trial authors as required. We used random‐effects analysis for comparisons in which high heterogeneity was present. We reported results using the average risk ratio (RR) for categorical data and mean difference (MD) for continuous data. Results should be interpreted with caution as the methodological quality of the 25 included trials (5218 women) was variable. For Comparison 1: Upright and ambulant positions versus recumbent positions and bed care, the first stage of labour was approximately one hour and 22 minutes shorter for women randomised to upright as opposed to recumbent positions (average MD ‐1.36, 95% confidence interval (CI) ‐2.22 to ‐0.51; 15 studies, 2503 women; random‐effects, T 2 = 2.39, Chi 2 = 203.55, df = 14, (P < 0.00001), I 2 = 93%). Women who were upright were also less likely to have caesarean section (RR 0.71, 95% CI 0.54 to 0.94; 14 studies, 2682 women) and less likely to have an epidural (RR 0.81, 95% CI 0.66 to 0.99, nine studies, 2107 women; random‐effects, T 2 = 0.02, I 2 = 61%). Babies of mothers who were upright were less likely to be admitted to the neonatal intensive care unit, however this was based on one trial (RR 0.20, 95% CI 0.04 to 0.89, one study, 200 women). There were no significant differences between groups for other outcomes including duration of the second stage of labour, or other outcomes related to the well being of mothers and babies. For Comparison 2: Upright and ambulant positions versus recumbent positions and bed care (with epidural: all women), there were no significant differences between groups for outcomes including duration of the second stage of labour, or other outcomes related to the well being of mothers and babies. There is clear and important evidence that walking and upright positions in the first stage of labour reduces the duration of labour, the risk of caesarean birth, the need for epidural, and does not seem to be associated with increased intervention or negative effects on mothers' and babies' well being. Given the great heterogeneity and high performance bias of study situations, better quality trials are still required to confirm with any confidence the true risks and benefits of upright and mobile positions compared with recumbent positions for all women. Based on the current findings, we recommend that women in low‐risk labour should be informed of the benefits of upright positions, and encouraged and assisted to assume whatever positions they choose. |
t112 | Infants born very early (preterm) or very small (low birth weight) need extra nutrients for growth compared to bigger or more mature infants. One way to deliver extra nutrition is to give infants more milk than usual ("high‐volume feeds"), typically more than 200 mL per kilogram per day. Although giving high volumes of milk to preterm or low birth weight infants might increase growth rates, concerns include that infants may not tolerate high‐volume feeds and may experience side effects including severe bowel problems. We have looked for evidence from clinical trials that assessed whether high‐volume feeds are beneficial or harmful for preterm or low birth weight infants. Through literature searches up‐to‐date until Novebember 2016, we found only one small randomised controlled trial (with 64 very low birth weight infant participants) that addressed this question. Very low birth weight infants who receive more milk than standard volumes gain weight more quickly during their hospital stay. We found no evidence suggesting that giving infants high volumes of milk causes feeding or gut problems, but this finding is not certain. Available evidence is insufficient to support or refute the use of high‐volume feeds in preterm or low birth weight infants. High‐volume feeds might increase the rate of weight gain, but more trials are needed to confirm this finding and to examine whether high‐volume feeds cause any problems for preterm or low birth weight infants. | Breast milk alone, given at standard recommended volumes (150 to 180 mL/kg/d), is not adequate to meet the protein, energy, and other nutrient requirements of growing preterm or low birth weight infants. One strategy that may be used to address these potential nutrient deficits is to give infants enteral feeds in excess of 200 mL/kg/d (’high‐volume’ feeds). This approach may increase nutrient uptake and growth rates, but concerns include that high‐volume enteral feeds may cause feed intolerance, gastro‐oesophageal reflux, aspiration pneumonia, necrotising enterocolitis, or complications related to fluid overload, including patent ductus arteriosus and bronchopulmonary dysplasia. Objectives To assess the effect on growth and safety of feeding preterm or low birth weight infants with high (> 200 mL/kg/d) versus standard (≤ 200 mL/kg/d) volume of enteral feeds. Infants in intervention and control groups should have received the same type of milk (breast milk, formula, or both), the same fortification or micronutrient supplements, and the same enteral feeding regimen (bolus, continuous) and rate of feed volume advancement. To conduct subgroup analyses based on type of milk (breast milk vs formula), gestational age or birth weight category of included infants (very preterm or VLBW vs preterm or LBW), presence of intrauterine growth restriction (using birth weight relative to the reference population as a surrogate), and income level of the country in which the trial was conducted (low or middle income vs high income) (see 'Subgroup analysis and investigation of heterogeneity'). Search methods We used the Cochrane Neonatal standard search strategy, which included searches of the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 2) in the Cochrane Library; MEDLINE (1946 to November 2016); Embase (1974 to November 2016); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL; 1982 to November 2016), as well as conference proceedings, previous reviews, and trial registries. Selection criteria Randomised and quasi‐randomised controlled trials that compared high‐volume versus standard‐volume enteral feeds for preterm or low birth weight infants. Data collection and analysis Two review authors assessed trial eligibility and risk of bias and independently extracted data. We analysed treatment effects in individual trials and reported the risk ratio and risk difference for dichotomous data, and the mean difference for continuous data, with respective 95% confidence intervals. . We assessed the quality of evidence at the outcome level via the GRADE approach. We found one eligible trial that included 64 infants. This trial was not blinded. Analysis showed a higher rate of weight gain in the high‐volume feeds group: mean difference 6.20 g/kg/d (95% confidence interval 2.71 to 9.69). There was no increase in the risk of feed intolerance or necrotising enterocolitis with high‐volume feeds, but 95% confidence intervals around these estimates were wide. We assessed the quality of evidence for these outcomes as 'low' or 'very low' because of imprecision of the estimates of effect and concern about risk of bias due to lack of blinding in the included trial. Trial authors provided no data on other outcomes, including gastro‐oesophageal reflux, aspiration pneumonia, necrotising enterocolitis, patent ductus arteriosus, bronchopulmonary dysplasia, or long‐term growth and neurodevelopment. We found only very limited data from one small unblinded trial on the effects of high‐volume feeds on important outcomes for preterm or low birth weight infants. The quality of evidence is low to very low. Hence, available evidence is insufficient to support or refute high‐volume enteral feeds in preterm or low birth weight infants. A large, pragmatic randomised controlled trial is needed to provide data of sufficient quality and precision to inform policy and practice. |
t113 | We reviewed the available evidence from randomised controlled trials about how effective and safe Haemophilus influenzae type b (Hib) conjugate vaccines are for people with sickle cell disease (SCD). People with SCD are at high risk of infection from Hib, which was responsible for a high death rate in children under five years of age before Hib conjugate vaccination was introduced in high‐income countries. In African countries, where coverage for this vaccination is extremely low, Hib remains one of the most common causes of bacteraemias (bacteria in the blood) in children with SCD. Another Cochrane Review on conjugate vaccines for preventing Hib infections in children under five years of age has shown that Hib conjugate vaccines were safe and effective but it did not specifically look at children with SCD, who have a high risk of this infection. We did not find any randomised controlled trials comparing Hib conjugate vaccines with placebo ('dummy' treatment) or no treatment in people with SCD. However, there has been a dramatic decrease in the occurrence of severe Hib infections in children with SCD living in high‐income countries since the vaccination has been included in childhood immunisation schedules. Therefore, including universal Hib conjugate vaccination in low‐income countries may improve the survival of children with SCD. There is not enough data to allow us to assess the potential effect of Hib vaccination in unvaccinated adults with SCD. | People affected with sickle cell disease (SCD) are at high risk of infection from Haemophilus influenzae type b (Hib). Before the implementation of Haemophilus influenzae type b conjugate vaccination in high‐income countries , this was responsible for a high mortality rate in children under five years of age . In African countries, where coverage of this vaccination is still extremely low, Hib remains one of the most common causes of bacteraemias in children with SCD. The increased uptake of this conjugate vaccination may substantially improve the survival of children with SCD. This is an update of a previously published Cochrane Review. Objectives The primary objective was to determine whether Hib conjugate vaccines reduce mortality and morbidity in children and adults with SCD. The secondary objectives were to assess the following in children and adults with SCD: the immunogenicity of Hib conjugate vaccines; the safety of these vaccines; and any variation in effect according to type of vaccine, mode of administration (separately or in combination with other vaccines), number of doses, and age at first dose. Search methods We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched trial registries (04 July 2018) and contacted relevant pharmaceutical companies to identify unpublished trials. Date of last search of the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinoapthies Trials Register: 18 December 2017. Selection criteria All randomised controlled trials (RCTs) and quasi‐RCTs comparing Hib conjugate vaccines with placebo or no treatment, or comparing different types of Hib conjugate vaccines in people with SCD. Data collection and analysis No trials of Hib conjugate vaccines in people with SCD were found. There is an absence of evidence from RCTs relating to the subject of this review. There has been a dramatic decrease in the incidence of invasive Hib infections observed in the post‐vaccination era in people with SCD living in high‐income countries. Therefore, despite the absence of evidence from RCTs, it is expected that Hib conjugate vaccines may be useful in children affected with SCD, especially in African countries where there is a high prevalence of the disease. The implementation of childhood immunisation schedules, including universal Hib conjugate vaccination, may substantially improve the survival of children with SCD living in low‐income countries. We currently lack data to evaluate the potential effect of Hib vaccination among unvaccinated adults with SCD. Further research should assess the optimal Hib immunisation schedule in children and adults with SCD. |
t114 | Cochrane authors reviewed the evidence about the effect of a surgical procedure called laparoscopic ovarian drilling (LOD) compared with medical treatment to cause ovulation in women with polycystic ovary syndrome (PCOS) who do not ovulate. We also reviewed the effect of different LOD techniques. Women with PCOS have problems with ovulating and therefore may have difficulty becoming pregnant. In the past clomiphene citrate (CC) used to be the first‐line treatment in women with PCOS. Ovulation induction with letrozole should be the first‐line treatment according to new guidelines, but the use of letrozole is not officially approved. Consequently, clomiphene citrate is still commonly used. Approximately 20% of women on CC do not ovulate. When this occurs, we call it CC‐resistant PCOS. For women with CC‐resistant PCOS there are different medications available to induce ovulation, such as gonadotrophins, metformin or aromatase inhibitors, but these medications are not always successful and can cause adverse events like multiple pregnancies and cycle cancellation due to an excessive response. Another option for treatment is a surgical procedure called laparoscopic ovarian drilling (LOD). This involves applying heat or laser to the ovaries with a laparoscope (a camera) passed through a small cut, usually just below the belly button. This procedure is thought to improve the way the ovaries produce and respond to hormones, increasing the chance of ovulation. However, there are risks associated with surgery, such as complications from anaesthesia, infection, and adhesions. LOD is a surgical alternative to medical treatment, and this review aimed to determine its benefits and risks. In this updated review we included 38 controlled trials comparing LOD with medical ovulation induction or comparing different techniques of LOD. The evidence is current to October 2019 Our main analysis with low‐quality evidence shows that LOD with and without medical ovulation induction may decrease the live birth rate slightly in women with anovulatory PCOS and CC‐resistance compared with medical ovulation induction alone. Analysis including only the higher‐quality RCTs shows uncertainty about any difference between the treatments. The evidence suggests that if the chance of live birth following medical ovulation induction alone is 44%, the chance following LOD would be between 32% and 52%. Moderate‐quality evidence shows that LOD probably reduces the number of multiple pregnancies. The evidence suggests that if we assume the chance of a multiple pregnancy following medical ovulation induction alone to be 5.0%, the chance following LOD would be between 0.9% and 3.4%. There may be little or no difference between the treatments for clinical pregnancy, and there is uncertainty about the effect of LOD compared with ovulation induction alone on miscarriage. Ovarian hyperstimulation syndrome (OHSS) may occur less often following LOD. | Polycystic ovary syndrome (PCOS) is a common condition affecting 8% to 13% of reproductive‐aged women. In the past clomiphene citrate (CC) used to be the first‐line treatment in women with PCOS. Ovulation induction with letrozole should be the first‐line treatment according to new guidelines, but the use of letrozole is off‐label. Consequently, CC is still commonly used. Approximately 20% of women on CC do not ovulate. Women who are CC‐resistant can be treated with gonadotrophins or other medical ovulation‐induction agents. These medications are not always successful, can be time‐consuming and can cause adverse events like multiple pregnancies and cycle cancellation due to an excessive response. Laparoscopic ovarian drilling (LOD) is a surgical alternative to medical treatment. There are risks associated with surgery, such as complications from anaesthesia, infection, and adhesions. Objectives To evaluate the effectiveness and safety of LOD with or without medical ovulation induction compared with medical ovulation induction alone for women with anovulatory polycystic PCOS and CC‐resistance. Search methods We searched the Cochrane Gynaecology and Fertility Group (CGFG) trials register, CENTRAL, MEDLINE, Embase, PsycINFO, CINAHL and two trials registers up to 8 October 2019, together with reference checking and contact with study authors and experts in the field to identify additional studies. Selection criteria We included randomised controlled trials (RCTs) of women with anovulatory PCOS and CC resistance who underwent LOD with or without medical ovulation induction versus medical ovulation induction alone, LOD with assisted reproductive technologies (ART) versus ART, LOD with second‐look laparoscopy versus expectant management, or different techniques of LOD. Data collection and analysis Two review authors independently selected studies, assessed risks of bias, extracted data and evaluated the quality of the evidence using the GRADE method. The primary effectiveness outcome was live birth and the primary safety outcome was multiple pregnancy. Pregnancy, miscarriage, ovarian hyperstimulation syndrome (OHSS), ovulation, costs, and quality of life were secondary outcomes. This updated review includes 38 trials (3326 women). The evidence was very low‐ to moderate‐quality; the main limitations were due to poor reporting of study methods, with downgrading for risks of bias (randomisation and allocation concealment) and lack of blinding. Laparoscopic ovarian drilling with or without medical ovulation induction versus medical ovulation induction alone Pooled results suggest LOD may decrease live birth slightly when compared with medical ovulation induction alone (odds ratio (OR) 0.71, 95% confidence interval (CI) 0.54 to 0.92; 9 studies, 1015 women; I 2 = 0%; low‐quality evidence). The evidence suggest that if the chance of live birth following medical ovulation induction alone is 42%, the chance following LOD would be between 28% and 40%. The sensitivity analysis restricted to only RCTs with low risk of selection bias suggested there is uncertainty whether there is a difference between the treatments (OR 0.90, 95% CI 0.59 to 1.36; 4 studies, 415 women; I 2 = 0%, low‐quality evidence). LOD probably reduces multiple pregnancy rates (Peto OR 0.34, 95% CI 0.18 to 0.66; 14 studies, 1161 women; I 2 = 2%; moderate‐quality evidence). This suggests that if we assume the risk of multiple pregnancy following medical ovulation induction is 5.0%, the risk following LOD would be between 0.9% and 3.4%. Restricting to RCTs that followed women for six months after LOD and six cycles of ovulation induction only, the results for live birth were consistent with the main analysis. There may be little or no difference between the treatments for the likelihood of a clinical pregnancy (OR 0.86, 95% CI 0.72 to 1.03; 21 studies, 2016 women; I 2 = 19%; low‐quality evidence). There is uncertainty about the effect of LOD compared with ovulation induction alone on miscarriage (OR 1.11, 95% CI 0.78 to 1.59; 19 studies, 1909 women; I 2 = 0%; low‐quality evidence). OHSS was a very rare event. LOD may reduce OHSS (Peto OR 0.25, 95% CI 0.07 to 0.91; 8 studies, 722 women; I 2 = 0%; low‐quality evidence). Unilateral LOD versus bilateral LOD Due to the small sample size, the quality of evidence is insufficient to justify a conclusion on live birth (OR 0.83, 95% CI 0.24 to 2.78; 1 study, 44 women; very low‐quality evidence). There were no data available on multiple pregnancy. The likelihood of a clinical pregnancy is uncertain between the treatments, due to the quality of the evidence and the large heterogeneity between the studies (OR 0.57, 95% CI 0.39 to 0.84; 7 studies, 470 women; I 2 = 60%, very low‐quality evidence). Due to the small sample size, the quality of evidence is not sufficient to justify a conclusion on miscarriage (OR 1.02, 95% CI 0.31 to 3.33; 2 studies, 131 women; I 2 = 0%; very low‐quality evidence). Other comparisons Due to lack of evidence and very low‐quality data there is uncertainty whether there is a difference for any of the following comparisons: LOD with IVF versus IVF, LOD with second‐look laparoscopy versus expectant management, monopolar versus bipolar LOD, and adjusted thermal dose versus fixed thermal dose. Laparoscopic ovarian drilling with and without medical ovulation induction may decrease the live birth rate in women with anovulatory PCOS and CC resistance compared with medical ovulation induction alone. But the sensitivity analysis restricted to only RCTs at low risk of selection bias suggests there is uncertainty whether there is a difference between the treatments, due to uncertainty around the estimate. Moderate‐quality evidence shows that LOD probably reduces the number of multiple pregnancy. Low‐quality evidence suggests that there may be little or no difference between the treatments for the likelihood of a clinical pregnancy, and there is uncertainty about the effect of LOD compared with ovulation induction alone on miscarriage. LOD may result in less OHSS. The quality of evidence is insufficient to justify a conclusion on live birth, clinical pregnancy or miscarriage rate for the analysis of unilateral LOD versus bilateral LOD. There were no data available on multiple pregnancy. |
t115 | Acute pain after surgery is a problem for patients undergoing abdominal surgery. In addition to postoperative pain, the side effects of treatment with pain killers, in particular those of opioids (drugs resembling morphine), need to be reduced. Dexmedetomidine is an opioid sparing drug (reduces the need for opioids). We reviewed the evidence about the effectiveness of dexmedetomidine in reducing the need for opioids and in preventing acute pain after abdominal surgery in adults. We wanted to discover how safe dexmedetomidine was and whether it was effective in preventing some of the known side effects of opioids, such as nausea and vomiting, reduced bowel function and delayed mobilization (getting up and moving around) after abdominal surgery. We included seven studies with 492 participants from five different countries and included 422 participants in our analysis. Most participants were middle‐aged. Participants had almost no diseases other than their reason for having surgery. The type of surgery was planned abdominal surgery. Three of the seven studies looked only at obesity surgery. Participants received dexmedetomidine right before or during their abdominal surgery. Six studies compared dexmedetomidine with no treatment, and one small study compared dexmedetomidine with fentanyl (a strong opioid). In total, 13 studies are awaiting classification. Most of the studies that compared dexmedetomidine with no treatment found that dexmedetomidine reduced the need for opioids for treating pain for 24 hours after surgery. During the same period, no important differences in pain were noted, except one study (80 participants) showed a reduction in intensity of pain at two hours after surgery with dexmedetomidine. The influence of dexmedetomidine on postoperative nausea and vomiting could not be determined because results were not similar across studies. No conclusion could be made for bowel function and mobilization and side effects such as postoperative sedation, as data were insufficient. One study with 80 participants reported a higher rate of low blood pressure ('low' meaning that medication was required) for participants receiving a high dose of dexmedetomidine compared with no treatment, but for lower doses of dexmedetomidine, they noted no differences compared with no treatment. For the comparison dexmedetomidine versus fentanyl, data were insufficient to allow conclusions (only one small study). Dexmedetomidine ‐ compared with no treatment ‐ seemed to reduce the need for opioids without worsening the experience of postoperative pain after abdominal surgery in adults. | Acute postoperative pain is still an issue in patients undergoing abdominal surgery. Postoperative pain and side effects of analgesic treatment, in particular those of opioids, need to be minimized. Opioid‐sparing analgesics, possibly including dexmedetomidine, seem a promising avenue by which to improve postoperative outcomes. Objectives Our primary aim was to determine the analgesic efficacy and opioid‐sparing effect of perioperative dexmedetomidine for acute pain after abdominal surgery in adults. Secondary aims were to establish effects of dexmedetomidine on postoperative nausea and vomiting (PONV), gastrointestinal function and mobilization, together with the side effect profile of dexmedetomidine. Search methods We searched the following databases: Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Institute for Scientific Information (ISI), Web of Science and Cumulative Index to Nursing and Allied Health Literature (CINAHL), and reference lists of articles to May 2014. We searched the Science Citation Index, ClinicalTrials.gov and Current Controlled Trials, and we contacted pharmaceutical companies to identify unpublished and ongoing studies. We applied no language restrictions. We reran the search in May 2015 and found nine studies of interest. We will deal with the studies of interest when we update the review. Selection criteria We included randomized, controlled trials of perioperative dexmedetomidine versus placebo or other drug during abdominal surgery in adults. Trials included one of the following outcomes: amount of 'rescue' opioid, postoperative pain, time to 'rescue' analgesia, participants requiring 'rescue' analgesia, postoperative sedation, PONV, time to first passage of flatus and stool or time to first out‐of‐bed mobilization. Data collection and analysis Two review authors independently screened the titles and abstracts for eligibility. We retrieved full trial reports if necessary, and we extracted relevant data from the included studies using a data collection form and assessed risk of bias. We resolved disagreements by discussion with the third review author. We sought additional information of relevance for risk of bias assessment or extraction of data by contacting study authors or, if necessary, co‐authors from present or former studies. Our systematic review included seven studies with a total of 492 participants. We included 422 participants in our analysis. Thirteen studies are awaiting classification. For the comparison dexmedetomidine versus placebo (six studies, 402 participants), most studies found a reduction in 'rescue' opioid consumption in the first 24 hours after surgery, together with in general no clinically important differences in postoperative pain (visual analogue scale (VAS) 0 to 100 mm, where 0 = no pain and 100 = worst imaginable pain) in the first 24 hours after surgery ‐ except for one study (80 participants) with a reduction in VAS pain at two hours after surgery in favour of dexmedetomidine, with a mean difference of ‐30.00 mm (95% confidence interval (CI) ‐38.25 to ‐21.75). As the result of substantial heterogeneity, pooling of data in statistical meta‐analyses was not appropriate. The quality of evidence was very low for our primary outcomes because of imprecision of results and risk of bias. Regarding our secondary aims, evidence was too scant in general to allow robust conclusions, or the estimates too imprecise or of poor methodological quality. Regarding adverse effects, low quality data (one study, 80 participants) suggest that the proportion of participants with hypotension requiring intervention was slightly higher in the high‐dose dexmedetomidine group with a risk ratio of 2.50 (95% CI 0.94 to 6.66), but lower doses of dexmedetomidine led to no differences compared with control. Evidence for the comparison dexmedetomidine versus fentanyl was insufficient to permit robust conclusions (one study, 20 participants). Dexmedetomidine, when administered perioperatively for acute pain after abdominal surgery in adults, seemed to have some opioid‐sparing effect together with in general no important differences in postoperative pain when compared with placebo. However the quality of the evidence was very low as the result of imprecision, methodological limitations and substantial heterogeneity among the seven included studies. The clinical importance for patients is uncertain, in as much as the influence of dexmedetomidine on patient‐important outcomes such as gastrointestinal function, mobilization and adverse effects could not be satisfactorily determined. All included studies were relatively small, and publication bias could not be ruled out. Applicability of evidence was limited to middle‐aged participants who were relatively free of co‐morbidity and were undergoing elective abdominal surgery. A potential bias was a considerable quantity of unobtainable data from studies with mixed surgery. To detect and investigate patient‐important outcomes, larger studies with longer periods of follow‐up are needed. |
t116 | We wanted to know whether using exercise was better than receiving no treatment, a treatment that gives you some attention but is not exercise, or currently recommended pharmaceutical medications for primary dysmenorrhoea, such as the oral contraceptive pill or non‐steroidal anti‐inflammatory drugs (NSAIDs). We found 12 studies including 854 women that examined the effect of exercise in women with period pain. Two trials did not report data suitable to be included in the meta‐analysis, so we included 10 trials with 754 women in our meta‐analysis. Eleven trials compared exercise with no treatment and one compared exercise with NSAIDs. Exercise, whether low‐intensity, such as yoga, or high‐intensity, such as aerobics, may provide a large reduction in the intensity of period pain, compared to not doing anything. This reduction in pain was likely to be important to women with period pain as it is over twice the minimum amount of pain reduction we think is needed to notice a difference. Most studies asked women to exercise at least three times per week, for about 45 to 60 minutes of exercise each time. It is unclear if exercising less frequently, or for a shorter duration would have the same results. Exercise was performed regularly throughout the month, with some studies asking women not to perform exercise during the period itself. Other outcomes, such as the effect on overall menstrual symptoms or overall quality of life, were not well reported and the evidence was of very low quality, so we cannot be sure if exercise has any effect on these outcomes. No studies reported on rates of being absent from work or school or on restrictions of daily life activities. There was not enough evidence to determine if there was any benefit of exercise when compared to NSAIDs, a class of medications (like ibuprofen) commonly used to treat period pain, on menstrual pain intensity, need for additional pain‐relieving medication, or absence from work or school. The main limitations were imprecision due to small sample sizes (too few women in the study), inconsistency (studies gave very different results) and risk of bias related to blinding (where researchers or participants knew what treatment they were getting). | Exercise has a number of health benefits and has been recommended as a treatment for primary dysmenorrhoea (period pain), but the evidence for its effectiveness on primary dysmenorrhoea is unclear. This review examined the available evidence supporting the use of exercise to treat primary dysmenorrhoea. Objectives To evaluate the effectiveness and safety of exercise for women with primary dysmenorrhoea. Search methods We searched the Cochrane Gynaecology and Fertility specialised register, CENTRAL, MEDLINE, Embase, PsycINFO, AMED and CINAHL (from inception to July 2019). We searched two clinical trial databases (inception to March 2019) and handsearched reference lists and previous systematic reviews. Selection criteria We included studies if they randomised women with moderate‐to‐severe primary dysmenorrhoea to receive exercise versus no treatment, attention control, non‐steroidal anti‐inflammatory drugs (NSAIDs) or the oral contraceptive pill. Cross‐over studies and cluster‐randomised trials were not eligible for inclusion. Data collection and analysis Two review authors independently selected the studies, assessed eligible studies for risk of bias, and extracted data from each study. We contacted study authors for missing information. We assessed the quality of the evidence using GRADE. Our primary outcomes were menstrual pain intensity and adverse events. Secondary outcomes included overall menstrual symptoms, usage of rescue analgesic medication, restriction of daily life activities, absence from work or school and quality of life. We included a total of 12 trials with 854 women in the review, with 10 trials and 754 women in the meta‐analysis. Nine of the 10 studies compared exercise with no treatment, and one study compared exercise with NSAIDs. No studies compared exercise with attention control or with the oral contraceptive pill. Studies used low‐intensity exercise (stretching, core strengthening or yoga) or high‐intensity exercise (Zumba or aerobic training); none of the included studies used resistance training. Exercise versus no treatment Exercise may have a large effect on reducing menstrual pain intensity compared to no exercise (standard mean difference (SMD) ‐1.86, 95% confidence interval (CI) ‐2.06 to ‐1.66; 9 randomised controlled trials (RCTs), n = 632; I 2 = 91%; low‐quality evidence). This SMD corresponds to a 25 mm reduction on a 100 mm visual analogue scale (VAS) and is likely to be clinically significant. We are uncertain if there is any difference in adverse event rates between exercise and no treatment. We are uncertain if exercise reduces overall menstrual symptoms (as measured by the Moos Menstrual Distress Questionnaire (MMDQ)), such as back pain or fatigue compared to no treatment (mean difference (MD) ‐33.16, 95% CI ‐40.45 to ‐25.87; 1 RCT, n = 120; very low‐quality evidence), or improves mental quality of life (MD 4.40, 95% CI 1.59 to 7.21; 1 RCT, n = 55; very low‐quality evidence) or physical quality of life (as measured by the 12‐Item Short Form Health Survey (SF‐12)) compared to no exercise (MD 3.40, 95% CI ‐1.68 to 8.48; 1 RCT, n = 55; very low‐quality evidence) when compared to no treatment. No studies reported on any changes in restriction of daily life activities or on absence from work or school. Exercise versus NSAIDs We are uncertain if exercise, when compared with mefenamic acid, reduced menstrual pain intensity (MD ‐7.40, 95% CI ‐8.36 to ‐6.44; 1 RCT, n = 122; very low‐quality evidence), use of rescue analgesic medication (risk ratio (RR) 1.77, 95% CI 1.21 to 2.60; 1 RCT, n = 122; very low‐quality evidence) or absence from work or school (RR 1.00, 95% CI 0.49 to 2.03; 1 RCT, n = 122; very low‐quality evidence). None of the included studies reported on adverse events, overall menstrual symptoms, restriction of daily life activities or quality of life. The current low‐quality evidence suggests that exercise, performed for about 45 to 60 minutes each time, three times per week or more, regardless of intensity, may provide a clinically significant reduction in menstrual pain intensity of around 25 mm on a 100 mm VAS. All studies used exercise regularly throughout the month, with some studies asking women not to exercise during menstruation. Given the overall health benefits of exercise, and the relatively low risk of side effects reported in the general population, women may consider using exercise, either alone or in conjunction with other modalities, such as NSAIDs, to manage menstrual pain. It is unclear if the benefits of exercise persist after regular exercise has stopped or if they are similar in women over the age of 25. Further research is required, using validated outcome measures, adequate blinding and suitable comparator groups reflecting current best practice or accounting for the extra attention given during exercise. |
t117 | Cinnamon for diabetes mellitus Diabetes mellitus is a chronic metabolic disorder. People with diabetes are known to be at greater risk of cardiovascular disease (including heart attack, stroke, and peripheral vascular disease such as acute or chronic ischaemia of a leg resulting in severe pain when walking short distances). There is also an increased risk of eye disease, kidney failure, nerve damage and sexual dysfunction when compared to the general population. Improvements in the regulation of blood sugar levels may help to reduce the risk of these complications. Cinnamon bark has been shown in a number of animal studies to improve blood sugar levels, though its effect in humans is not too clear. Hence, the review authors set out to determine the effect of oral cinnamon extract on blood sugar and other outcomes. The authors identified 10 randomised controlled trials, which involved 577 participants with diabetes mellitus. Cinnamon was administered in tablet or capsule form, at a mean dose of 2 g daily, for four to 16 weeks. The review authors found cinnamon to be no more effective than placebo, another active medication or no treatment in reducing glucose levels and glycosylated haemoglobin A1c (HbA1c), a long‐term measurement of glucose control. None of the trials looked at health‐related quality of life, morbidity, death from any cause or costs. Adverse reactions to cinnamon treatment were generally mild and infrequent. | Diabetes mellitus is a chronic metabolic disorder that is associated with an increased risk of cardiovascular disease, retinopathy, nephropathy, neuropathy, sexual dysfunction and periodontal disease. Improvements in glycaemic control may help to reduce the risk of these complications. Several animal studies show that cinnamon may be effective in improving glycaemic control. While these effects have been explored in humans also, findings from these studies have not yet been systematically reviewed. Objectives To evaluate the effects of cinnamon in patients with diabetes mellitus. Search methods Pertinent randomised controlled trials were identified through AARP Ageline, AMED, AMI, BioMed Central gateway, CAM on PubMed, CINAHL, Dissertations Abstracts International, EMBASE, Health Source Nursing/Academic edition, International Pharmaceutical Abstracts, MEDLINE, Natural medicines comprehensive database, The Cochrane Library and TRIP database. Clinical trial registers and the reference lists of included trials were searched also (all up to January 2012). Content experts and manufacturers of cinnamon extracts were also contacted. Selection criteria All randomised controlled trials comparing the effects of orally administered monopreparations of cinnamon ( Cinnamomum spp.) to placebo, active medication or no treatment in persons with either type 1 or type 2 diabetes mellitus. Data collection and analysis Two review authors independently selected trials, assessed risk of bias and trial quality, and extracted data. We contacted study authors for missing information. Ten prospective, parallel‐group design, randomised controlled trials, involving a total of 577 participants with type 1 and type 2 diabetes mellitus, were identified. Risk of bias was high or unclear in all but two trials, which were assessed as having moderate risk of bias. Risk of bias in some domains was high in 50% of trials. Oral monopreparations of cinnamon (predominantly Cinnamomum cassia ) were administered at a mean dose of 2 g daily, for a period ranging from 4 to 16 weeks. The effect of cinnamon on fasting blood glucose level was inconclusive. No statistically significant difference in glycosylated haemoglobin A1c (HbA1c), serum insulin or postprandial glucose was found between cinnamon and control groups. There were insufficient data to pool results for insulin sensitivity. No trials reported health‐related quality of life, morbidity, mortality or costs. Adverse reactions to oral cinnamon were infrequent and generally mild in nature. There is insufficient evidence to support the use of cinnamon for type 1 or type 2 diabetes mellitus. Further trials, which address the issues of allocation concealment and blinding, are now required. The inclusion of other important endpoints, such as health‐related quality of life, diabetes complications and costs, is also needed. |
t118 | Survey questionnaires are important tools in public health and clinical research as they offer a convenient way of collecting data from a large number of respondents, dealing with sensitive topics, and are less resource intensive than other data collection techniques. The delivery of survey questionnaires via apps running on smartphones or tablets could maximise the scalability and speed of data collection offered by these tools, whilst reducing costs. However, before this technology becomes widely adopted, we need to understand how it could affect the quality of the responses collected. Particularly, if we consider the impact that data quality can have on the evidence base that supports many public health and healthcare decisions. Objective In this Cochrane review, we assessed the impact that using apps to deliver a survey can have on various aspects of the quality of responses. These include response rates, data accuracy, data completeness, time taken to complete a survey questionnaire, and acceptability to respondents. We included 14 studies and analysed data from 2272 participants. We did not conduct a meta‐analysis because of differences across the studies. The studies took place in two types of setting: controlled and uncontrolled. The former refers to research or clinical environments in which healthcare practitioners or researchers were able to better control for potential confounders, such as the location and time of day in which surveys were completed, the type of technology used and the level of help available to respondents deal with technical difficulties. Uncontrolled settings refer to locations outside these research or clinical environments (e.g., the respondent's home). We found that apps may be equivalent to other delivery modes such as paper, laptops and SMS in both settings. It is unclear if apps could result in faster completion times than other delivery modes. Instead, our findings suggest that factors such as the characteristics of the clinical population, and survey and interface design could moderate the effect on this outcome. Data completeness and adherence to sampling protocols were only reported in uncontrolled settings. Our results indicate that apps may result in more complete datasets, and may improve adherence to sampling protocols compared to paper but not to SMS. There were multiple definitions of acceptability to respondents, which could not be standardised across the included studies. Lastly, none of the included studies reported on response rates or data accuracy. Overall, there is not enough evidence to make clear recommendations about the impact that apps may have on survey questionnaire responses. | Self‐administered survey questionnaires are an important data collection tool in clinical practice, public health research and epidemiology. They are ideal for achieving a wide geographic coverage of the target population, dealing with sensitive topics and are less resource‐intensive than other data collection methods. These survey questionnaires can be delivered electronically, which can maximise the scalability and speed of data collection while reducing cost. In recent years, the use of apps running on consumer smart devices (i.e., smartphones and tablets) for this purpose has received considerable attention. However, variation in the mode of delivering a survey questionnaire could affect the quality of the responses collected. Objectives To assess the impact that smartphone and tablet apps as a delivery mode have on the quality of survey questionnaire responses compared to any other alternative delivery mode: paper, laptop computer, tablet computer (manufactured before 2007), short message service (SMS) and plastic objects. Search methods We searched MEDLINE, EMBASE, PsycINFO, IEEEXplore, Web of Science, CABI: CAB Abstracts, Current Contents Connect, ACM Digital, ERIC, Sociological Abstracts, Health Management Information Consortium, the Campbell Library and CENTRAL. We also searched registers of current and ongoing clinical trials such as ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform. We also searched the grey literature in OpenGrey, Mobile Active and ProQuest Dissertation & Theses. Lastly, we searched Google Scholar and the reference lists of included studies and relevant systematic reviews. We performed all searches up to 12 and 13 April 2015. Selection criteria We included parallel randomised controlled trials (RCTs), crossover trials and paired repeated measures studies that compared the electronic delivery of self‐administered survey questionnaires via a smartphone or tablet app with any other delivery mode. We included data obtained from participants completing health‐related self‐administered survey questionnaire, both validated and non‐validated. We also included data offered by both healthy volunteers and by those with any clinical diagnosis. We included studies that reported any of the following outcomes: data equivalence; data accuracy; data completeness; response rates; differences in the time taken to complete a survey questionnaire; differences in respondent's adherence to the original sampling protocol; and acceptability to respondents of the delivery mode. We included studies that were published in 2007 or after, as devices that became available during this time are compatible with the mobile operating system (OS) framework that focuses on apps. Data collection and analysis Two review authors independently extracted data from the included studies using a standardised form created for this systematic review in REDCap. They then compared their forms to reach consensus. Through an initial systematic mapping on the included studies, we identified two settings in which survey completion took place: controlled and uncontrolled. These settings differed in terms of (i) the location where surveys were completed, (ii) the frequency and intensity of sampling protocols, and (iii) the level of control over potential confounders (e.g., type of technology, level of help offered to respondents). We conducted a narrative synthesis of the evidence because a meta‐analysis was not appropriate due to high levels of clinical and methodological diversity. We reported our findings for each outcome according to the setting in which the studies were conducted. We included 14 studies (15 records) with a total of 2275 participants; although we included only 2272 participants in the final analyses as there were missing data for three participants from one included study. Regarding data equivalence, in both controlled and uncontrolled settings, the included studies found no significant differences in the mean overall scores between apps and other delivery modes, and that all correlation coefficients exceeded the recommended thresholds for data equivalence. Concerning the time taken to complete a survey questionnaire in a controlled setting, one study found that an app was faster than paper, whereas the other study did not find a significant difference between the two delivery modes. In an uncontrolled setting, one study found that an app was faster than SMS. Data completeness and adherence to sampling protocols were only reported in uncontrolled settings. Regarding the former, an app was found to result in more complete records than paper, and in significantly more data entries than an SMS‐based survey questionnaire. Regarding adherence to the sampling protocol, apps may be better than paper but no different from SMS. We identified multiple definitions of acceptability to respondents, with inconclusive results: preference; ease of use; willingness to use a delivery mode; satisfaction; effectiveness of the system informativeness; perceived time taken to complete the survey questionnaire; perceived benefit of a delivery mode; perceived usefulness of a delivery mode; perceived ability to complete a survey questionnaire; maximum length of time that participants would be willing to use a delivery mode; and reactivity to the delivery mode and its successful integration into respondents' daily routine. Finally, regardless of the study setting, none of the included studies reported data accuracy or response rates. Our results, based on a narrative synthesis of the evidence, suggest that apps might not affect data equivalence as long as the intended clinical application of the survey questionnaire, its intended frequency of administration and the setting in which it was validated remain unchanged. There were no data on data accuracy or response rates, and findings on the time taken to complete a self‐administered survey questionnaire were contradictory. Furthermore, although apps might improve data completeness, there is not enough evidence to assess their impact on adherence to sampling protocols. None of the included studies assessed how elements of user interaction design, survey questionnaire design and intervention design might influence mode effects. Those conducting research in public health and epidemiology should not assume that mode effects relevant to other delivery modes apply to apps running on consumer smart devices. Those conducting methodological research might wish to explore the issues highlighted by this systematic review. |
t119 | Chinese herbal medicine may help reduce menstrual pain. Dysmenorrhoea is a very common complaint that refers to painful menstrual cramps in abdomen. Primary dysmenorrhoea refers to pain of an unknown cause (i.e. no medical condition is identified). Nonsteroidal anti‐inflammatory drugs or the contraceptive pill have been used successfully for treatment but more women are looking for non‐drug therapies. Chinese herbal medicine has been used for centuries in China and it is currently used in public hospitals in China for the treatment of primary dysmenorrhoea. The review found promising evidence for the use of Chinese herbal medicine in reducing menstrual pain in the treatment of primary dysmenorrhoea, compared to conventional medicine such as NSAIDs and the oral contraceptive pill, acupuncture and heat compression. | Conventional treatment for primary dysmenorrhoea has a failure rate of 20% to 25% and may be contraindicated or not tolerated by some women. Chinese herbal medicine may be a suitable alternative. Objectives To determine the efficacy and safety of Chinese herbal medicine for primary dysmenorrhoea when compared with placebo, no treatment, and other treatment. Search methods The Cochrane Menstrual Disorders and Subfertility Group Trials Register (to 2006), MEDLINE (1950 to January 2007), EMBASE (1980 to January 2007), CINAHL (1982 to January 2007), AMED (1985 to January 2007), CENTRAL (The Cochrane Library issue 4, 2006), China National Knowledge Infrastructure (CNKI, 1990 to January 2007), Traditional Chinese Medicine Database System (TCMDS, 1990 to December 2006), and the Chinese BioMedicine Database (CBM, 1990 to December 2006) were searched. Citation lists of included trials were also reviewed. Selection criteria Any randomised controlled trials involving Chinese herbal medicine versus placebo, no treatment, conventional therapy, heat compression, another type of Chinese herbal medicine, acupuncture or massage. Exclusion criteria were identifiable pelvic pathology and dysmenorrhoea resulting from the use of an intra‐uterine contraceptive device. Data collection and analysis Quality assessment, data extraction and data translation were performed independently by two review authors. Attempts were made to contact study authors for additional information and data. Data were combined for meta‐analysis using either Peto odds ratios or relative risk (RR) for dichotomous data or weighted mean difference for continuous data. A fixed‐effect statistical model was used, where suitable. If data were not suitable for meta‐analysis, any available data from the trial were extracted and presented as descriptive data. Thirty‐nine randomised controlled trials involving a total of 3475 women were included in the review. A number of the trials were of small sample size and poor methodological quality. Results for Chinese herbal medicine compared to placebo were unclear as data could not be combined (3 RCTs). Chinese herbal medicine resulted in significant improvements in pain relief (14 RCTs; RR 1.99, 95% CI 1.52 to 2.60), overall symptoms (6 RCTs; RR 2.17, 95% CI 1.73 to 2.73) and use of additional medication (2 RCTs; RR 1.58, 95% CI 1.30 to 1.93) when compared to use of pharmaceutical drugs. Self‐designed Chinese herbal formulae resulted in significant improvements in pain relief (18 RCTs; RR 2.06, 95% CI 1.80 to 2.36), overall symptoms (14 RCTs; RR 1.99, 95% CI 1.65 to 2.40) and use of additional medication (5 RCTs; RR 1.58, 95% CI 1.34 to 1.87) after up to three months of follow‐up when compared to commonly used Chinese herbal health products. Chinese herbal medicine also resulted in better pain relief than acupuncture (2 RCTs; RR 1.75, 95% CI 1.09 to 2.82) and heat compression (1 RCT; RR 2.08, 95% CI 2.06 to 499.18). The review found promising evidence supporting the use of Chinese herbal medicine for primary dysmenorrhoea; however, results are limited by the poor methodological quality of the included trials. |
t120 | We investigated whether exhaled (breathing out) nitric oxide (a marker in the breath which can show a type of lung inflammation) can be useful to adjust asthma medications in children with asthma instead of following the usual ways that asthma medications are adjusted to get the best dose to control the asthma. Exhaled nitric oxide levels are easily obtained by getting the person to breathe into a commercially available analyser. We included all randomised controlled trials that compared adjustment of asthma medications by either usual clinical care (control group) versus using exhaled nitric oxide. The participants included in the trials had asthma diagnosed as per relevant asthma guidelines. The review included nine studies (involving 1426 children) that varied in a several ways including length of the study, exhaled nitric oxide cut‐off levels used for altering medicines and the way each study defined flare‐ups or attacks (called exacerbations). The exhaled nitric oxide cut‐off values used by the different studies as a basis for decreasing or increasing medicines also varied. The mean age of the participants ranged from 10 to 14 years old. In this review, we found that guiding asthma medicines based on exhaled nitric oxide (compared to a control group) was beneficial in reducing the number of children who had at least one exacerbation during the study. In the control group where therapy was guided according to clinical symptoms, 40 children out of 100 had at least one exacerbation over 48.5 weeks, compared to 28 out of 100 children where treatment was guided by exhaled nitric oxide. However, we found no difference between groups in other measures of asthma severity that impact on day‐to‐day clinical symptoms or inhaled corticosteroid dose (medications used to control asthma). Therefore, using exhaled nitric oxide levels to adjust asthma therapy may reduce the number of attacks that children with asthma have but does not impact on the day‐to‐day symptoms. The level of evidence found ranged from moderate, when comparing the two groups for the number of children who had one or more exacerbations, to very low when comparing the number of exacerbations. | Asthma guidelines aim to guide health practitioners to optimise treatment for patients to minimise symptoms, improve or maintain good lung function, and prevent acute exacerbations. The principle of asthma guidelines is based on a step‐up or step‐down regimen of asthma medications to maximise health using minimum doses. Fractional exhaled nitric oxide (FeNO) is a marker of eosinophilic inflammation and tailoring asthma medications in accordance to airway eosinophilic levels may improve asthma outcomes such as indices of control or reduce exacerbations, or both. Objectives To evaluate the efficacy of tailoring asthma interventions based on fractional exhaled nitric oxide (FeNO), in comparison to not using FeNO, that is, management based on clinical symptoms (with or without spirometry/peak flow) or asthma guidelines (or both), for asthma‐related outcomes in children. Search methods We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and reference lists of articles. The last searches were in June 2016. Selection criteria All randomised controlled trials (RCTs) comparing adjustment of asthma medications based on FeNO levels compared to those not using FeNO, that is, management based on clinical symptoms or asthma guidelines (or both) involving children. Data collection and analysis We reviewed results of searches against predetermined criteria for inclusion. Two review authors independently selected relevant studies, assessed trial quality and extracted data. We contacted study authors for further information with responses provided from three. The review included nine studies; these studies differed in a variety of ways including definition of asthma exacerbations, FeNO cut‐off levels used (12 parts per billion (ppb) to 30 ppb), the way in which FeNO was used to adjust therapy and duration of study (6 to 12 months). Of 1426 children randomised, 1329 completed the studies. The inclusion criteria for the participants in each study varied but all had a diagnosis of asthma. There was a significant difference in the number of children having one or more asthma exacerbations over the study period, they were significantly lower in the FeNO group in comparison to the control group (odds ratio (OR) 0.62, 95% confidence interval (CI) 0.49 to 0.80; 1279 participants; 8 studies). The number needed to treat for an additional beneficial outcome (NNTB) over 52 weeks was 10 (95% CI 7 to 20). There was no difference between the groups when comparing exacerbation rates (mean difference (MD) ‐0.37, 95% CI ‐0.8 to 0.06; 736 participants; 4 studies; I 2 = 67%). The number of children in the FeNO group requiring oral corticosteroid courses was lower in comparison to the children in the control group (OR 0.63, 95% CI 0.48 to 0.83; 1169 participants; 7 studies; I 2 = 0%). There was no statistically significant difference between the groups for exacerbations requiring hospitalisation (OR 0.75, 95% CI 0.41 to 1.36; 1110 participants; 6 studies; I 2 = 0%). There were no significant differences between the groups for any of the secondary outcomes (forced expiratory volume in one second (FEV 1 ), FeNO levels, symptom scores or inhaled corticosteroid doses at final visit). The included studies recorded no adverse events. Three studies had inadequate blinding and were thus considered to have a high risk of bias. However, when these studies were removed in subgroup analysis, the difference between the groups for the primary outcome (exacerbations) remained statistically significant. The GRADE quality of the evidence ranged from moderate (for the outcome 'Number of participants who had one or more exacerbations over the study period') to very low (for the outcome 'Exacerbation rates'), based on lack of blinding, statistical heterogeneity and imprecision. In this updated review with five new included studies, tailoring asthma medications based on FeNO levels (in comparison with primarily guideline management) significantly decreased the number of children who had one or more exacerbations over the study period but did not impact on the day‐to‐day clinical symptoms or inhaled corticosteroid doses. Therefore, the use of FeNO to guide asthma therapy in children may be beneficial in a subset of children, it cannot be universally recommended for all children with asthma. Further RCTs need to be conducted and these should encompass different asthma severities, different settings including primary care and less affluent settings, and consider different FeNO cut‐offs. |
t121 | Routine digital vaginal examination (examination of the cervix with a finger) during pregnancy, used to reduce the prevalence of preterm birth, is not supported by evidence from randomized controlled trials. Preterm labour is often preceded by changes in the cervix although the woman does not experience any symptoms. Effective detection and appropriate management of risk of preterm birth is key to improved care. Repeat digital cervical assessment is a simple inexpensive technique that uses a disposable glove and takes only one or two minutes to complete. It has been promoted as a routine intervention during pregnancy as a screening test for the risk of preterm birth (that is, birth occurring before 37 weeks of gestation), which can then be managed. It is in standard use in many parts of Europe, Africa and to a lesser extent in the US. The review included two randomized controlled trials that enrolled a total of 7163 pregnant women. The number of women experiencing preterm birth was similar with and without routine digital vaginal examination when it was not medically indicated. One was a multicentre performed in countries where the intervention was routine and in countries where it was not. Causes for concern included the potential risk of infection and preterm labour from the vaginal examination as well as discomfort and embarrassment for the woman. | Repeat digital cervical assessment (RDCA ‐ examination of the cervix with a finger) has been promoted as a routine intervention in the antenatal clinic as a screening test for the risk of preterm birth (that is, birth occurring before 37 weeks of gestation). Objectives To assess the effect of repeat digital cervical assessment during pregnancy for the risk of preterm birth and other adverse effects for mother and baby. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 2009) and CENTRAL ( The Cochrane Library 2009, Issue 3 ). Selection criteria All known randomized clinical trials comparing repeat digital cervical assessment with internal examination limited to clinical indication or no internal examination. We have not included studies where repeat cervical assessment is only a component of complex interventions targeted at decreasing preterm birth. Data collection and analysis We evaluated relevant studies for meeting the inclusion criteria and methodological quality without considering their results. Three review authors extracted the data. For all data analyses, we entered data based on the principle of intention to treat. We calculated odds ratios and 95% confidence intervals for dichotomous data. We included two trials that enrolled a total of 7163 women. Preterm birth before 37 weeks, was reported in both trials. The odds ratio for birth before 37 weeks was 1.05 (95% confidence interval 0.85 to 1.31; two trials, 6070 women). One trial (involving 5836 women) found no significant difference between the two treatment arms for the following outcomes: preterm birth before 34 weeks; preterm, prelabour rupture of membranes; hospital admission before 37 weeks; caesarean section; use of tocolytic drugs; low birthweight; very low birthweight, stillbirth, neonatal death, neonatal intensive care admissions; use of health services. The other prespecified outcomes were not evaluated in the included studies. We did not conduct the planned subgroup analyses due to insufficient data. We found no evidence to support the use of RDCA in pregnancy to reduce the prevalence of preterm birth. We have found insufficient evidence to assess adverse effects of the intervention. |
t122 | Abdominal tuberculosis (TB) is a type of TB that affects the gut, the peritoneum (the lining of the abdominal cavity), abdominal lymph nodes, and, more rarely, the solid organs in the abdomen (liver, pancreas, and spleen). Abdominal TB leads to severe illness in adults and children, and can cause complications, such as bowel rupture, which can lead to death. Most current guidelines recommend treating people that have abdominal TB with antituberculous treatment (ATT) for six months, but some clinicians treat for longer periods due to concerns that six months is not adequate to achieve cure and prevent relapse of the disease after the end of treatment. Longer ATT regimens have disadvantages: patients may find it more difficult to adhere to the tablets; patients are exposed to the risk of side effects of ATT for longer periods; and the cost to health systems and to patients is greater. We included three trials with 328 participants that compared six‐month ATT with nine‐month ATT; two were from India and one was from South Korea. The trials were mostly of high quality, although two had concerns of risk of bias for detecting relapse of the disease. All the trials included HIV‐negative adults with TB of the gut (gastrointestinal TB), and one also included TB of the peritoneum (peritoneal TB). The results show that relapse was an uncommon event, but we are uncertain whether or not there is a difference between the six‐month and nine‐month groups as numbers of participants are small ( very low quality evidence ). Six‐month and nine‐month regimens are probably similarly effective in terms of the chances of achieving cure ( moderate quality evidence ). Death was uncommon in both groups, and all deaths occurred during the first four months of ATT, which suggests that duration of treatment did not have an effect on risk of death. Few people had poor treatment compliance, and few participants experienced side effects that led to their treatment being stopped or changed, and it was not possible to detect a difference between the groups. Six‐month regimens are probably as good as nine‐month regimens in terms of numbers of people cured. We found no evidence to suggest that six‐month regimens are less safe for gastrointestinal and peritoneal TB than nine‐month regimens, but we still do not know whether there is a difference in risk of relapse between the two regimens. Further studies are needed to increase our confidence as to whether six‐month regimens are as good as nine‐month regimens for preventing relapse; and to provide information about treating abdominal TB in children and in people with HIV. | Tuberculosis (TB) of the gastrointestinal tract and any other organ within the abdominal cavity is abdominal TB, and most guidelines recommend the same six‐month regimen used for pulmonary TB for people with this diagnosis. However, some physicians are concerned whether a six‐month treatment regimen is long enough to prevent relapse of the disease, particularly in people with gastrointestinal TB, which may sometimes cause antituberculous drugs to be poorly absorbed. On the other hand, longer regimens are associated with poor adherence, which could increase relapse, contribute to drug resistance developing, and increase costs to patients and health providers. Objectives To compare six‐month versus longer drug regimens to treat people that have abdominal TB. Search methods We searched the following electronic databases up to 2 September 2016: the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase (accessed via OvidSP), LILACS, INDMED, and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists. Selection criteria We included randomized controlled trials (RCTs) that compared six‐month regimens versus longer regimens that consisted of isoniazid, rifampicin, pyrazinamide, and ethambutol to treat adults and children that had abdominal TB. The primary outcomes were relapse, with a minimum of six‐month follow‐up after completion of antituberculous treatment (ATT), and clinical cure at the end of ATT. Data collection and analysis Two review authors independently selected trials, extracted data, and assessed the risk of bias in the included trials. For analysis of dichotomous outcomes, we used risk ratios (RR) with 95% confidence intervals (CIs). Where appropriate, we pooled data from the included trials in meta‐analyses. We assessed the quality of the evidence using the GRADE approach. We included three RCTs, with 328 participants, that compared six‐month regimens with nine‐month regimens to treat adults with intestinal and peritoneal TB. All trials were conducted in Asia, and excluded people with HIV, those with co‐morbidities and those who had received ATT in the previous five years. Antituberculous regimens were based on isoniazid, rifampicin, pyrazinamide, and ethambutol, and these drugs were administered daily or thrice weekly under a directly observed therapy programme. The median duration of follow‐up after completion of treatment was between 12 and 39 months. Relapse was uncommon, with two cases among 140 participants treated for six months, and no events among 129 participants treated for nine months. The small number of participants means we do not know whether or not there is a difference in risk of relapse between the two regimens ( very low quality evidence ). At the end of therapy, there was probably no difference in the proportion of participants that achieved clinical cure between six‐month and nine‐month regimens (RR 1.02, 95% CI 0.97 to 1.08; 294 participants, 3 trials, moderate quality evidence ). For death, there were 2/150 (1.3%) in the six‐month group and 4/144 (2.8%) in the nine‐month group. All deaths occurred in the first four months of treatment, so was not linked to the duration of treatment in the included trials. Similarly, the number of participants that defaulted from treatment was small in both groups, and there may be no difference between them (RR 0.50, 95% CI 0.10 to 2.59; 294 participants, 3 trials, low quality evidence ). Only one trial reported on adherence to treatment, with only one participant allocated to the nine‐month regimen presenting poor adherence to treatment. We do not know whether six‐month regimens are associated with fewer people experiencing adverse events that lead to treatment interruption (RR 0.53, 95% CI 0.18 to 1.55; 318 participants, 3 trials, very low quality evidence ). We found no evidence to suggest that six‐month treatment regimens are inadequate for treating people that have intestinal and peritoneal TB, but numbers are small. We did not find any incremental benefits of nine‐month regimens regarding relapse at the end of follow‐up, or clinical cure at the end of therapy, but our confidence in the relapse estimate is very low because of size of the trials. Further research is required to make confident conclusions regarding the safety of six‐month treatment for people with abdominal TB. Larger studies that include HIV‐positive people, with long follow‐up for detecting relapse with reliability, would help improve our knowledge around this therapeutic question. 2 April 2019 Up to date All studies incorporated from most recent search All eligible published studies found in the last search (2 Sep, 2016) were included |
t123 | Many people in northern latitudes suffer from winter blues, which occurs as a reaction to reduced sunlight. Three‐quarters of those affected are women. Lethargy, overeating, craving for carbohydrates and depressed mood are common symptoms. In some people, winter blues becomes depression, which seriously affects their daily lives. Up to two‐thirds experience depressive symptoms every winter. In light of the seasonal pattern and the high rate of recurrence, beginning antidepressant therapy in early autumn (fall) when people are still free of depressive symptoms can prevent the onset of depressed mood. The goal of this review is to examine whether benefits outweigh harms of antidepressants when they are used in healthy people with a history of winter depression to prevent onset of depression the next winter. We searched databases up to June 2018 for studies on antidepressants given to prevent winter depression. Of 3745 records, we found three randomised controlled studies including 1100 people who received bupropion extended‐release (only one of many available antidepressants, but the only one licensed for prevention of winter depression) or placebo. In populations with a high risk of developing a new depressive episode in the next winter, results show that antidepressants can prevent winter depression in about one in four people. In populations with a lower risk of recurrence, antidepressants can prevent a new depressive episode in one of eight people. The other seven people suffer from winter depression despite treatment or would not have suffered from winter depression anyway. People using antidepressants are at slightly higher risk of experiencing headaches, nausea or insomnia when compared with people not taking antidepressants. Doctors need to discuss with patients the advantages and disadvantages of antidepressants and other potentially preventive treatments for winter depression, such as light treatment, psychological therapies or lifestyle interventions. As no available studies have compared these treatments, the decision for or against preventive treatment of SAD and the treatment selected should be strongly based on patient preferences. | Seasonal affective disorder (SAD) is a seasonal pattern of recurrent major depressive episodes that most commonly occurs during autumn or winter and remits in spring. The prevalence of SAD ranges from 1.5% to 9%, depending on latitude. The predictable seasonal aspect of SAD provides a promising opportunity for prevention. This review ‐ one of four reviews on efficacy and safety of interventions to prevent SAD ‐ focuses on second‐generation antidepressants (SGAs). Objectives To assess the efficacy and safety of SGAs (in comparison with other SGAs, placebo, light therapy, melatonin or agomelatine, psychological therapies or lifestyle interventions) in preventing SAD and improving patient‐centred outcomes among adults with a history of SAD. Search methods We searched Ovid MEDLINE (1950‐ ), Embase (1974‐ ), PsycINFO (1967‐ ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 19 June 2018. An earlier search of these databases was conducted via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD‐CTR) (all years to 11 August 2015). Furthermore, we searched the Cumulative Index to Nursing and Allied Health Literature, Web of Science, the Cochrane Library , the Allied and Complementary Medicine Database and international trial registers (to 19 June 2018). We also conducted a grey literature search and handsearched the reference lists of included studies and pertinent review articles. Selection criteria For efficacy, we included randomised controlled trials (RCTs) on adults with a history of winter‐type SAD who were free of symptoms at the beginning of the study. For adverse events, we planned to include non‐randomised studies. Eligible studies compared a SGA versus another SGA, placebo, light therapy, psychological therapy, melatonin, agomelatine or lifestyle changes. We also intended to compare SGAs in combination with any of the comparator interventions versus placebo or the same comparator intervention as monotherapy. Data collection and analysis Two review authors independently screened abstracts and full‐text publications, extracted data and assessed risk of bias of included studies. When data were sufficient, we conducted random‐effects (Mantel‐Haenszel) meta‐analyses. We assessed statistical heterogeneity by calculating the Chi 2 statistic and the Cochran Q. We used the I 2 statistic to estimate the magnitude of heterogeneity. We assessed publication bias by using funnel plots.We rated the strength of the evidence using the system developed by the GRADE Working Group. We identified 3745 citations after de‐duplication of search results and excluded 3619 records during title and abstract reviews. We assessed 126 full‐text papers for inclusion in the review, of which four publications (on three RCTs) providing data from 1100 people met eligibility criteria for this review. All three RCTs had methodological limitations due to high attrition rates. Overall, moderate‐quality evidence indicates that bupropion XL is an efficacious intervention for prevention of recurrence of depressive episodes in people with a history of SAD (risk ratio (RR) 0.56, 95% confidence interval (CI) 0.44 to 0.72; 3 RCTs, 1100 participants). However, bupropion XL leads to greater risk of headaches (moderate‐quality evidence), insomnia and nausea (both low‐quality evidence) when compared with placebo. Numbers needed to treat for additional beneficial outcomes (NNTBs) vary by baseline risks. For a population with a yearly recurrence rate of 30%, the NNTB is 8 (95% CI 6 to 12). For populations with yearly recurrence rates of 50% and 60%, NNTBs are 5 (95% CI 4 to 7) and 4 (95% CI 3 to 6), respectively. We could find no studies on other SGAs and no studies comparing SGAs with other interventions of interest, such as light therapy, psychological therapies, melatonin or agomelatine. Available evidence indicates that bupropion XL is an effective intervention for prevention of recurrence of SAD. Nevertheless, even in a high‐risk population, three out of four people will not benefit from preventive treatment with bupropion XL and will be at risk for harm. Clinicians need to discuss with patients advantages and disadvantages of preventive SGA treatment, and might want to consider offering other potentially efficacious interventions, which might confer a lower risk of adverse events. Given the lack of comparative evidence, the decision for or against initiating preventive treatment of SAD and the treatment selected should be strongly based on patient preferences. Future researchers need to assess the effectiveness and risk of harms of SGAs other than bupropion for prevention of SAD. Investigators also need to compare benefits and harms of pharmacological and non‐pharmacological interventions. |
t124 | The addition of anti‐leukotriene agents to inhaled corticosteroids versus placebo for chronic asthma Inhaled steroids remain the cornerstone of asthma treatment. Anti‐leukotrienes constitute a new class of drugs that can be taken by mouth and do not have the side effects associated with steroids. We looked to see how effective these drugs were when they were added to the treatment of patients who needed steroid inhalers to control their asthma.In asthmatics that are not well controlled on inhaled steroids, the addition of anti‐leukotrienes brings modest improvement in asthma control but it remains unclear whether they are as effective as increasing the dose of inhaled steroids. Higher doses of anti‐leukotrienes are more effective, but associated with an increased risk of side effect that occurs with these particular drugs. In asthmatics that are well controlled on inhaled steroids, the addition of anti‐leukotrienes did not allow a reduction in the amount of inhaled steroid used but they seemed to have a beneficial effect on the asthma control. There are only two studies that have looked at these issues in children; this is insufficient to firmly conclude whether anti‐leukotrienes are useful in children. | Anti‐leukotriene (AL) agents are being considered as 'add‐on' therapy to inhaled corticosteroids (ICS), in chronic asthma. Objectives To examine the safety and efficacy of daily AL plus ICS compared to ICS alone, and determine the corticosteroid‐sparing effect of AL when added to ICS in chronic asthma. Search methods We searched MEDLINE, EMBASE, CINAHL (until August 2003), reference lists of review articles and trials, contacted international headquarters of AL manufacturers and looked at American Thoracic Society and European Respiratory Society meeting abstracts (1998 to 2003). Selection criteria Randomised placebo‐controlled trials of asthmatics aged two years and older with at least one month intervention. Data collection and analysis Two reviewers assessed quality and extracted data independently. Trials were grouped by asthma control at baseline (symptomatic or well‐controlled) and dose of ICS in the control group (same or double). Of 587citations, 27 (25 adult and 2 paediatric) trials met inclusion criteria. Sixteen trials were published in full‐text and 16 trials reported data in a way that allowed meta‐analysis. In symptomatic patients, addition of licensed doses of anti‐leukotrienes to ICS resulted in a non‐significant reduction in the risk of exacerbations requiring systemic steroids: Relative Risk (RR) 0.64; 95% Confidence Interval (CI) 0.38 to 1.07). A modest improvement group difference in PEF was seen (Weighted Mean Difference (WMD) 7.7 L/min; 95% CI 3.6 to 11.8 L/min) together with decrease in use of rescue short‐acting beta2‐agonist use (WMD 1 puff/week; 95%CI 0.5 to 2). With only 3 trials comparing the use of licensed doses of anti‐leukotrienes with increasing the dose of inhaled glucocorticoids, no firm conclusion can be drawn about the equivalence of both treatment options. In ICS‐sparing studies of patients who were well controlled at baseline, addition of anti‐leukotrienes produced no overall difference in dose of inhaled glucocorticoids (WMD ‐21 mcg/d, 95%CI ‐65, 23 mcg/d), but it was associated with fewer withdrawals due to poor asthma control (RR 0.63, 95% CI 0.42 to 0.95). The addition of licensed doses of anti‐leukotrienes to add‐on therapy to inhaled glucocorticoids brings modest improvement in lung function. Although addition of anti‐leukotrienes to inhaled glucocorticoids appears comparable to increasing the dose of inhaled steroids, the power of the review is insufficient to confirm the equivalence of both treatment options. Addition of anti‐leukotrienes is associated with superior asthma control after glucocorticoid tapering; although the glucocorticoid‐sparing effect cannot be quantified at present, it appears modest. |
t125 | Subfertility due to the absence of ovulation is a common problem in women. Medical treatment may help these women ovulate. For example, oral antioestrogens such as clomiphene cause increased stimulation of the ovaries and aid ovulation. Miscarriage, multiple pregnancy rates, and adverse events such as ovarian hyperstimulation syndrome were poorly reported. We found evidence suggesting that clomiphene citrate improves the chance of a clinical pregnancy compared with placebo. There was no evidence of a difference between clomiphene and tamoxifen, a similar antioestrogen drug. Women treated with clomiphene citrate were less likely to get pregnant or have a live baby compared with women who had received gonadotropins; there was no evidence for a difference in the chance of a multiple pregnancy. The numbers of women getting pregnant in these trials were very small, therefore we cannot be certain of the results. Both dexamethasone (a steroid) and combined oral contraceptives are used to supplement clomiphene and show promise, but more studies are needed to confirm this. Few studies reported beyond the establishment of early pregnancy; given the reported risks of miscarriage with clomiphene treatment, no definitive conclusions can be drawn about effective treatment. We found evidence suggesting that a 10‐day regimen of clomiphene citrate improved pregnancy outcomes when compared with a 5‐day regimen, although the volume of data is limited and further research is required. There were insufficient data reported for early versus late regimens of clomiphene citrate to be able to make a judgement on differences for pregnancy outcomes. | Subfertility due to anovulation is a common problem in women. First‐line oral treatment is with antioestrogens such as clomiphene citrate, but resistance may be apparent with clomiphene. Alternative and adjunctive treatments have been used including tamoxifen, dexamethasone, and bromocriptine. The effectiveness of these is to be determined. Objectives To determine the relative effectiveness of antioestrogen agents including clomiphene alone or in combination with other medical therapies in women with subfertility associated with anovulation, possibly caused by polycystic ovarian syndrome. Search methods We conducted a search of the Cochrane Gynaecology and Fertility Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, PsycINFO, and CINAHL (all from inception to August 2016) to identify relevant randomised controlled trials (RCTs). We searched the United Kingdom National Institute for Clinical Excellence (NICE) guidelines and the references of relevant reviews and RCTs. We also searched the clinical trial registries for ongoing trials (inception until August 2016). Selection criteria We considered RCTs comparing oral antioestrogen agents for ovulation induction (alone or in conjunction with medical therapies) in anovulatory subfertility. We excluded insulin‐sensitising agents, aromatase inhibitors, and hyperprolactinaemic infertility. Data collection and analysis Two review authors independently performed data extraction and quality assessment. The primary outcome was live birth; secondary outcomes were pregnancy, ovulation, miscarriage, multiple pregnancy, ovarian hyperstimulation syndrome, and adverse effects. This is a substantive update of a previous review. We identified an additional 13 studies in the 2016 update. The review now includes 28 RCTs (3377 women) and five RCTs awaiting classification. Five of the 28 included trials reported live birth/ongoing pregnancy. The primary reasons for downgrading the evidence were imprecision and risk of bias associated with poor reporting. Antioestrogen versus placebo Live birth rate, miscarriage rate, multiple pregnancy rate, and ovarian hyperstimulation syndrome (OHSS) No data were reported for these outcomes. Clinical pregnancy rate Clomiphene citrate was associated with an increased chance of a clinical pregnancy compared with placebo, though the size of the benefit was very uncertain (odds ratio (OR) 5.91, 95% confidence interval (CI) 1.77 to 19.68; 3 studies; 133 women; low‐quality evidence). If the chance of a clinical pregnancy was 5% in the placebo group, then between 8% and 50% of women would have a clinical pregnancy in the clomiphene group. Clomiphene citrate versus tamoxifen Live birth rate There was no clear evidence of a difference in the chance of a live birth between the clomiphene citrate and tamoxifen groups (OR 1.24, 95% CI 0.59 to 2.62; 2 studies; 195 women; low‐quality evidence). If 20% of women in the tamoxifen group had a live birth, then between 13% and 40% of women in the clomiphene citrate group would have a live birth. Miscarriage rate There was no clear evidence of a difference in the chance of a miscarriage between the clomiphene citrate and tamoxifen groups (OR 1.81, 95% CI 0.80 to 4.12; 4 studies; 653 women; low‐quality evidence). If 3% of women in the tamoxifen group had a miscarriage, then between 2% and 10% in the clomiphene citrate group would have a miscarriage. Clinical pregnancy rate There was no clear evidence of a difference in the chance of a clinical pregnancy between the clomiphene citrate and tamoxifen groups (OR 1.30, 95% CI 0.92 to 1.85; 5 studies; 757 women; I 2 = 69%; low‐quality evidence). If 22% of women in the tamoxifen group had a clinical pregnancy, then between 21% and 35% in the clomiphene citrate group would have a clinical pregnancy. Multiple pregnancy rate There was insufficient evidence of a difference in the chance of a multiple pregnancy between the clomiphene citrate group (OR 2.34, 95% CI 0.34 to 16.04; 3 studies; 567 women; very low‐quality evidence). If 0% of women in the tamoxifen group had a multiple pregnancy, then between 0% and 0.5% of women in the clomiphene group would have a multiple pregnancy. OHSS There were no instances of OHSS in either the clomiphene citrate or the tamoxifen group reported from three studies. Clomiphene citrate with tamoxifen versus tamoxifen alone Clinical pregnancy rate There was insufficient evidence to determine whether there was a difference between groups (OR 3.32, 95% CI 0.12 to 91.60; 1 study; 20 women; very low‐quality evidence). No data were reported for the other outcomes. Other comparisons of interest Limited evidence suggested that compared with a gonadotropin, clomiphene citrate was associated with a reduced chance of a pregnancy, ongoing pregnancy, or live birth, with no clear evidence of a difference in multiple pregnancy rates. The comparison of clomiphene citrate plus medical adjunct versus clomiphene alone was limited by the number of trials reporting the comparison and poor reporting of clinical outcomes relevant to this systematic review and by the number of adjuncts reported (ketoconazole, bromocriptine, dexamethasone, combined oral contraceptive, human chorionic gonadotropin, hormone supplementation). The addition of dexamethasone or combined oral contraceptive suggested a possible benefit in pregnancy outcomes, but findings were very uncertain and further research is required to confirm this. There was limited evidence suggesting that a 10‐day regimen of clomiphene citrate improves pregnancy outcomes compared with a 5‐day regimen. Data for early versus late regimens of clomiphene citrate were insufficient to be able to make a judgement on differences for pregnancy outcomes. We found evidence suggesting that clomiphene citrate improves the chance of a clinical pregnancy compared with placebo, but may reduce the chance of live birth or ongoing pregnancy when compared with a gonadotropin. Due to low event rates, we advise caution interpreting these data. The comparison of clomiphene citrate plus medical adjunctive versus clomiphene alone was limited by the number of trials reporting the comparison. The evidence was very low quality and no firm conclusions could be drawn, but very limited evidence suggested a benefit from adjunctive dexamethasone or combined oral contraceptives. Low‐quality evidence suggested that a 10‐day regimen of clomiphene citrate improves pregnancy rates compared with a 5‐day regimen, but further research is required. |
t126 | Calcium channel blockers have not been shown to reduce preterm birth or improve the outcomes for babies when given to women after contractions of preterm labour have been stopped. Babies born premature (before 37 weeks of pregnancy) may not survive, or may have serious long‐term problems if they do survive. Women who have had their preterm labour stopped with tocolytic treatment (medication to reduce uterine contractions), remain at risk of giving birth preterm. After this initial tocolytic treatment has been given to stop early labour, a maintenance tocolytic treatment may be given to try to prevent further early contractions and early birth. Calcium channel blockers are one of the types of tocolytic therapy that have been used in an attempt to prevent the onset of further preterm contractions. We identified six randomised controlled trials involving a total of 794 women and their babies for this review. The trials did not demonstrate differences between calcium channel blocker maintenance therapy and placebo or no treatment in the prevention of preterm birth or perinatal death (fetal or neonatal deaths). None of the trials included any follow‐up of the infants to assess longer‐term development. Calcium channel blocker maintenance therapy (with a drug called nifedipine) was more likely than placebo or no treatment to prolong pregnancy, however the infants of these mothers were more likely to have a longer hospital stay. Based on the current studies, we found no convincing evidence that calcium channel blocker maintenance therapy prevents preterm birth for women after threatened preterm labour, or that it improves outcomes for babies. | Calcium channel blocker maintenance therapy is one of the types of tocolytic therapy that may be used after an episode of threatened preterm labour (and usually an initial dose of tocolytic therapy) in an attempt to prevent the onset of further preterm contractions. Objectives To assess the effects of calcium channel blockers as maintenance therapy on preventing preterm birth after threatened preterm labour. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013) and reference lists of retrieved studies. Selection criteria Randomised controlled trials of calcium channel blockers used as maintenance therapy to prevent preterm birth after threatened preterm labour, compared with placebo or no treatment. Data collection and analysis Two review authors independently assessed study eligibility, extracted data and assessed the risk of bias of included studies. We included six trials that enrolled 794 women and their babies and all assessed nifedipine as calcium channel blocker maintenance therapy. The six trials were judged to be at a moderate risk of bias overall. No differences in the incidence of preterm birth (risk ratio (RR) 0.97; 95% confidence interval (CI) 0.87 to 1.09; five trials, 681 women), birth within 48 hours of treatment (RR 0.46; 95% CI 0.07 to 3.00; two trials, 128 women) or neonatal mortality (average RR 0.75; 95% CI 0.05 to 11.76; two trials, 133 infants) were seen when nifedipine maintenance therapy was compared with placebo or no treatment. No stillbirths were reported in the one trial that provided data for this outcome. No trials reported on longer‐term follow‐up of infants. Women receiving nifedipine maintenance therapy were significantly more likely to have their pregnancy prolonged (mean difference (MD) 5.35 days; 95% CI 0.49 to 10.21; four trials, 275 women); however, no differences between groups were shown for birth at less than 34 weeks' gestation, birth at less than 28 weeks' gestation, birth within seven days of treatment, or gestational age at birth. No significant differences were shown between the nifedipine and control groups for any of the secondary neonatal morbidities reported. Similarly, no significant differences were seen for the outcomes relating to the use of health services, except for in one trial, where infants whose mothers received nifedipine were significantly more likely to have a longer length of hospital stay as compared with infants born to mothers who received a placebo (MD 14.00 days; 95% CI 4.21 to 23.79; 60 infants). Based on the current available evidence, maintenance treatment with a calcium channel blocker after threatened preterm labour does not prevent preterm birth or improve maternal or infant outcomes. |
t127 | Children who need a general anaesthetic sometimes need a breathing tube placed in their throat, known as intubation. Intubations are also performed in emergency situations such as trauma, severe breathing difficulty, and heart dysfunction. Intubation is traditionally performed with a laryngoscope, a device that lifts the tongue to allow a direct view of the vocal cords. This is known as direct laryngoscopy. New devices have been developed that show the vocal cords through a fine video camera placed on the tip of the device; this is known as indirect laryngoscopy, or videolaryngoscopy. Indirect laryngoscopes, or videolaryngoscopes, are thought to provide a better view of the vocal cords when compared with direct laryngoscopes, but whether this equipment allows easier placement of the breathing tube remains unclear. We reviewed the evidence on how effective indirect laryngoscopy, or videolaryngoscopy, is when compared with direct laryngoscopy for intubation in children from 28 days to 18 years old. We found 12 randomized controlled trials (803 children) that met our inclusion criteria. For intubation, use of indirect laryngoscopy, or videolaryngoscopy, took longer and was more likely to be unsuccessful (very low‐quality evidence). No significant difference was found between direct and indirect laryngoscopy when success of the first attempt at intubation was assessed (low‐quality evidence). Only a few studies reported the effect of intubation on adverse haemodynamic response, including changes in oxygen saturation, heart rate, and trauma to the mouth and windpipe. Therefore, it was difficult to conclude on the overall adverse effect (very low‐quality evidence). Indirect laryngoscopy might provide better views of the vocal cords. We found considerable variation in results from included studies in terms of assessment of intubation time, number of attempts at intubation, number of unsuccessful intubations, adverse effects, and assessments of how well the vocal cords were seen. None of the included studies was funded by a laryngoscope manufacturer, hence minimizing the risk of other bias. | Direct laryngoscopy is the method currently used for tracheal intubation in children. It occasionally offers unexpectedly poor laryngeal views. Indirect laryngoscopy involves visualizing the vocal cords by means other than obtaining a direct sight, with the potential to improve outcomes. We reviewed the current available literature and performed a meta‐analysis to compare direct versus indirect laryngoscopy, or videolaryngoscopy, with regards to efficacy and adverse effects. Objectives To assess the efficacy of indirect laryngoscopy, or videolaryngoscopy, versus direct laryngoscopy for intubation of children with regards to intubation time, number of attempts at intubation, and adverse haemodynamic responses to endotracheal intubation. We also assessed other adverse responses to intubation, such as trauma to oral, pharyngeal, and laryngeal structures, and we assessed vocal cord view scores. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and trial registers ( www.clinicaltrials.gov and www.controlledtrials ) in November 2015. We reran the search in January 2017. We added new studies of potential interest to a list of ‘Studies awaiting classification' and will incorporate them into formal review findings during the review update. We performed reference checking and citation searching and contacted the authors of unpublished data to ask for more information. We applied no language restrictions. Selection criteria We included only randomized controlled trials. Participants were children aged 28 days to 18 years. Investigators performed intubations using any type of indirect laryngoscopes, or videolaryngoscopes, versus direct laryngoscopes. Data collection and analysis We used Cochrane standard methodological procedures. Two review authors independently reviewed titles, extracted data, and assessed risk of bias. We included 12 studies (803 children) in this review and meta‐analysis. We identified three studies that are awaiting classification and two ongoing studies. Trial results show that a longer intubation time was required when indirect laryngoscopy, or videolaryngoscopy, was used instead of direct laryngoscopy (12 trials; n = 798; mean difference (MD) 5.49 seconds, 95% confidence interval (CI) 1.37 to 9.60; I 2 = 90%; very low‐quality evidence). Researchers found no significant differences between direct and indirect laryngoscopy on assessment of success of the first attempt at intubation (11 trials; n = 749; risk ratio (RR) 0.96, 95% CI 0.91 to 1.02; I 2 = 67%; low‐quality evidence) and observed that unsuccessful intubation (five trials; n = 263) was significantly increased in the indirect laryngoscopy, or videolaryngoscopy, group (RR 4.93, 95% CI 1.33 to 18.31; I 2 = 0%; low‐quality evidence). Five studies reported the effect of intubation on oxygen saturation (n = 272; very low‐quality evidence). Five children had desaturation during intubation: one from the direct laryngoscopy group and four from the indirect laryngoscopy, or videolaryngoscopy, group. Two studies (n = 100) reported other haemodynamic responses to intubation (very low‐quality evidence). One study reported a significant increase in heart rate five minutes after intubation in the indirect laryngoscopy group (P = 0.007); the other study found that the heart rate change in the direct laryngoscopy group was significantly less than the heart rate change in the indirect laryngoscopy, or videolaryngoscopy, group (P < 0.001). A total of five studies (n = 244; very low‐quality evidence) looked at evidence of trauma resulting from intubation. Investigators reported that only two children from the direct laryngoscopy group had trauma compared with no children in the indirect laryngoscopy, or videolaryngoscopy, group. Use of indirect laryngoscopy, or videolaryngoscopy, improved the percentage of glottic opening (five trials; n = 256). Studies noted no significant difference in Cormack and Lehane score (C&L) grade 1 (three trials; n = 190; RR 1.06, 95% CI 0.93 to 1.21; I 2 = 59%). Evidence suggests that indirect laryngoscopy, or videolaryngoscopy, leads to prolonged intubation time with an increased rate of intubation failure when compared with direct laryngoscopy (very low‐quality evidence due to imprecision, inconsistency, and study limitations). Review authors had difficulty reaching conclusions on adverse haemodynamic responses and other adverse effects of intubation, as only a few children were reported to have these outcomes. Use of indirect laryngoscopy, or videolaryngoscopy, might lead to improved vocal cord view, but marked heterogeneity between studies made it difficult for review authors to reach conclusions on this outcome. |
t128 | Rupture of the anterior cruciate ligament (ACL) in the knee is a common injury in young, active individuals. It often results in an unstable knee that increases the risk of further knee damage, such as to the knee meniscii. Anterior cruciate ligament injuries in athletic individuals are often treated surgically. Surgery usually entails ACL reconstruction, that involves removing the torn ligament and replacing it with a tendon graft, often taken from another part of the patient's knee. Conservative (non‐surgical) interventions are also used as treatment for this injury. This usually takes the form of a progressive rehabilitation programme that includes exercises aimed at improving strength and balance. We aimed to assess the effects of surgical versus conservative interventions for treating ACL injuries. Results of the search We performed a systematic literature search (up to 18 January 2016) for studies that compared surgery and conservative interventions for treating ACL injuries. This review identified one study of 121 young, active adults with an ACL injury in the preceding four weeks. The study compared surgery (ACL reconstruction followed by structured rehabilitation) with conservative treatment (structured rehabilitation alone). The study found there was no difference between surgery and conservative treatment in patient‐reported knee scores at two or five years. The study failed to report on the number of participants in each group who had any type of serious or non‐serious complications. However, surgery‐related complications included three cases of graft rupture in the surgery group and several participants of the conservative treatment group had unstable knees. Twenty‐three of the 59 participants in the conservative treatment group (39%) had either reconstruction of the ACL or repair of a meniscus tear within two years and 30 (51%) underwent surgery within five years. There was some evidence that similar numbers of participants in the two groups had surgical treatment of knee meniscal injuries at five years. | Rupture of the anterior cruciate ligament (ACL) is a common injury, mainly affecting young, physically active individuals. The injury is characterised by joint instability, leading to decreased activity, which can lead to poor knee‐related quality of life. It is also associated with increased risk of secondary osteoarthritis of the knee. It is unclear whether stabilising the knee surgically via ACL reconstruction produces a better overall outcome than non‐surgical (conservative) treatment. Objectives To assess the effects of surgical versus conservative interventions for treating ACL injuries. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (18 January 2016), the Cochrane Central Register of Controlled Trials (2016, Issue 1), MEDLINE (1946 to January Week 1 2016), MEDLINE In‐Process & Other Non‐Indexed Citations (18 January 2016), EMBASE (1974 to 15 January 2016), trial registers (February 2016) and reference lists. Selection criteria We included randomised controlled trials that compared the use of surgical and conservative interventions in participants with an ACL rupture. We included any trial that evaluated surgery for ACL reconstruction using any method of reconstruction, type of reconstruction technique, graft fixation or type of graft. Data collection and analysis Three review authors independently screened all titles and abstracts for potentially eligible studies, for which we then obtained full‐text reports. Two authors then independently confirmed eligibility, extracted data and assessed the risk of bias using the Cochrane 'Risk of bias' tool. We identified one study in which 141 young, active adults with acute ACL injury were randomised to either ACL reconstruction followed by structured rehabilitation (results reported for 62 participants) or conservative treatment comprising structured rehabilitation alone (results reported for 59 participants). Built into the study design was a formal option for subsequent (delayed) ACL reconstruction in the conservative treatment group, if the participant requested surgery and met pre‐specified criteria. This study was deemed at low risk of selection and reporting biases, at high risk of performance and detection biases because of the lack of blinding and at unclear risk of attrition bias because of an imbalance in the post‐randomisation exclusions. This study identified no difference in subjective knee score (measured using the average score on four of the five sub‐scales of the KOOS score (range from 0 (extreme symptoms) to 100 (no symptoms)) between ACL reconstruction and conservative treatment at two years (difference in KOOS‐4 change from baseline scores: MD ‐0.20, 95% confidence interval (CI) ‐6.78 to 6.38; N = 121 participants; low‐quality evidence), or at five years (difference in KOOS‐4 final scores: MD ‐2.0, 95% CI ‐8.27 to 4.27; N = 120 participants; low‐quality evidence). The total number of participants incurring one or more complications in each group was not reported; serious events reported in the surgery group were predominantly surgery‐related, while those in conservative treatment group were predominantly knee instability. There were also incomplete data for total participants with treatment failure, including subsequent surgery. In the surgical group at two years, there was low‐quality evidence of far fewer ACL‐related treatment failures, when defined as either graft rupture or subsequent ACL reconstruction. This result is dominated by the uptake by 39% (23/59) of the participants in the conservative treatment group of ACL reconstruction for knee instability at two years and by 51% (30/59) of the participants at five years. There was low‐quality evidence of little difference between the two groups in participants who had undergone meniscal surgery at anytime up to five years. There was low‐quality evidence of no clinically important between‐group differences in SF‐36 physical component scores at two years. There was low‐quality evidence of a higher return to the same or greater level of sport activity at two years in the ACL reconstruction group, but the wide 95% CI also included the potential for a higher return in the conservative treatment group. Based on an illustrative return to sport activities of 382 per 1000 conservatively treated patients, this amounts to an extra 84 returns per 1000 ACL‐reconstruction patients (95% CI 84 fewer to 348 more). There was very low‐quality evidence of a higher incidence of radiographically‐detected osteoarthritis in the surgery group (19/58 (35%) versus 10/55 (18%)). For adults with acute ACL injuries, we found low‐quality evidence that there was no difference between surgical management (ACL reconstruction followed by structured rehabilitation) and conservative treatment (structured rehabilitation only) in patient‐reported outcomes of knee function at two and five years after injury. However, these findings need to be viewed in the context that many participants with an ACL rupture remained symptomatic following rehabilitation and later opted for ACL reconstruction surgery. Further research, including the two identified ongoing trials, will help to address the limitations in the current evidence, which is from one small trial in a young, active, adult population. |
t129 | Riluzole for amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) Amyotrophic lateral sclerosis (ALS)/motor neuron disease (MND) is a fatal neurological disease which produces paralysis of the limb, swallowing and breathing muscles. There is no available treatment to stop or reverse its progressive course. In this review, we examine the evidence from four randomized clinical trials involving 1477 people with ALS. The methodological quality of the trials was acceptable and three of the trials were easily comparable (although one of them included older patients with more advanced ALS). The results indicate that riluzole 100 mg probably prolongs median survival in people with ALS by two to three months and the safety of the drug is not a major concern. The evidence from randomized controlled trials indicates that participants taking riluzole probably survive longer than participants taking placebo. The beneficial effects are very modest and the drug is expensive. There was a small beneficial effect on both bulbar and limb function, but not on muscle strength. Adverse effects from riluzole are relatively minor and for the most part reversible after stopping the drug. | Riluzole is approved for the treatment of amyotrophic lateral sclerosis in most countries. Questions persist about its clinical utility because of high cost and modest efficacy. Objectives To examine the efficacy of riluzole in prolonging survival and in delaying the use of surrogates (tracheostomy and mechanical ventilation) to sustain survival, and to assess the effect of riluzole upon functional health. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (20 April 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (2011, Issue 2), MEDLINE (1966 to April 2011), EMBASE (1980 to May 2011) and made enquiries of authors of trials, Aventis (manufacturer of riluzole) and other experts in the field. Selection criteria Types of studies: randomized controlled trials Types of participants: adults with a diagnosis of amyotrophic lateral sclerosis Types of interventions: treatment with riluzole or placebo Types of outcome measures: Primary: pooled hazard ratio of tracheostomy‐free survival over all time points with riluzole 100 mg. Secondary: per cent mortality with riluzole 50 mg, 100 mg and 200 mg; neurologic function, muscle strength and adverse events. Data collection and analysis One author performed data extraction and two other authors checked them. One author checked the data and entered them into the computer. The other authors verified the data entry. We obtained missing data from the trial authors whenever possible. The four trials examining tracheostomy‐free survival included a total of 974 riluzole‐treated patients and 503 placebo‐treated patients. No new randomized controlled trials were found when we updated the searches for this update in 2011. The methodological quality was acceptable and three trials were easily comparable, although one trial (169 participants) included older patients in more advanced stages of amyotrophic lateral sclerosis and one (195 participants) had multiple primary endpoints. Riluzole 100 mg per day provided a benefit for the homogeneous group of patients in the first two trials (hazard ratio (HR) 0.80, 95% confidence internal (CI) 0.64 to 0.99, P= 0.042) and there was no evidence of heterogeneity (P = 0.33). When the third trial (which included older and more seriously affected patients) was added, there was evidence of heterogeneity (P < 0.0001) and the overall treatment effect was reduced but still significant (HR 0.84, 95% CI 0.698 to 0.997, P= 0.046). This represented a 9% gain in the probability of surviving one year (49% in the placebo and 58% in the riluzole group), and increased median survival from 11.8 to 14.8 months. There was a small beneficial effect on both bulbar and limb function, but not on muscle strength. A three‐fold increase in serum alanine transferase was more frequent in riluzole‐treated patients than controls (mean difference 2.62, 95% CI 1.59 to 4.31). Riluzole 100 mg daily is reasonably safe and probably prolongs median survival by about two to three months in patients with amyotrophic lateral sclerosis. |
t130 | Fixation devices secured across the fracture that are placed either directly or externally for treating hip fractures located outside the hip joint Hip fractures located outside the hip joint capsule (extracapsular hip fractures) may be surgically fixed using metal implants. Often these are extramedullary devices consisting of a screw or rod, inserted in the upper part of the thigh bone (femur) to bridge (fix) the fracture, connected to a plate secured to the femur. Sometimes external fixators are used. In these, the stabilising component is held outside the thigh by pins or screws driven into the bone on either side of the fracture. The 18 randomised controlled trials included in this review tested seven comparisons in a total of 2615 mainly female and older participants. All trials had methodological flaws that may affect the validity of their results and there was a general lack of evidence on long‐term effects and functional recovery. Some extramedullary implants appeared to be associated with an increased risk of fixation complications and reoperation. In particular, three trials comparing a fixed nail plate (Jewett or McLaughlin) with the sliding hip screw (the 'standard' extramedullary device for these fractures) found an increased risk of fixation failure for fixed nail plates. Less invasive implants, such as the external fixator, which require smaller incisions resulted in less blood loss and often quicker operations than the sliding hip screw. We concluded that the sliding hip screw seems preferable to older types of fixed nail plates given their high rate of implant and fixation failure. | Extramedullary fixation of hip fractures involves the application of a plate and screws to the lateral side of the proximal femur. In external fixators, the stabilising component is held outside the thigh by pins or screws driven into the bone. This is an update of a Cochrane review first published in 1998, and last updated in 2005. Objectives To assess the relative effects of different types of extramedullary fixation implant, as well as external fixators, for treating extracapsular proximal femoral (hip) fractures in adults. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (July 2011), the Cochrane Central Register of Controlled Trials ( The Cochrane Library 2011, Issue 2), MEDLINE (1966 to June Week 4 2011), EMBASE (1988 to 2011 Week 25), various other databases, conference proceedings and reference lists. Selection criteria Randomised or quasi‐randomised controlled trials comparing extramedullary implants or external fixators for fixing extracapsular hip fracture in adults were included. Data collection and analysis Two review authors independently selected trials, assessed risk of bias and extracted data. Data were pooled where appropriate. The 18 included trials tested seven comparisons in a total of 2615 mainly female and older participants with a total of 2619 fractures. All trials had methodological flaws that may affect the validity of their results. Three trials of 355 participants comparing a fixed nail plate (Jewett or McLaughlin) with the sliding hip screw (SHS) found an increased risk of fixation failure for fixed nail plates. The two trials of 433 participants comparing the Resistance Augmented Bateaux (RAB) plate with the SHS had contrasting results, notably in terms of operative complications, fixation failure and anatomical restoration. One trial of 100 participants comparing the Pugh nail and the SHS found no significant difference between implants. Three trials of 458 participants compared the Medoff plate with the SHS. There was a trend to higher blood losses and longer operation times for the Medoff plate along with a trend to a lower risk of fixation failure with the Medoff plate for unstable trochanteric fractures. Two trials of 676 participants compared the Medoff plate with three different screw‐plate systems. There were no statistically significant differences in outcome for trochanteric fractures. For subtrochanteric fractures, there was a lower fixation failure rate for the Medoff plate but no evidence for differences in longer‐term outcomes. Four trials of 396 participants comparing the Gotfried percutaneous compression plate (PCCP) with a SHS found a trend to lower blood loss and transfusion requirements for the PCCP but no other confirmed differences in outcomes between implants. Three of the trials reported intra‐operative problems with the PCCP, some of which precluded its use. Three trials of 200 participants comparing external fixation with a SHS found less operative trauma for the external fixation. Final outcome appeared similar. The markedly increased fixation failure rate of fixed nail plates compared with the SHS is a major consideration and thus the SHS appears preferable. There was insufficient evidence from other comparisons of extramedullary implants or on the use of external fixators to draw definite conclusions. |
t131 | Conventionally, recuperation after bowel surgery followed the patients progress. Mobilisation and expansion of diet after surgery was progressed slowly in a stepwise manner following patients progression. This is because it was believed that faster recovery would be unwise. In recent years, however, a new concept has been introduced, called Enhanced Recovery after surgery (ERAS) or fast track. This program, introduced by Kehlet et al, is based on the principle that reducing the body's stress response after surgery reduces the time needed to recuperate. This is achieved by interventions around the operation, involving good information, better feeding before the operation and better pain treatment, so patients can get out of bed earlier and start a normal diet earlier and thereby reducing the risk of complications. This review investigated whether this intervention is safe and whether it is more effective than the traditional treatment. In order to answer this question, 4 randomised trials were found, comparing these two interventions. We found that ERAS can be viewed as safe, i.e. not resulting in more complications or deaths, and at the same time decreases the days spent in hospital following major bowel surgery. | In recent years the Enhanced Recovery after Surgery (ERAS) postoperative pathway in (ileo‐)colorectal surgery, aiming at improving perioperative care and decreasing postoperative complications, has become more common. Objectives We investigated the effectiveness and safety of the ERAS multimodal strategy, compared to conventional care after (ileo‐)colorectal surgery. The primary research question was whether ERAS protocols lead to less morbidity and secondary whether length of stay was reduced. Search methods To answer the research question we entered search strings containing keywords like "fast track", "colorectal and surgery" and "enhanced recovery" into major databases. We also hand searched references in identified reviews concerning ERAS. Selection criteria We included published randomised clinical trials, in any language, comparing ERAS to conventional treatment in patients with (ileo‐) colorectal disease requiring a resection. RCT's including at least 7 ERAS items in the ERAS group and no more than 2 in the conventional arm were included. Data collection and analysis Data of included trials were independently extracted by the reviewers. Analyses were performed using "REVMAN 5.0.22". Data were pooled and rate differences as well as weighted mean differences with their 95% confidence intervals were calculated using either fixed or random effects models, depending on heterogeneity (I 2 ). 4 RCTs were included and analysed. Methodological quality of included studies was considered low, when scored according to GRADE methodology. Total numbers of inclusion were limited. The trials included in primary analysis reported 237 patients, (119 ERAS vs 118 conventional). Baseline characteristics were comparable. The primary outcome measure, complications, showed a significant risk reduction for all complications (RR 0.50; 95% CI 0.35 to 0.72). This difference was not due to reduction in major complications. Length of hospital stay was significantly reduced in the ERAS group (MD ‐2.94 days; 95% CI ‐3.69 to ‐2.19), and readmission rates were equal in both groups. Other outcome parameters were unsuitable for meta‐analysis, but seemed to favour ERAS. The quantity and especially quality of data are low. Analysis shows a reduction in overall complications, but major complications were not reduced. Length of stay was reduced significantly. We state that ERAS seems safe, but the quality of trials and lack of sufficient other outcome parameters do not justify implementation of ERAS as the standard of care. Within ERAS protocols included, no answer regarding the role for minimally invasive surgery (i.e. laparoscopy) was found. Furthermore, protocol compliance within ERAS programs has not been investigated, while this seems a known problem in the field. Therefore, more specific and large RCT's are needed. |
t132 | This review aimed to find out which type of treatment works best for preventing future stroke and other blood clotting (thrombotic) events, in people with antiphospholipid syndrome (APS). APS is a disease where the immune system produces antibodies directed against the proteins attached to their own cells. The presence of such antibodies may increase the risk of developing blood clots (thrombosis) in the blood vessels, or causing pregnancy‐related complications (such as recurrent miscarriage, death of a baby in womb, premature birth, poor growth of the baby, or serious illness in a pregnant women). Blood clots in the arteries can cause strokes, resulting in brain damage or reversible nerve symptoms. Blood clots in veins are associated with pain and limb swelling, and if they move they can block blood flow to the lungs. Two types of drugs are commonly used to prevent blood clots in people with APS: anticoagulants and antiplatelets. Anticoagulants prevent blood clot formation by interfering with the activity of proteins involved in blood clotting (clotting factors); while antiplatelets, usually aspirin, prevent platelets from sticking together and impair clot formation. Treatment with some anticoagulants (such as warfarin) requires regular blood tests to ensure their adequate action, and a balanced diet in terms of vitamin K intake, mainly in green leafy vegetables. We looked for studies that randomly allocated people with APS to different treatments, including anticoagulants, antiplatelets, or both. We identified five studies involving 419 participants. The average age of the participants was between 41 and 50 years, and the studies included people with previous stroke or previous blood clots in large veins or arteries. Studies took place in eight different countries and had a variety of funding sources. One trial compared a novel anticoagulant (rivaroxaban) with the standard anticoagulant (warfarin). Two studies compared a high dose versus standard dose of warfarin , and two studies compared combinations of antiplatelets, anticoagulants, or both. Interventions lasted from 180 days to an average of 3.9 years (SD 2.0). In one study with an anticoagulant (rivaroxaban), participants had no episodes of blood clotting, and there was no difference in the risk of bleeding (moderate‐quality evidence). In the two studies comparing higher and lower doses of anticoagulant (warfarin), similar proportions of participants had blood clotting and major bleeding problems (low‐quality evidence), but the higher dose warfarin group had a greater risk of minor bleeding problems and any bleeding problems (low‐quality evidence). | Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by arterial or venous thrombosis (or both) and/or pregnancy morbidity in association with the presence of antiphospholipid antibodies. The prevalence is estimated at 40 to 50 cases per 100,000 people. The most common sites of thrombosis are cerebral arteries and deep veins of the lower limbs. People with a definite APS diagnosis have an increased lifetime risk of recurrent thrombotic events. Objectives To assess the effects of antiplatelet or anticoagulant agents, or both, for the secondary prevention of recurrent thrombosis, particularly ischemic stroke, in people with antiphospholipid syndrome. Search methods We searched the Cochrane Stroke Group Trials Register (February 2017), CENTRAL (last search February 2017), MEDLINE (from 1948 to February 2017), Embase (from 1980 to February 2017), and several ongoing trials registers. We also checked the reference lists of included studies, systematic reviews, and practice guidelines, and we contacted experts in the field. Selection criteria We included randomized controlled trials (RCTs) that evaluated any anticoagulant or antiplatelet agent, or both, in the secondary prevention of thrombosis in people diagnosed with APS according to the criteria valid when the study took place. We did not include studies specifically addressing women with obstetrical APS. Data collection and analysis Pairs of review authors independently selected studies for inclusion, extracted data, and assessed the risk of bias for the included studies. We resolved any discrepancies through discussion or by consulting a third review author and, in addition, one review author checked all the extracted data. We included five studies involving 419 randomized participants with APS. Only one study was at low risk of bias in all domains. One study was at low risk of bias in all domains for objective outcomes but not for quality of life (measured using the EQ‐5D‐5L questionnaire). We judged the other three studies to be at unclear or high risk of bias in three or more domains. The duration of intervention ranged from 180 days to a mean of 3.9 years. One study compared rivaroxaban (a novel oral anticoagulant: NOAC) with standard warfarin treatment and reported no thrombotic or major bleeding events, but it was not powered to detect such differences (low‐quality evidence). Investigators reported similar rates of clinically relevant non‐major bleeding (risk ratio (RR) 1.45, 95% confidence interval (CI) 0.25 to 8.33; moderate‐quality evidence) and minor bleeding (RR 1.21, 95% CI 0.51 to 2.83) for participants receiving rivaroxaban and the standard vitamin K antagonists (VKA). This study also reported some small benefit with rivaroxaban over the standard VKA treatment in terms of quality of life health state measured at 180 days with the EQ‐5D‐5L 100 mm visual analogue scale (mean difference (MD) 7 mm, 95% CI 2.01 to 11.99; low‐quality evidence) but not measured as health utility (MD 0.04, 95% CI −0.02 to 0.10 [on a scale from 0 to 1]). Two studies compared high dose VKA (warfarin) with moderate/standard intensity VKA and found no differences in the rates of any thrombotic events (RR 2.22, 95% CI 0.79 to 6.23) or major bleeding (RR 0.74, 95% CI 0.24 to 2.25) between the groups (low‐quality evidence). Minor bleeding analyzed using the RR and any bleeding using the hazard ratio (HR) were more frequent in participants receiving high‐intensity warfarin treatment compared to the standard‐intensity therapy (RR 2.55, 95% CI 1.07 to 6.07; and HR 2.03, 95% CI 1.12 to 3.68; low‐quality evidence). In one study, it was not possible to estimate the RR for stroke with a combination of VKA plus antiplatelet agent compared to a single antiplatelet agent, while for major bleeding, a single event occurred in the single antiplatelet agent group. In one study, comparing combined VKA plus antiplatelet agent with dual antiplatelet therapy, the RR of the risk of stroke over three years of observation was 5.00 (95% CI 0.26 to 98.0). In a single small study, the RR for stroke during one year of observation with a dual antiplatelet therapy compared to single antiplatelet drug was 0.14 (95% CI 0.01 to 2.60). There is not enough evidence for or against NOACs or for high‐intensity VKA compared to the standard VKA therapy in the secondary prevention of thrombosis in people with APS. There is some evidence of harm for high‐intensity VKA regarding minor and any bleeding. The evidence was also not sufficient to show benefit or harm for VKA plus antiplatelet agent or dual antiplatelet therapy compared to a single antiplatelet drug. Future studies should be adequately powered, with proper adherence to treatment, in order to evaluate the effects of anticoagulants, antiplatelets, or both, for secondary thrombosis prevention in APS. We have identified five ongoing trials mainly using NOACs in APS, so increasing experimental efforts are likely to yield additional evidence of clinical relevance in the near future. |
t133 | Of all the gynaecological cancers, ovarian cancer has the highest death rate and epithelial ovarian cancer accounts for about 90% of all cases. Surgery and six courses of platinum‐based chemotherapy is the standard treatment and 75% of the women may not have any evidence of disease at the end of this treatment. However, 75% of the women who respond to initial treatment will relapse within 18 to 28 months and only 20% to 40% of all women will survive beyond five years.Some doctors suggest giving maintenance chemotherapy for epithelial ovarian cancer. Maintenance chemotherapy refers to the chemotherapy given to women who have achieved remission after initial surgery and induction chemotherapy.The aim of maintenance chemotherapy is to prolong the duration of remission and improve the overall length of survival. Some studies indicate that maintenance chemotherapy can improve the time without cancer progression, while others do not show any effect. The aim of this review was to estimate whether using maintenance chemotherapy is better than observation alone for women with epithelial ovarian cancer. We identified eight trials that used different types of chemotherapy (e.g. platinum agents, doxorubicin, topotecan or paclitaxel) but there was not sufficient evidence to prove any of the drugs were better than observation alone. An important consideration for women with advanced disease is the balance between the benefit of treatment and the harms or adverse effects that these treatments may cause. | This review is an update of a previously published review in the Cochrane Database of Systematic Reviews (2010, Issue 9 and 2013, Issue 6). Epithelial ovarian cancer accounts for about 90% of all cases of ovarian cancer. Debulking surgery and six courses of platinum‐based chemotherapy results in complete clinical remission (CCR) in up to 75% of cases. However, 75% of the responders will relapse within a median time of 18 to 28 months and only 20% to 40% of women will survive beyond five years. It has been suggested that maintenance chemotherapy could assist in prolonging remission. To date, there has not been a systematic review on the impact of maintenance chemotherapy for epithelial ovarian cancer. Objectives To assess the effectiveness and toxicity of maintenance chemotherapy for epithelial ovarian cancer and to evaluate the impact on quality of life (QoL). Search methods In the original review we searched the Cochrane Gynaecological Cancer Review Group Specialised Register, Cochrane Central Register of Controlled Trails (CENTRAL, the Cochrane Library 2009, Issue 1), MEDLINE, Embase, PubMed, CBMdisc, CNKI and VIP (to May 2009). We collected information from ongoing trials, checked reference lists of published articles and consulted experts in the field. For the first update the searches were extended to October 2012 and for this update to February 2017. Selection criteria Randomised controlled trials (RCTs) comparing maintenance chemotherapy with no further intervention, maintenance radiotherapy or other maintenance therapy. Data collection and analysis Two review authors independently assessed trials for eligibility and quality and extracted data. We analysed overall survival (OS) and progression‐free survival (PFS) rates as dichotomous variables. Toxicity and QoL data were extracted where present. All analyses were based on intention‐to‐treat (ITT) on the endpoint of survival. We also analysed data by subgroups of drugs. No new studies were found for inclusion in this update from the latest searches. We included eight trials (1644 women). When all chemotherapy regimens were combined, meta‐analysis indicated no significant difference in three‐, five‐ and 10‐year OS or PFS. For five‐year OS, the combined risk ratio (RR) was 1.03 (95% confidence interval (CI) 0.96 to 1.10; 4 studies, 899 participants; moderate‐certainly evidence) and for the five‐year PFS, the combined RR was 1.06 (95% CI 0.97 to 1.17; 3 studies, 761 participants; moderate‐certainly evidence). Results were very similar when trials of different regimens were analysed. Comparing chemotherapy with radiotherapy, only the RR for 10‐year PFS in pathological complete remission (PCR) was in favour of whole abdominal radiotherapy 0.51 (95% CI 0.27 to 1.00), while three‐ and five‐year OS rates have no significant difference between the two groups. There is no evidence to suggest that the use of platinum agents, doxorubicin or paclitaxel used as maintenance chemotherapy is more effective than observation alone. Further investigations regarding the effect of paclitaxel used as maintenance chemotherapy are required. |
t134 | A cramp is a sudden, involuntary painful contraction of a muscle. Many people with amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND), experience cramps during the course of the disease. These range from mild cramps that do not affect daily activities and sleep, through to very severe, painful cramps. Some medications that are used to treat cramps in people with no medical condition or with conditions other than ALS have been tested in ALS clinical trials. These medicines include vitamin E, creatine, quinidine, and gabapentin. Other medications such as quinine sulfate, magnesium, lioresal, dantrolene, clonazepam, diphenylhydantoin, and gabapentin have been used to treat cramps in people with ALS but their effectiveness is unknown. In 2006 and 2010 the US Food and Drugs Administration issued warnings concerning the use of quinine sulfate, which was the previously most widely prescribed medication for cramps in the US. This review sought to find out how effective medications and physical treatments for cramps are for people with ALS. The reviewers identified 20 randomised controlled trials in people with ALS comprising a total of 4789 participants. Only one trial, of the drug tetrahydrocannabinol (THC), directly investigated the effectiveness of an intervention for cramps. Thirteen randomised controlled ALS trials investigated cramps secondarily among other variables. The medications comprised vitamin E, baclofen, riluzole, L‐threonine, xaliproden, indinavir, and memantine. Six randomised controlled ALS trials investigated cramps as adverse events. The medications comprised creatine, gabapentin, dextromethorphan, quinidine and lithium. | Cramps are painful, involuntary muscle contractions. They commonly affect people with amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) at all stages of the disease. To date, the treatment of muscle cramps in ALS has been largely empirical without any evidence from randomised controlled trials. Objectives To systematically assess the effect of interventions on muscle cramps as a primary or secondary endpoint or adverse event in people with ALS/MND. Search methods We searched the Cochrane Neuromuscular Disease Group Specialized Register (14 February 2011), the Cochrane Central Register of Controlled Trials (Issue 1, 2011 in The Cochrane Library ), MEDLINE (January 1966 to January 2011) and EMBASE (January 1980 to January 2011) and reference lists of articles searched using the terms motor neuron disease, motor neurone disease, motoneuron disease or amyotrophic lateral sclerosis. We contacted authors of trials for further information. Selection criteria We included all randomised and quasi‐randomised trials of oral medications in people with ALS which assessed cramps as a primary or secondary outcome measure or as an adverse event. We also included trials using subcutaneous or intravenous medications or physical therapy. Data collection and analysis All authors applied the selection criteria and assessed study quality independently, and all authors performed independent data extraction. Twenty studies including 4789 participants were identified. Only one trial, of tetrahydrocannabinol (THC), assessed cramps as the primary endpoint. Thirteen studies assessed cramps as a secondary endpoint. The medications comprised vitamin E, baclofen, riluzole, L‐threonine, xaliproden, indinavir, and memantine. Six studies assessed cramps as an adverse event. The medications comprised creatine, gabapentin, dextromethorphan, quinidine, and lithium. In all 20 studies no favourable effect for the treatment of cramps in ALS/MND could be demonstrated, but many studies were underpowered to draw a definite conclusion. A meta‐analysis of two small studies showed a statistically nonsignificant result for the amino acid L‐threonine for the treatment of cramps in ALS/MND. No study was identified using physical therapy as a therapeutic intervention for cramps. There is no evidence to support the use of any intervention for muscle cramps in ALS/MND. More and larger randomised controlled trials evaluating treatments for muscle cramps in ALS/MND are needed. |
t135 | Granulosa cell tumours (GCTs) of the ovary are rare ovarian tumours (2% to 5% of all ovarian cancers). Most ovarian tumours arise from the outer surface layer of the ovary, but GCTs arise from granulosa cells (sex cord cells) within the ovaries that produce oestrogen (primary female sex hormones). These tumours grow relatively slowly and can recur 10 to 15 years after primary treatment. If women with these tumours want to have children, the surgeon usually removes only the diseased ovary. However, standard treatment has consisted of surgery to remove tubes, ovaries and uterus, as most women develop GCTs around the time of the menopause, when fertility is no longer a matter of concern. Previous studies have assessed chemotherapy (different combination regimens) with or without radiotherapy following surgery. This review aimed to examine the effects of various treatment methods, including fertility‐sparing surgery, on the survival of women with GCT of the ovary. Five retrospective studies (including 535 women with a diagnosis of GCT) met our inclusion criteria. Two studies, which attempted to identify factors associated with better outcomes (in terms of overall survival), suggested that no apparent evidence could be found of differences in overall survival between surgical approaches (including whether the surgery was keyhole or open) whether a patient underwent lymphadenectomy (removal of lymph nodes) or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all women combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent only surgery. In three studies, no apparent evidence to suggest that disease recurrence was associated with type of adjuvant chemotherapy or type of surgery, although surgical staging may be important. In one study, disease recurrence was not noted to be different between patients who underwent fertility‐sparing surgery, where only the affected fallopian tube and ovary were removed, and those treated with conventional surgery, in which both tubes and ovaries were removed. Given the high overall survival rate, fertility‐sparing surgery may be an important treatment option for young patients wishing to have children in the future. Toxicity and adverse event data were incompletely reported in the five studies. All five studies were retrospective (looked at past findings) and were at very high risk of bias (low quality); therefore future studies should look at current evidence in randomised studies on adult GCT of the ovary. Three randomised studies comparing chemotherapy are ongoing. The study that may be able to answer the question regarding best choice of chemotherapy in sex cord stromal tumours is an ongoing randomised study comparing the efficacy of two drugs (carboplatin and paclitaxel) versus standard chemotherapy (BEP ‐ bleomycin, etoposide, cisplatin). The effectiveness and safety of different ways of treating patients with adult‐onset granulosa cell tumour of the ovary have not yet been assessed by high‐quality studies. Such trials are required to assess toxicity and quality of life associated with different treatments and to assess the safety of the types of surgery used. | Granulosa cell tumour is a rare gynaecological tumour of the ovary with recurrences many years after initial diagnosis and treatment. Evidence‐based management of granulosa cell tumour of the ovary is limited, and treatment has not been standardised. Surgery, including fertility‐sparing procedures for young women, has traditionally been the standard treatment. Adjuvant treatments following surgery have been based on non‐randomised trials. A combination of bleomycin, etoposide and cisplatin (BEP) has traditionally been used for treatment of advanced and/or recurrent disease that cannot be optimally managed surgically. Objectives To evaluate the effectiveness and safety of different treatment modalities offered in current practice for the management of primary, residual and recurrent adult‐onset granulosa cell tumours (GCTs) of the ovary. Search methods We searched the Cochrane Gynaecological Cancer Group Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE up to December 2013. We also searched registers of clinical trials, abstracts of scientific meetings and reference lists of included studies. Selection criteria We searched for randomised controlled trials (RCTs), quasi‐RCTs and observational studies that examined women with adult‐onset granulosa cell tumours of the ovary (primary and recurrent). For non‐randomised studies, we included studies that used multivariate analysis to adjust for baseline characteristics. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Studies were heterogeneous with respect to treatment comparisons, so data were not synthesised in meta‐analyses, and methods for assessing heterogeneity were not needed. Risk of bias in included studies was assessed by using the six core items used to assess RCTs and by evaluating four additional criteria specifically addressing risk of bias in non‐randomised studies. Five retrospective cohort studies (535 women with a diagnosis of GCT) that used appropriate statistical methods for adjustment were included in the review. Two studies, which carried out multivariate analyses that attempted to identify factors associated with better outcomes (in terms of overall survival), reported no apparent evidence of a difference in overall survival between surgical approaches, whether a participant underwent lymphadenectomy or received adjuvant chemotherapy or radiotherapy. Only percentage of survival for all participants combined was reported in two trials and was not reported at all in one study. One study showed that women who received postoperative radiotherapy had lower risk of disease recurrence compared with those who underwent surgery alone (adjusted hazard ratio (HR) 0.3, 95% confidence interval (CI) 0.1 to 0.6, P value 0.04). Three studies reportedthat there was no evidence of differences in disease recurrence based on execution and type of adjuvant chemotherapy or on type of surgery or surgical approach, other than that surgical staging may be important. One study described no apparent evidence of a difference in disease recurrence between fertility‐sparing surgery and conventional surgery. Recurrence‐free survival was not reported in one study. Toxicity and adverse event data were incompletely reported in the five studies. None of the five studies reported on quality of life (QoL). All studies were at very high risk of bias. One study showed a lower recurrence rate with the use of adjuvant radiotherapy, although this study was at high risk of bias and the results should be interpreted with caution. After evaluating the five small retrospective studies, we are unable to reach any firm conclusions as to the effectiveness and safety of different types and approaches of surgery, including conservative surgery, as well as adjuvant chemotherapy or radiotherapy, for management of GCTs of the ovary. The available evidence is very limited, and the review provides only low‐quality evidence. Further research is very likely to have an important impact on our confidence in the estimate of effect and may alter our findings. Ideally, multinational RCTs are needed to answer these questions. The disease is relatively rare and generally has a good prognosis. RCTs are challenging to conduct, but three ongoing trials have been identified, demonstrating that they are feasible, although two of these studies are single‐arm trials. The study that may be able to provide answers to the question of which chemotherapeutic regimen should be selected for management of sex cord stromal tumours is an ongoing, randomised, phase 2 study, led by the Gynaecological Oncology Group to compare the efficacy of carboplatin and paclitaxel versus standard BEP. These investigators are also looking into the value of inhibin A and inhibin B as predictive biomarkers. Additional trials are required to assess toxicity and QoL associated with different treatment regimens as well as the safety of conservative surgical options. |
t136 | Tuberculosis causes more deaths in people living with HIV than any other disease. The lateral flow urine lipoarabinomannan assay (LF‐LAM, Alere Determine™ TB LAM Ag assay) is a World Health Organization‐recommended rapid test to assist in detection of active tuberculosis in HIV‐positive people with severe HIV disease. Rapid and early tuberculosis diagnosis may allow for prompt treatment and alleviate severe illness and death. An incorrect tuberculosis diagnosis may result in anxiety and unnecessary treatment. To find out how accurate LF‐LAM is for diagnosing tuberculosis in HIV‐positive people with tuberculosis symptoms (symptomatic participants) and those not assessed for tuberculosis symptoms (unselected participants). LF‐LAM is a commercially available point‐of‐care test that detects lipoarabinomannan (LAM), a component of the bacterial cell walls, present in some people with active tuberculosis. LF‐LAM results were measured against culture or molecular tests (benchmark). Fifteen studies: eight studies evaluated LF‐LAM for tuberculosis among symptomatic participants and seven studies among unselected participants. Tuberculosis diagnosis among symptomatic participants: LF‐LAM registered positive in 42% (sensitivity) of people who actually had tuberculosis and did not register positive in 91% of people who were actually negative (specificity). Tuberculosis diagnosis among unselected participants: LF‐LAM sensitivity was 35% and specificity 95%. Several studies excluded participants who could not produce sputum and most studies relied on a lower quality benchmark. Few studies and participants were included in some analyses and only one study was conducted outside of sub‐Saharan Africa. Among symptomatic participants, in theory, for a population of 1000 people where 300 have microbiologically‐confirmed tuberculosis, the utilization of LF‐LAM would result in: 189 to be LF‐LAM positive: of these, 63 (33%) would not have tuberculosis (false‐positives); and 811 to be LF‐LAM negative: of these, 174 (21%) would have tuberculosis (false‐negatives). Among unselected participants, in theory, for a population of 1000 people where 100 have microbiologically‐confirmed tuberculosis, the utilization of LF‐LAM would result in: 80 to be LF‐LAM positive: of these, 45 (56%) would not have tuberculosis (false‐positives); and 920 to be LF‐LAM negative: of these, 65 (7%) would have tuberculosis (false‐negatives). HIV‐positive people with tuberculosis symptoms and those not assessed for tuberculosis symptoms. LF‐LAM has sensitivity around 40% to detect tuberculosis. As the test does not require sputum collection, LF‐LAM may be the only way to diagnose tuberculosis when sputum cannot be produced. | The lateral flow urine lipoarabinomannan (LF‐LAM) assay Alere Determine™ TB LAM Ag is recommended by the World Health Organization (WHO) to help detect active tuberculosis in HIV‐positive people with severe HIV disease. This review update asks the question, "does new evidence justify the use of LF‐LAM in a broader group of people?”, and is part of the WHO process for updating guidance on the use of LF‐LAM. Objectives To assess the accuracy of LF‐LAM for the diagnosis of active tuberculosis among HIV‐positive adults with signs and symptoms of tuberculosis (symptomatic participants) and among HIV‐positive adults irrespective of signs and symptoms of tuberculosis (unselected participants not assessed for tuberculosis signs and symptoms). The proposed role for LF‐LAM is as an add on to clinical judgement and with other tests to assist in diagnosing tuberculosis. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register; MEDLINE, Embase, Science Citation Index, Web of Science, Latin American Caribbean Health Sciences Literature, Scopus, the WHO International Clinical Trials Registry Platform, the International Standard Randomized Controlled Trial Number Registry, and ProQuest, without language restriction to 11 May 2018. Selection criteria Randomized trials, cross‐sectional, and observational cohort studies that evaluated LF‐LAM for active tuberculosis (pulmonary and extrapulmonary) in HIV‐positive adults. We included studies that used the manufacturer's recommended threshold for test positivity, either the updated reference card with four bands (grade 1 of 4) or the corresponding prior reference card grade with five bands (grade 2 of 5). The reference standard was culture or nucleic acid amplification test from any body site (microbiological). We considered a higher quality reference standard to be one in which two or more specimen types were evaluated for tuberculosis diagnosis and a lower quality reference standard to be one in which only one specimen type was evaluated. Data collection and analysis Two review authors independently extracted data using a standardized form and REDCap electronic data capture tools. We appraised the quality of studies using the Quality Assessment of Diagnostic Accuracy Studies‐2 (QUADAS‐2) tool and performed meta‐analyses to estimate pooled sensitivity and specificity using a bivariate random‐effects model and a Bayesian approach. We analyzed studies enrolling strictly symptomatic participants separately from those enrolling unselected participants. We investigated pre‐defined sources of heterogeneity including the influence of CD4 count and clinical setting on the accuracy estimates. We assessed the certainty of the evidence using the GRADE approach. We included 15 unique studies (nine new studies and six studies from the original review that met the inclusion criteria): eight studies among symptomatic adults and seven studies among unselected adults. All studies were conducted in low‐ or middle‐income countries. Risk of bias was high in the patient selection and reference standard domains, mainly because studies excluded participants unable to produce sputum and used a lower quality reference standard. Participants with tuberculosis symptoms LF‐LAM pooled sensitivity (95% credible interval (CrI) ) was 42% (31% to 55%) (moderate‐certainty evidence) and pooled specificity was 91% (85% to 95%) (very low‐certainty evidence), (8 studies, 3449 participants, 37% with tuberculosis). For a population of 1000 people where 300 have microbiologically‐confirmed tuberculosis, the utilization of LF‐LAM would result in: 189 to be LF‐LAM positive: of these, 63 (33%) would not have tuberculosis (false‐positives); and 811 to be LF‐LAM negative: of these, 174 (21%) would have tuberculosis (false‐negatives). By clinical setting, pooled sensitivity was 52% (40% to 64%) among inpatients versus 29% (17% to 47%) among outpatients; and pooled specificity was 87% (78% to 93%) among inpatients versus 96% (91% to 99%) among outpatients. Stratified by CD4 cell count, pooled sensitivity increased, and specificity decreased with lower CD4 cell count. Unselected participants not assessed for signs and symptoms of tuberculosis LF‐LAM pooled sensitivity was 35% (22% to 50%), (moderate‐certainty evidence) and pooled specificity was 95% (89% to 96%), (low‐certainty evidence), (7 studies, 3365 participants, 13% with tuberculosis). For a population of 1000 people where 100 have microbiologically‐confirmed tuberculosis, the utilization of LF‐LAM would result in: 80 to be LF‐LAM positive: of these, 45 (56%) would not have tuberculosis (false‐positives); and 920 to be LF‐LAM negative: of these, 65 (7%) would have tuberculosis (false‐negatives). By clinical setting, pooled sensitivity was 62% (41% to 83%) among inpatients versus 31% (18% to 47%) among outpatients; pooled specificity was 84% (48% to 96%) among inpatients versus 95% (87% to 99%) among outpatients. Stratified by CD4 cell count, pooled sensitivity increased, and specificity decreased with lower CD4 cell count. We found that LF‐LAM has a sensitivity of 42% to diagnose tuberculosis in HIV‐positive individuals with tuberculosis symptoms and 35% in HIV‐positive individuals not assessed for tuberculosis symptoms, consistent with findings reported previously. Regardless of how people are enrolled, sensitivity is higher in inpatients and those with lower CD4 cell, but a concomitant lower specificity. As a simple point‐of‐care test that does not depend upon sputum evaluation, LF‐LAM may assist with the diagnosis of tuberculosis, particularly when a sputum specimen cannot be produced. 17 October 2019 Up to date All studies incorporated from most recent search All studies identified during the most recent search (11 May, 2018) have been incorporated in the review, and no ongoing studies identified. |
t137 | Melatonin is widely used for management of sleep disorders in children with poor or no vision. The current review planned to examine studies on the use of melatonin in these children to determine whether this drug is effective for improving their sleep (safety is not mentioned in objectives or abstract and adverse effects is a secondary outcome). We only wanted to use studies where the children had been randomly allocated to a treatment group and a control group that got no treatment or another medication or a placebo. We did not find any of these studies that were suitable to be included in our review and so we are unable to draw any conclusions about whether or not melatonin improves sleep for visually impaired children. To find out, we need appropriately designed clinical trials. Due to lack of knowledge about best practice in the use of melatonin with these children, it would be useful to have researchers involved who are experienced in sleep disorders and in evidence‐based practice research. In addition, studies involving more than one location would be beneficial to increase the number of children being evaluated and make it more likely we will reach solid conclusions about whether melatonin works for this group of children, as well as details about the most effective dosage and timing of the treatment. | Exogenous melatonin helps in regulating the circadian rhythm and is widely used for the management of sleep disorders in visually impaired children. Objectives The aim of the review was to assess melatonin therapy for treatment of non‐respiratory sleep disorders in visually impaired children, with regard to improvement in sleep habit, sleep scheduling and sleep maintenance, when compared with placebo or no treatment. Search methods We searched the following databases between February 2011 and July 2011: the Cochrane Central Register of Controlled Trials (CENTRAL) 2011(1) searched on 4th February 2011; MEDLINE (1950 to June Week 3, 2011) searched on 20th June 2011; EMBASE (1980 to June Week 4, 2011) searched on 7th July 2011; CINAHL (1937 to 21 September 2011); the metaRegister of Controlled Trials (this includes ClinicalTrial.gov) searched 20 July 2011, and reference lists of papers identified after initial screening. Selection criteria We planned to include randomized controlled trials (RCTs) and quasi‐RCTs, including cross‐over studies. Treatment would be exogenous melatonin. Control groups could be placebo, other medication for sleep disorders or no treatment. Outcomes sought were improved sleep with regard to timing and duration, quality of life and adverse events. Data collection and analysis Three review authors independently assessed trials for inclusion in the review. We did not find any studies fulfilling the inclusion criteria, therefore no outcome data are reported. We identified nine studies after initial screening and, after further evaluation, we excluded these. The excluded studies involved a total of 163 individuals aged two years to 18 years. We excluded studies for three main reasons: they were non‐randomized or case series studies, they were studies of people over 18 years of age or even where the study was randomised, the study population was mixed and results pertaining to the visually impaired cohort could not be independently evaluated. No significant adverse effects of melatonin were reported in these excluded studies. There is currently no high quality data to support or refute the use of melatonin for sleep disorders in visually impaired children. Placebo‐controlled trials examining important clinical outcomes such as sleep quality, sleep latency, duration of sleep and night‐time awakenings are needed. As the numbers of children meeting study inclusion criteria are likely to be low at individual sites, multicentre collaboration between developmental paediatricians, sleep physicians and other health care professionals is essential to achieve sufficient sample size for controlled studies. Such collaboration would help facilitate local recruitment at multiple sites, with study oversight being provided by paediatricians with expertise in sleep disorders. Participation of collaborators with experience in evidence‐based practice research is also desirable due to the lack of protocols on melatonin therapy in the target population. |
t138 | Toxic epidermal necrolysis (TEN or Lyell's disease) is a rare life‐threatening skin condition. It is probably an immune response triggered by some drugs or infection, which is more likely to happen in people with suppressed immunity. TEN causes extensive blistering and shedding of skin, similar to burns. Drugs used include oral steroids, thalidomide, immunosuppressants and immunoglobulins. This review of trials did not find any reliable evidence for the treatment of TEN. The only trial available used thalidomide, but this trial did not show any benefit from treatment compared against placebo but highlighted increased chances of dying from the treatment. Thalidomide is not safe or effective for the skin condition toxic epidermal necrolysis, but there is not enough evidence to show which treatments are effective. | Toxic epidermal necrolysis is a rare condition where a drug reaction induces skin loss, similar to that seen in extensive burns. It is associated with high morbidity and mortality and there is no clear agreement on effective treatment. Objectives To assess the effects of all interventions for the treatment of toxic epidermal necrolysis. Search methods We searched the Cochrane Skin Group Specialised Register (March 2001), the Cochrane Controlled Trials Register (March 2001), MEDLINE (1966 to December 2001), EMBASE (1980 to December 2001), DARE (4th Quarter 2001) and CINAHL (1982 to October 2001). Selection criteria Randomised controlled trials of therapeutic and supportive interventions that included participants clinically diagnosed with toxic epidermal necrolysis were included. Data collection and analysis Two independent authors carried out study selection and assessment of methodological quality. Only one randomised controlled trial of treatment was identified. This trial compared the effectiveness of thalidomide with placebo and included 22 patients, 12 in the treatment group and 10 in the placebo group. Patients on the treatment arm received thalidomide 200 mg twice daily for 5 days. The main end point was the measurement of the progression of skin detachment after seven days. Other end points were the overall mortality and severity of the disease evaluated with the simplified acute physiology score. The study was terminated as the mortality on the treatment arm was 83% compared to 30% on the control arm (relative risk 2.78, 95% confidence interval 1.04 to 7.40). No randomised controlled trials of the most commonly used current treatments i.e. systemic steroids, cyclosporin A and intravenous immunoglobulins were found. Treatment with thalidomide was not shown to be effective and was associated with significantly higher mortality than placebo. There is no reliable evidence on which to base treatment for toxic epidermal necrolysis, a disease commonly associated with mortality rates of around 30%. More research is required to understand the mechanisms of toxic epidermal necrolysis. International multi‐centre studies are needed in the form of randomised controlled trials, to evaluate treatments for toxic epidermal necrolysis, especially those using high doses of steroid and intravenous immunoglobulins. |
t139 | Neovascular age‐related macular degeneration (AMD) is a progressive and chronic disease of the eye, and a leading cause of severe blindness in elderly populations. The disease is characterised by the abnormal growth of arteries and veins (neovascularisation) in the macula, a region of the retina (back portion of eye) responsible for central vision. Without treatment, the leakage of these blood vessels causes swelling and damage to the macula, resulting in a fibrous scar that impairs eyesight. Approximately one out of 10 people with neovascular AMD suffer legal blindness, accounting for 90% of all cases of severe vision loss due to AMD. Therapies against neovascular AMD target new blood vessels. Bevacizumab (commercial name Avastin®) and ranibizumab (Lucentis®) are biological drugs that bind to and block the function of vascular endothelial growth factor (VEGF), a protein released by cells in the body that stimulates the growth and leakage of blood vessels. The two drugs, accordingly, inhibit the process of neovascularisation. Ranibizumab is approved to treat neovascular AMD by injection into the eye (intravitreal injection), while bevacizumab is approved as a cancer therapy by injection into the vein through the skin. The two drugs have similar chemical structures and the same mechanism of action. Although their benefits are equivalent, it has been hypothesised that the two drugs have different systemic safety profiles, such that one drug might cause more adverse events (harms) at the level of whole body compared to the other. We evaluated whether the two drugs differed in terms of deaths or serious systemic adverse events (SSAEs) in people with neovascular AMD. The latter refers to medically related events that result in death, are life‐threatening, require hospital admission or prolong hospital stay, or cause persistent or significant disability. We included nine randomised controlled trials (RCTs), none supported by industry, with 3665 participants directly comparing bevacizumab with ranibizumab. Six RCTs were completed and published, two RCTs were completed, but unpublished, and one was still in progress. We were able to include safety information from all trials, accessing both published and unpublished data. Drugs were administered for up to two years according to continuous or discontinuous treatment. In the first, drugs were regularly administered, irrespective of the remission or progression of the disease; the latter involved 'as needed' (pro re nata, PRN) or 'treat‐and‐extend' regimens in which the drug was injected less frequently as long as there was no recurrence of neovascular manifestations. Follow‐up for adverse events occurred at regular intervals up to one or two years, irrespective of continuous or discontinuous treatment. All studies used the approved dosage of ranibizumab (0.5 mg) according to the 'Summary of Product Characteristics', and the dosage of bevacizumab most recommended by ophthalmologists for intravitreal injection (1.25 mg). Three studies excluded patients at high cardiovascular risk. However, four RCTs considered patients at different cardiovascular risks, representing a wide spectrum of risks and routine practice in hospital settings. Our review found the systemic safety of bevacizumab for neovascular AMD to be similar to that of ranibizumab, except for gastrointestinal disorders, which was a part of a secondary analysis. Deaths are likely to be unrelated to the administration of drugs. | Neovascular age‐related macular degeneration (AMD) is the leading cause of legal blindness in elderly populations of industrialised countries. Bevacizumab (Avastin®) and ranibizumab (Lucentis®) are targeted biological drugs (a monoclonal antibody) that inhibit vascular endothelial growth factor, an angiogenic cytokine that promotes vascular leakage and growth, thereby preventing its pathological angiogenesis. Ranibizumab is approved for intravitreal use to treat neovascular AMD, while bevacizumab is approved for intravenous use as a cancer therapy. However, due to the biological similarity of the two drugs, bevacizumab is widely used off‐label to treat neovascular AMD. Objectives To assess the systemic safety of intravitreal bevacizumab (brand name Avastin®; Genentech/Roche) compared with intravitreal ranibizumab (brand name Lucentis®; Novartis/Genentech) in people with neovascular AMD. Primary outcomes were death and All serious systemic adverse events (All SSAEs), the latter as a composite outcome in accordance with the International Conference on Harmonisation Good Clinical Practice. Secondary outcomes examined specific SSAEs: fatal and non‐fatal myocardial infarctions, strokes, arteriothrombotic events, serious infections, and events grouped in some Medical Dictionary for Regulatory Activities System Organ Classes (MedDRA SOC). We assessed the safety at the longest available follow‐up to a maximum of two years. Search methods We searched CENTRAL, MEDLINE, EMBASE and other online databases up to 27 March 2014. We also searched abstracts and clinical study presentations at meetings, trial registries, and contacted authors of included studies when we had questions. Selection criteria Randomised controlled trials (RCTs) directly comparing intravitreal bevacizumab (1.25 mg) and ranibizumab (0.5 mg) in people with neovascular AMD, regardless of publication status, drug dose, treatment regimen, or follow‐up length, and whether the SSAEs of interest were reported in the trial report. Data collection and analysis Two authors independently selected studies and assessed the risk of bias for each study. Three authors independently extracted data. We conducted random‐effects meta‐analyses for the primary and secondary outcomes. We planned a pre‐specified analysis to explore deaths and All SSAEs at the one‐year follow‐up. We included data from nine studies (3665 participants), including six published (2745 participants) and three unpublished (920 participants) RCTs, none supported by industry. Three studies excluded participants at high cardiovascular risk, increasing clinical heterogeneity among studies. The studies were well designed, and we did not downgrade the quality of the evidence for any of the outcomes due to risk of bias. Although the estimated effects of bevacizumab and ranibizumab on our outcomes were similar, we downgraded the quality of the evidence due to imprecision. At the maximum follow‐up (one or two years), the estimated risk ratio (RR) of death with bevacizumab compared with ranibizumab was 1.10 (95% confidence interval (CI) 0.78 to 1.57, P value = 0.59; eight studies, 3338 participants; moderate quality evidence). Based on the event rates in the studies, this gives a risk of death with ranibizumab of 3.4% and with bevacizumab of 3.7% (95% CI 2.7% to 5.3%). For All SSAEs, the estimated RR was 1.08 (95% CI 0.90 to 1.31, P value = 0.41; nine studies, 3665 participants; low quality evidence). Based on the event rates in the studies, this gives a risk of SSAEs of 22.2% with ranibizumab and with bevacizumab of 24% (95% CI 20% to 29.1%). For the secondary outcomes, we could not detect any difference between bevacizumab and ranibizumab, with the exception of gastrointestinal disorders MedDRA SOC where there was a higher risk with bevacizumab (RR 1.82; 95% CI 1.04 to 3.19, P value = 0.04; six studies, 3190 participants). Pre‐specified analyses of deaths and All SSAEs at one‐year follow‐up did not substantially alter the findings of our review. Fixed‐effect analysis for deaths did not substantially alter the findings of our review, but fixed‐effect analysis of All SSAEs showed an increased risk for bevacizumab (RR 1.12; 95% CI 1.00 to 1.26, P value = 0.04; nine studies, 3665 participants): the meta‐analysis was dominated by a single study (weight = 46.9%). The available evidence was sensitive to the exclusion of CATT or unpublished results. For All SSAEs, the exclusion of CATT moved the overall estimate towards no difference (RR 1.01; 95% CI 0.82 to 1.25, P value = 0.92), while the exclusion of LUCAS yielded a larger RR, with more SSAEs in the bevacizumab group, largely driven by CATT (RR 1.19; 95% CI 1.06 to 1.34, P value = 0.004). The exclusion of all unpublished studies produced a RR of 1.12 for death (95% CI 0.78 to 1.62, P value = 0.53) and a RR of 1.21 for SSAEs (95% CI 1.06 to 1.37, P value = 0.004), indicating a higher risk of SSAEs in those assigned to bevacizumab than ranibizumab. This systematic review of non‐industry sponsored RCTs could not determine a difference between intravitreal bevacizumab and ranibizumab for deaths, All SSAEs, or specific subsets of SSAEs in the first two years of treatment, with the exception of gastrointestinal disorders. The current evidence is imprecise and might vary across levels of patient risks, but overall suggests that if a difference exists, it is likely to be small. Health policies for the utilisation of ranibizumab instead of bevacizumab as a routine intervention for neovascular AMD for reasons of systemic safety are not sustained by evidence. The and quality of evidence should be verified once all trials are fully published. |
t140 | Seizures (epileptic attacks) after stroke are a major clinical problem. It is unclear whether antiepileptic drugs are effective in preventing seizures after stroke in adults. We found only one high quality clinical trial that looked at whether antiepileptic drugs may be more effective than placebo in preventing seizures after stroke. This was a prospective randomised, double‐blind, placebo controlled trial studying the efficacy of valproic acid versus placebo in the primary prevention of seizure in 72 adults (over 18 years of age) with spontaneous non‐aneurysmal, non‐traumatic intracerebral haemorrhage. Patients were randomly allocated to either the treatment or the placebo group with active treatment lasting one month; the primary outcome was seizure occurrence at one year. People with very early seizures (within 24 hours of onset of haemorrhage) were excluded from the study. Seizure was diagnosed on the basis of eye‐witness evidence from staff, relatives or other eye witnesses. There does not appear to be bias in Gilad 2011 , on the basis of the information available within the study. Gilad 2011 did not show a statistically significant benefit when comparing valproic acid with placebo for the primary prevention of seizures after spontaneous non‐aneurysmal, non‐traumatic intracerebral haemorrhage. | This is an updated version of the original Cochrane review published in 2010, Issue 1. Seizures after stroke are an important clinical problem, and they may be associated with poor outcome. The effects of antiepileptic drugs for the primary and secondary prevention of seizures after stroke remain unclear. Objectives We aimed to assess the effects of antiepileptic drugs for the primary and secondary prevention of seizures after stroke. Search methods We searched the Specialised Registers of the Cochrane Epilepsy Group (12 August 2013) and the Cochrane Stroke Group (12 August 2013), the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2013, Issue 7), and MEDLINE (OVID, 1946 to 12 August 2013). We also checked the reference lists of articles retrieved from these searches. Selection criteria Randomised and quasi‐randomised controlled trials in which participants were assigned to treatment or control group (placebo or no drug). Data collection and analysis Two review authors independently screened all the titles, abstracts, and keywords of publications identified by the searches to assess their eligibility, and both review authors assessed their suitability for inclusion according to prespecified selection criteria. We included only one study for data collection and analysis. We found only one trial that fulfilled the study inclusion criteria of comparison of the effects of an antiepileptic drug with placebo (or no drug) for the primary or secondary prevention of seizures after stroke. This was a prospective randomised, double‐blind, placebo‐controlled trial comparing valproic acid with placebo for primary prevention of seizures in 72 adults (over 18 years of age) with spontaneous non‐aneurysmal, non‐traumatic intracerebral haemorrhage; no statistically significant difference in outcome (seizure occurrence at one year) was demonstrated between groups. Currently, there is insufficient evidence to support the routine use of antiepileptic drugs for the primary or secondary prevention of seizures after stroke. Further well‐conducted research is needed for this important clinical problem. |
t141 | As many as half of all children with tic disorders (a combination of repetitive motions vocalizations), also have ADHD (issues with hyperactivity, impulsivity and maintaining attention). Symptoms of ADHD are often more disabling for children than their tics. Historically, the reported ability of stimulant medications to worsen tics has limited their use in children who have both a chronic tic disorder (lasting over a year since the first tic onset) and ADHD. To evaluate evidence for this reported phenomenon, we searched for clinical trials of medications for ADHD used specifically in children with tic disorders. Participants in these studies were children with both ADHD and a chronic tic disorder. The included studies evaluated several different medications for ADHD, including stimulants (methylphenidate, dextroamphetamine) and non‐stimulants (clonidine, guanfacine, desipramine, atomoxetine, and deprenyl). Study funding sources Five of the eight studies were funded by charitable organizations or government agencies, or both. One study was funded by the drug manufacturer. The other two studies did not specify the source of funding for the study. The trials in this review suggested that several stimulant and non‐stimulant medications may improve ADHD symptoms in children with ADHD and tics. At high doses, dextroamphetamine may initially worsen tics in some children, and dose increases of both dextroamphetamine and methylphenidate may be limited due to tic exacerbation. However, for most children, both tics and ADHD symptoms can improve with use of stimulant medications. | This is an update of the original Cochrane Review published in Issue 4, 2011. Attention deficit hyperactivity disorder (ADHD) is the most prevalent of the comorbid psychiatric disorders that complicate tic disorders. Medications commonly used to treat ADHD symptoms include stimulants such as methylphenidate and amphetamine; non‐stimulants, such as atomoxetine; tricyclic antidepressants; and alpha agonists. Alpha agonists are also used as a treatment for tics. Due to the impact of ADHD symptoms on the child with tic disorder, treatment of ADHD is often of greater priority than the medical management of tics. However, for many decades, clinicians have been reluctant to use stimulants to treat children with ADHD and tics for fear of worsening their tics. Objectives To assess the effects of pharmacological treatments for ADHD in children with comorbid tic disorders on symptoms of ADHD and tics. Search methods In September 2017, we searched CENTRAL, MEDLINE, Embase, and 12 other databases. We also searched two trial registers and contacted experts in the field for any ongoing or unpublished studies. Selection criteria We included randomized, double‐blind, controlled trials of any pharmacological treatment for ADHD used specifically in children with comorbid tic disorders. We included both parallel‐group and cross‐over study designs. Data collection and analysis We used standard methodological procedures of Cochrane, in that two review authors independently selected studies, extracted data using standardized forms, assessed risk of bias, and graded the overall quality of the evidence by using the GRADE approach. We included eight randomized controlled trials (four of which were cross‐over trials) with 510 participants (443 boys, 67 girls) in this review. Participants in these studies were children with both ADHD and a chronic tic disorder. All studies took place in the USA and ranged from three to 22 weeks in duration. Five of the eight studies were funded by charitable organizations or government agencies, or both. One study was funded by the drug manufacturer. The other two studies did not specify the source of funding. Risk of bias of included studies was low for blinding; low or unclear for random sequence generation, allocation concealment, and attrition bias; and low or high for selective outcome reporting. We were unable to combine any of the studies in a meta‐analysis due to important clinical heterogeneity and unit‐of‐analysis issues. Several of the trials assessed multiple agents. Medications assessed included methylphenidate, clonidine, desipramine, dextroamphetamine, guanfacine, atomoxetine, and deprenyl. There was low‐quality evidence for methylphenidate, atomoxetine, and clonidine, and very low‐quality evidence for desipramine, dextroamphetamine, guanfacine and deprenyl in the treatment of ADHD in children with tics. All studies, with the exception of a study using deprenyl, reported improvement in symptoms of ADHD. Tic symptoms also improved in children treated with guanfacine, desipramine, methylphenidate, clonidine, and a combination of methylphenidate and clonidine. In one study, tics limited further dosage increases of methylphenidate. High‐dose dextroamphetamine appeared to worsen tics in one study, although the length of this study was limited to three weeks. There was appetite suppression or weight loss in association with methylphenidate, dextroamphetamine, atomoxetine, and desipramine. There was insomnia associated with methylphenidate and dextroamphetamine, and sedation associated with clonidine. Following an updated search of potentially relevant studies, we found no new studies that matched our inclusion criteria and thus our conclusions have not changed. Methylphenidate, clonidine, guanfacine, desipramine, and atomoxetine appear to reduce ADHD symptoms in children with tics though the quality of the available evidence was low to very low. Although stimulants have not been shown to worsen tics in most people with tic disorders, they may, nonetheless, exacerbate tics in individual cases. In these instances, treatment with alpha agonists or atomoxetine may be an alternative. Although there is evidence that desipramine may improve tics and ADHD in children, safety concerns will likely continue to limit its use in this population. |
t142 | General anaesthetic reduces reflexes that stop regurgitated gastric juices reaching the lungs. As this can be dangerous, people are often advised to have nothing to eat or drink from the midnight before surgery. However, the review of trials found that drinking clear fluids up to a few hours before surgery did not increase the risk of regurgitation during or after surgery. Some people are considered more likely to regurgitate under anaesthetic, including those who are pregnant, elderly, obese or have stomach disorders. More research is needed to determine whether these people can also safely drink up to a few hours before surgery. | Fasting before general anaesthesia aims to reduce the volume and acidity of stomach contents during surgery, thus reducing the risk of regurgitation/aspiration. Recent guidelines have recommended a shift in fasting policy from the standard 'nil by mouth from midnight' approach to more relaxed policies which permit a period of restricted fluid intake up to a few hours before surgery. The evidence underpinning these guidelines however, was scattered across a range of journals, in a variety of languages, used a variety of outcome measures and methodologies to evaluate fasting regimens that differed in duration and the type and volume of intake permitted during a restricted fasting period. Practice has been slow to change. Objectives To systematically review the effect of different preoperative fasting regimens (duration, type and volume of permitted intake) on perioperative complications and patient wellbeing (including aspiration, regurgitation and related morbidity, thirst, hunger, pain, nausea, vomiting, anxiety) in different adult populations. Search methods Electronic databases, conference proceedings and reference lists from relevant articles were searched for studies of preoperative fasting in August 2003 and experts in the area were consulted. Selection criteria Randomised controlled trials which compared the effect on postoperative complications of different preoperative fasting regimens on adults were included. Data collection and analysis Details of the eligible studies were independently extracted by two reviewers and where relevant information was unavailable from the text attempts were made to contact the authors. Thirty eight randomised controlled comparisons (made within 22 trials) were identified. Most were based on 'healthy' adult participants who were not considered to be at increased risk of regurgitation or aspiration during anaesthesia. Few trials reported the incidence of aspiration/regurgitation or related morbidity but relied on indirect measures of patient safety i.e. intra‐operative gastric volume and pH. There was no evidence that the volume or pH of participants' gastric contents differed significantly depending on whether the groups were permitted a shortened preoperative fluid fast or continued a standard fast. Fluids evaluated included water, coffee, fruit juice, clear fluids and other drinks (e.g. isotonic drink, carbohydrate drink). Participants given a drink of water preoperatively were found to have a significantly lower volume of gastric contents than the groups that followed a standard fasting regimen. This difference was modest and clinically insignificant. There was no indication that the volume of fluid permitted during the preoperative period (i.e. low or high) resulted in a difference in outcomes from those participants that followed a standard fast. Few trials specifically investigated the preoperative fasting regimen for patient populations considered to be at increased risk during anaesthesia of regurgitation/aspiration and related morbidity. There was no evidence to suggest a shortened fluid fast results in an increased risk of aspiration, regurgitation or related morbidity compared with the standard 'nil by mouth from midnight' fasting policy. Permitting patients to drink water preoperatively resulted in significantly lower gastric volumes. Clinicians should be encouraged to appraise this evidence for themselves and when necessary adjust any remaining standard fasting policies (nil‐by‐mouth from midnight) for patients that are not considered 'at‐risk' during anaesthesia. |
t143 | There is much debate on the diagnostic performance of endoscopic ultrasound (EUS) in the preoperative staging of gastric cancer. The aim of this review was to collect the available evidence and then to calculate how well EUS stages stomach cancer. EUS is a diagnostic test that can be used to determine how far (stage) cancer of the stomach reaches prior to surgery. It consists of an endoscope coupled with an ultrasound device capable of scanning the stomach wall, which shows the different layers of the stomach. Changes from the normal ultrasonographic patterns due to the tumor growth can be used to determine the extent of cancer in the stomach wall (T‐stage) and the lymph nodes related to the stomach (N‐stage). Since the correct staging of the tumor enables physicians to personalize cancer treatment, it is important to understand the reliability of staging devices. We conducted a meta‐analysis according to the most recent methods for diagnostic tests. We included 66 studies (of 7747 patients) in the review. We found that EUS can distinguish between superficial (T1 ‐ T2) and advanced (T3 ‐ T4) primary tumors with a sensitivity and a specificity greater than 85%. This performance is maintained for the discrimination between T1 and T2 superficial tumors. However, EUS diagnostic accuracy is lower when it comes to distinguishing between the different types of early tumors (T1a versus T1b) and between tumors with versus those without lymph node disease. Overall, EUS provides physicians with some helpful information on the stage of gastric cancer. Nevertheless, in the light of the variability of the results reported in the international medical literature, its limitations in terms of performance must be kept in mind in order to make the most out of the diagnostic potential of this tool. | Endoscopic ultrasound (EUS) is proposed as an accurate diagnostic device for the locoregional staging of gastric cancer, which is crucial to developing a correct therapeutic strategy and ultimately to providing patients with the best chance of cure. However, despite a number of studies addressing this issue, there is no consensus on the role of EUS in routine clinical practice. Objectives To provide both a comprehensive overview and a quantitative analysis of the published data regarding the ability of EUS to preoperatively define the locoregional disease spread (i.e., primary tumor depth (T‐stage) and regional lymph node status (N‐stage)) in people with primary gastric carcinoma. Search methods We performed a systematic search to identify articles that examined the diagnostic accuracy of EUS (the index test) in the evaluation of primary gastric cancer depth of invasion (T‐stage, according to the AJCC/UICC TNM staging system categories T1, T2, T3 and T4) and regional lymph node status (N‐stage, disease‐free (N0) versus metastatic (N+)) using histopathology as the reference standard. To this end, we searched the following databases: the Cochrane Library (the Cochrane Central Register of Controlled Trials (CENTRAL)), MEDLINE, EMBASE , NIHR Prospero Register, MEDION, Aggressive Research Intelligence Facility (ARIF), ClinicalTrials.gov, Current Controlled Trials MetaRegister, and World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), from 1988 to January 2015. Selection criteria We included studies that met the following main inclusion criteria: 1) a minimum sample size of 10 patients with histologically‐proven primary carcinoma of the stomach (target condition); 2) comparison of EUS (index test) with pathology evaluation (reference standard) in terms of primary tumor (T‐stage) and regional lymph nodes (N‐stage). We excluded reports with possible overlap with the selected studies. Data collection and analysis For each study, two review authors extracted a standard set of data, using a dedicated data extraction form. We assessed data quality using a standard procedure according to the Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) criteria. We performed diagnostic accuracy meta‐analysis using the hierarchical bivariate method. We identified 66 articles (published between 1988 and 2012) that were eligible according to the inclusion criteria. We collected the data on 7747 patients with gastric cancer who were staged with EUS. Overall the quality of the included studies was good: in particular, only five studies presented a high risk of index test interpretation bias and two studies presented a high risk of selection bias. For primary tumor (T) stage, results were stratified according to the depth of invasion of the gastric wall. The meta‐analysis of 50 studies (n = 4397) showed that the summary sensitivity and specificity of EUS in discriminating T1 to T2 (superficial) versus T3 to T4 (advanced) gastric carcinomas were 0.86 (95% confidence interval (CI) 0.81 to 0.90) and 0.90 (95% CI 0.87 to 0.93) respectively. For the diagnostic capacity of EUS to distinguish T1 (early gastric cancer, EGC) versus T2 (muscle‐infiltrating) tumors, the meta‐analysis of 46 studies (n = 2742) showed that the summary sensitivity and specificity were 0.85 (95% CI 0.78 to 0.91) and 0.90 (95% CI 0.85 to 0.93) respectively. When we addressed the capacity of EUS to distinguish between T1a (mucosal) versus T1b (submucosal) cancers the meta‐analysis of 20 studies (n = 3321) showed that the summary sensitivity and specificity were 0.87 (95% CI 0.81 to 0.92) and 0.75 (95% CI 0.62 to 0.84) respectively. Finally, for the metastatic involvement of lymph nodes (N‐stage), the meta‐analysis of 44 studies (n = 3573) showed that the summary sensitivity and specificity were 0.83 (95% CI 0.79 to 0.87) and 0.67 (95% CI 0.61 to 0.72), respectively. Overall, as demonstrated also by the Bayesian nomograms, which enable readers to calculate post‐test probabilities for any target condition prevalence, the EUS accuracy can be considered clinically useful to guide physicians in the locoregional staging of people with gastric cancer. However, it should be noted that between‐study heterogeneity was not negligible: unfortunately, we could not identify any consistent source of the observed heterogeneity. Therefore, all accuracy measures reported in the present work and summarizing the available evidence should be interpreted cautiously. Moreover, we must emphasize that the analysis of positive and negative likelihood values revealed that EUS diagnostic performance cannot be considered optimal either for disease confirmation or for exclusion, especially for the ability of EUS to distinguish T1a (mucosal) versus T1b (submucosal) cancers and positive versus negative lymph node status. By analyzing the data from the largest series ever considered, we found that the diagnostic accuracy of EUS might be considered clinically useful to guide physicians in the locoregional staging of people with gastric carcinoma. However, the heterogeneity of the results warrants special caution, as well as further investigation for the identification of factors influencing the outcome of this diagnostic tool. Moreover, physicians should be warned that EUS performance is lower in diagnosing superficial tumors (T1a versus T1b) and lymph node status (positive versus negative). Overall, we observed large heterogeneity and its source needs to be understood before any definitive conclusion can be drawn about the use of EUS can be proposed in routine clinical settings. |
t144 | To find out what strategies can be used to improve how well healthcare workers follow a system of actions known as 'Standard Precautions' to decrease infection in healthcare settings. Review authors identified a variety of strategies, most of which involved education of healthcare workers alone or with an additional strategy. It is unclear which strategy or combination of strategies is most effective for improving healthcare workers' adherence to Standard Precautions or their knowledge of Standard Precautions, or for reducing colonisation (potential infection) rates, as we found little evidence; this fact, along with the inconsistency of results, reduced our confidence or certainty about the evidence found. It is estimated that over four million patients in Europe and 1.7 million in the USA develop an infection each year, and that prevalence is higher in developing countries. Infection is associated with increased length of hospital stay, excess mortality, and billions of dollars in associated hospital costs. Adhering to Standard Precautions, such as using personal protective equipment or following practices for safe handling of needles, can reduce the spread of germs in healthcare settings. The aim of this review was to find out which methods are effective in improving healthcare workers' adherence to Standard Precautions. Review authors found eight relevant studies with a total of 673 participants. Three studies were reported from Asia, two from Europe, two from North America, and one from Australia. Intevention strategies consisted of education for healthcare workers, given alone or with other types of education, such as showing how respiratory droplets are spread, or with additional infection control supports. Other intervention strategies were peer evaluation and use of a checklist and coloured cues. All studies used different measures to assess how well healthcare workers followed or adhered to Standard Precautions. Two studies also assessed whether there was any improvement in healthcare workers' knowledge (of Standard Precautions), and one measured rates of colonisation of MRSA (carriage of MRSA with increased potential for infection) among residents and staff of long‐term care facilities Education showing spread of respiratory droplets, peer evaluation, and use of checklists and coloured cues probably improve adherence to Standard Precautions, and education alone and education with additional infection control support may slightly improve adherence to Standard Precautions. Education alone may slightly improve knowledge, and education showing spread of respiratory droplets probably leads to little or no difference in knowledge. Education with additional infection control support probably leads to little or no difference in rates of MRSA colonisation. | 'Standard Precautions' refers to a system of actions, such as using personal protective equipment or adhering to safe handling of needles, that healthcare workers take to reduce the spread of germs in healthcare settings such as hospitals and nursing homes. Objectives To assess the effectiveness of interventions that target healthcare workers to improve adherence to Standard Precautions in patient care. Search methods We searched CENTRAL, MEDLINE, Embase, CINAHL, LILACS, two other databases, and two trials registers. We applied no language restrictions. The date of the most recent search was 14 February 2017. Selection criteria We included randomised trials of individuals, cluster‐randomised trials, non‐randomised trials, controlled before‐after studies, and interrupted time‐series studies that evaluated any intervention to improve adherence to Standard Precautions by any healthcare worker with responsibility for patient care in any hospital, long‐term care or community setting, or artificial setting, such as a classroom or a learning laboratory. Data collection and analysis Two review authors independently screened search results, extracted data from eligible trials, and assessed risk of bias for each included study, using standard methodological procedures expected by Cochrane. Because of substantial heterogeneity among interventions and outcome measures, meta‐analysis was not warranted. We used the GRADE approach to assess certainty of evidence and have presented results narratively in 'Summary of findings' tables. We included eight studies with a total of 673 participants; three studies were conducted in Asia, two in Europe, two in North America, and one in Australia. Five studies were randomised trials, two were cluster‐randomised trials, and one was a non‐randomised trial. Three studies compared different educational approaches versus no education, one study compared education with visualisation of respiratory particle dispersion versus education alone, two studies compared education with additional infection control support versus no intervention, one study compared peer evaluation versus no intervention, and one study evaluated use of a checklist and coloured cues. We considered all studies to be at high risk of bias with different risks. All eight studies used different measures to assess healthcare workers' adherence to Standard Precautions. Three studies also assessed healthcare workers' knowledge, and one measured rates of colonisation with methicillin‐resistant Staphylococcus aureus (MRSA) among residents and staff of long‐term care facilities. Because of heterogeneity in interventions and outcome measures, we did not conduct a meta‐analysis. Education may slightly improve both healthcare workers' adherence to Standard Precautions (three studies; four centres) and their level of knowledge (two studies; three centres; low certainty of evidence for both outcomes). Education with visualisation of respiratory particle dispersion probably improves healthcare workers' use of facial protection but probably leads to little or no difference in knowledge (one study; 20 nurses; moderate certainty of evidence for both outcomes). Education with additional infection control support may slightly improve healthcare workers' adherence to Standard Precautions (two studies; 44 long‐term care facilities; low certainty of evidence) but probably leads to little or no difference in rates of health care‐associated colonisation with MRSA (one study; 32 long‐term care facilities; moderate certainty of evidence). Peer evaluation probably improves healthcare workers' adherence to Standard Precautions (one study; one hospital; moderate certainty of evidence). Checklists and coloured cues probably improve healthcare workers' adherence to Standard Precautions (one study; one hospital; moderate certainty of evidence). Considerable variation in interventions and in outcome measures used, along with high risk of bias and variability in the certainty of evidence, makes it difficult to draw conclusions about effectiveness of the interventions. This review underlines the need to conduct more robust studies evaluating similar types of interventions and using similar outcome measures. |
t145 | Physicians and other healthcare professionals often prescribe drugs that will only work at certain concentrations. These drugs are said to have a narrow therapeutic window. This means that if the concentration of the drug is too high or too low, they may cause serious side effects or not provide the benefits they should. For example, blood thinners (anticoagulants) are prescribed to thin the blood to prevent clots. If the concentration is too high, people may experience excessive bleeding and even death. In contrast, if the concentration is too low, a clot could form and cause a stroke. For these types of drugs, it is important that the correct amount of the drug be prescribed. Calculating and prescribing the correct amount can be complicated and time‐consuming for healthcare professionals. Sometimes determining the correct dose can take a long time since healthcare professionals may not want to prescribe high doses of the drugs initially because they make mistakes in calculations. Several computer systems have been designed to do these calculations and assist healthcare professionals in prescribing these types of drugs. We sought clinical trial evidence from scientific databases to evaluate the effectiveness of these computer systems. We found data from 42 trials (40 randomized controlled trials (trials that allocate people at random to receive one of a number of drugs or procedures) and two non‐randomized controlled trials). Computerized advice for drug dosage can benefit people taking certain drugs compared with empiric dosing (where a dose is chosen based on a doctor's observations and experience) without computer assistance. When using the computer system, healthcare professionals prescribed appropriately higher doses of the drugs initially for aminoglycoside antibiotics and the correct drug dose was reached more quickly for oral anticoagulants. It significantly decreased thromboembolism (blood clotting) events for anticoagulants and tended to reduce unwanted effects for aminoglycoside antibiotics and anti‐rejection drugs (although not an important difference). It tended to reduce the length of hospital stay compared with routine care with comparable or better cost‐effectiveness. | Maintaining therapeutic concentrations of drugs with a narrow therapeutic window is a complex task. Several computer systems have been designed to help doctors determine optimum drug dosage. Significant improvements in health care could be achieved if computer advice improved health outcomes and could be implemented in routine practice in a cost‐effective fashion. This is an updated version of an earlier Cochrane systematic review, first published in 2001 and updated in 2008. Objectives To assess whether computerized advice on drug dosage has beneficial effects on patient outcomes compared with routine care (empiric dosing without computer assistance). Search methods The following databases were searched from 1996 to January 2012: EPOC Group Specialized Register, Reference Manager; Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Ovid; EMBASE, Ovid; and CINAHL, EbscoHost. A "top up" search was conducted for the period January 2012 to January 2013; these results were screened by the authors and potentially relevant studies are listed in Studies Awaiting Classification. The review authors also searched reference lists of relevant studies and related reviews. Selection criteria We included randomized controlled trials, non‐randomized controlled trials, controlled before‐and‐after studies and interrupted time series analyses of computerized advice on drug dosage. The participants were healthcare professionals responsible for patient care. The outcomes were any objectively measured change in the health of patients resulting from computerized advice (such as therapeutic drug control, clinical improvement, adverse reactions). Data collection and analysis Two review authors independently extracted data and assessed study quality. We grouped the results from the included studies by drug used and the effect aimed at for aminoglycoside antibiotics, amitriptyline, anaesthetics, insulin, anticoagulants, ovarian stimulation, anti‐rejection drugs and theophylline. We combined the effect sizes to give an overall effect for each subgroup of studies, using a random‐effects model. We further grouped studies by type of outcome when appropriate (i.e. no evidence of heterogeneity). Forty‐six comparisons (from 42 trials) were included (as compared with 26 comparisons in the last update) including a wide range of drugs in inpatient and outpatient settings. All were randomized controlled trials except two studies. Interventions usually targeted doctors, although some studies attempted to influence prescriptions by pharmacists and nurses. Drugs evaluated were anticoagulants, insulin, aminoglycoside antibiotics, theophylline, anti‐rejection drugs, anaesthetic agents, antidepressants and gonadotropins. Although all studies used reliable outcome measures, their quality was generally low. This update found similar results to the previous update and managed to identify specific therapeutic areas where the computerized advice on drug dosage was beneficial compared with routine care: 1. it increased target peak serum concentrations (standardized mean difference (SMD) 0.79, 95% CI 0.46 to 1.13) and the proportion of people with plasma drug concentrations within the therapeutic range after two days (pooled risk ratio (RR) 4.44, 95% CI 1.94 to 10.13) for aminoglycoside antibiotics; 2. it led to a physiological parameter more often within the desired range for oral anticoagulants (SMD for percentage of time spent in target international normalized ratio +0.19, 95% CI 0.06 to 0.33) and insulin (SMD for percentage of time in target glucose range: +1.27, 95% CI 0.56 to 1.98); 3. it decreased the time to achieve stabilization for oral anticoagulants (SMD ‐0.56, 95% CI ‐1.07 to ‐0.04); 4. it decreased the thromboembolism events (rate ratio 0.68, 95% CI 0.49 to 0.94) and tended to decrease bleeding events for anticoagulants although the difference was not significant (rate ratio 0.81, 95% CI 0.60 to 1.08). It tended to decrease unwanted effects for aminoglycoside antibiotics (nephrotoxicity: RR 0.67, 95% CI 0.42 to 1.06) and anti‐rejection drugs (cytomegalovirus infections: RR 0.90, 95% CI 0.58 to 1.40); 5. it tended to reduce the length of time spent in the hospital although the difference was not significant (SMD ‐0.15, 95% CI ‐0.33 to 0.02) and to achieve comparable or better cost‐effectiveness ratios than usual care; 6. there was no evidence of differences in mortality or other clinical adverse events for insulin (hypoglycaemia), anaesthetic agents, anti‐rejection drugs and antidepressants. For all outcomes, statistical heterogeneity quantified by I 2 statistics was moderate to high. This review update suggests that computerized advice for drug dosage has some benefits: it increases the serum concentrations for aminoglycoside antibiotics and improves the proportion of people for which the plasma drug is within the therapeutic range for aminoglycoside antibiotics. It leads to a physiological parameter more often within the desired range for oral anticoagulants and insulin. It decreases the time to achieve stabilization for oral anticoagulants. It tends to decrease unwanted effects for aminoglycoside antibiotics and anti‐rejection drugs, and it significantly decreases thromboembolism events for anticoagulants. It tends to reduce the length of hospital stay compared with routine care while comparable or better cost‐effectiveness ratios were achieved. However, there was no evidence that decision support had an effect on mortality or other clinical adverse events for insulin (hypoglycaemia), anaesthetic agents, anti‐rejection drugs and antidepressants. In addition, there was no evidence to suggest that some decision support technical features (such as its integration into a computer physician order entry system) or aspects of organization of care (such as the setting) could optimize the effect of computerized advice. Taking into account the high risk of bias of, and high heterogeneity between, studies, these results must be interpreted with caution. |
t146 | The common cold is probably the most common illness known and usually presents with a range of symptoms such as sore throat, nasal stuffiness and discharge, sneezing and cough. On average, young children have six to eight colds per year and adults have two to four. It is caused by viruses (more than 200 viruses have been implicated) and is generally not a serious condition which usually resolves by itself within one to two weeks. However, the common cold has a large impact on time lost from work or school and causes substantial discomfort. As there is no cure for the common cold, only symptomatic treatment is available. Many people use oral over‐the‐counter (OTC) medications that contain antihistamines, decongestants, analgesics or a combination to self treat the symptoms of the common cold. Our review of 27 trials with over 5000 participants shows some benefit of these treatments in adults and older children with regards to general recovery and symptoms. The combination of antihistamine‐decongestant is the most effective combination but many people experience adverse effects such as drowsiness, dry mouth, insomnia and dizziness. | Although combination formulas containing antihistamines, decongestants and/or analgesics are sold over‐the‐counter (OTC) in large quantities for the common cold, the evidence of effectiveness is limited. Objectives To assess the effectiveness of antihistamine‐decongestant‐analgesic combinations in reducing the duration and alleviating the symptoms of the common cold in adults and children. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library 2011, Issue 4), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, OLDMEDLINE (1953 to 1965), MEDLINE (1966 to November Week 3, 2011) and EMBASE (1990 to December 2011). Selection criteria Randomised controlled trials (RCTs) investigating the effectiveness of antihistamine‐decongestant‐analgesic combinations compared with placebo, other active treatment (excluding antibiotics) or no treatment in children and adults with the common cold. Data collection and analysis Two review authors independently extracted and summarised data on general recovery, nasal obstruction, rhinorrhoea, sneezing, cough and side effects. We categorised the trials according to the active ingredients. We included 27 trials (5117 participants) of common cold treatments. Fourteen trials studied antihistamine‐decongestant combinations; two antihistamine‐analgesic; six analgesic‐decongestant; and five antihistamine‐analgesic‐decongestant combinations. In 21 trials the control intervention was placebo and in six trials an active substance. Reporting of methods in most trials was poor and there were large differences in design, participants, interventions and outcomes. Pooling was only possible for a limited number of studies and outcomes. Antihistamine‐decongestant: 12 trials. Eight trials report on global effectiveness, six could be pooled; n = 309 on active treatment, n = 312 placebo) the odds ratio (OR) of treatment failure was 0.27 (95% confidence interval (CI) 0.15 to 0.50); the number needed to treat for an additional beneficial outcome (NNTB) was four (95% CI 3 to 5.6). On the final evaluation day 41% of participants in the placebo group had a favourable response compared to 66% on active treatment. Of the two trials that were not included in the pooling, one showed some global effect, the other showed no effect. Antihistamine‐analgesic : three trials. Two reported on global effectiveness, data from one study was presented. (n = 290 on active treatment, n = 292 ascorbic acid). The OR of treatment failure was 0.33 (95% CI 0.23 to 0.46) and the NNTB was 6.67 (95% CI 4.76 to 12.5). After six days of treatment 43% were cured in the control group and 70% in the active treatment group. The second study also showed an effect in favour of active treatment. Analgesic‐decongestant: six trials. One trial reported on global effectiveness: 73% benefited compared with 52% in the control group (paracetamol) (OR 0.28, 95% CI 0.15 to 0.52). Antihistamine‐analgesic‐decongestant: Five trials. Four trials reported on global effectiveness, two could be pooled: global effect reported (less than one severity point on a four or five‐point scale) with active treatment (52%) and placebo (34%); the OR of treatment failure was 0.47 (95% CI 0.33 to 0.67) and the NNTB was 5.6 (95% CI 3.8 to 10.2). Two other trials found no beneficial effect. Two other studies did not show any effect. Two studies with antihistamine‐decongestant (113 children) could not be pooled. There was no significant effect of the active treatment. Adverse effects : the combination of antihistamine‐decongestant had more adverse effects than the control intervention but the difference was not significant: 157/810 (19%) versus 60/477 (13%) participants suffered one or more adverse effects (OR 1.58, 95% CI 0.78 to 3.21). Analgesic‐decongestant combinations had significantly more adverse effects than control (OR 1.71, 95% CI 1.23 to 2.37); the number needed to treat for an additional harmful outcome (NNTH) was 14. None of the other two combinations caused significantly more adverse effects. Antihistamine‐analgesic: 11/90 with combination suffered one or more adverse effects (12%) versus 9/91 (10%) with control (OR 1.27, 95% CI 0.50 to 3.23). Antihistamine‐analgesic‐decongestant: in one study 5/224 (2%) suffered adverse effects with active treatment versus 9/208 (4%) with placebo. Two other trials reported no differences between treatment groups but numbers were not reported. Current evidence suggests that antihistamine‐analgesic‐decongestant combinations have some general benefit in adults and older children. These benefits must be weighed against the risk of adverse effects. There is no evidence of effectiveness in young children. |
t147 | We found that psychological therapies may improve parenting behavior for parents of children with cancer, chronic pain, diabetes or traumatic brain injury, and may improve mental health of parents of children with cancer or chronic pain. Cognitive‐behavioral therapy (CBT) and problem‐solving therapy (PST) are promising types of therapy. We were not able to answer questions about whether psychological therapies are helpful for parents of children with other medical conditions, or whether other types of therapy are helpful, because there were not enough data. Our findings may have been impacted by differences in measures used across studies. New studies may change the results of this review, and so our findings should be interpreted cautiously. We have updated our previously published review of psychological therapies for parents of children with a longstanding or life‐threatening physical illness to include studies published through July 2018. Parenting a child with a longstanding illness is challenging. Parents may have difficulty balancing caring for their child with other demands and can experience increased stress, sadness, or family conflict. Their children may have emotional or behavioral concerns. Parents can influence their child's adaptation to living with their medical condition. Psychological therapies for parents provide training in skills to modify emotions or behaviors that aim to improve parent, child, and family well‐being. We wanted to understand whether psychological therapies are helpful for parents of children and adolescents (up to age 19) with longstanding illness. We included studies of interventions that were predominantly psychological and delivered to parents compared with non‐psychological treatment, treatment as usual, or wait‐list. Outcomes were parenting behavior (e.g. protective behaviors), parent mental health, child behavior/disability, child mental health, child medical symptoms, family functioning, and side effects. We added 21 new studies in this update and we removed 23 studies that no longer met our inclusion criteria, resulting in 44 randomized controlled trials (randomized controlled trials, where participants are assigned randomly to either one treatment or a different treatment or no treatment, provide the most reliable evidence) with a total of 4697 participants (average child age = 11 years). Studies included children with asthma (4), cancer (7), chronic pain (recurrent or persistent pain for more than three months, including two studies of children with inflammatory bowel disease (15)), diabetes (15), skin diseases (1), and traumatic brain injury (3); one study included children with eczema and children with asthma. Therapy types included CBT (21), family therapy (4), motivational interviewing (3), multisystemic therapy (4), and PST (12). Funding sources included federal and local governments, hospitals, universities, and foundations. We found that parenting behavior improved in studies of children with cancer, chronic pain, diabetes, and traumatic brain injury immediately after treatment, which continued long‐term for parents of children with cancer and chronic pain. Parent mental health improved in studies of children with cancer and chronic pain immediately after treatment, which continued long‐term. Parent mental health did not improve in studies of children with diabetes. We found that CBT and PST improved parenting behavior immediately after treatment, which continued long‐term. PST also improved parent mental health immediately after treatment and long‐term, but CBT did not. We found that these treatment effects were generally small. We found that most studies (32 studies) did not report on whether side effects occurred. | Psychological therapies for parents of children and adolescents with chronic illness aim to improve parenting behavior and mental health, child functioning (behavior/disability, mental health, and medical symptoms), and family functioning. This is an updated version of the original Cochrane Review (2012) which was first updated in 2015. Objectives To evaluate the efficacy and adverse events of psychological therapies for parents of children and adolescents with a chronic illness. Search methods We searched CENTRAL, MEDLINE, Embase, PsycINFO, and trials registries for studies published up to July 2018. Selection criteria Included studies were randomized controlled trials (RCTs) of psychological interventions for parents of children and adolescents with a chronic illness. In this update we included studies with more than 20 participants per arm. In this update, we included interventions that combined psychological and pharmacological treatments. We included comparison groups that received either non‐psychological treatment (e.g. psychoeducation), treatment as usual (e.g. standard medical care without added psychological therapy), or wait‐list. Data collection and analysis We extracted and outcomes post‐treatment and at first available follow‐up. Primary outcomes were parenting behavior and parent mental health. Secondary outcomes were child behavior/disability, child mental health, child medical symptoms, and family functioning. We pooled data using the standardized mean difference (SMD) and a random‐effects model, and evaluated outcomes by medical condition and by therapy type. We assessed risk of bias per Cochrane guidance and quality of evidence using GRADE. We added 21 new studies. We removed 23 studies from the previous update that no longer met our inclusion criteria. There are now 44 RCTs, including 4697 participants post‐treatment. Studies included children with asthma (4), cancer (7), chronic pain (13), diabetes (15), inflammatory bowel disease (2), skin diseases (1), and traumatic brain injury (3). Therapy types included cognitive‐behavioural therapy (CBT; 21), family therapy (4), motivational interviewing (3), multisystemic therapy (4), and problem‐solving therapy (PST; 12). We rated risk of bias as low or unclear for most domains, except selective reporting bias, which we rated high for 19 studies due to incomplete outcome reporting. Evidence quality ranged from very low to moderate. We downgraded evidence due to high heterogeneity, imprecision, and publication bias. Evaluation of parent outcomes by medical condition Psychological therapies may improve parenting behavior (e.g. maladaptive or solicitous behaviors; lower scores are better) in children with cancer post‐treatment and follow‐up (SMD −0.28, 95% confidence interval (CI) −0.43 to −0.13; participants = 664; studies = 3; SMD −0.21, 95% CI −0.37 to −0.05; participants = 625; studies = 3; I 2 = 0%, respectively, low‐quality evidence), chronic pain post‐treatment and follow‐up (SMD −0.29, 95% CI −0.47 to −0.10; participants = 755; studies = 6; SMD −0.35, 95% CI −0.50 to −0.20; participants = 678; studies = 5, respectively, moderate‐quality evidence), diabetes post‐treatment (SMD −1.39, 95% CI −2.41 to −0.38; participants = 338; studies = 5, very low‐quality evidence), and traumatic brain injury post‐treatment (SMD −0.74, 95% CI −1.25 to −0.22; participants = 254; studies = 3, very low‐quality evidence). For the remaining analyses data were insufficient to evaluate the effect of treatment. Psychological therapies may improve parent mental health (e.g. depression, anxiety, lower scores are better) in children with cancer post‐treatment and follow‐up (SMD −0.21, 95% CI −0.35 to −0.08; participants = 836, studies = 6, high‐quality evidence; SMD −0.23, 95% CI −0.39 to −0.08; participants = 667; studies = 4, moderate‐quality evidence, respectively), and chronic pain post‐treatment and follow‐up (SMD −0.24, 95% CI −0.42 to −0.06; participants = 490; studies = 3; SMD −0.20, 95% CI −0.38 to −0.02; participants = 482; studies = 3, respectively, low‐quality evidence). Parent mental health did not improve in studies of children with diabetes post‐treatment (SMD −0.24, 95% CI −0.90 to 0.42; participants = 211; studies = 3, very low‐quality evidence). For the remaining analyses, data were insufficient to evaluate the effect of treatment on parent mental health. Evaluation of parent outcomes by psychological therapy type CBT may improve parenting behavior post‐treatment (SMD −0.45, 95% CI −0.68 to −0.21; participants = 1040; studies = 9, low‐quality evidence), and follow‐up (SMD −0.26, 95% CI −0.42 to −0.11; participants = 743; studies = 6, moderate‐quality evidence). We did not find evidence for a beneficial effect for CBT on parent mental health at post‐treatment or follow‐up (SMD −0.19, 95% CI −0.41 to 0.03; participants = 811; studies = 8; SMD −0.07, 95% CI −0.34 to 0.20; participants = 592; studies = 5; respectively, very low‐quality evidence). PST may improve parenting behavior post‐treatment and follow‐up (SMD −0.39, 95% CI −0.64 to −0.13; participants = 947; studies = 7, low‐quality evidence; SMD −0.54, 95% CI −0.94 to −0.14; participants = 852; studies = 6, very low‐quality evidence, respectively), and parent mental health post‐treatment and follow‐up (SMD −0.30, 95% CI −0.45 to −0.15; participants = 891; studies = 6; SMD −0.21, 95% CI −0.35 to −0.07; participants = 800; studies = 5, respectively, moderate‐quality evidence). For the remaining analyses, data were insufficient to evaluate the effect of treatment on parent outcomes. Adverse events We could not evaluate treatment safety because most studies (32) did not report on whether adverse events occurred during the study period. In six studies, the authors reported that no adverse events occurred. The remaining six studies reported adverse events and none were attributed to psychological therapy. We rated the quality of evidence for adverse events as moderate. Psychological therapy may improve parenting behavior among parents of children with cancer, chronic pain, diabetes, and traumatic brain injury. We also found beneficial effects of psychological therapy may also improve parent mental health among parents of children with cancer and chronic pain. CBT and PST may improve parenting behavior. PST may also improve parent mental health. However, the quality of evidence is generally low and there are insufficient data to evaluate most outcomes. Our findings could change as new studies are conducted. |
t148 | Breathlessness is a common and distressing symptom in advanced cancer and other diseases at the end of life. Treating breathlessness sufficiently remains very difficult. Benzodiazepines are a group of sedating medicines (drugs), including lorazepam, clorazepate, diazepam, alprazolam, and temazepam, that are used mainly for sleep disturbance and anxiety, but are widely used for the relief of breathlessness. In this updated systematic review we aimed to determine whether benzodiazepines relieved breathlessness in adults with advanced disease. Benzodiazepines caused more side effects such as drowsiness or somnolence when compared to placebo but caused less side effects when compared to morphine. Our review therefore supports the use of benzodiazepines only if other first‐line treatments, such as opioids and non‐drug treatments, have failed. However, there is still an urgent need for more studies in this field to find better ways to relieve this burdensome symptom in people with advanced diseases. We concluded in summary that there is no evidence that benzodiazepines relieve breathlessness in adults with advanced disease. | This is an updated version of the original Cochrane review published in Issue 1, 2010, on 'Benzodiazepines for the relief of breathlessness in advanced malignant and non‐malignant diseases in adults'. Breathlessness is one of the most common symptoms experienced in the advanced stages of malignant and non‐malignant disease. Benzodiazepines are widely used for the relief of breathlessness in advanced diseases and are regularly recommended in the literature. At the time of the previously published Cochrane review, there was no evidence for a beneficial effect of benzodiazepines for the relief of breathlessness in people with advanced cancer and chronic obstructive pulmonary disease (COPD). Objectives The primary objective of this review was to determine the efficacy of benzodiazepines for the relief of breathlessness in people with advanced disease. Secondary objectives were to determine the efficacy of different benzodiazepines, different doses of benzodiazepines, different routes of application, adverse effects of benzodiazepines, and the efficacy in different disease groups. Search methods This is an update of a review published in 2010. We searched 14 electronic databases up to September 2009 for the original review. We checked the reference lists of all relevant studies, key textbooks, reviews, and websites. For the update, we searched CENTRAL, MEDLINE, and EMBASE and registers of clinical trials for further ongoing or unpublished studies, up to August 2016. We contacted study investigators and experts in the field of palliative care asking for further studies, unpublished data, or study details when necessary. Selection criteria We included randomised controlled trials (RCTs) and controlled clinical trials (CCTs) assessing the effect of benzodiazepines compared with placebo or active control in relieving breathlessness in people with advanced stages of cancer, chronic obstructive pulmonary disease (COPD), chronic heart failure (CHF), motor neurone disease (MND), and idiopathic pulmonary fibrosis (IPF). Data collection and analysis Two review authors independently assessed identified titles and abstracts. Three review authors independently performed assessment of all potentially relevant studies (full text), data extraction, and assessment of methodological quality. We carried out meta‐analysis where appropriate. Overall, we identified eight studies for inclusion: seven in the previous review and an additional study for this update. We also identified two studies awaiting classification in this update. The studies were small (a maximum number of 101 participants) and comprised data from a total of 214 participants with advanced cancer or COPD, which we analysed. There was only one study of low risk of bias. Most of the studies had an unclear risk of bias due to lack of information on random sequence generation, concealment, and attrition. Analysis of all studies did not show a beneficial effect of benzodiazepines for the relief of breathlessness (the primary outcome) in people with advanced cancer and COPD (8 studies, 214 participants) compared to placebo, midazolam, morphine, or promethazine. Furthermore, we observed no statistically significant effect in the prevention of episodic breathlessness (breakthrough dyspnoea) in people with cancer (after 48 hours: risk ratio of 0.76 (95% CI 0.53 to 1.09; 2 studies, 108 participants)) compared to morphine. Sensitivity analyses demonstrated no statistically significant differences regarding type of benzodiazepine, dose, route and frequency of delivery, duration of treatment, or type of control. Benzodiazepines caused statistically significantly more adverse events, particularly drowsiness and somnolence, when compared to placebo (risk difference 0.74 (95% CI 0.37, 1.11); 3 studies, 38 participants). In contrast, two studies reported that morphine caused more adverse events than midazolam (RD ‐0.18 (95% CI ‐0.31, ‐0.04); 194 participants). Since the last version of this review, we have identified one new study for inclusion, but the conclusions remain unchanged. There is no evidence for or against benzodiazepines for the relief of breathlessness in people with advanced cancer and COPD. Benzodiazepines caused more drowsiness as an adverse effect compared to placebo, but less compared to morphine. Benzodiazepines may be considered as a second‐ or third‐line treatment, when opioids and non‐pharmacological measures have failed to control breathlessness. There is a need for well‐conducted and adequately powered studies. |
t149 | Hyaluronidase injected into the cervix increased cervical favourability but its effect on induction of labour is unknown and its use is not recommended. Sometimes it is considered beneficial to bring labour on artificially and there are many methods currently used. One method is an injection of hyaluronidase into the cervix. The review of trials found one study, which showed hyaluronidase was more effective than placebo, resulting in fewer caesarean sections, less oxytocin augmentation and greater cervical favourability. However, it is an invasive procedure that women may find unacceptable in the presence of less invasive methods of cervical ripening. Given this, the review authors do not recommend it for clinical practice. | Dilatation and effacement of the cervix are not only a result of uterine contractions, but are also dependant upon ripening processes within the cervix. The cervix is a fibrous organ composed principally of hyaluronic acid, collagen and proteoglycan. Hyaluronic acid increases markedly after the onset of labour. An increase in the level of hyaluronic acid is associated with an increase in tissue water content. Cervical ripening during labour is characterised by changes of the cervix and an increased water content. Cervical injection of hyaluronidase was postulated to increase cervical ripening. This is one of a series of reviews of methods of cervical ripening and labour induction using standardised methodology. Objectives To determine the effects of hyaluronidase for third trimester cervical ripening or induction of labour in comparison with other methods of induction of labour. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (July 2009) and bibliographies of relevant papers. Selection criteria Clinical trials of hyaluronidase for third trimester cervical ripening or labour induction. Data collection and analysis A strategy was developed to deal with the large volume and complexity of trial data relating to labour induction. This involved a two‐stage method of data extraction. We assessed trial quality. We contacted study authors for additional information. We collected adverse effects information from the trials. One trial, with 168 women participating, was included in the review. When compared with placebo for cervical ripening intracervical injections of hyaluronidase resulted in women receiving significantly fewer caesarean sections (18% versus 49%, relative risk (RR) 0.37, 95% confidence interval (CI) 0.22 to 0.61), less need for oxytocin augmentation (10% versus 47%, RR 0.20, 95% CI 0.10 to 0.41), and increased cervical favourability after 24 hours (60% versus 98%, RR 0.62, 95% CI 0.52 to 0.74). No side‐effects for mother or baby were reported in this trial. Intracervical injections of hyaluronidase for cervical ripening appear beneficial. However, this is not common practice. In addition it is an invasive procedure that women may find unacceptable in the presence of less invasive methods. |
t150 | Antibiotics are among the most prescribed medications worldwide. Antibiotic treatment may disturb the balance of organisms that normally populate the gut. This can result in a range of symptoms, most notably, diarrhea. Clostridium difficile ( C. difficile ) is a particularly dangerous organism that may colonize the gut if the normal healthy balance has been disturbed. Clostridium difficile‐ related disease varies from asymptomatic infection, diarrhea, colitis, and pseudo‐membranous colitis to toxic megacolon and death. The cost of treatment is expensive and the financial burden on the medical system is substantial. Probiotics are live organisms (bacteria or yeast). thought to improve the balance of organisms that populate the gut, counteracting potential disturbances to the gut microbial balance that are associated with antibiotic use, and reducing the risk of colonization by pathogenic bacteria. Probiotics can be found in dietary supplements or yogurts and are becoming increasingly available as capsules sold in health food stores and supermarkets. As 'functional food' or 'good bacteria', probiotics have been suggested as a means of both preventing and treating C. difficile ‐associated diarrhea (CDAD). The researchers investigated whether probiotics prevent CDAD in adults and children receiving antibiotic therapy and whether probiotics causes any harms (side effects). This review includes 39 randomized trials with a total of 9955 participants. Thirty‐one studies (8672 participants) assessed the effectiveness of probiotics for preventing CDAD among participants taking antibiotics. Our results suggest that when probiotics are given with antibiotics the risk of developing CDAD is reduced by 60% on average. Among trials enrolling participants at high risk of developing CDAD (> 5%), the potential benefit of probiotics is more pronounced with a 70% risk reduction on average. Side effects were assessed in 32 studies (8305 participants) and our results suggest that taking probiotics does not increase the risk of developing side effects. The most common side effects reported in these studies include abdominal cramping, nausea, fever, soft stools, flatulence, and taste disturbance. The short‐term use of probiotics appears to be safe and effective when used along with antibiotics in patients who are not immunocompromised or severely debilitated. Despite the need for further research, hospitalized patients, particularly those at high risk of CDAD, should be informed of the potential benefits and harms of probiotics. | Antibiotics can disturb gastrointestinal microbiota which may lead to reduced resistance to pathogens such as Clostridium difficile ( C. difficile) . Probiotics are live microbial preparations that, when administered in adequate amounts, may confer a health benefit to the host, and are a potential C. difficile prevention strategy. Recent clinical practice guidelines do not recommend probiotic prophylaxis, even though probiotics have the highest quality evidence among cited prophylactic therapies. Objectives To assess the efficacy and safety of probiotics for preventing C.difficile ‐associated diarrhea (CDAD) in adults and children. Search methods We searched PubMed, EMBASE, CENTRAL, and the Cochrane IBD Group Specialized Register from inception to 21 March 2017. Additionally, we conducted an extensive grey literature search. Selection criteria Randomized controlled (placebo, alternative prophylaxis, or no treatment control) trials investigating probiotics (any strain, any dose) for prevention of CDAD, or C. difficile infection were considered for inclusion. Data collection and analysis Two authors (independently and in duplicate) extracted data and assessed risk of bias. The primary outcome was the incidence of CDAD. Secondary outcomes included detection of C. difficile infection in stool, adverse events, antibiotic‐associated diarrhea (AAD) and length of hospital stay. Dichotomous outcomes (e.g. incidence of CDAD) were pooled using a random‐effects model to calculate the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We calculated the number needed to treat for an additional beneficial outcome (NNTB) where appropriate. Continuous outcomes (e.g. length of hospital stay) were pooled using a random‐effects model to calculate the mean difference and corresponding 95% CI. Sensitivity analyses were conducted to explore the impact of missing data on efficacy and safety outcomes. For the sensitivity analyses, we assumed that the event rate for those participants in the control group who had missing data was the same as the event rate for those participants in the control group who were successfully followed. For the probiotic group, we calculated effects using the following assumed ratios of event rates in those with missing data in comparison to those successfully followed: 1.5:1, 2:1, 3:1, and 5:1. To explore possible explanations for heterogeneity, a priori subgroup analyses were conducted on probiotic species, dose, adult versus pediatric population, and risk of bias as well as a post hoc subgroup analysis on baseline risk of CDAD (low 0% to 2%; moderate 3% to 5%; high > 5%). The overall quality of the evidence supporting each outcome was independently assessed using the GRADE criteria. Thirty‐nine studies (9955 participants) met the eligibility requirements for our review. Overall, 27 studies were rated as either high or unclear risk of bias. A complete case analysis (i.e. participants who completed the study) among trials investigating CDAD (31 trials, 8672 participants) suggests that probiotics reduce the risk of CDAD by 60%. The incidence of CDAD was 1.5% (70/4525) in the probiotic group compared to 4.0% (164/4147) in the placebo or no treatment control group (RR 0.40, 95% CI 0.30 to 0.52; GRADE = moderate). Twenty‐two of 31 trials had missing CDAD data ranging from 2% to 45%. Our complete case CDAD results proved robust to sensitivity analyses of plausible and worst‐plausible assumptions regarding missing outcome data and results were similar whether considering subgroups of trials in adults versus children, inpatients versus outpatients, different probiotic species, lower versus higher doses of probiotics, or studies at high versus low risk of bias. However, in a post hoc analysis, we did observe a subgroup effect with respect to baseline risk of developing CDAD. Trials with a baseline CDAD risk of 0% to 2% and 3% to 5% did not show any difference in risk but trials enrolling participants with a baseline risk of > 5% for developing CDAD demonstrated a large 70% risk reduction (interaction P value = 0.01). Among studies with a baseline risk > 5%, the incidence of CDAD in the probiotic group was 3.1% (43/1370) compared to 11.6% (126/1084) in the control group (13 trials, 2454 participants; RR 0.30, 95% CI 0.21 to 0.42; GRADE = moderate). With respect to detection of C. difficile in the stool pooled complete case results from 15 trials (1214 participants) did not show a reduction in infection rates. C. difficile infection was 15.5% (98/633) in the probiotics group compared to 17.0% (99/581) in the placebo or no treatment control group (RR 0.86, 95% CI 0.67 to 1.10; GRADE = moderate). Adverse events were assessed in 32 studies (8305 participants) and our pooled complete case analysis indicates probiotics reduce the risk of adverse events by 17% (RR 0.83, 95% CI 0.71 to 0.97; GRADE = very low). In both treatment and control groups the most common adverse events included abdominal cramping, nausea, fever, soft stools, flatulence, and taste disturbance. Based on this systematic review and meta‐analysis of 31 randomized controlled trials including 8672 patients, moderate certainty evidence suggests that probiotics are effective for preventing CDAD (NNTB = 42 patients, 95% CI 32 to 58). Our post hoc subgroup analyses to explore heterogeneity indicated that probiotics are effective among trials with a CDAD baseline risk >5% (NNTB = 12; moderate certainty evidence), but not among trials with a baseline risk ≤5% (low to moderate certainty evidence). Although adverse effects were reported among 32 included trials, there were more adverse events among patients in the control groups. The short‐term use of probiotics appears to be safe and effective when used along with antibiotics in patients who are not immunocompromised or severely debilitated. Despite the need for further research, hospitalized patients, particularly those at high risk of CDAD, should be informed of the potential benefits and harms of probiotics. |
t151 | Not enough evidence to know whether giving antibiotics as a routine to new born babies reduces group B streptococcus infection in the first week of life. Group‐B Streptococcus (GBS) is a common bacteria which can be passed from the mother to the newborn and can lead to infection in the first week of life (neonatal Early Onset Group‐B Streptococcal Disease or EOGBSD). Although rare, (approximately one per thousand births) it is the most common cause of serious infection in newborn babies. Currently, usual management to reduce the risk of infection is to give antibiotics to women at increased risk in labour and to observe the newborn baby closely for signs of infection. Giving an injection of penicillin immediately after birth to newborn babies routinely has been proposed as another way of preventing infection. This review included only one trial and does not have enough data to show whether treating the newborn with intramuscular penicillin should be used to prevent infection in newborn babies. | Early‐onset group B streptococcal disease (EOGBSD) is the most frequent cause of serious infection in the newborn period. Current strategies used to prevent EOGBSD are focused upon maternal antibiotic prophylaxis to reduce transmission of GBS to the infant. Observational studies have suggested that the administration of intramuscular penicillin to the newborn immediately following delivery may be an effective strategy to reduce the incidence of EOGBSD. Objectives To determine if the administration of intramuscular penicillin to newborns at birth is a safe and effective method to prevent morbidity and mortality from EOGBSD. Search methods The standard search strategy of the Neonatal Review Group was used. This included searches of electronic databases: Oxford Database of Perinatal Trials, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library Issue 1, 2004), and MEDLINE (1966 ‐ Dec 2003); and previous reviews including cross references, expert informants and journal hand searching in the English language as well as conference and symposia proceedings published in Pediatric Research. Selection criteria Randomised trials in which intramuscular penicillin was administered as prophylaxis for EOGBSD within four hours of birth. Outcomes considered were EOGBSD, neonatal mortality, late‐onset GBSD, neonatal sepsis, and other secondary outcomes such as neurodevelopmental status and length of hospital stay. Data collection and analysis The search for and assessment of trials for inclusion, quality assessment and data extraction were undertaken independently by the reviewers. Meta‐analysis was not undertaken as data from only one trial is included in this review. Data were analysed using relative risk (RR) with 95% confidence intervals (CI). One randomised controlled trial was included in this review. In this trial of 1187 infants of birthweight 501 to 2000 grams, there were no significant differences found for the outcomes of EOGBSD (RR 0.73; 95%CI 0.32, 1.62), or neonatal mortality (RR 0.78; 95% CI 0.55, 1.11). No other outcomes were able to be assessed. This review does not support the routine use of intramuscular penicillin to prevent EOGBSD in newborn infants. There is a discrepancy between this finding and the results of a number of larger non‐randomised trials. Explanations for this are proposed. There is a need for this intervention to be tested as a component of the existing prevention strategies in widespread use. |
t152 | A person with diseased arteries in the legs can experience pain on walking (also known as intermittent claudication), pain at rest (especially at night), or ulcers due to poor blood flow. Established treatments include surgery, where a bypass is inserted to carry blood from an artery above the diseased (blocked or narrowed) section to below the diseased section, and balloon angioplasty, where a deflated balloon is inserted into the vessel and then blown up to stretch the artery thus opening up the narrow or blocked section. Stents may be inserted during angioplasty. In addition to these two established treatments, a less commonly used technique is to core out the artery, cutting or grinding away the disease which is causing the vessel to narrow or block. This is known as atherectomy. In this review, we compared atherectomy to the more established treatments such as balloon angioplasty and bypass surgery. We identified four studies with a total of 220 participants. All studies compared atherectomy with balloon angioplasty. The studies were of low quality as there was no blinding of the procedures, the studies were not properly powered to show an effect, not all study outcomes were reported and a large number of the initial study populations did not complete the studies. Although the results of the meta‐analyses were imprecise, the average effect of the two treatments was similar in terms of initial success and unobstructed arteries (patency) at six months or 12 months following the procedure. There was a lower risk of death with atherectomy, most likely due to an unexpectedly high number of deaths in the balloon angioplasty group in one of the two trials reporting deaths. Cardiovascular events were not reported in any of the included studies. There was a reduction in the rate of emergency stenting procedures following atherectomy, and balloon inflation pressures were lower following atherectomy. Complications such as formation of clots (embolisation) and tears along the vessels (vessel dissection) were reported in two trials indicating more embolisations in the atherectomy group and more vessel dissections in the angioplasty group but the data could not be combined. The limited data available indicated that there was no clear evidence of a difference between the atherectomy and balloon angioplasty groups for adverse events such as the need for re‐intervention due to obstruction of the treated vessel and above‐knee amputation. We showed that the limited evidence available does not support a significant advantage of atherectomy over conventional balloon angioplasty. | Symptomatic peripheral arterial disease may be treated by a number of options including exercise therapy, angioplasty, stenting and bypass surgery. Atherectomy is an alternative technique where atheroma is excised by a rotating cutting blade. Objectives The objective of this review was to analyse randomised controlled trials comparing atherectomy against any established treatment for peripheral arterial disease in order to evaluate the effectiveness of atherectomy. Search methods The Cochrane Peripheral Vascular Diseases Group Trials Search Co‐ordinator searched the Specialised Register (last searched November 2013) and CENTRAL (2013, Issue 10). Trials databases were searched for details of ongoing or unpublished studies. Selection criteria Randomised controlled trials (RCTs) comparing atherectomy and other established treatments were selected for inclusion. All participants had symptomatic peripheral arterial disease with either claudication or critical limb ischaemia and evidence of lower limb arterial disease. Data collection and analysis Two review authors (GA and CT) screened studies for inclusion, extracted data and assessed the quality of the trials. Any disagreements were resolved through discussion. Four trials were included with a total of 220 participants (118 treated with atherectomy, 102 treated with balloon angioplasty) and 259 treated vessels (129 treated with atherectomy, 130 treated with balloon angioplasty). All studies compared atherectomy with angioplasty. No study was properly powered or assessors blinded to the procedures and there was a high risk of selection, attrition, detection and reporting biases. The estimated risk of success was similar between the treatment modalities although the confidence interval (CI) was compatible with small benefits of either treatment for the initial procedural success rate (Mantel‐Haenszel risk ratio (RR) 0.92, 95% CI 0.44 to 1.91, P = 0.82), patency at six months (Mantel‐Haenszel RR 0.92, 95% CI 0.51 to 1.66, P = 0.79) and patency at 12 months (Mantel‐Haenszel RR 1.17, 95% CI 0.72 to 1.90, P = 0.53) following the procedure. The reduction in all‐cause mortality with atherectomy was most likely due to an unexpectedly high mortality in the balloon angioplasty group in one of the two trials that reported mortality (Mantel‐Haenszel RR 0.24, 95% CI 0.06 to 0.91, P = 0.04). Cardiovascular events were not reported in any study. There was a reduction in the rate of bailout stenting following atherectomy (Mantel‐Haenszel RR 0.45, 95% CI 0.24 to 0.84, P = 0.01), and balloon inflation pressures were lower following atherectomy (mean difference ‐2.73 mmHg, 95% CI ‐3.48 to ‐1.98, P < 0.00001). Complications such as embolisation and vessel dissection were reported in two trials indicating more embolisations in the atherectomy group and more vessel dissections in the angioplasty group, but the data could not be pooled. From the limited data available, there was no clear evidence of different rates of adverse events between the atherectomy and balloon angioplasty groups for target vessel revascularisation and above‐knee amputation. Quality of life and clinical and symptomatic outcomes such as walking distance or symptom relief were not reported in the studies. This review has identified poor quality evidence to support atherectomy as an alternative to balloon angioplasty in maintaining primary patency at any time interval. There was no evidence for superiority of atherectomy over angioplasty on any outcome, and distal embolisation was not reported in all trials of atherectomy. Properly powered trials are recommended. |
t153 | Cystic fibrosis is a serious genetic disorder that affects many organs (e.g. lung and pancreas). It commonly leads to reduced bone mineral density, known as osteoporosis, which increases the likelihood of fractures. The short‐term and long‐term effects of fractures (e.g . rib and vertebral) may make lung disease worse. Bisphosphonates are drugs that increase bone mineral density by slowing down bone resorption. They are used to treat osteoporosis caused by menopause or the use of corticosteroid drugs. The evidence available was limited to six trials with participants who had not undergone lung transplants (total of 203 adults) and one trial with 34 adults who had undergone lung transplantation. Bisphosphonates consistently increased bone mineral density at the lumbar spine and hip regions. The rates of fractures (vertebral and non‐vertebral) or deaths were not reduced by bisphosphonate therapy. However, this may be related to the small numbers of participants involved and the short duration of the trials. Severe bone pain and flu‐like symptoms were commonly linked to intravenous bisphosphonates, especially in people not using corticosteroids. | Osteoporosis is a bone mineralisation disorder occurring in about one third of adults with cystic fibrosis. Bisphosphonates can increase bone mineral density and decrease the risk of new fractures in post‐menopausal women and people receiving long‐term oral corticosteroids. Objectives To assess the effects of bisphosphonates on the frequency of fractures, bone mineral density, quality of life, adverse events, trial withdrawals, and survival in people with cystic fibrosis. Search methods We searched the Cystic Fibrosis and Genetic Disorders Group Trials Register of references (identified from electronic database searches and handsearches of journals and abstract books) on 13 January 2014. Additional searches of PubMed were performed on 13 January 2014. Selection criteria Randomised controlled trials of at least six months duration studying bisphosphonates in people with cystic fibrosis. Data collection and analysis Two authors independently selected trials and extracted data. Trial investigators were contacted to obtain missing data. Nine trials were identified and seven (with a total of 237 adult participants) were included. Data were combined (when available) from six included studies in participants without a lung transplant. Data showed that there was no significant reduction in fractures between treatment and control groups at 12 months, odds ratio 0.72 (95% confidence interval 0.13 to 3.80). No fractures were reported in studies with follow‐up at 24 months. However, in patients taking bisphosphonates after six months the percentage change in bone mineral density increased at the lumbar spine, mean difference 4.61 (95% confidence interval 3.90 to 5.32) and at the hip or femur, mean difference 3.35 (95% confidence interval 1.63 to 5.07); but did not significantly change at the distal forearm, mean difference ‐0.49 (95% confidence interval ‐2.42 to 1.45). In patients taking bisphosphonates, at 12 months the percentage change in bone mineral density increased at the lumbar spine, mean difference 6.10 (95% confidence interval 5.10 to 7.10) and at the hip or femur, mean difference 4.35 (95% confidence interval 2.99 to 5.70). At 24 months, in patients treated with bisphosphonates the percentage change in bone mineral density also increased at the lumbar spine, mean difference 5.49 (95% confidence interval 4.38 to 6.60) and at the hip or femur, mean difference 6.05 (95% confidence interval 3.74 to 8.36). There was clinical heterogeneity between studies and not all studies reported all outcomes. Bone pain was the most common adverse event with intravenous agents. Flu‐like symptoms were also increased in those taking bisphosphonates. In participants with a lung transplant (one study), intravenous pamidronate did not change the number of new fractures. At axial sites, bone mineral density increased with treatment compared to controls: percentage change in bone mineral density at lumbar spine, mean difference 6.20 (95% confidence interval 4.28 to 8.12); and femur mean difference 7.90 (95% confidence interval 5.78 to 10.02). Oral and intravenous bisphosphonates increase bone mineral density in people with cystic fibrosis. Severe bone pain and flu‐like symptoms may occur with intravenous agents. Additional trials are needed to determine if bone pain is more common or severe (or both) with the more potent zoledronate and if corticosteroids ameliorate or prevent these adverse events. Additional trials are also required to further assess gastrointestinal adverse effects associated with oral bisphosphonates. Trials in larger populations are needed to determine effects on fracture rate and survival. |
t154 | The human brain has two hemispheres. For people who have had a stroke, activity in the affected hemisphere is disrupted not only by the damage caused by the stroke itself, but also by the reaction of the unaffected hemisphere, which tries to limit the damage caused by the stroke. This limiting effect, while beneficial in the initial stage after stroke, may subsequently become detrimental as it interferes with the brain’s capacity to recover functional ability. Repetitive transcranial magnetic stimulation (rTMS) is a method of non‐invasive brain stimulation that can help the affected hemisphere to repair the damage of the stroke, while decreasing the limiting effect on recovery caused by undamaged hemisphere. rTMS has been investigated in the treatment of many conditions, including depression, tinnitus and movement disorders. The aim of this review was to assess randomised controlled trials of rTMS on functional recovery in patients with stroke. We included 19 trials with a total of 588 patients in the review. We found that rTMS treatment was not associated with improved activities of daily living nor had a statistically significant effect on motor function. | It had been assumed that suppressing the undamaged contralesional motor cortex by repetitive low‐frequency transcranial magnetic stimulation (rTMS) or increasing the excitability of the damaged hemisphere cortex by high‐frequency rTMS will promote function recovery after stroke. Objectives To assess the efficacy and safety of rTMS for improving function in people with stroke. Search methods We searched the Cochrane Stroke Group Trials Register (April 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library 2012, Issue 4), the Chinese Stroke Trials Register (April 2012), MEDLINE (1950 to May 2012), EMBASE (1980 to May 2012), Science Citation Index (1981 to April 2012), Conference Proceedings Citation Index‐Science (1990 to April 2012), CINAHL (1982 to May 2012), AMED (1985 to May 2012), PEDro (April 2012), REHABDATA (April 2012) and CIRRIE Database of International Rehabilitation Research (April 2012). In addition, we searched five Chinese databases, ongoing trials registers and relevant reference lists. Selection criteria We included randomised controlled trials comparing rTMS therapy with sham therapy or no therapy. We excluded trials that reported only laboratory parameters. Data collection and analysis Two review authors independently selected trials, assessed trial quality and extracted the data. We resolved disagreements by discussion. We included 19 trials involving a total of 588 participants in this review. Two heterogenous trials with a total of 183 participants showed that rTMS treatment was not associated with a significant increase in the Barthel Index score (mean difference (MD) 15.92, 95% CI ‐2.11 to 33.95). Four trials with a total of 73 participants were not found to have a statistically significant effect on motor function (standardised mean difference (SMD) 0.51, 95% CI ‐0.99 to 2.01). Subgroup analyses of different stimulation frequencies or duration of illness also showed no significant difference. Few mild adverse events were observed in the rTMS groups, with the most common events being transient or mild headaches (2.4%, 8/327) and local discomfort at the site of the stimulation. Current evidence does not support the routine use of rTMS for the treatment of stroke. Further trials with larger sample sizes are needed to determine a suitable rTMS protocol and the long‐term functional outcome. |
t155 | Each year approximately one million people receive a tube feeding (gastric tube) in the US. Gastric tubes are commonly used for giving drugs and nutrition directly into the gastrointestinal tract (tube that digests food) for people who are unable to swallow. Feeding via a tube that is misplaced in the trachea (wind pipe) can result in severe pneumonia (infection of the lungs). Therefore, confirmation of tube placement in the stomach after tube insertion is important. Gastric tubes are also used to reduce the pressure of the stomach after providing breathing assistance through masks, which is mainly used in resuscitation. Medical ultrasound is one of the diagnostic imaging techniques using sound waves to create images of the inside of the body. Recent studies suggest that ultrasound provides good diagnostic accuracy in the confirmation of appropriate tube placement. Hence, ultrasound could provide a promising alternative to X‐rays in confirming tube placement, especially where X‐ray facilities are unavailable or difficult to access. We included 10 studies involving 545 participants for evaluation of the diagnostic accuracy of ultrasound for confirmation of gastric tube placement. Most studies showed good performance for correct placement of the tube. However, few data were available for incorrect placement of the tube and the possible complications of a misplaced tube. Among the included studies, only 43 participants had a misplaced tube. None of the studies reported complications during ultrasound use. Three methods of ultrasound were reported: neck approach, upper abdominal (tummy) approach and a combination of both. No included studies indicated that ultrasound had sufficient accuracy as a single test for the confirmation of gastric tube placement for feeding. In contrast, ultrasound combined with other tests (e.g. saline flush visualization (pushing salt solution through the tube and seeing it inside the stomach by ultrasound)) might be useful for the confirmation of tubes used for gastric drainage. Limitations of the review Generally, the studies were of low or unclear methodological quality. We considered only three (30%) of the 10 included studies to be representative of patients in practice because they performed ultrasound after they confirmed correct position by other methods. The studies reported a variety of results for incorrect tube placement. | Gastric tubes are commonly used for the administration of drugs and tube feeding for people who are unable to swallow. Feeding via a tube misplaced in the trachea can result in severe pneumonia. Therefore, the confirmation of tube placement in the stomach after tube insertion is important. Recent studies have reported that ultrasonography provides good diagnostic accuracy estimates in the confirmation of appropriate tube placement. Hence, ultrasound could provide a promising alternative to X‐rays in the confirmation of tube placement, especially in settings where X‐ray facilities are unavailable or difficult to access. Objectives To assess the diagnostic accuracy of ultrasound for gastric tube placement confirmation. Search methods We searched the Cochrane Library (2016, Issue 3), MEDLINE (to March 2016), Embase (to March 2016), National Institute for Health Research (NIHR) PROSPERO Register (to May 2016), Aggressive Research Intelligence Facility Databases (to May 2016), ClinicalTrials.gov (to May 2016), ISRCTN registry (May 2016), World Health Organization International Clinical Trials Registry Platform (to May 2016) and reference lists of articles, and contacted study authors. Selection criteria We included studies that evaluated the diagnostic accuracy of naso‐ and orogastric tube placement confirmed by ultrasound visualization using X‐ray visualization as the reference standard. We included cross‐sectional studies, and case‐control studies. We excluded case series or case reports. Studies were excluded if X‐ray visualization was not the reference standard or if the tube being placed was a gastrostomy or enteric tube. Data collection and analysis Two review authors independently assessed the risk of bias and extracted data from each of the included studies. We contacted authors of the included studies to obtain missing data. We identified 10 studies (545 participants and 560 tube insertions) which met our inclusion criteria. No study was assigned low risk of bias or low concern in every QUADAS‐2 domain. We judged only three (30%) studies to have low risk of bias in the participant selection domain because they performed ultrasound after they confirmed correct position by other methods. Few data (43 participants) were available for misplacement detection (specificity) due to the low incidence of misplacement. We did not perform a meta‐analysis because of considerable heterogeneity of the index test such as the difference of echo window, the combination of ultrasound with other confirmation methods (e.g. saline flush visualization by ultrasound) and ultrasound during the insertion of the tube. For all settings, sensitivity estimates for individual studies ranged from 0.50 to 1.00 and specificity estimates from 0.17 to 1.00. For settings where X‐ray was not readily available and participants underwent gastric tube insertion for drainage (four studies, 305 participants), sensitivity estimates of ultrasound in combination with other confirmatory tests ranged from 0.86 to 0.98 and specificity estimates of 1.00 with wide confidence intervals. For the studies using ultrasound alone (four studies, 314 participants), sensitivity estimates ranged from 0.91 to 0.98 and specificity estimates from 0.67 to 1.00. Of 10 studies that assessed the diagnostic accuracy of gastric tube placement, few studies had a low risk of bias. Based on limited evidence, ultrasound does not have sufficient accuracy as a single test to confirm gastric tube placement. However, in settings where X‐ray is not readily available, ultrasound may be useful to detect misplaced gastric tubes. Larger studies are needed to determine the possibility of adverse events when ultrasound is used to confirm tube placement. |
t156 | Vaginal deliveries are associated with perineal trauma that may be unexpected tears or surgical as a result of episiotomy. Many techniques have been used to prevent perineal trauma, such as antenatal perineal massage or perineum warm compresses. Their effectiveness in reducing perineal trauma has been identified by researchers. Perineal hyaluronidase (HAase) injection was widely used in the 1950s and 1960s to reduce the occurrence of perineal trauma, pain, and the need for episiotomy. The review authors searched the medical literature for randomised controlled trials that compared perineal HAase injection during the second stage of labour with perineal placebo injection or no intervention. They identified four randomised controlled trials involving 599 women (with data available for 595 women). The methodological quality of two out of the four trials included in this review was poor. Two trials involving 283 women compared the effects of perineal HAase injection with placebo injection during second stage of labour and were at low risk of bias. Three trials (one three‐armed trial was analysed twice) with 373 women compared the effects of perineal HAase injection during second stage of labour with no intervention. The overall results showed that perineal HAase injection had a significantly lower incidence of perineal trauma compared with control or no intervention, but there was no difference in the incidence of episiotomy, first and second degree and more severe (third and fourth degree) perineal tears. There was no clear evidence that HAase injection lowered the incidence of perineal trauma, episiotomy, first and second degree and more severe (third and fourth degree) perineal tears when compared with placebo injection. Other measures such as perineal pain and other pre‐specified secondary outcomes were not measured by the included trials. The difference in the incidence of perineal trauma may be due to bias and confounding in the non‐placebo controlled comparison, this result should be interpreted cautiously. The potential use of this intervention as a method to reduce perineal trauma are yet to be determined as there was no appropriate established dose for HAase, no evidence of follow‐up and side effects, and the number of high‐quality trials and outcomes reported was too limited to draw conclusions on its effectiveness and safety. | Perineal hyaluronidase (HAase) injection was widely used to reduce the occurrence of perineal trauma, pain and need for episiotomy in the 1950s to 1960s. Reports suggested that the administration of HAase was a simple, low risk, low cost and effective way to decrease perineal trauma without adverse effects. Objectives The objective of this review was to assess the effectiveness and safety of perineal HAase injection for reducing spontaneous perineal trauma, episiotomy and perineal pain in vaginal deliveries. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2013), the International Clinical Trials Registry Platform ( ICTRP ) and the Networked Digital Library of Theses and Dissertations (both on 1 April 2013), and reference lists of retrieved studies. We also contacted relevant organisations. Selection criteria Published and unpublished randomised and quasi‐randomised controlled trials comparing perineal HAase injection with placebo injection or no intervention in vaginal deliveries. Data collection and analysis Two review authors independently assessed trials for inclusion, extracted data and evaluated methodological quality. Data were checked for accuracy. The search strategy identified six potentially eligible studies. Two studies were excluded. We included four randomised controlled trials that randomised a total of 599 women (data were available for 595 women). Two trials (283 women) compared the effects of perineal HAase injection during the second stage of labour with placebo injection and were at low risk of bias. Three trials (one three‐armed trial was analysed twice) (373 women) compared the effects of perineal HAase injection during second stage of labour with no intervention and two out of the three trials were at high risk of bias. Data from four trials involving 599 women suggested that perineal HAase injection during second stage of labour had a lower incidence of perineal trauma (average risk ratio (RR) 0.69, 95% confidence interval (CI) 0.50 to 0.95,Tau² = 0.08, I² = 82% compared with women in the control group, but there was no clear evidence of a reduction in the incidence of episiotomy (average RR 0.74, 95% CI 0.43 to 1.29, Tau² = 0.17, I² = 66%), first and second degree perineal lacerations (average RR 0.54, 95% CI 0.38 to 1.33, Tau² = 0.30 , I² = 85%) and third and fourth degree perineal lacerations (RR 0.12, 95% CI 0.01 to 2.13). Data from two trials involving 283 women indicated that there was no clear evidence of a reduction in the incidence of perineal trauma (RR 0.90, 95% CI 0.77 to 1.06, Tau²=1.07, I² = 7%), episiotomy (RR 0.77, 95% CI 0.32 to 1.89, Tau² = 0.27, I² = 54%), first and second degree perineal lacerations (RR 1.08, 95% CI 0.83 to 1.40, Tau² = 1.11, I² = 10%) and third and fourth degree perineal lacerations (RR 0.12, 95% CI 0.01 to 2.13) with perineal HAase injection. Data from three trials involving 373 women suggested that perineal HAase injection during second stage of labour had a lower incidence of perineal trauma (RR 0.61, 95% CI 0.42 to 0.88, Tau² = 0.08, I² = 78%) compared with no intervention, but had no clear effect on in the incidence of episiotomy (RR 0.79, 95% CI 0.44 to 1.42, Tau² = 0.16, I² = 70%) and first and second degree perineal lacerations (RR 0.58, 95% CI 0.31 to 1.10, Tau² = 0.18, I² = 59%). No side effects were reported in the included trials. No included trials reported on perineal pain and other pre‐specified secondary outcomes: perineal trauma requiring suturing; blood loss; dyspareunia; urinary incontinence; faecal incontinence; assisted delivery rate; women's satisfaction; Apgar score less than seven at five minutes and need for admission to special care baby unit. Perineal HAase injection during second stage of labour had a lower incidence of perineal trauma compared with control or no intervention, but there was no clear evidence of benefit compared with placebo injection. The difference in incidence of perineal trauma may probably be due to bias and confounding in the non‐placebo controlled comparison, this result should be interpreted cautiously. The potential use of perineal HAase injection as a method to reduce perineal trauma were yet to be determined as there was no appropriate established dose for HAase, no evidence of follow up, and the number of high‐quality trials and outcomes reported were too limited to draw conclusions on its effectiveness and safety. Further rigorous randomised controlled trials are required to evaluate the role of perineal HAase injection in vaginal deliveries. |
t157 | We assessed the evidence from randomized controlled trials to determine whether not drinking alcohol during the perioperative period reduces postoperative complications for people with risky alcohol consumption. These programmes supported participants in quitting drinking or in reducing their alcohol consumption before, during, and after surgery. 'Risky drinking' was defined as alcohol consumption equivalent to more than 3 alcoholic units (three small glasses of wine) per day or 21 units per week ‐ with or without alcohol abuse or dependency. Most clinical studies report that consuming this amount of alcohol increases postoperative complication rates. Risky consumption of alcohol is a global problem, and alcohol is an important threat to world health. More than 3.3 million deaths annually are associated with risky use of alcohol, and global alcohol consumption continues to increase. People who have a high level of alcohol consumption often require planned and emergency surgical procedures. Risky drinking affects surgical outcomes ‐ even when the disease is not alcohol related. Typical surgical complications include infections, heart and breathing problems, and bleeding episodes. Alcohol causes disorders of the liver, pancreas, and nervous system. Stopping drinking of alcohol can normalize these organ systems to some degree and may reduce the occurrence of complications after surgery. Quitting drinking can result in mild to severe alcohol withdrawal symptoms and may lead to a change in lifestyle. We included three randomized controlled trials with a total of 140 participants. All three studies included participants with risky alcohol intake (3 to 40 AU daily) who were in need of surgery. These studies investigated intensive alcohol interventions aimed at complete alcohol cessation at the time of surgery compared with no intervention. Interventions included educational strategies for alcohol withdrawal and relapse prevention. Programmes were started three months before surgery, four weeks before surgery, and from the time of admission to surgery, and continued for six weeks after surgery, respectively. In all three studies, intensive intervention programmes clearly increased the number of participants who quit drinking alcohol. The occurrence of postoperative complications appeared to be reduced as well. Of 61 participants in the intervention groups, 20 had complications requiring treatment, compared with 33 of 61 participants in the control groups (moderate‐quality evidence). Of 70 participants in the intervention groups, 41 successfully quit drinking, compared to five of 70 participants in the control groups (moderate‐quality evidence). Data were insufficient to show the effect of quitting drinking on the number of deaths (low‐quality evidence), and results show no effect on length of hospital stay. None of the included studies reported on the number of participants who continued to avoid risky drinking in the longer term (at three‐, six‐, nine‐, and 12‐month follow‐up). Included studies were few and reported small sample sizes; therefore one should be careful about drawing firm conclusions based on these results. All three studies were conducted in Denmark, and most participants were men. The included participants may represent a selective group, as they could be more motivated and/or more interested in participating in clinical research or otherwise different, and effects may therefore have been overestimated for both intervention and control groups in these studies. | Risky consumption of alcohol is a global problem. More than 3.3 million deaths annually are associated with risky use of alcohol, and global alcohol consumption continues to increase. People who have high alcohol consumption often require planned and emergency surgical procedures. Risky drinking is associated with increased postoperative complications such as infections, cardiopulmonary complications, and bleeding episodes. Alcohol causes disorders of the liver, pancreas, and nervous system. Stopping consumption of alcohol can normalize these organ systems to some degree and may reduce the occurrence of complications after surgery. This review was first published in 2012 and was updated in 2018. Objectives To assess the effects of perioperative alcohol cessation interventions on rates of postoperative complications and alcohol consumption. Search methods We searched the following databases up until 21 September 2018: Cochrane Central Register of Controlled Trials (CENTRAL), in the Cochrane Library; MEDLINE; Embase; CINAHL via EBSCOhost; and two trials registers. We scanned the reference lists and citations of included trials and any identified relevant systematic reviews for further references to additional trials. When necessary, we contacted trial authors to ask for additional information. Selection criteria We included all randomized controlled trials (RCTs) that evaluated the effects of perioperative alcohol cessation interventions on postoperative complications and alcohol consumption. We included participants with risky consumption of alcohol who were undergoing all types of elective or acute surgical procedures under general or regional anaesthesia or sedation, who were offered a perioperative alcohol cessation intervention or no intervention. We defined 'risky drinking' as alcohol consumption equivalent to more than 3 alcoholic units (AU)/d or 21 AU/week (with 1 AU containing 12 grams of ethanol) with or without symptoms of alcohol abuse or dependency. This corresponds to the amount of alcohol associated with increased postoperative complication rates in most clinical studies. Data collection and analysis We used guidance provided in the Cochrane Handbook for Systematic Reviews of Interventions . We presented main outcomes as dichotomous variables in a meta‐analysis. When data were available, we conducted subgroup and sensitivity analyses to explore the risk of bias. Primary outcome measures were postoperative complications and in‐hospital and 30‐day mortality. Secondary outcomes were successful quitting at the end of the programme, postoperative alcohol use, and length of hospital stay. We assessed the quality of evidence using the GRADE approach. We included in this updated review one new study (70 participants), resulting in a total of three RCTs (140 participants who drank 3 to 40 AU/d). All three studies were of moderate to good quality. All studies evaluated the effects of intensive alcohol cessation interventions, including pharmacological strategies for alcohol withdrawal symptoms, patient education, and relapse prophylaxis. We identified one ongoing study. Overall, 53 of the 122 participants from three studies who underwent surgery developed any type of postoperative complication that required treatment. Of 61 participants in the intervention groups, 20 had complications, compared with 33 of 61 participants in the control groups (risk ratio (RR) 0.62, 95% confidence interval (CI) 0.40 to 0.96). Results show differences between the three clinical studies regarding outcome measurement and intensity of the interventions. However, all alcohol cessation programmes were intensive and included pharmacological therapy. The overall quality of evidence for this outcome is moderate. In‐hospital and 30‐day postoperative mortality rates were low in the three studies. Researchers reported one death among 61 participants in the intervention groups, and three deaths among 61 participants in the control groups (RR 0.47, 95% CI 0.07 to 2.96). The quality of evidence for this outcome is low. Investigators describe more successful quitters at the end of the intervention programme than among controls. Forty‐one out of 70 participants in the intervention groups successfully quit drinking compared with only five out of 70 participants in the control groups (RR 8.22, 95% CI 1.67 to 40.44). The quality of evidence for this outcome is moderate. All three studies reported postoperative alcohol consumption (grams of alcohol/week) at the end of the programme as median and range values; therefore it was not possible to estimate the mean and the standard deviation (SD). We performed no meta‐analysis. All three studies reported length of stay, and none of these studies described a significant difference in length of stay. Data were insufficient for review authors to perform a meta‐analysis. No studies reported on the prevalence of participants without risky drinking in the longer term. This systematic review assessed the efficacy of perioperative alcohol cessation interventions for postoperative complications and alcohol consumption. All three studies showed a significant reduction in the number of participants who quit drinking alcohol during the intervention period. Intensive alcohol cessation interventions offered for four to eight weeks to participants undergoing all types of surgical procedures to achieve complete alcohol cessation before surgery probably reduced the number of postoperative complications. Data were insufficient for review authors to assess their effects on postoperative mortality. No studies reported an effect on length of stay, and no studies addressed the prevalence of risky drinking in the longer term. Included studies were few and reported small sample sizes; therefore one should be careful about drawing firm conclusions based on these study results. All three studies were conducted in Denmark, and most participants were men. The included participants may represent a selective group, as they could have been more motivated and/or more interested in participating in clinical research or otherwise different, and effects may have been overestimated for both intervention and control groups in these studies. Trial results indicate that these studies are difficult to perform, that strong research competencies are necessary for future studies, and that further evaluation of perioperative alcohol cessation interventions in high‐quality randomized controlled trials is needed. Once published and assessed, the one 'ongoing' study identified may alter the conclusions of this review. |
t158 | Cochrane authors reviewed the evidence on the effectiveness and safety of acupuncture or acupressure in women with premenstrual syndrome (PMS) or premenstrual dysphoric disorder. We wanted to know whether using acupuncture or acupressure therapy was better than receiving sham acupuncture, no treatment or currently recommended pharmaceutical medications for PMS such as serotonin reuptake inhibitors (SSRIs ‐ a type of anti‐depressant). We found five randomised controlled trials including 277 women that examined the effect of acupuncture or acupressure in women with PMS. Three trials compared acupuncture with sham acupuncture, one compared acupuncture with no treatment and one compared acupressure with sham acupressure. Acupuncture may reduce overall mood and physical PMS symptoms when compared to sham. Acupressure may reduce the number of women having moderate to severe PMS symptoms when compared to sham acupressure. | Acupuncture has a history of traditional use in China for women's health conditions including premenstrual syndrome (PMS), but its effectiveness for this condition remains unclear. This review examined the available evidence supporting the use of acupuncture or acupressure to treat PMS. Objectives To evaluate the effectiveness and safety of acupuncture or acupressure for women with PMS or premenstrual dysphoric disorder (PMDD). Search methods We searched the Cochrane Gynaecology and Fertility Specialised Register, Cochrane Central Register of Studies Online (CENTRAL CRSO), MEDLINE, Embase, AMED, PsycINFO, CINAHL (from inception to 21 September 2017), two clinical trial databases (from their inception to 21 September 2017), and four electronic databases in China (from their inception to 15 October 2017): Chinese Biomedical Literature database (CBM), China National Knowledge Infrastructure (CNKI), VIP information/ Chinese Scientific Journals database and WANFANG. Reference lists from included articles were handsearched. Selection criteria We included studies if they randomised women with PMS and associated disorders (PMDD and late luteal phase dysphoric disorder/LPDD) to receive acupuncture or acupressure versus sham, usual care/waiting‐list control or pharmaceutical interventions mentioned by the International Society for Premenstrual Disorders (ISPMD). If acupuncture or acupressure were combined with another therapy, these studies were also included where the additional therapy was the same in both groups. Cross‐over studies were eligible for inclusion, but only data from the first phase could be used. Data collection and analysis Two review authors independently selected the studies, assessed eligible studies for risk of bias, and extracted data from each study. Study authors were contacted for missing information. The quality of the evidence was assessed using GRADE. Our primary outcomes were overall premenstrual symptoms and adverse events. Secondary outcomes included specific PMS symptoms, response rate and quality of life. Five trials (277 women) were included in this review. No trials compared acupuncture or acupressure versus other active treatments. The number of treatment sessions ranged from seven to 28. The quality of the evidence ranged from low to very low quality, the main limitations being imprecision due to small sample sizes and risk of bias related to detection bias and selective reporting. Acupuncture versus sham acupuncture Acupuncture may provide a greater reduction in mood‐related PMS symptoms (mean difference (MD) ‐9.03, 95% confidence interval (CI) ‐10.71 to ‐7.35, one randomised controlled trial (RCT), n = 67, low‐quality evidence) and in physical PMS symptoms (MD ‐9.11, 95% CI ‐10.82 to ‐7.40, one RCT, n = 67, low‐quality evidence) than sham acupuncture, as measured by the Daily Record of Severity of Problems scale (DRSP). The evidence suggests that if women have a mood score of 51.91 points with sham acupuncture, their score with acupuncture would be between 10.71 and 7.35 points lower and if women have a physical score of 46.11 points, their score with acupuncture would be between 10.82 and 7.4 points lower.There was insufficient evidence to determine whether there was any difference between the groups in the rate of adverse events (risk ratio (RR) 1.74, 95% CI 0.39 to 7.76, three RCTs, n = 167, I 2 = 0%, very low‐quality evidence). Specific PMS symptoms were not reported There may be little or no difference between the groups in response rates. Use of a fixed‐effect model suggested a higher response rate in the acupuncture group than in the sham group (RR 2.59, 95% CI 1.71 to 3.92; participants = 100; studies = 2; I 2 = 82%), but owing to the high heterogeneity we tested the effect of using a random‐effects model, which provided no clear evidence of benefit for acupuncture (RR 4.22, 95% CI 0.45 to 39.88, two RCTs, n = 100, I 2 = 82%, very low‐quality evidence ). Acupuncture may improve quality of life (measured by the WHOQOL‐BREF) compared to sham (MD 2.85, 95% CI 1.47 to 4.23, one RCT, n = 67, l ow‐quality evidence). Acupuncture versus no treatment Due to the very low quality of the evidence, we are uncertain whether acupuncture reduces PMS symptoms compared to a no treatment control (MD ‐13.60, 95% CI ‐15.70 to ‐11.50, one RCT, n = 14 ) . No adverse events were reported in either group. No data were available on specific PMS symptoms, response rate or quality of life outcomes. Acupressure versus sham acupressure We found low‐quality evidence that acupressure may reduce the number of women with moderate to severe PMS symptoms at the end of the trial compared to sham acupressure (RR 0.64 95% CI 0.52 to 0.79, one RCT, n = 90, low‐quality evidence). The evidence suggests that if 97 women out of 100 in the sham acupressure group had moderate to severe PMS symptoms, the number of women in the acupressure group with moderate to severe symptoms would be 50 to 76 women. Acupressure may improve both physical (MD 24.3, 95% CI 17.18 to 31.42, one RCT, n = 90, low‐quality evidence) and mental (MD 17.17, 95% CI 13.08 to 21.26, one RCT, n = 90, low‐quality evidence) quality of life. No data were available on adverse events, specific symptoms or response rates. The limited evidence available suggests that acupuncture and acupressure may improve both physical and psychological symptoms of PMS when compared to a sham control. There was insufficient evidence to determine whether there was a difference between the groups in rates of adverse events.There is no evidence comparing acupuncture or acupressure versus current ISPMD recommended treatments for PMS such as selective serotonin reuptake inhibitors (SSRIs). Further research is required, using validated outcome measures for PMS, adequate blinding and suitable comparator groups reflecting current best practice. |
t159 | Sexually transmitted infections (STI) are a major global cause of acute illness, infertility and death. Every year there are an estimated 499 million new cases of the most common curable STIs (trichomoniasis, chlamydia, syphilis and gonorrhoea), and between two and three million new cases of HIV. The presence of several STIs, including syphilis and herpes can increase the risk of acquiring or transmitting HIV. Partner notification (PN) is a process whereby sexual partners of patients given a diagnosis of STI are informed of their exposure to infection and the need to receive treatment. PN for curable STI may prevent re‐infection of the patient and reduce the risk of complications and further spread. A review update of the research of the strategies of partner notification in people with STI, including human immunodeficiency virus (HIV) infection was conducted by researchers in the Cochrane Collaboration. This review covers four main PN strategies: 1) Patient referral means that the patient tells their sexual partners that they need to be treated, either with (enhanced) or without (simple) additional support to enhance outcomes. 2) Expedited partner therapy means that the patient delivers medication or a prescription for medication to their partner(s) without the need for a medical examination of the partner. 3) Provider referral means that health service personnel notify the partners. 4) Contract referral means that the patient is encouraged to notify partners but health service personnel will contact them if they do not visit the health service by a certain date. Five trials were conducted in developing countries and only two trials were performed among HIV‐positive patients. Expedited partner therapy was more successful than simple patient referral in reducing repeat infection in patients with gonorrhoea, chlamydia or non‐gonococcal urethritis (six trials). Expedited partner therapy and enhanced patient referral resulted in similar levels of repeat infection (three trials). Evidence about the effects of home sampling, where patients with chlamydia received a sample kit for the partner, was inconsistent (three trials). There were too few trials to allow consistent conclusions about the relative effects of provider, contract or other patient referral methods for different STIs. | Partner notification (PN) is the process whereby sexual partners of an index patient are informed of their exposure to a sexually transmitted infection (STI) and the need to obtain treatment. For the person (index patient) with a curable STI, PN aims to eradicate infection and prevent re‐infection. For sexual partners, PN aims to identify and treat undiagnosed STIs. At the level of sexual networks and populations, the aim of PN is to interrupt chains of STI transmission. For people with viral STI, PN aims to identify undiagnosed infections, which can facilitate access for their sexual partners to treatment and help prevent transmission. Objectives To assess the effects of different PN strategies in people with STI, including human immunodeficiency virus (HIV) infection. Search methods We searched electronic databases (the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and EMBASE) without language restrictions. We scanned reference lists of potential studies and previous reviews and contacted experts in the field. We searched three trial registries. We conducted the most recent search on 31 August 2012. Selection criteria Published or unpublished randomised controlled trials (RCTs) or quasi‐RCTs comparing two or more PN strategies. Four main PN strategies were included: patient referral, expedited partner therapy, provider referral and contract referral. Patient referral means that the patient notifies their sexual partners, either with (enhanced patient referral) or without (simple patient referral) additional verbal or written support. In expedited partner therapy, the patient delivers medication or a prescription for medication to their partner(s) without the need for a medical examination of the partner. In provider referral, health service personnel notify the partners. In contract referral, the index patient is encouraged to notify partner, with the understanding that the partners will be contacted if they do not visit the health service by a certain date. Data collection and analysis We analysed data according to paired partner referral strategies. We organised the comparisons first according to four main PN strategies (1. enhanced patient referral, 2. expedited partner therapy, 3. contract referral, 4. provider referral). We compared each main strategy with simple patient referral and then with each other, if trials were available. For continuous outcome measures, we calculated the mean difference (MD) with 95% confidence intervals (CI). For dichotomous variables, we calculated the risk ratio (RR) with 95% CI. We performed meta‐analyses where appropriate. We performed a sensitivity analysis for the primary outcome re‐infection rate of the index patient by excluding studies with attrition of greater than 20%. Two review authors independently assessed the risk of bias and extracted data. We contacted study authors for additional information. We included 26 trials (17,578 participants, 9015 women and 8563 men). Five trials were conducted in developing countries. Only two trials were conducted among HIV‐positive patients. There was potential for selection bias, owing to the methods of allocation used and of performance bias, owing to the lack of blinding in most included studies. Seven trials had attrition of greater than 20%, increasing the risk of bias. The review found moderate‐quality evidence that expedited partner therapy is better than simple patient referral for preventing re‐infection of index patients when combining trials of STIs that caused urethritis or cervicitis (6 trials; RR 0.71, 95% CI 0.56 to 0.89, I 2 = 39%). When studies with attrition greater than 20% were excluded, the effect of expedited partner therapy was attenuated (2 trials; RR 0.8, 95% CI 0.62 to 1.04, I 2 = 0%). In trials restricted to index patients with chlamydia, the effect was attenuated (2 trials; RR 0.90, 95% CI 0.60 to 1.35, I 2 = 22%). Expedited partner therapy also increased the number of partners treated per index patient (three trials) when compared with simple patient referral in people with chlamydia or gonorrhoea (MD 0.43, 95% CI 0.28 to 0.58) or trichomonas (MD 0.51, 95% CI 0.35 to 0.67), and people with any STI syndrome (MD 0.5, 95% CI 0.34 to 0.67). Expedited partner therapy was not superior to enhanced patient referral in preventing re‐infection (3 trials; RR 0.96, 95% CI 0.60 to 1.53, I 2 = 33%, low‐quality evidence). Home sampling kits for partners (four trials) did not result in lower rates of re‐infection in the index case (measured in one trial), or higher numbers of partners elicited (three trials), notified (two trials) or treated (one trial) when compared with simple patient referral. There was no consistent evidence for the relative effects of provider, contract or other patient referral methods. In one trial among men with non‐gonococcal urethritis, more partners were treated with provider referral than with simple patient referral (MD 0.5, 95% CI 0.37 to 0.63). In one study among people with syphilis, contract referral elicited treatment of more partners than provider referral (MD 2.2, 95% CI 1.95 to 2.45), but the number of partners receiving treatment was the same in both groups. Where measured, there was no statistical evidence of differences in the incidence of adverse effects between PN strategies. The evidence assessed in this review does not identify a single optimal strategy for PN for any particular STI. When combining trials of STI causing urethritis or cervicitis, expedited partner therapy was more successful than simple patient referral for preventing re‐infection of the index patient but was not superior to enhanced patient referral. Expedited partner therapy interventions should include all components that were part of the trial intervention package. There was insufficient evidence to determine the most effective components of an enhanced patient referral strategy. There are too few trials to allow consistent conclusions about the relative effects of provider, contract or other patient referral methods for different STIs. More high‐quality RCTs of PN strategies for HIV and syphilis, using biological outcomes, are needed. |
t160 | Unhealthy patterns of consumption of food, alcohol, and tobacco products are important causes of ill health. Changing the availability (the range or amount of options, or both) of these products or their proximity (the distance at which they are positioned) to potential consumers could help people make healthier choices. This review investigated whether altering the availability or proximity of food (including non‐alcoholic beverages), alcohol, and tobacco products changed people's selection (such as purchasing) or consumption of those products. We searched for all available evidence from randomised controlled trials (a type of study in which participants are assigned to one of two or more treatment groups using a random method) to answer this question, and found 24 studies, all of which were conducted in high‐income countries. Six studies involved availability interventions, of which four changed the relative proportion of less‐healthy to healthier options, and two changed the absolute number of different options available. In statistical analyses that combined results from multiple studies, it was found that reducing the number of available options for a particular range or category of food(s) reduced selection of those food products (from analysing 154 participants) and possibly reduced consumption of those products (from 150 participants). However, the certainty of the evidence for these effects was low. Eighteen studies involved proximity interventions. Most (14/18) changed the distance at which a snack food or drink was placed from the participants, whilst four studies changed the order of meal components encountered along a line. One study found that this reduced selection of food (from analysing 41 participants), whilst in a statistical analysis combining results from multiple studies, it was found that placing food farther away reduced consumption of those food products (from analysing 1098 participants). However, the certainty of the evidence for these effects was very low and low, respectively. Mindful of its limitations, the current evidence suggests that changing the number of available food options or changing where foods are positioned could contribute to meaningful changes in behaviour, justifying policy actions to promote such changes to food environments. | Overconsumption of food, alcohol, and tobacco products increases the risk of non‐communicable diseases. Interventions to change characteristics of physical micro‐environments where people may select or consume these products ‐ including shops, restaurants, workplaces, and schools – are of considerable public health policy and research interest. This review addresses two types of intervention within such environments: altering the availability (the range and/or amount of options) of these products, or their proximity (the distance at which they are positioned) to potential consumers. Objectives 1. To assess the impact on selection and consumption of altering the availability or proximity of (a) food (including non‐alcoholic beverages), (b) alcohol, and (c) tobacco products. 2. To assess the extent to which the impact of these interventions is modified by characteristics of: i. studies, ii. interventions, and iii. participants. Search methods We searched CENTRAL, MEDLINE, Embase, PsycINFO, and seven other published or grey literature databases, as well as trial registries and key websites, up to 23 July 2018, followed by citation searches. Selection criteria We included randomised controlled trials with between‐participants (parallel group) or within‐participants (cross‐over) designs. Eligible studies compared effects of exposure to at least two different levels of availability of a product or its proximity, and included a measure of selection or consumption of the manipulated product. Data collection and analysis We used a novel semi‐automated screening workflow and applied standard Cochrane methods to select eligible studies, collect data, and assess risk of bias. In separate analyses for availability interventions and proximity interventions, we combined results using random‐effects meta‐analysis and meta‐regression models to estimate summary effect sizes (as standardised mean differences (SMDs)) and to investigate associations between summary effect sizes and selected study, intervention, or participant characteristics. We rated the certainty of evidence for each outcome using GRADE. We included 24 studies, with the majority (20/24) giving concerns about risk of bias. All of the included studies investigated food products; none investigated alcohol or tobacco. The majority were conducted in laboratory settings (14/24), with adult participants (17/24), and used between‐participants designs (19/24). All studies were conducted in high‐income countries, predominantly in the USA (14/24). Six studies investigated availability interventions, of which two changed the absolute number of different options available, and four altered the relative proportion of less‐healthy (to healthier) options. Most studies (4/6) manipulated snack foods or drinks. For selection outcomes, meta‐analysis of three comparisons from three studies (n = 154) found that exposure to fewer options resulted in a large reduction in selection of the targeted food(s): SMD −1.13 (95% confidence interval (CI) −1.90 to −0.37) (low certainty evidence). For consumption outcomes, meta‐analysis of three comparisons from two studies (n = 150) found that exposure to fewer options resulted in a moderate reduction in consumption of those foods, but with considerable uncertainty: SMD −0.55 (95% CI −1.27 to 0.18) (low certainty evidence). Eighteen studies investigated proximity interventions. Most (14/18) changed the distance at which a snack food or drink was placed from the participants, whilst four studies changed the order of meal components encountered along a line. For selection outcomes, only one study with one comparison (n = 41) was identified, which found that food placed farther away resulted in a moderate reduction in its selection: SMD −0.65 (95% CI −1.29 to −0.01) (very low certainty evidence). For consumption outcomes, meta‐analysis of 15 comparisons from 12 studies (n = 1098) found that exposure to food placed farther away resulted in a moderate reduction in its consumption: SMD −0.60 (95% CI −0.84 to −0.36) (low certainty evidence). Meta‐regression analyses indicated that this effect was greater: the farther away the product was placed; when only the targeted product(s) was available; when participants were of low deprivation status; and when the study was at high risk of bias. The current evidence suggests that changing the number of available food options or altering the positioning of foods could contribute to meaningful changes in behaviour, justifying policy actions to promote such changes within food environments. However, the certainty of this evidence as assessed by GRADE is low or very low. To enable more certain and generalisable conclusions about these potentially important effects, further research is warranted in real‐world settings, intervening across a wider range of foods ‐ as well as alcohol and tobacco products ‐ and over sustained time periods. |
t161 | Roughly half of all hip fractures are outside the hip joint capsule (extracapsular proximal femoral fractures). Many of these will be fixed or stabilised using metal implants which are a combination of screws, rods and plates attached to the thigh bone. Various techniques such as the selective removal of bone (osteotomy), the pressing together of bone fragments (compression), the addition of bone cement, and methods for insertion of nails such as reaming, are used during surgery. This review included 11 randomised or quasi‐randomised trials. The majority of the participants were female, usually aged around 80 years. There were seven comparisons but the evidence for each of these was insufficient to draw conclusions. Thus, the review found that there was too little evidence from randomised trials to show which, if any, specific surgical techniques used during operations for extracapsular proximal femoral fractures are better. | Many different surgical techniques have been described for the internal fixation of extracapsular hip fractures. Objectives To compare different aspects of surgical technique used in operations for internal fixation of extracapsular hip fractures in adults. Search methods We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (January 2008), the Cochrane Central Register of Controlled Trials ( The Cochrane Library 2008, Issue 1), MEDLINE, EMBASE, CINAHL, Current Controlled Trials, orthopaedic journals, conference proceedings and reference lists of articles. Date of last search was January 2008. No language restriction was applied. Selection criteria All randomised and quasi‐randomised trials investigating operative techniques used in operations for the treatment of extracapsular hip fractures in adults. Data collection and analysis Two review authors independently selected trials, assessed trial quality and extracted data. Wherever appropriate, data were pooled. Predominantly older people with trochanteric fractures were treated in the 11 included trials. One trial (65 participants undergoing fixation with a fixed nail‐plate) found no statistically significant differences between osteotomy versus anatomical reduction. Four trials, involving 465 participants undergoing fixation with a sliding hip screw (SHS), compared osteotomy versus anatomical reduction. Osteotomy was associated with an increased operative blood loss and length of surgery. There were no statistically significant differences for mortality, morbidity or measures of anatomical deformity. Two trials (138 participants) compared SHS fixation of a trochanteric hip fracture augmented with cement against a standard fixation. There were no reoperations even for the four cases of fixation failure in the cement group. The cement group had significantly better quality of life scores at six months. One trial (200 participants) comparing compression versus no compression of a trochanteric fracture in conjunction with SHS fixation found no significant differences between the two groups. One trial (120 participants) found a tendency to improved outcomes with a hydroxyapatite coated lag screw, but none reached statistical significance. One trial (19 participants) reported reduced temperatures when using a modified reaming method. Another trial (50 participants) found reduced bone marrow intravascular embolism, detected by oesophageal ultrasound, when a Gamma nail was inserted with a distal pressure venting hole in the femur. There is inadequate evidence to support the use of osteotomy for internal fixation of a trochanteric hip fracture. Similarly, there is insufficient evidence to support the use of the other techniques examined in the trials included in this review. |
t162 | Endometriosis is the presence in inappropriate sites of tissue that normally lines the uterus. It can cause pain and subfertility. Different treatments for endometriosis are available, one of which is laparoscopic ('key hole') surgery, performed to remove visible areas of endometriosis. Cochrane review authors assessed the evidence on the use of laparoscopic surgery to treat pain and fertility problems in women with endometriosis. Laparoscopic surgical techniques include ablation, which means destruction of a lesion (for example by burning), and excision, which means cutting a lesion out. We included 10 randomised controlled trials (involving 973 participants). They were conducted in Australia, Canada, Egypt, Iran and the United Kingdom. Most compared laparoscopic ablation or excision versus diagnostic laparoscopy only. We found that laparoscopic surgery may be of benefit in treating overall pain and subfertility associated with mild to moderate endometriosis. Laparoscopic excision and ablation were similarly effective in relieving pain, although this result came from a single study. | Endometriosis is the presence of endometrial glands or stroma in sites other than the uterine cavity and is associated with pain and subfertility. Surgical interventions aim to remove visible areas of endometriosis and restore the anatomy. Objectives To assess the effectiveness and safety of laparoscopic surgery in the treatment of painful symptoms and subfertility associated with endometriosis. Search methods This review has drawn on the search strategy developed by the Cochrane Menstrual Disorders and Subfertility Group including searching CENTRAL, MEDLINE, EMBASE, PsycINFO, and trial registries from inception to July 2013. Selection criteria Randomised controlled trials (RCTs) were selected in which the effectiveness and safety of laparoscopic surgery used to treat pain or subfertility associated with endometriosis was compared with any other laparoscopic or robotic intervention, holistic or medical treatment or diagnostic laparoscopy only. Data collection and analysis Selection of studies, assessment of trial quality and extraction of relevant data were performed independently by two review authors with disagreements resolved by a third review author. The quality of evidence was evaluated using GRADE methods. Ten RCTs were included in the review. The studies randomised 973 participants experiencing pain or subfertility associated with endometriosis. Five RCTs compared laparoscopic ablation or excision versus diagnostic laparoscopy only. Two RCTs compared laparoscopic excision versus diagnostic laparoscopy only. Two RCTs compared laparoscopic excision versus ablation. One RCT compared laparoscopic ablation versus diagnostic laparoscopy and injectable gonadotropin‐releasing hormone analogue (GnRHa) (goserelin) with add‐back therapy. Common limitations in the primary studies included lack of clearly‐described blinding, failure to fully describe methods of randomisation and allocation concealment, and risk of attrition bias. Laparoscopic surgery was associated with decreased overall pain (measured as ‘pain better or improved’) compared with diagnostic laparoscopy, both at six months (odds ratio (OR) 6.58, 95% CI 3.31 to 13.10, 3 RCTs, 171 participants, I 2 = 0%, moderate quality evidence) and at 12 months (OR 10.00, 95% CI 3.21 to 31.17, 1 RCT, 69 participants, low quality evidence). Compared with diagnostic laparoscopy, laparoscopic surgery was also associated with an increased live birth or ongoing pregnancy rate (OR 1.94, 95% CI 1.20 to 3.16, P = 0.007, 2 RCTs, 382 participants, I 2 = 0%, moderate quality evidence) and increased clinical pregnancy rate (OR 1.89, 95% CI 1.25 to 2.86, P = 0.003, 3 RCTs, 528 participants, I 2 = 0%, moderate quality evidence). Two studies collected data on adverse events (including infection, vascular and visceral injury and conversion to laparotomy) and reported no events in either arm. Other studies did not report this outcome. The similar effect of laparoscopic surgery and diagnostic laparotomy on the rate of miscarriage per pregnancy was imprecise (OR 0.94, 95% CI 0.35 to 2.54, 2 studies, 112 women, moderate quality evidence). When laparoscopic ablation was compared with diagnostic laparoscopy plus medical therapy (GnRHa plus add‐back therapy), more women in the ablation group reported that they were pain free at 12 months (OR 5.63, 95% CI 1.18 to 26.85, 1 RCT, 35 participants, low quality evidence). The difference between laparoscopic ablation and laparoscopic excision in the proportion of women reporting overall pain relief at 12 months on a VAS 0 to 10 pain scale was 0 (95% CI ‐1.22 to 1.22, P = 1.00, 1 RCT, 103 participants, low quality evidence). There is moderate quality evidence that laparoscopic surgery to treat mild and moderate endometriosis reduces overall pain and increases live birth or ongoing pregnancy rates. There is low quality evidence that laparoscopic excision and ablation were similarly effective in relieving pain, although there was only one relevant study. More research is needed considering severe endometriosis, different types of pain associated with endometriosis (for example dysmenorrhoea (pain with menstruation)) and comparing laparoscopic interventions with holistic and medical interventions. There was insufficient evidence on adverse events to allow any conclusions to be drawn regarding safety. |
t163 | At present, doctors are not sure whether women with early cervical cancer who have had their womb and pelvic lymph nodes removed should be given radiotherapy. If the woman has a combination of certain risk factors that put her at high risk of having a recurrence of her cancer, doctors often think that it would be a good idea to give her radiotherapy. However, radiotherapy has never been shown to improve overall survival for these women and the combination of surgery and radiotherapy increases the risk of side effects and complications. We searched for all the available randomised controlled trials (RCTs) that assessed whether radiotherapy (with or without chemotherapy) could improve survival in these women. We found only two trials that compared the use of radiotherapy with no radiotherapy in women with early cervical cancer who had had their womb and pelvic lymph nodes removed and who were at risk of having a recurrence of their cancer. These two trials enrolled 397 women. When we combined the findings from these two trials, we found that, on average, women who received radiotherapy were between 40% and 90% less likely to have a relapse of their cancer within 5 years than women who did not. However, because of the low number of deaths in the trials, we could not confirm whether radiotherapy helped to prolong life: our best estimate was that, 5 years after treatment, women who received radiotherapy were about 20% more likely to be alive than those who did not, but this estimate may not be very accurate and women's actual prospects could be anywhere between being three times more likely to be alive and being 60% more likely to be dead. Although women who had radiotherapy tended to have more complications than women who did not, we could not be sure whether this was due to chance rather than the radiotherapy because few women reported complications. The main limitations of the review were that we did not find any trials that evaluated a combination of radiotherapy and chemotherapy and that the two trials of radiotherapy gave very little information about side effects. | This is an updated version of the original Cochrane review first published in Issue 4, 2009. There is an ongoing debate about the indications for, and value of, adjuvant pelvic radiotherapy after radical surgery in women with early cervical cancer. Certain combinations of pathological risk factors are thought to represent sufficient risk for recurrence, that they justify the use of postoperative pelvic radiotherapy, though this has never been shown to improve overall survival, and use of more than one type of treatment (surgery and radiotherapy) increases the risks of side effects and complications. Objectives To evaluate the effectiveness and safety of adjuvant therapies (radiotherapy, chemotherapy followed by radiotherapy, chemoradiation) after radical hysterectomy for early‐stage cervical cancer (FIGO stages IB1, IB2 or IIA). Search methods For the original review, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), Issue 4, 2008. The Cochrane Gynaecological Cancer Group Trials Register, MEDLINE (January 1950 to November 2008), EMBASE (1950 to November 2008). We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. For this update, we extended the database searches to September 2011 and searched the MetaRegister for ongoing trials. Selection criteria Randomised controlled trials (RCTs) that compared adjuvant therapies (radiotherapy, chemotherapy followed by radiotherapy, or chemoradiation) with no radiotherapy or chemoradiation, in women with a confirmed histological diagnosis of early cervical cancer who had undergone radical hysterectomy and dissection of the pelvic lymph nodes. Data collection and analysis Two review authors independently abstracted data and assessed risk of bias. Information on grade 3 and 4 adverse events was collected from the trials. Results were pooled using random‐effects meta‐analyses. Two RCTs, which compared adjuvant radiotherapy with no adjuvant radiotherapy, met the inclusion criteria; they randomised and assessed 397 women with stage IB cervical cancer. Meta‐analysis of these two RCTs indicated no significant difference in survival at 5 years between women who received radiation and those who received no further treatment (risk ratio (RR) = 0.8; 95% confidence interval (CI) 0.3 to 2.4). However, women who received radiation had a significantly lower risk of disease progression at 5 years (RR 0.6; 95% CI 0.4 to 0.9). Although the risk of serious adverse events was consistently higher if women received radiotherapy rather than no further treatment, these increased risks were not statistically significant, probably because the rate of adverse events was low. We found evidence, of moderate quality, that radiation decreases the risk of disease progression compared with no further treatment, but little evidence that it might improve overall survival, in stage IB cervical cancer. The evidence on serious adverse events was equivocal. |
t164 | Pneumonia is an inflammatory condition of the lungs. Treatment for pneumonia includes antibiotics, rest, fluids, management of complications and professional home care. Oxygen supplementation is one way to help patients who cannot breathe adequately on their own. Management of oxygen supplementation is divided into nasal cannula and mechanical ventilation. Mechanical ventilation is life‐supporting ventilation that involves the use of a machine called a ventilator, or respirator. There are two main types of mechanical ventilation: non‐invasive ventilation (NIV) and invasive ventilation. The former provides ventilatory support to a patient through a tightly fitted facial or nasal mask and the latter through a tube inserted into the windpipe through the mouth or the nose or a hole made in the windpipe through the front of the throat. At present, oxygen therapy for individuals with pneumonia is commonly prescribed. However, inconsistent results on the effects of oxygen therapy on pneumonia have been reported and no systematic review has been conducted in patients with pneumonia to determine which delivery system of oxygen therapy leads to the best clinical outcomes. We searched the related literature and included three randomised controlled trials involving 151 adults with pneumonia aged around 60 years. We did not include patients with pulmonary tuberculosis or cystic fibrosis. We found that NIV can reduce the risk of death in the intensive care unit (ICU) and the need for endotracheal intubation, shorten ICU stay and length of intubation. Some outcomes and complications of oxygen therapy depended upon the delivery system and primary diseases. The most common complications of invasive ventilation are ventilator‐associated pneumonia. However, we must be aware that oxygen therapy is just one of the treatments for pneumonia and the other standard treatments used by physicians are of equal importance. | Oxygen therapy is widely used in the treatment of lung diseases. However, the effectiveness of oxygen therapy as a treatment for pneumonia is not well known. Objectives To determine the effectiveness and safety of oxygen therapy in the treatment of pneumonia in adults older than 18 years. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) 2011, Issue 4, part of The Cochrane Library, www.thecochranelibrary.com (accessed 9 December 2011), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1948 to November week 3, 2011) and EMBASE (1974 to December 2011). Selection criteria Randomised controlled trials (RCTs) of oxygen therapy for adults with community‐acquired pneumonia (CAP) and nosocomial (hospital‐acquired) pneumonia (HAP or NP) in intensive care units (ICU). Data collection and analysis Two review authors independently reviewed abstracts and assessed data for methodological quality. Three RCTs met our inclusion criteria. The studies enrolled 151 participants with CAP or immunosuppressed patients with pulmonary infiltrates. Overall, we found that non‐invasive ventilation can reduce the risk of death in the ICU, odd ratio (OR) 0.28, 95% confidence interval (CI) 0.09 to 0.88; endotracheal intubation, OR 0.26, 95% CI 0.11 to 0.61; complications, OR 0.23, 95% CI 0.08 to 0.70; and shorten ICU length of stay, mean duration (MD) ‐3.28, 95% CI ‐5.41 to ‐1.61. Non‐invasive ventilation and standard oxygen supplementation via a Venturi mask were similar when measuring mortality in hospital, OR 0.54, 95% CI 0.11 to 2.68; two‐month survival, OR 1.67, 95% CI 0.53 to 5.28; duration of hospital stay, MD ‐1.00, 95% CI ‐2.05 to 0.05; and duration of mechanical ventilation, standard MD ‐0.26, 95% CI ‐0.66 to 0.14. Some outcomes and complications of non‐invasive ventilation were varied according to different participant populations. We also found that some subgroups had a high level of heterogeneity when conducting pooled analyses. Non‐invasive ventilation can reduce the risk of death in the ICU, endotracheal intubation, shorten ICU stay and length of intubation. Some outcomes and complications of non‐invasive ventilation were varied according to different participant populations. Other than the oxygen therapy, we must mention the importance of standard treatment by physicians. The evidence is weak and we did not include participants with pulmonary tuberculosis and cystic fibrosis. More RCTs are required to answer these clinical questions. However, the review indicates that non‐invasive ventilation may be more beneficial than standard oxygen supplementation via a Venturi mask for pneumonia. |
t165 | Nonsteroidal anti‐inflammatory drugs and opioids can significantly relieve the pain in acute renal colic, but opioids (especially pethidine) cause more adverse effects Acute renal colic occurs when mineral or organic solids pass though the urinary tract and obstruct the urinary flow. It causes a sudden onset of severe pain, which radiates from the flank to the groin and requires immediate treatment with pain‐killers. It can also cause nausea, vomiting, hypertension and blood in the urine. Opioids and non‐steroidal anti‐inflammatory drugs (NSAIDs) are commonly used to reduce the pain. The review found that both NSAIDs and opioids significantly reduce the pain. People experienced more adverse effects, such as vomiting, when using opioids (particularly pethidine) than when using NSAIDs. | Renal colic is a common cause of acute severe pain. Both opioids and nonsteroidal anti‐inflammatory drugs (NSAIDs) are recommended for treatment, but the relative efficacy of these drugs is uncertain. Objectives To examine the benefits and disadvantages of NSAIDs and opioids for the management of pain in acute renal colic. Search methods We searched the Cochrane Renal Group's specialised register, the Cochrane Central Register of Randomised Controlled Trials (CENTRAL ‐ The Cochrane Library , MEDLINE, EMBASE and handsearched reference lists of retrieved articles. Selection criteria Randomised controlled trials (RCTs) comparing any opioid with any NSAID, regardless of dose or route of administration were included. Data collection and analysis Data was extracted and quality assessed independently by two reviewers, with differences resolved by discussion. Dichotomous outcomes are reported as risk ratio (RR) and measurements on continuous scales are reported as mean differences (MD) with 95% confidence intervals. Subgroup analysis by study quality, drug type and drug route have been performed where possible to explore reasons for heterogeneity. Twenty trials from nine countries with a total of 1613 participants were identified. Both NSAIDs and opioids lead to clinically significant falls in patient‐reported pain scores. Due to unexplained heterogeneity these results could not be pooled although 10/13 studies reported lower pain scores in patients receiving NSAIDs. Patients treated with NSAIDs were significantly less likely to require rescue medication (RR 0.75, 95% CI 0.61 to 0.93, P = 0.007), though most of these trials used pethidine. The majority of trials showed a higher incidence of adverse events in patients treated with opioids, but there was significant heterogeneity between studies so the results could not be pooled. There was significantly less vomiting in patients treated with NSAIDs (RR 0.35, 95% CI 0.23 to 0.53, P < 0.00001). In particular, patients receiving pethidine had a much higher rate of vomiting compared with patients receiving NSAIDs. Gastrointestinal bleeding and renal impairment were not reported. Both NSAIDs and opioids can provide effective analgesia in acute renal colic. Opioids are associated with a higher incidence of adverse events, particularly vomiting. Given the high rate of vomiting associated with the use of opioids, particularly pethidine, and the greater likelihood of requiring further analgesia, we recommend that if an opioid is to be used it should not be pethidine. |
t166 | Acute postoperative pain is one of the most disturbing complaints after open heart surgery. It is related to impaired wound healing, chronic pain, or depression. Psychological treatment is designed to improve participant’ knowledge and to alter surgery‐related mental distress, negative beliefs and noncompliance. It aims to reduce pain and anxiety, and to improve the postoperative recovery after open heart surgery. This is an update of a review previously published in 2014 investigating whether psychological treatment could successfully reduce acute postoperative pain and improve the course of physical and psychological recovery of people undergoing open heart surgery. We found 23 studies, including a total of 2669 participants, which reported effects of psychological treatment compared to a control group without psychological treatment on pain intensity, use of pain medication, mental distress, mobility, or time to extubation after surgery. We do not know if psychological treatment reduces pain intensity, enhances mobility, or decreases intubation time after open heart surgery. This is because there were not enough data to answer some parts of our review question, because there were problems with the design of some studies, or because results were conflicting. | This is an update of a Cochrane review previously published in 2014. Acute postoperative pain is one of the most disturbing complaints in open heart surgery, and is associated with a risk of negative consequences. Several trials investigated the effects of psychological interventions to reduce acute postoperative pain and improve the course of physical and psychological recovery of participants undergoing open heart surgery. Objectives To compare the efficacy of psychological interventions as an adjunct to standard care versus standard care alone or standard care plus attention control in adults undergoing open heart surgery for pain, pain medication, psychological distress, mobility, and time to extubation. Search methods For this update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Web of Science, and PsycINFO for eligible studies up to February 2017. We used the 'related articles' and 'cited by' options of eligible studies to identify additional relevant studies. We checked lists of references of relevant articles and previous reviews. We searched the ProQuest Dissertations and Theses Full Text Database, ClinicalTrials and the WHO International Clinical Trials Registry Platform to identify any unpublished material or ongoing trials. We also contacted the authors of primary studies to identify any unpublished material. In addition, we wrote to all leading heart centres in Germany, Switzerland, and Austria to check whether they were aware of any ongoing trials. Selection criteria Randomised controlled trials comparing psychological interventions as an adjunct to standard care versus standard care alone or standard care plus attention in adults undergoing open heart surgery. Data collection and analysis Two review authors (SZ and SK) independently assessed trials for eligibility, estimated the risk of bias and extracted all data. We calculated effect sizes for each comparison (Hedges’ g) and meta‐analysed data using a random‐effects model. We assessed the evidence using GRADE and created 'Summary of findings' tables. We added six studies to this update. Overall, we included 23 studies (2669 participants). For the majority of outcomes (two‐thirds), we could not perform a meta‐analysis since outcomes were not measured, or data were provided by one trial only. No study reported data on the number of participants with pain intensity reduction of at least 50% from baseline. Only one study reported data on the number of participants below 30/100 mm on the Visual Analogue Scale (VAS) in pain intensity (very low‐quality evidence). Psychological interventions did not reduce pain intensity in the short‐term interval (g 0.39, 95% CI ‐0.18 to 0.96, 2 studies, 104 participants, low‐quality evidence), medium‐term interval (g ‐0.02, 95% CI ‐0.24 to 0.20, 4 studies, 413 participants, moderate‐quality evidence) or in the long‐term interval (g 0.05, 95% CI ‐0.20 to 0.30, 2 studies, 200 participants, moderate‐quality evidence). No study reported data on median time to re‐medication or on number of participants re‐medicated. Only two studies provided data on postoperative analgesic use in the short‐term interval, showing that psychological interventions did not reduce the use of analgesic medication (g 1.18, 95% CI ‐2.03 to 4.39, 2 studies, 104 participants, low‐quality evidence). Studies revealed that psychological interventions reduced mental distress in the medium‐term (g 0.37, 95% CI 0.13 to 0.60, 13 studies, 1388 participants, moderate‐quality evidence) and likewise in the long‐term interval (g 0.32, 95% CI 0.10 to 0.53, 14 studies, 1586 participants, moderate‐quality evidence). Psychological interventions did not improve mobility in the medium‐term interval (g 0.23, 95% CI ‐0.22 to 0.67, 3 studies, 444 participants, low‐quality evidence), nor in the long‐term interval (g 0.09, 95% CI ‐0.10 to 0.28, 4 studies, 458 participants, moderate‐quality evidence). Only two studies reported data on time to extubation, indicating that psychological interventions reduced the time to extubation (g 0.56, 95% CI 0.08 to 1.03, 2 studies, 154 participants, low‐quality evidence). Overall, the very low to moderate quality of the body of evidence on the efficacy of psychological interventions for acute pain after open heart surgery cannot be regarded as sufficient to draw robust conclusions. Most 'Risk of bias' assessments were low or unclear. We judged selection bias (random sequence generation) and attrition bias to be mostly low risk for included studies. However, we judged the risk of selection bias (allocation concealment), performance bias, detection bias and reporting bias to be mostly unclear. In line with the conclusions of our previous review, there is a lack of evidence to support or refute psychological interventions in order to reduce postoperative pain in participants undergoing open heart surgery. We found moderate‐quality evidence that psychological interventions reduced mental distress in participants undergoing open heart surgery. Given the small numbers of studies, it is not possible to draw robust conclusions on the efficacy of psychological interventions on outcomes such as analgesic use, mobility, and time to extubation respectively on adverse events or harms of psychological interventions. |
t167 | We reviewed the evidence about the effects of eculizumab for treating patients with paroxsymal nocturnal hemoglobinuria. Paroxysmal nocturnal hemoglobinuria is a disorder of the hematopoietic stem cells (a cell that can self renew and differentiate into one or more cell types). It is characterized by episodes of intravascular hemolysis (destruction of red blood cells), and chronic hemolytic anemia. The intravascular destruction of red blood cells involves clinical findings in gastrointestinal, cardiovascular, pulmonary, cerebral, and urogenital systems, as well as clotting disorders. The treatment of paroxysmal nocturnal hemoglobinuria has been largely empirical and symptomatic, with packed red blood cell transfusions, anticoagulation, and supplementation with folic acid or iron. Many different pharmacological interventions that are used for treating this medical disorder are not standardized. Eculizumab is a newly available biological agent for preventing hemolytic anemia and severe clotting episodes. We identified one study that included a limited number of patients comparing eculizumab with placebo. The study was published in 2006, and was conducted in the US, Canada, Europe, and Australia with 26 weeks of follow‐up. No patients died during the performance of this single study. The study showed a moderate improvement in the quality of life in patients treated with eculizumab. In addition, eculizumab reduced fatigue and the number of patients that withdrew from the study for any reason. Eculizumab showed a higher proportion of patients with transfusion independence. There was no difference between eculizumab and placebo in terms of adverse events, probably due to the low rate of events observed during the study. The trial did not assess other relevant outcomes such as overall survival, transformation to myelodysplastic syndrome and acute myelogenous leukemia, or development or recurrence of aplastic anemia on treatment. | Paroxysmal nocturnal hemoglobinuria (PNH) is a chronic, not malignant, disease of the hematopoietic stem cells, associated with significant morbidity and mortality. It is a rare disease with an estimated incidence of 1.3 new cases per one million individuals per year. The treatment of PNH has been largely empirical and symptomatic, with blood transfusions, anticoagulation, and supplementation with folic acid or iron. Eculizumab, a biological agent that inhibits complement cascade, was developed for preventing hemolytic anemia and severe thrombotic episodes. Objectives To assess the clinical benefits and harms of eculizumab for treating patients with paroxysmal nocturnal hemoglobinuria (PNH). Search methods We conducted a comprehensive search strategy. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library 2014, Issue 5), Ovid MEDLINE (from 1946 to 15 May 2014), EMBASE (from 1980 to 25 June 2014), and LILACS (from 1982 to 25 June 2014). We did not apply any language restrictions. Selection criteria We included randomized controlled trials (RCTs) irrespective of their publication status or language. No limits were applied with respect to period of follow‐up. We excluded quasi‐RCTs. We included trials comparing eculizumab with placebo or best available therapy. We included any patient with a confirmed diagnosis of PNH. Primary outcome was overall survival. Data collection and analysis We independently performed a duplicate selection of eligible trials, risk of bias assessment, and data extraction. We estimated risk ratios (RRs) and 95% confidence interval (CIs) for dichotomous outcomes, and mean differences (MDs) and 95% CIs for continuous outcomes. We used a random‐effects model for analysis. We identified one multicenter (34 sites) phase III RCT involving 87 participants. The trial compared eculizumab versus placebo, and was conducted in the US, Canada, Europe, and Australia with 26 weeks of follow‐up. This small trial had high risk of bias in many domains (attrition and selective reporting). It was sponsored by a pharmaceutical company. No patients died during the study. By using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (scores can range from 0 to 100, with higher scores on the global health status and functioning scales indicating improvement), the trial showed improvement in health‐related quality of life in patients treated with eculizumab (mean difference (MD) 19.4, 95% CI 8.25 to 30.55; P = 0.0007; low quality of evidence). By using the Functional Assessment of Chronic Illness Therapy Fatigue instrument (scores can range from 0 to 52, with higher scores indicating improvement in fatigue), the trial showed a reduction in fatigue (MD 10.4, 95% CI 9.97 to 10.83; P = 0.00001; moderate quality of evidence) in the eculizumab group compared with placebo. Eculizumab compared with placebo showed a greater proportion of patients with transfusion independence: 51% (22/43) versus 0% (0/44); risk ratio (RR) 46.02, 95% CI 2.88 to 735.53; P = 0.007; moderate quality of evidence; and withdrawal for any reason: 4.7% (2/43) versus 22.72% (10/44); RR 0.20, 95% CI 0.05 to 0.88; P = 0.03; moderate quality of evidence. Due to the low rate of events observed, the included trial did not show any difference between eculizumab and placebo in terms of serious adverse events: 9.3% (4/43) versus 20.4% (9/44); RR 0.15, 95% CI 0.15 to 1.37; P = 0.16; low quality of evidence. We did not observe any difference between intervention and placebo for the most frequent adverse events. One participant receiving placebo showed an episode of thrombosis. The trial did not assess overall survival, transformation to myelodysplastic syndrome and acute myelogenous leukemia, or development or recurrence of aplastic anemia on treatment. This review has detected an absence of evidence for eculizumab compared with placebo for treating paroxysmal nocturnal hemoglobinuria (PNH), in terms of overall survival, nonfatal thrombotic events, transformation to myelodysplastic syndrome and acute myelogenous leukemia, and development and recurrence of aplastic anemia on treatment. Current evidence indicates that compared with placebo, eculizumab increases health‐related quality of life and increases transfusion independence. During the execution of the included trial, no patients died. Furthermore, the intervention seems to reduce fatigue and withdrawals for any reason. The safety profile of eculizumab is unclear. These conclusions are based on one small trial with risk of attrition and selective reporting bias. Therefore, prescription of eculizumab for treating patients with PNH can neither be supported nor rejected, unless new evidence from a large high quality trial alters this conclusion. Therefore, we urge the reader to interpret the trial results with much caution. Future trials on this issue should be conducted according to the SPIRIT statement and reported according to the CONSORT statement by independent investigators, and using the Foundation of Patient‐Centered Outcomes Research recommendations. |
t168 | Colony stimulating factors (CSFs) are naturally occurring hormones that control the production of circulating blood cells by the bone marrow. Some CSFs also release stem cells from the bone marrow into the blood stream; these could help the brain repair itself after stroke. In experiments of stroke, CSFs show the potential to improve disability caused by a stroke. In this analysis, we assessed the effect of CSFs on outcome after stroke using data from clinical trials of people with recent stroke. We included a total of 11 studies and 1275 participants. A higher death rate was observed in participants treated with erythropoietin (EPO) in three trials (782 participants); whether further trials of EPO will be performed early after stroke remains unclear. In eight small trials involving 548 participants, patterns of improvement after a stroke were observed using granulocyte colony stimulating factor (G‐CSF) and further trials are ongoing. Currently, there is insufficient evidence to support the use of CSFs in the treatment of people with recent stroke. | Colony stimulating factors (CSFs), also called haematopoietic growth factors, regulate bone marrow production of circulating red and white cells, and platelets. Some CSFs also mobilise the release of bone marrow stem cells into the circulation. CSFs have been shown to be neuroprotective in experimental stroke. Objectives To assess (1) the safety and efficacy of CSFs in people with acute or subacute ischaemic or haemorrhagic stroke, and (2) the effect of CSFs on circulating stem and blood cell counts. Search methods We searched the Cochrane Stroke Group Trials Register (last searched September 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library 2012, Issue 4), MEDLINE (1985 to September 2012), EMBASE (1985 to September 2012) and Science Citation Index (1985 to September 2012). In an attempt to identify further published, unpublished and ongoing trials we contacted manufacturers and principal investigators of trials (last contacted April 2012). We also searched reference lists of relevant articles and reviews. Selection criteria We included randomised controlled trials recruiting people with acute or subacute ischaemic or haemorrhagic stroke. CSFs included stem cell factor (SCF), erythropoietin (EPO), granulocyte colony stimulating factor (G‐CSF), granulocyte‐macrophage colony stimulating factor (GM‐CSF), macrophage‐colony stimulating factor (M‐CSF, CSF‐1), thrombopoietin (TPO), or analogues of these. The primary outcome was functional outcome at the end of the trial. Secondary outcomes included safety at the end of treatment, death at the end of follow‐up, infarct volume and haematology measures. Data collection and analysis Two review authors (TE and NS) independently extracted data and assessed trial quality. We contacted study authors for additional information. We included a total of 11 studies involving 1275 participants. In three trials (n = 782), EPO therapy was associated with a significant increase in death by the end of the trial (odds ratio (OR) 1.98, 95% confidence interval (CI) 1.19 to 3.3, P = 0.009) and a non‐significant increase in serious adverse events. EPO significantly increased the red cell count with no effect on platelet or white cell count, or infarct volume. Two small trials of carbamylated EPO have been completed but have yet to be reported. We included eight small trials (n = 548) of G‐CSF. G‐CSF was associated with a non‐significant reduction in early impairment (mean difference (MD) ‐0.4, 95% CI ‐1.82 to 1.01, P = 0.58) but had no effect on functional outcome at the end of the trial. G‐CSF significantly elevated the white cell count and the CD34+ cell count, but had no effect on infarct volume. Further trials of G‐CSF are ongoing. There are significant safety concerns regarding EPO therapy for stroke. It is too early to know whether other CSFs improve functional outcome. |
t169 | Traditional Chinese Medicine has been practised for over 2000 years in China and the Far East, especially in Korea and Japan, it is a relatively new form of treament for physical and psychological conditions in the West. Acupuncture inserts needles into the skin to stimulate specific points of the body (acupoints). The aim is to achieve balance and harmony of the body. Schizophrenia is a serious mental illness and is usually treated using antipsychotic medication. However, although effective, antipsychotic medication can cause side‐effects (such as sleepiness, weight gain and even dribbling). Acupuncture has been shown to have very few negative effects on the individual and could be more socially acceptable and tolerable for people with mental health problems. Acupuncture may also be less expensive than drugs made by pharmaceutical companies, so reducing costs to individuals and health services. This reviews looks at the effectiveness of various types of acupuncture as treatment for people with schizophrenia. An update search for studies was carried out in 2012 and found 30 studies that randomised participants who were receiving antipsychotic medication to receive additional acupuncture or standard care. Although some of the studies did favour acupuncture when combined with antipsychotics, the information available was small scale and rated to be very low or low quality by the review authors, so not completely provable and valid. Depression was reduced when combining acupuncture with antipsychotic medication, but again this finding came from small‐scale research, so cannot be clearly shown to be true. The review concludes that people with mental health problems, policy makers and health professionals need much better evidence in order to establish if there are any potential benefits to acupuncture. This means that the question of whether acupuncture is of benefit to people, and whether it is of greater benefit than antipsychotic medication, remains unanswered. There is not enough information to establish that acupuncture is of benefit or harm to people with mental health problems. | Acupuncture, with many categories such as traditional acupuncture, electroacupuncture, laser acupuncture, and acupoint injection, has been shown to be relatively safe with few adverse effects. It is accessible and inexpensive, at least in China, and is likely to be widely used there for psychotic symptoms. Objectives To review the effects of acupuncture, alone or in combination treatments compared with placebo (or no treatment) or any other treatments for people with schizophrenia or related psychoses. Search methods We searched Cochrane Schizophrenia Group’s Trials Register (February 2012), which is based on regular searches of CINAHL, BIOSIS, AMED, EMBASE, PubMed, MEDLINE, PsycINFO and clinical trials registries. We also inspected references of identified studies and contacted relevant authors for additional information. Selection criteria We included all relevant randomised controlled trials involving people with schizophrenia‐like illnesses, comparing acupuncture added to standard dose antipsychotics with standard dose antipsychotics alone, acupuncture added to low dose antipsychotics with standard dose antipsychotics, acupuncture with antipsychotics, acupuncture added to Traditional Chinese Medicine (TCM) drug with TCM drug, acupuncture with TCM drug, electric acupuncture convulsive therapy with electroconvulsive therapy. Data collection and analysis We reliably extracted data from all included studies, discussed any disagreement, documented decisions and contacted authors of studies when necessary. We analysed binary outcomes using a standard estimation of risk ratio (RR) and its 95% confidence interval (CI). For continuous data, we calculated mean differences with 95% CI. For homogeneous data we used fixed‐effect model. We assessed risk of bias for included studies and created 'Summary of findings' tables using GRADE. After an update search in 2012 the review now includes 30 studies testing different forms of acupuncture across six different comparisons. All studies were at moderate risk of bias. When acupuncture plus standard antipsychotic treatment was compared with standard antipsychotic treatment alone, people were at less risk of being 'not improved' (n = 244, 3 RCTs, medium‐term RR 0.40 CI 0.28 to 0.57, very low quality evidence ). Mental state findings were mostly consistent with this finding as was time in hospital (n = 120, 1 RCT, days MD ‐16.00 CI ‐19.54 to ‐12.46, moderate quality evidence ). If anything, adverse effects were less for the acupuncture group (e.g. central nervous system, insomnia, short‐term, n = 202, 3 RCTs, RR 0.30 CI 0.11 to 0.83, low quality evidence ). When acupuncture was added to low dose antipsychotics and this was compared with standard dose antipsychotic drugs, relapse was less in the experimental group (n = 170, 1 RCT, long‐term RR 0.57 CI 0.37 to 0.89, very low quality evidence ) but there was no difference for the outcome of 'not improved'. Again, mental state findings were mostly consistent with the latter. Incidences of extrapyramidal symptoms ‐ akathisia, were less for those in the acupuncture added to low dose antipsychotics group (n = 180, 1 RCT, short‐term RR 0.03 CI 0.00 to 0.49, low quality evidence ) ‐ as dry mouth, blurred vision and tachycardia. When acupuncture was compared with antipsychotic drugs of known efficacy in standard doses, there were equivocal data for outcomes such as 'not improved' using different global state criteria. Traditional acupuncture added to TCM drug had benefit over use of TCM drug alone (n = 360, 2 RCTs, RR no clinically important change 0.11 CI 0.02 to 0.59, low quality evidence ), but when traditional acupuncture was compared with TCM drug directly there was no significant difference in the short‐term. However, we found that participants given electroacupuncture were significantly less likely to experience a worsening in global state (n = 88, 1 RCT, short‐term RR 0.52 CI 0.34 to 0.80, low quality evidence ). In the one study that compared electric acupuncture convulsive therapy with electroconvulsive therapy there were significantly different rates of spinal fracture between the groups (n = 68, 1 RCT, short‐term RR 0.33 CI 0.14 to 0.81, low quality evidence ). Attrition in all studies was minimal. No studies reported death, engagement with services, satisfaction with treatment, quality of life, or economic outcomes. Limited evidence suggests that acupuncture may have some antipsychotic effects as measured on global and mental state with few adverse effects. Better designed large studies are needed to fully and fairly test the effects of acupuncture for people with schizophrenia. |
t170 | We reviewed the evidence about the effect of blood pressure control to prevent diabetic retinopathy and/or to slow progression of diabetic retinopathy. Diabetes is characterized by high levels of blood glucose (sugar circulating in the blood) and is classified as either type 1 or type 2, depending on the underlying cause of increased blood glucose. A common complication in people with diabetes is diabetic retinopathy, often called 'diabetic eye disease,' which affects the blood vessels in the back of the eye. Diabetic retinopathy is a major cause of poor vision and blindness worldwide among adults of working age. Research has shown that control of blood glucose reduces the risk of diabetic retinopathy and prevents worsening of the condition once it develops. However, the current diabetes epidemic suggests that the rates of new and worsening diabetic retinopathy will increase without effective means of prevention and treatment in addition to blood glucose control. Simultaneous treatment to reduce blood pressure among diabetics has been suggested as one approach. We found 15 randomized controlled trials, conducted primarily in North America and Europe, to investigate the effects of methods to lower blood pressure (drug‐based in 14 trials; lifestyle change in 1 trial) in 4157 type 1 and 9512 type 2 diabetics, ranging from 16 to 2130 participants in individual trials. The follow‐up period ranged from one to nine years for included trials. Of the 15 trials, six were funded in full by one or more drug companies. Seven more studies received drug company support, usually in the form of study medications. The remaining two studies were conducted with support from government‐sponsored grants and institutional support. Overall, the included trials provided modest support for lowering blood pressure to prevent diabetic retinopathy, regardless of diabetes type or baseline blood pressure level. However, the evidence did not indicate that lowering blood pressure kept diabetic retinopathy from worsening once it had developed or that it prevented advanced stages of diabetic retinopathy that required laser or other treatment of affected eyes. Treatment to reduce the blood pressure of people with diabetes is warranted for other health reasons, but the available evidence does not justify reduction of blood pressure solely to prevent or slow diabetic retinopathy. | Diabetic retinopathy is a common complication of diabetes and a leading cause of visual impairment and blindness. Research has established the importance of blood glucose control to prevent development and progression of the ocular complications of diabetes. Simultaneous blood pressure control has been advocated for the same purpose, but findings reported from individual studies have supported varying conclusions regarding the ocular benefit of interventions on blood pressure. Objectives The primary aim of this review was to summarize the existing evidence regarding the effect of interventions to control or reduce blood pressure levels among diabetics on incidence and progression of diabetic retinopathy, preservation of visual acuity, adverse events, quality of life, and costs. A secondary aim was to compare classes of anti‐hypertensive medications with respect to the same outcomes. Search methods We searched a number of electronic databases including CENTRAL as well as ongoing trial registries. We last searched the electronic databases on 25 April 2014. We also reviewed reference lists of review articles and trial reports selected for inclusion. In addition, we contacted investigators of trials with potentially pertinent data. Selection criteria We included in this review randomized controlled trials (RCTs) in which either type 1 or type 2 diabetic participants, with or without hypertension, were assigned randomly to intense versus less intense blood pressure control, to blood pressure control versus usual care or no intervention on blood pressure, or to different classes of anti‐hypertensive agents versus placebo. Data collection and analysis Pairs of review authors independently reviewed titles and abstracts from electronic and manual searches and the full text of any document that appeared to be relevant. We assessed included trials independently for risk of bias with respect to outcomes reported in this review. We extracted data regarding trial characteristics, incidence and progression of retinopathy, visual acuity, quality of life, and cost‐effectiveness at annual intervals after study entry whenever provided in published reports and other documents available from included trials. We included 15 RCTs, conducted primarily in North America and Europe, that had enrolled 4157 type 1 and 9512 type 2 diabetic participants, ranging from 16 to 2130 participants in individual trials. In 10 of the 15 RCTs, one group of participants was assigned to one or more anti‐hypertensive agents and the control group received placebo. In three trials, intense blood pressure control was compared to less intense blood pressure control. In the remaining two trials, blood pressure control was compared with usual care. Five of the 15 trials enrolled type 1 diabetics, and 10 trials enrolled type 2 diabetics. Six trials were sponsored entirely by pharmaceutical companies, seven trials received partial support from pharmaceutical companies, and two studies received support from government‐sponsored grants and institutional support. Study designs, populations, interventions, and lengths of follow‐up (range one to nine years) varied among the included trials. Overall, the quality of the evidence for individual outcomes was low to moderate. For the primary outcomes, incidence and progression of retinopathy, the quality of evidence was downgraded due to inconsistency and imprecision of estimates from individual studies and differing characteristics of participants. For primary outcomes among type 1 diabetics, one of the five trials reported incidence of retinopathy and one trial reported progression of retinopathy after 4 to 5 years of treatment and follow‐up; four of the five trials reported a combined outcome of incidence and progression over the same time interval. Among type 2 diabetics, 5 of the 10 trials reported incidence of diabetic retinopathy and 3 trials reported progression of retinopathy; one of the 10 trials reported a combined outcome of incidence and progression during a 4‐ to 5‐year follow‐up period. One trial in which type 2 diabetics participated had reported no primary (or secondary) outcome targeted for this review. The evidence from these trials supported a benefit of more intensive blood pressure control intervention with respect to 4‐ to 5‐year incidence of diabetic retinopathy (estimated risk ratio (RR) 0.80; 95% confidence interval (CI) 0.71 to 0.92) and the combined outcome of incidence and progression (estimated RR 0.78; 95% CI 0.63 to 0.97). The available evidence provided less support for a benefit with respect to 4‐ to 5‐year progression of diabetic retinopathy (point estimate was closer to 1 than point estimates for incidence and combined incidence and progression, and the CI overlapped 1; estimated RR 0.88; 95% CI 0.73 to 1.05). The available evidence regarding progression to proliferative diabetic retinopathy or clinically significant macular edema or moderate to severe loss of best‐corrected visual acuity did not support a benefit of intervention on blood pressure: estimated RRs and 95% CIs 0.95 (0.83 to 1.09) and 1.06 (0.85 to 1.33), respectively, after 4 to 5 years of follow‐up. Findings within subgroups of trial participants (type 1 and type 2 diabetics; participants with normal blood pressure levels at baseline and those with elevated levels) were similar to overall findings. The adverse event reported most often (7 of 15 trials) was death, yielding an estimated RR 0.86 (95% CI 0.64 to 1.14). Hypotension was reported from three trials; the estimated RR was 2.08 (95% CI 1.68 to 2.57). Other adverse ocular events were reported from single trials. Hypertension is a well‐known risk factor for several chronic conditions in which lowering blood pressure has proven to be beneficial. The available evidence supports a beneficial effect of intervention to reduce blood pressure with respect to preventing diabetic retinopathy for up to 4 to 5 years. However, the lack of evidence to support such intervention to slow progression of diabetic retinopathy or to prevent other outcomes considered in this review, along with the relatively modest support for the beneficial effect on incidence, weakens the conclusion regarding an overall benefit of intervening on blood pressure solely to prevent diabetic retinopathy. |
t171 | People with schizophrenia often hear voices and see things (hallucinations) and have strange beliefs (delusions). The main treatment for these symptoms of schizophrenia is antipsychotic drugs. Zuclopenthixol is an older antipsychotic drug, first introduced in 1962, that has three distinct formulations zuclopenthixol dihydrochloride, zuclopenthixol acetate (or Acuphase), and zuclopenthixol decanoate. Although zuclopenthixol has been in common use for many years, no previous systematic review of its effectiveness compared to placebo (‘dummy’ treatment) in schizophrenia has been undertaken. Given the widespread use of this drug, it is important to look at the effectiveness of all three formulations of this commonly‐used drug so that health professionals, policy makers and people with schizophrenia can make better‐informed choices. Overall the quality of these studies was low, with small numbers of people and significant bias. Only short‐term information and data could be found, and only about zuclopenthixol dihydrochloride. The information is very limited but suggests that zuclopenthixol can lead to improvement in global state in comparison with placebo. However, there is also increased risk of side effects such as sedation,and tiredness. | Zuclopenthixol is an older antipsychotic that has three distinct formulations (zuclopenthixol dihydrochloride, zuclopenthixol acetate or Acuphase and zuclopenthixol decanoate). Although it has been in common use for many years no previous systematic review of its efficacy compared to placebo in schizophrenia has been undertaken. Objectives To evaluate the effectiveness of all formulations of zuclopenthixol when compared with a placebo in schizophrenia. Search methods On 6 November 2013 and 20 October 2015, we searched the Cochrane Schizophrenia Group Trials Register, which is based on regular searches of MEDLINE, EMBASE, CINAHL, BIOSIS, AMED, PubMed, PsycINFO, and registries of clinical trials. We also checked the references of all included studies and contacted authors of included studies for relevant studies and data. Selection criteria We included all randomised controlled trials comparing zuclopenthixol of any form with placebo for treatment of schizophrenia or schizophrenia‐like psychoses. Data collection and analysis We extracted and cross‐checked data independently. We identified only a small number of studies so we cross checked all studies. We calculated fixed‐effect relative risks (RR) and 95% confidence intervals (CI) for dichotomous data. We analysed by intention‐to‐treat. Where possible we converted continuous outcomes into dichotomous outcomes. When this was not possible we used mean differences (MD) for continuous variables. We assessed risk of bias for included studies and used GRADE (Grading of Recommendations Assessment, Development and Evaluation) to create a 'Summary of findings' table. Only two studies, with a total of 65 participants, were eligible for inclusion in the review. Overall the quality of the two studies was low, with small study populations and significant sources of bias, so we were not able to use all the data in our comparisons. . The studies were old from 1968 and 1972, and would be unlikely to pass modern peer review standard. We were only able to find short‐term data and only trials randomising zuclopenthixol dihydrochloride. We also hoped to identify data for zuclopenthixol acetate versus placebo and zuclopenthixol decanoate versus placebo comparisons. We were unable to identify any studies that included data on these two fairly widely used drugs. For our primary outcome of interest, clinically significant improvement, we found one study that provided useable data. Global state measured by clinical global impression scale (CGI) improvement showed different ratings when assessed by a psychiatrist or a nurse.The psychiatrist scores failed to achieve statistical significance, however when assessed by nursing staff, the difference favouring zuclopenthixol did reach statistical significance (1 RCT n = 29, RR 2.57 95% CI 1.06 to 6.20, very low quality data). There was also evidence of increased sedation with those treated with zuclopenthixol when compared with placebo (1 RCT n = 29, RR 4.67 95% CI 1.23 to 17.68, very low quality data). 'Leaving the study early' data were equivocal. No useable data were available for outcomes such as relapse, mental state, death, quality of life, service use or economic costs. For people with schizophrenia this review shows that zuclopenthixol dihydrochloride may help with the symptoms of schizophrenia. The review provides some trial evidence that, if taking zuclopenthixol dihydrochloride, people may experience some adverse effects and sedation compared with placebo. However this evidence is of very low quality and with some significant sources of bias. There are no data for zuclopenthixol decanoate or zuclopenthixol acetate. For clinicians, the available trial data on the absolute effectiveness of zuclopenthixol dihydrochloride do support its use but the limited nature of the data and significant sources of bias make conclusions hard to draw. Zuclopenthixol in all three forms is a commonly used antipsychotic and it is disappointing that there are so few data regarding its use. |
t172 | We reviewed the effects of bronchial thermoplasty in people with asthma. Asthma is a chronic condition in which people experience symptoms of breathlessness, wheezing, coughing and chest tightness due to airway inflammation and airway muscle contraction. With inhaled treatments, including bronchodilators (drugs that relax airway muscle and so open up the airways) and steroids (which treat underlying inflammation in the lungs), symptoms usually can be controlled. However, for some people, asthma cannot be adequately controlled with these drugs, either because they are truly resistant or because they do not take them. The muscle in the airways of the lungs is thicker in people with asthma than in people who do not have asthma. During asthma attacks, these muscles tighten, making it hard to breathe. Bronchial thermoplasty is a relatively new procedure that reduces the amount of muscle bulk in the airways of the lungs. A long flexible tube, called a bronchoscope, is passed down into the lung under direct observation, and the walls of specific areas of the lungs are heated to 65 degrees Celsius. This causes some of the muscle to break up, making it harder for the muscles to tighten. Generally, three sessions of treatment are given. We found three trials comparing groups of adults treated with bronchial thermoplasty versus adults who received standard medical treatment or a "sham" (simulated) bronchial thermoplasty treatment. These studies showed moderate improvement only in quality of life of patients treated with bronchial thermoplasty and in the number of asthma attacks (exacerbations) that they experienced. In addition, patients treated with this procedure had more respiratory problems than patients who received the alternative intervention during the period when they were undergoing treatment, resulting in increased risk of hospitalisation due to a respiratory symptom during this phase, but not afterward. | Bronchial thermoplasty is a procedure that consists of the delivery of controlled radiofrequency‐generated heat via a catheter inserted into the bronchial tree of the lungs through a flexible bronchoscope. It has been suggested that bronchial thermoplasty works by reducing airway smooth muscle, thereby reducing the ability of the smooth muscle to bronchoconstrict. This treatment could then reduce asthma symptoms and exacerbations, resulting in improved asthma control and quality of life. Objectives To determine the efficacy and safety of bronchial thermoplasty in adults with bronchial asthma. Search methods We searched the Cochrane Airways Group Specialised Register of Trials (CAGR) up to January 2014. Selection criteria We included randomised controlled clinical trials that compared bronchial thermoplasty versus any active control in adults with moderate or severe persistent asthma. Our primary outcomes were quality of life, asthma exacerbations and adverse events. Data collection and analysis Two review authors independently extracted data and assessed risk of bias. We included three trials (429 participants) with differences regarding their design (two trials compared bronchial thermoplasty vs medical management and the other compared bronchial thermoplasty vs a sham intervention) and participant characteristics; one of the studies included participants with more symptomatic asthma compared with the others. The pooled analysis showed improvement in quality of life at 12 months in participants who received bronchial thermoplasty that did not reach the threshold for clinical significance (3 trials, 429 participants; mean difference (MD) in Asthma Quality of Life Questionnaire (AQLQ) scores 0.28, 95% confidence interval (CI) 0.07 to 0.50; moderate‐quality evidence). Measures of symptom control showed no significant differences (3 trials, 429 participants; MD in Asthma Control Questionnaire (ACQ) scores ‐0.15, 95% CI ‐0.40 to 0.10; moderate‐quality evidence). The risk of bias for these outcomes was high because two of the studies did not have a sham intervention for the control group. The results from two trials showed a lower rate of exacerbation after 12 months of treatment for participants who underwent bronchial thermoplasty. The trial with sham intervention showed a significant reduction in the proportion of participants visiting the emergency department for respiratory symptoms, from 15.3% on sham treatment to 8.4% over 12 months following thermoplasty. The trials showed no significant improvement in pulmonary function parameters (with the exception of a greater increase in morning peak expiratory flow (PEF) in one trial). Treated participants who underwent bronchial thermoplasty had a greater risk of hospitalisation for respiratory adverse events during the treatment period (3 trials, 429 participants; risk ratio 3.50, 95% CI 1.26 to 9.68; high‐quality evidence), which represents an absolute increase from 2% to 8% (95% CI 3% to 23%) over the treatment period. This means that six of 100 participants treated with thermoplasty (95% CI 1 to 21) would require an additional hospitalisation over the treatment period. No significant difference in the risk of hospitalisation was noted at the end of the treatment period. Bronchial thermoplasty was associated with an increase in respiratory adverse events, mainly during the treatment period. Most of these events were mild or moderate, appeared in the 24‐hour post‐treatment period, and were resolved within a week. Bronchial thermoplasty for patients with moderate to severe asthma provides a modest clinical benefit in quality of life and lower rates of asthma exacerbation, but no significant difference in asthma control scores. The quality of life findings are at risk of bias, as the main benefits were seen in the two studies that did not include a sham treatment arm. This procedure increases the risk of adverse events during treatment but has a reasonable safety profile after completion of the bronchoscopies. The overall quality of evidence regarding this procedure is moderate. For clinical practice, it would be advisable to collect data from patients systematically in independent clinical registries. Further research should provide better understanding of the mechanisms of action of bronchial thermoplasty, as well as its effect in different asthma phenotypes or in patients with worse lung function. |
t173 | Respiratory distress syndrome (RDS) is the most common cause of disease and death in babies born before 34 weeks' gestation. Intermittent positive pressure ventilation (IPPV) has been the standard way of helping these babies breathe. A simpler method of assisting breathing is to provide continuous distending pressure of the lung, either as continuous positive pressure to the airway or as continuous negative pressure (partial vacuum). The source of distending pressure was a negative pressure chamber in two studies, face mask continuous positive airway pressure (CPAP) in two studies, nasal CPAP in one study and negative pressure for less severe illness and endotracheal CPAP when more severe in another study. The studies were small, and four of the six were conducted before surfactant therapy was available. The review of trials found that outcomes for babies were improved. Fewer required IPPV and fewer died, and with these two outcomes combined, fewer babies died or required IPPV. It was also found that CDP can increase the rate of pneumothorax (air outside the lung within the chest cavity). Some meaningful benefits were found when continuous distending pressure (CDP) was used for respiratory distress syndrome in preterm babies. | Respiratory distress syndrome (RDS) is the single most important cause of morbidity and mortality in preterm infants. In infants with progressive respiratory insufficiency, intermittent positive pressure ventilation (IPPV) with surfactant is the standard treatment for the condition, but it is invasive, potentially resulting in airway and lung injury. Continuous distending pressure (CDP) has been used for the prevention and treatment of RDS, as well as for the prevention of apnoea, and in weaning from IPPV. Its use in the treatment of RDS might reduce the need for IPPV and its sequelae. Objectives To determine the effect of continuous distending pressure (CDP) on the need for IPPV and associated morbidity in spontaneously breathing preterm infants with respiratory distress. Subgroup analyses were planned on the basis of birth weight (> or < 1000 or 1500 g), gestational age (groups divided at about 28 weeks and 32 weeks), methods of application of CDP (i.e. CPAP and CNP), application early versus late in the course of respiratory distress and high versus low pressure CDP and application of CDP in tertiary compared with non‐tertiary hospitals, with the need for sensitivity analysis determined by trial quality. At the 2008 update, the objectives were modified to include preterm infants with respiratory failure. Search methods We used the standard search strategy of the Neonatal Review Group. This included searches of the Oxford Database of Perinatal Trials, the Cochrane Central Register of Controlled Trials (CENTRAL, 2015 Issue 4), MEDLINE (1966 to 30 April 2015) and EMBASE (1980 to 30 April 2015) with no language restriction, as well as controlled‐trials.com, clinicaltrials.gov and the International Clinical Trials Registry Platform of the World Health Organization (WHO). Selection criteria All random or quasi‐random trials of preterm infants with respiratory distress were eligible. Interventions were continuous distending pressure including continuous positive airway pressure (CPAP) by mask, nasal prong, nasopharyngeal tube or endotracheal tube, or continuous negative pressure (CNP) via a chamber enclosing the thorax and the lower body, compared with spontaneous breathing with oxygen added as necessary. Data collection and analysis We used standard methods of The Cochrane Collaboration and its Neonatal Review Group, including independent assessment of trial quality and extraction of data by each review author. We included six studies involving 355 infants ‐ two using face mask CPAP, two CNP, one nasal CPAP and one both CNP (for less ill babies) and endotracheal CPAP (for sicker babies). For this update, we included no new trials. Continuous distending pressure (CDP) is associated with lower risk of treatment failure (death or use of assisted ventilation) (typical risk ratio (RR) 0.65, 95% confidence interval (CI) 0.52 to 0.81; typical risk difference (RD) ‐0.20, 95% CI ‐0.29 to ‐0.10; number needed to treat for an additional beneficial outcome (NNTB) 5, 95% CI 4 to 10; six studies; 355 infants), lower overall mortality (typical RR 0.52, 95% CI 0.32 to 0.87; typical RD ‐0.15, 95% CI ‐0.26 to ‐0.04; NNTB 7, 95% CI 4 to 25; six studies; 355 infants) and lower mortality in infants with birth weight above 1500 g (typical RR 0.24, 95% CI 0.07 to 0.84; typical RD ‐0.28, 95% CI ‐0.48 to ‐0.08; NNTB 4, 95% CI 2.00 to 13.00; two studies; 60 infants). Use of CDP is associated with increased risk of pneumothorax (typical RR 2.64, 95% CI 1.39 to 5.04; typical RD 0.10, 95% CI 0.04 to 0.17; number needed to treat for an additional harmful outcome (NNTH) 17, 95% CI 17.00 to 25.00; six studies; 355 infants). We found no difference in bronchopulmonary dysplasia (BPD), defined as oxygen dependency at 28 days (three studies, 260 infants), as well as no difference in outcome at nine to 14 years (one study, 37 infants). In preterm infants with respiratory distress, the application of CDP as CPAP or CNP is associated with reduced respiratory failure and mortality and an increased rate of pneumothorax. Four out of six of these trials were done in the 1970s. Therefore, the applicability of these results to current practice is difficult to assess. Further research is required to determine the best mode of administration. |
t174 | In areas where malaria is common, younger children have repeated episodes of malarial illness, which can sometimes be severe and life‐threatening. In areas where malaria is seasonal, a practical policy option is to give drugs to prevent malaria at regular intervals during the transmission season, regardless of wether the child has malaria symptoms or not. This is known as Intermittent Preventive Treatment (IPTc). The authors identified seven trials (12,589 participants); all were conducted in West Africa, and six of seven trials were restricted to children aged less than 5 years. The results show IPTc prevents three quarters of all malaria episodes, including severe episodes, and probably prevents some deaths. Several antimalarial drugs or combinations have been tried, and shown to be effective. The most studied is amodiaquine plus sulphadoxine‐pyrimethamine (AQ+SP). This combination probably doesn't have serious side effects but does cause vomiting in some children. | In malaria endemic areas, pre‐school children are at high risk of severe and repeated malaria illness. One possible public health strategy, known as Intermittent Preventive Treatment in children (IPTc), is to treat all children for malaria at regular intervals during the transmission season, regardless of whether they are infected or not. Objectives To evaluate the effects of IPTc to prevent malaria in preschool children living in endemic areas with seasonal malaria transmission. Search methods We searched the Cochrane Infectious Diseases Group Specialized Register (July 2011), CENTRAL ( The Cochrane Library 2011, Issue 6), MEDLINE (1966 to July 2011), EMBASE (1974 to July 2011), LILACS (1982 to July 2011), m RCT (July 2011), and reference lists of identified trials. We also contacted researchers working in the field for unpublished and ongoing trials. Selection criteria Individually randomized and cluster‐randomized controlled trials of full therapeutic dose of antimalarial or antimalarial drug combinations given at regular intervals compared with placebo or no preventive treatment in children aged six years or less living in an area with seasonal malaria transmission. Data collection and analysis Two authors independently assessed eligibility, extracted data and assessed the risk of bias in the trials. Data were meta‐analysed and measures of effects (ie rate ratio, risk ratio and mean difference) are presented with 95% confidence intervals (CIs). The quality of evidence was assessed using the GRADE methods. Seven trials (12,589 participants), including one cluster‐randomized trial, met the inclusion criteria. All were conducted in West Africa, and six of seven trials were restricted to children aged less than 5 years. IPTc prevents approximately three quarters of all clinical malaria episodes (rate ratio 0.26; 95% CI 0.17 to 0.38; 9321 participants, six trials, high quality evidence ), and a similar proportion of severe malaria episodes (rate ratio 0.27, 95% CI 0.10 to 0.76; 5964 participants, two trials, high quality evidence ). These effects remain present even where insecticide treated net (ITN) usage is high (two trials, 5964 participants, high quality evidence ). IPTc probably produces a small reduction in all‐cause mortality consistent with the effect on severe malaria, but the trials were underpowered to reach statistical significance (risk ratio 0.66, 95% CI 0.31 to 1.39, moderate quality evidence). The effect on anaemia varied between studies, but the risk of moderately severe anaemia is probably lower with IPTc (risk ratio 0.71, 95% CI 0.52 to 0.98; 8805 participants, five trials, moderate quality evidence ). Serious drug‐related adverse events, if they occur, are probably rare, with none reported in the six trials (9533 participants, six trials, moderate quality evidence). Amodiaquine plus sulphadoxine‐pyrimethamine is the most studied drug combination for seasonal chemoprevention. Although effective, it causes increased vomiting in this age‐group (risk ratio 2.78, 95% CI 2.31 to 3.35; two trials, 3544 participants, high quality evidence ). When antimalarial IPTc was stopped, no rebound increase in malaria was observed in the three trials which continued follow‐up for one season after IPTc. In areas with seasonal malaria transmission, giving antimalarial drugs to preschool children (age < 6 years) as IPTc during the malaria transmission season markedly reduces episodes of clinical malaria, including severe malaria. This benefit occurs even in areas where insecticide treated net usage is high. 16 April 2019 Update pending Studies awaiting assessment The CIDG is currently examining a new search conducted up to 17 Jul, 2018 for potentially relevant studies. These studies have not yet been incorporated into this Cochrane Review. |
t175 | Endometriomata are benign growths of the ovary. Evidence suggests that surgery to remove the endometrioma provides better results than draining and destroying the lining of the cyst with regard to the recurrence of the cyst, pain symptoms and also the chance of a spontaneous pregnancy in women who were previously subfertile. Surgery to excise the cyst should be the favoured surgical approach. Evidence that one technique is favoured in women who desire to conceive and who seek in vitro fertilization (IVF) treatment is however lacking. An additional randomised trial demonstrated that in women trying to conceive the ovarian response to stimulation, as part of fertility treatment, is better in women who have undergone surgery to remove the cyst rather than draining and destroying the endometrioma. The subsequent likelihood of pregnancy was not affected. Further research is required in this field to assess quality of life after surgery, clarify the effect of surgery on fertility with IVF treatment and to study the effect of surgery on ovarian function. | Endometriomata are endometriotic deposits within the ovary. The surgical management of these blood filled cysts is controversial. The laparoscopic approach to the management of endometriomata is favoured over a laparotomy approach as it offers the advantage of a shorter hospital stay, faster patient recovery and decreased hospital costs. Currently the commonest procedures for the treatment of ovarian endometriomata are either excision of the cyst capsule or drainage and electrocoagulation of the cyst wall. Objectives The objective of this review was to determine the most effective technique for treating an ovarian endometrioma, either excision of the cyst capsule or drainage and electrocoagulation of the cyst wall, measuring the outcomes improvement in pain symptoms and fertility. The primary endpoints assessed were the relief of pain and, in women desiring to conceive, the subsequent pregnancy rate (either spontaneous or as part of fertility treatment). Secondary outcomes assessed were the recurrence of the endometrioma and the recurrence of symptoms. Search methods The review authors searched the Cochrane Menstrual Disorders and Subfertility Group Specialised Register of trials (to 31st August 2009), the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library 2009, Issue 3), MEDLINE (1966 to August 2009), EMBASE (1980 to August 2009) and reference lists of articles; and handsearched relevant journals and conference proceedings and contacted leaders in the field of endoscopic surgery throughout the world.The Cochrane Menstrual Disorders and Subfertility Group Specialised Register is based on regular searches of MEDLINE, EMBASE, CINHAL and CENTRAL. Selection criteria Randomised controlled trials of excision of the cyst capsule versus drainage and electrocoagulation of the cyst in the management of ovarian endometriomata. Data collection and analysis Review authors assessed eligibility and trial quality. Two randomised studies of the laparoscopic management of ovarian endometriomata, size greater than 3 cm, for the primary symptom of pain were included. For the primary outcome measures laparoscopic excision of the cyst wall of the endometrioma was associated with a reduced recurrence rate of the symptoms of dysmenorrhoea (painful periods) (odds ratio (OR) 0.15, 95% CI 0.06 to 0.38), dyspareunia (OR 0.08, 95% CI 0.01 to 0.51) and non‐menstrual pelvic pain (OR 0.10, 95% CI 0.02 to 0.56). In those women subsequently attempting to conceive excision of the cyst wall was also associated with a subsequent increased spontaneous pregnancy rate in women who had documented prior subfertility (OR 5.21, 95% CI 2.04 to13.29) compared to women who underwent laparoscopic ablation of the endometrioma. For the secondary outcome measures laparoscopic excision of the cyst wall was associated with a reduced rate of recurrence of the endometrioma (OR 0.41, 95% CI 0.18 to 0.93) and with a reduced requirement for further surgery (OR 0.21, 95% CI 0.05 to 0.79) compared with surgery to ablate the endometrioma. A further randomised study was identified that demonstrated an increased ovarian follicular response to gonadotrophin stimulation for women who had undergone excisional surgery when compared to ablative surgery (mean difference (MD) 0.6, 95% CI 0.04 to1.16). There is insufficient evidence to support excisional surgery over ablative surgery with respect to the chances of pregnancy after controlled ovarian stimulation and intra‐uterine insemination (OR 1.40, 95% CI 0.47 to 4.15). There is good evidence that excisional surgery for endometriomata provides a more favourable outcome than drainage and ablation with regard to the recurrence of the endometrioma, recurrence of pain symptoms, and subsequent spontaneous pregnancy in women who were previously subfertile. Consequently this approach should be the favoured surgical approach. However in women who may subsequently undergo fertility treatment, insufficient evidence exists to determine the favoured surgical approach. |
t176 | Depressive disorders that persist for at least two years cause considerable problems. Even after successful treatment, they frequently recur. Common treatments are antidepressant medicines and psychological treatments (talking therapies), or a combination of both. Long‐term treatments should prevent the recurrence of depressive symptoms. People with persisting depression (longer than two years), friends, families, and carers. General practitioners, psychiatrists, clinical psychologists, psychological therapists, and pharmacists. The studies had to compare antidepressant treatment, psychological treatment, or a combination of both, with each other, with placebo, or with care as usual for preventing recurrence of depression in adults diagnosed with persistent depression. We included 10 studies involving 840 participants. Five studies compared antidepressant medicine with placebo. One study compared psychological therapies versus attention placebo/non‐specific control. One study compared psychotherapy with medication. Three studies compared combined psychological and pharmacological therapies with pharmacological therapies alone. One study compared combined psychological and pharmacological therapies with psychotherapeutic therapies alone. Two studies compared two different antidepressants with each other. Overall, the included studies were at low‐to‐moderate risk of bias. According to GRADE, there was moderate quality evidence that participants taking medication treatment probably had less relapses/recurrences and may have lower dropouts than those taking placebo. The risk of depression returning in participants receiving a placebo (instead of antidepressant medicine) was 34%. In comparison, participants who remained on antidepressant medicines had a lower risk for recurrence of 13%. The continued treatment lasted between four months and two years. Antidepressant were as well accepted as placebo. However, as most of the included studies showed risk of bias and there were some inconsistent results between the different studies, it cannot be concluded with certainty whether continued or maintained pharmacotherapy (or both) is a convincing treatment for people with PDD. Additionally, as studies on the long‐term effects of medication are lacking, recommendations on the necessary duration of medication treatment cannot be drawn. The benefits of psychological therapies or combined treatment remained unclear, due to the small number of studies. This review cannot provide clear, certain evidence regarding whether continued antidepressant medication (compared to placebo tablet) reduces the risk of depression recurring in adults with persistent depression. | Persistent depressive disorder (PDD) is defined as a depressive disorder with a minimum illness duration of two years, including four diagnostic subgroups (dysthymia, chronic major depression, recurrent major depression with incomplete remission between episodes, and double depression). Persistent forms of depression represent a substantial proportion of depressive disorders, with a lifetime prevalence ranging from 3% to 6% in the Western world. Growing evidence indicates that PDD responds well to several acute interventions, such as combined psychological and pharmacological treatments. Yet, given the high rates of relapse and recurrences of depression following response to acute treatment, long‐term continuation and maintenance therapy are of great importance. To date, there has been no evidence synthesis available on continuation and maintenance treatments of PDDs. Objectives To assess the effects of pharmacological and psychological (either alone or combined) continuation and maintenance treatments for persistent depressive disorder, in comparison with each other, placebo (drug/attention placebo/non‐specific treatment control), and treatment as usual (TAU). Continuation treatments are defined as treatments given to currently remitted people (remission is defined as depressive symptoms dropping below case level) or to people who previously responded to an antidepressant treatment. Maintenance therapy is given during recovery (which is defined as remission lasting longer than six months). Search methods We searched Ovid MEDLINE (1950‐ ), Embase (1974‐ ), PsycINFO (1967‐ ) and the Cochrane Central Register of Controlled Trials (CENTRAL) to 28 September 2018. An earlier search of these databases was also conducted for RCTs via the Cochrane Common Mental Disorders Controlled Trial Register (CCMD‐CTR) (all years to 11 Dec 2015). In addition we searched grey literature resources as well as the international trial registers ClinicalTrials.gov and ICTRP to 28 September 2018. We screened reference lists of included studies and contacted the first author of all included studies. Selection criteria We included randomized (RCTs) and non‐randomized controlled trials (NRCTs) in adults with formally diagnosed PDD, receiving pharmacological, psychological, or combined continuation and maintenance interventions. Data collection and analysis Two review authors independently selected studies and extracted and analyzed data. The primary efficacy outcome was relapse/recurrence rate of depression. The primary acceptance outcome was dropout due to any reason other than relapse/recurrence. We performed random‐effects meta‐analyses using risk ratios (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). We included 10 studies (seven RCTs, three NRCTs) involving 840 participants in this review, from which five studies investigated continuation treatments and five studies investigated maintenance treatments. Overall, the included studies were at low‐to‐moderate risk of bias. For the three NRCTs, the most common source of risk of bias was selection of reported results. For the seven RCTs, the most common sources of risk of bias was non‐blinding of outcome assessment and other bias (especially conflict of interest due to pharmaceutical sponsoring). Pharmacological continuation and maintenance therapies The most common comparison was antidepressant medication versus tablet placebo (five studies). Participants taking antidepressant medication were probably less likely to relapse or to experience a recurrent episode compared to participants in the placebo group at the end of the intervention (13.9% versus 33.8%, RR 0.41, 95% CI 0.21 to 0.79; participants = 383; studies = 4; I² = 54%, moderate quality evidence). Overall dropout rates may be similar between participants in the medication and placebo group (23.0% versus 25.5%, RR 0.90, 95% CI 0.39 to 2.11; RCTs = 4; participants = 386; I² = 64%, low quality evidence). However, sensitivity analyses showed that the primary outcome (rate of relapse/recurrence) showed no evidence of a difference between groups when only including studies with low risk of bias. None of the studies compared pharmacological or psychological treatments versus TAU. Psychological continuation and maintenance therapies One study compared psychological therapies versus attention placebo/non‐specific control. One study compared psychotherapy with medication. The results of the studies including psychotherapy might indicate that continued or maintained psychotherapy could be a useful intervention compared to no treatment or antidepressant medication. However, the body of evidence for these comparisons was too small and uncertain to draw any high quality conclusions. Combined psychological and pharmacological continuation and maintenance therapies Three studies compared combined psychological and pharmacological therapies with pharmacological therapies alone. One study compared combined psychological and pharmacological therapies with psychotherapeutic therapies alone. However, the body of evidence for these comparisons was too small and uncertain to draw any high quality conclusions Comparison of different antidepressant medications Two studies reported data on the direct comparison of two antidepressants. However, the body of evidence for this comparison was too small and uncertain to draw any high quality conclusions. Currently, it is uncertain whether continued or maintained pharmacotherapy (or both) with the reviewed antidepressant agents is a robust treatment for preventing relapse and recurrence in people with PDD, due to moderate or high risk of bias as well as clinical heterogeneity in the analyzed studies. For all other comparisons, the body of evidence was too small to draw any final conclusions, although continued or maintained psychotherapy might be effective compared to no treatment. There is need for more high quality trials of psychological interventions. Further studies should address health‐related quality of life and adverse events more precisely, as well as assessing follow‐up data. |
t177 | Cholera is caused by pathogenic bacteria ingested with contaminated food or water and is commonly found where sanitation measures are poor. It causes severe diarrhoea and vomiting, which can lead to profound dehydration and potentially death. Oral rehydration solution (ORS) is an effective treatment for diarrhoea, and ORS with a salt concentration of ≤ 270 mOsm/L, which has a lower electrolyte content than the earlier ORS ≥ 310 mOsm/L, is safe and more effective in people with non‐cholera diarrhoea. This review found that ORS ≤ 270 mOsm/L appears to be as effective as ORS ≥ 310 mOsm/L at rehydrating people with cholera, but may lead to low blood salt levels. More research is needed to better understand these potential safety issues. | Oral rehydration solution (ORS) is used to treat the dehydration caused by diarrhoeal diseases, including cholera. ORS formulations with an osmolarity (a measure of solute concentration) of ≤ 270 mOsm/L (ORS ≤ 270) are safe and more effective than ORS formulations with an osmolarity of ≥ 310 mOsm/L (ORS ≥ 310) for treating non‐cholera diarrhoea. As cholera causes rapid electrolyte loss, it is important to know if these benefits are similar for people suffering from cholera. Objectives To compare the safety and efficacy of ORS ≤270 with ORS ≥ 310 for treating dehydration due to cholera. Search methods We searched the Cochrane Infectious Disease Group Specialized Register (April 2011), CENTRAL ( The Cochrane Library Issue 4, 2011), MEDLINE (1966 to April 2011), EMBASE (1974 to April 2011), and LILACS (1982 to April 2011). We also contacted organizations and searched reference lists. Selection criteria Randomized controlled trials comparing ORS ≤ 270 with ORS ≥ 310 for treating adults and children with acute diarrhoea due to cholera. Data collection and analysis Two reviewers independently applied eligibility criteria, assessed trial quality, and extracted data. We pooled dichotomous data using risk ratio (RR), pooled continuous data using mean difference (MD) or the standardized mean difference (SMD), and presented the results with 95% confidence intervals (CI). For glucose‐based ORS, seven trials (718 participants) met the inclusion criteria. Biochemical hyponatraemia (blood sodium levels < 130 mmol/L) was more common with ORS ≤ 270 (RR 1.67, CI 1.09 to 2.57; 465 participants, four trials), while a higher level of severe biochemical hyponatraemia (blood sodium levels < 125 mmol/L) in the same group was not significant (RR 1.58, CI 0.62 to 4.04; 465 participants, four trials). No instances of symptomatic hyponatraemia or death were noted in the trials that intended to record them. We found no statistically significant difference in the need for unscheduled intravenous infusion. Analyses separating children and adults showed no obvious trends. Two trials also examined rice‐based ORS. In the ORS ≤ 270 group, duration of diarrhoea was shorter (MD ‐11.42 hours, CI ‐13.80 to ‐9.04; 102 participants, two trials). In people with cholera, ORS ≤ 270 is associated with biochemical hyponatraemia when compared with ORS ≥ 310, but there are no differences in terms of other outcomes. Although this risk does not appear to be associated with any serious consequences, the total patient experience in existing trials is small. Under wider practice conditions, especially where patient monitoring is difficult, caution is warranted. 23 April 2019 No update planned Research area no longer active This is not a current research question. |
t178 | In most parts of the world there are increasing numbers of older adults, and memory complaints and conditions such as Alzheimer's disease and other forms of dementia are becoming increasingly common as a result. Most individuals with memory difficulties will first seek out care or be identified in the healthcare system through their primary care health care providers, which may include family physicians or nurses. Therefore, there is a need for tools that could identify individuals who may have dementia or significant memory problems. These tools should also be able to rule out dementia in those individuals with memory complaints who do not have dementia or significant memory problems. Such tools in primary care must be relatively easy to use, quick to administer, and accurate so as to be feasible to use in primary care while at the same time not overdiagnose or underdiagnose dementia. The Mini‐Cog, a brief cognitive screening tool, has been suggested as a possible screening test for dementia in primary care as it has been reported to be accurate and relatively easy to administer in primary care settings. The Mini‐Cog consists of a memory task that involves recall of three words and an evaluation of a clock drawing task. The purpose of our review was to compare the accuracy of the Mini‐Cog for diagnosing dementia of any type in primary care settings when compared to in‐depth evaluation conducted by dementia specialists. We included studies that evaluated individuals with any potential severity of dementia and regardless of whether previous cognitive testing had been completed prior to the Mini‐Cog. Overall, our review identified four studies conducted in primary care settings that compared the accuracy of the Mini‐Cog to detailed assessment of dementia by dementia specialists. Of the four studies included in the review, all except one study had limitations in how the Mini‐Cog was evaluated, which may have led to an overestimation of the accuracy of the Mini‐Cog in the remaining studies. Notably, the most problematic issue in study quality related to how participants were selected to participate in research studies, which may have further contributed to an overestimation of the accuracy of the Mini‐Cog in most of the studies included in our review. Holsinger found that the Mini‐Cog had a sensitivity of 76%, indicating that the Mini‐Cog failed to detect up to 24% of individuals who have dementia (e.g. false negatives). In this same study, the specificity of the Mini‐Cog was 73% indicating that up to 27% of individuals may be incorrectly identified as having dementia on the Mini‐Cog when these individuals do not actually have an underlying dementia (e.g. false positives). We conclude that at the present time there is not enough evidence to support the routine use of the Mini‐Cog as a screening test for dementia in primary care and additional studies are required before concluding that the Mini‐Cog is useful in this setting. | Alzheimer's disease and other forms of dementia are becoming increasingly common with the aging of most populations. The majority of individuals with dementia will first present for care and assessment in primary care settings. There is a need for brief dementia screening instruments that can accurately diagnose dementia in primary care settings. The Mini‐Cog is a brief, cognitive screening test that is frequently used to evaluate cognition in older adults in various settings. Objectives To determine the diagnostic accuracy of the Mini‐Cog for diagnosing Alzheimer’s disease dementia and related dementias in a primary care setting. Search methods We searched the Cochrane Dementia and Cognitive Improvement Register of Diagnostic Test Accuracy Studies, MEDLINE, Embase and four other databases, initially to September 2012. Since then, four updates to the search were performed using the same search methods, and the most recent was January 2017. We used citation tracking (using the databases' ‘related articles’ feature, where available) as an additional search method and contacted authors of eligible studies for unpublished data. Selection criteria We only included studies that evaluated the Mini‐Cog as an index test for the diagnosis of Alzheimer's disease dementia or related forms of dementia when compared to a reference standard using validated criteria for dementia. We only included studies that were conducted in primary care populations. Data collection and analysis We extracted and described information on the characteristics of the study participants and study setting. Using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS‐2) criteria we evaluated the quality of studies, and we assessed risk of bias and applicability of each study for each domain in QUADAS‐2. Two review authors independently extracted information on the true positives, true negatives, false positives, and false negatives and entered the data into Review Manager 5 (RevMan 5). We then used RevMan 5 to determine the sensitivity, specificity, and 95% confidence intervals. We summarized the sensitivity and specificity of the Mini‐Cog in the individual studies in forest plots and also plotted them in a receiver operating characteristic plot. We also created a 'Risk of bias' and applicability concerns graph to summarize information related to the quality of included studies. There were a total of four studies that met our inclusion criteria, including a total of 1517 total participants. The sensitivity of the Mini‐Cog varied between 0.76 to 1.00 in studies while the specificity varied between 0.27 to 0.85. The included studies displayed significant heterogeneity in both methodologies and clinical populations, which did not allow for a meta‐analysis to be completed. Only one study ( Holsinger 2012 ) was found to be at low risk of bias on all methodological domains. The results of this study reported that the sensitivity of the Mini‐Cog was 0.76 and the specificity was 0.73. We found the quality of all other included studies to be low due to a high risk of bias with methodological limitations primarily in their selection of participants. There is a limited number of studies evaluating the accuracy of the Mini‐Cog for the diagnosis of dementia in primary care settings. Given the small number of studies, the wide range in estimates of the accuracy of the Mini‐Cog, and methodological limitations identified in most of the studies, at the present time there is insufficient evidence to recommend that the Mini‐Cog be used as a screening test for dementia in primary care. Further studies are required to determine the accuracy of Mini‐Cog in primary care and whether this tool has sufficient diagnostic test accuracy to be useful as a screening test in this setting. |
t179 | Malignant ascites is the build‐up of fluid within the abdominal cavity caused by underlying cancer. Women with advanced ovarian cancer and some women with advanced uterine cancer (also known as womb cancer) often need drainage for malignant ascites to alleviate discomfort. Guidelines to advise healthcare professionals involved in the drainage of ascites are usually produced locally and are generally based on clinicians' experience. We searched for studies up to Novemeber 2019 that compared different ways of managing the drainage of fluid collected in the abdomen of women with gynaecological cancer (cancer that starts in a woman's reproductive organs).This updated review included one randomised controlled trial (RCT: a type of study in which people are randomly assigned to receive different treatments) involving 245 women that compared drainage combined with catumaxomab (a medicine used to treatment malignant ascites) versus drainage alone. However, the results were insufficient to assess the difference between these treatments. Although women receiving drainage combined with catumaxomab had better quality of life (the general well‐being of a person) for longer compared to drainage alone, we are very unsure of this evidence due to the small number of participants and trials. There were some side effects in the drainage plus catumaxomab group (e.g. pain, low white blood cell count), but they were not well reported. | Ascites is the accumulation of fluid within the abdominal cavity. Most women with advanced ovarian cancer and some women with advanced endometrial cancer need repeated drainage for ascites. Guidelines to advise those involved in the drainage of ascites are usually produced locally and are generally not evidence‐based. Managing drains that improve the efficacy and quality of the procedure is key in making recommendations that could improve the quality of life (QoL) for women at this critical period of their lives. Objectives To evaluate the effectiveness and adverse events of different interventions for the management of malignant ascites drainage in the palliative care of women with gynaecological cancer. Search methods We searched CENTRAL, MEDLINE, and Embase to 4 November 2019. We checked clinical trial registries, grey literature, reports of conferences, citation lists of included studies, and key textbooks for potentially relevant studies. Selection criteria We included randomised controlled trials (RCTs) of women with malignant ascites with gynaecological cancer. If studies also included women with non‐gynaecological cancer, we planned to extract data specifically for women with gynaecological cancers or request the data from trial authors. If this was not possible, we planned to include the study only if at least 50% of participants were diagnosed with gynaecological cancer. Data collection and analysis Two review authors independently selected studies, extracted data, evaluated the quality of the included studies, compared results, and assessed the certainty of the evidence using Cochrane methodology. In the original 2010 review, we identified no relevant studies. This updated review included one RCT involving 245 participants that compared abdominal paracentesis and intraperitoneal infusion of catumaxomab versus abdominal paracentesis alone. The study was at high risk of bias in almost all domains. The data were not suitable for analysis. The median time to the first deterioration of QoL ranged from 19 to 26 days in participants receiving paracentesis alone compared to 47 to 49 days among participants receiving paracentesis with catumaxomab infusion (very low‐certainty evidence). Adverse events were only reported among participants receiving catumaxomab infusion. The most common severe adverse events were abdominal pain and lymphopenia (157 participants; very low‐certainty evidence). There were no data on the improvement of symptoms, satisfaction of participants and caregivers, and cost‐effectiveness. Currently, there is insufficient evidence to recommend the most appropriate management of drainage for malignant ascites among women with gynaecological cancer, as there was only very low‐certainty evidence from one small RCT at overall high risk of bias. |
t180 | Basilar skull fracture (7% to 15.8% of all skull fractures) places the central nervous system in contact with bacteria from the nose and throat and may be associated with cerebrospinal fluid leakage (occurring in 2% to 20.8% of patients). Blood or watery discharge from the nose or ears, bruising behind the ear or around the eyes, hearing loss, inability to perceive odours or facial asymmetry may lead physicians to the diagnosis of basilar skull fracture. Patients with a basilar skull fracture may develop meningitis and some doctors give antibiotics in an attempt to reduce this risk. This review examined five randomised controlled trials, comprising a total of 208 participants with basilar skull fracture, which compared those who received preventive antibiotic therapy with those who did not receive antibiotics, to establish how many participants developed meningitis. The available data did not support the use of prophylactic antibiotics, as there is no proven benefit of such therapy. There was a possible adverse effect of increased susceptibility to infection with more pathogenic (disease‐causing) organisms. We suggest that research is needed to address this question, as there are too few studies available on this subject and they have overall design shortcomings and small combined numbers of participants studied. | Basilar skull fractures predispose patients to meningitis because of the possible direct contact of bacteria in the paranasal sinuses, nasopharynx or middle ear with the central nervous system (CNS). Cerebrospinal fluid (CSF) leakage has been associated with a greater risk of contracting meningitis. Antibiotics are often given prophylactically, although their role in preventing bacterial meningitis has not been established. Objectives To evaluate the effectiveness of prophylactic antibiotics for preventing meningitis in patients with basilar skull fractures. Search methods We searched CENTRAL (2014, Issue 5), MEDLINE (1966 to June week 1, 2014), EMBASE (1974 to June 2014) and LILACS (1982 to June 2014). We also performed an electronic search of meeting proceedings from the American Association of Neurological Surgeons (1997 to September 2005) and handsearched the abstracts of meeting proceedings of the European Association of Neurosurgical Societies (1995, 1999 and 2003). Selection criteria Randomised controlled trials (RCTs) comparing any antibiotic versus placebo or no intervention. We also identified non‐RCTs to perform a separate meta‐analysis in order to compare results. Data collection and analysis Three review authors independently screened and selected trials, assessed risk of bias and extracted data. We sought clarification with trial authors when needed. We pooled risk ratios (RRs) for dichotomous data with their 95% confidence intervals (CIs) using a random‐effects model. We assessed the overall quality of evidence using the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach. In this update we did not identify any new trials for inclusion. We included five RCTs with 208 participants in the review and meta‐analysis. We also identified 17 non‐RCTs comparing different types of antibiotic prophylaxis with placebo or no intervention in patients with basilar skull fractures. Most trials presented insufficient methodological detail. All studies included meningitis in their primary outcome. When we evaluated the five included RCTs, there were no significant differences between antibiotic prophylaxis groups and control groups in terms of reduction of the frequency of meningitis, all‐cause mortality, meningitis‐related mortality and need for surgical correction in patients with CSF leakage. There were no reported adverse effects of antibiotic administration, although one of the five RCTs reported an induced change in the posterior nasopharyngeal flora towards potentially more pathogenic organisms resistant to the antibiotic regimen used in prophylaxis. We performed a subgroup analysis to evaluate the primary outcome in patients with and without CSF leakage. We also completed a meta‐analysis of all the identified controlled non‐RCTs (enrolling a total of 2168 patients), which produced results consistent with the randomised data from the included studies. Using the GRADE approach, we assessed the quality of trials as moderate. Currently available evidence from RCTs does not support prophylactic antibiotic use in patients with basilar skull fractures, whether there is evidence of CSF leakage or not. Until more research is available, the effectiveness of antibiotics in patients with basilar skull fractures cannot be determined because studies published to date are flawed by biases. Large, appropriately designed RCTs are needed. |
t181 | Neck pain (NP) is defined as pain, muscle tension, or stiffness localized in the neck and may originate from many structures, including the spine or soft tissues. Risk factors include age, gender, a history of pain, poor posture, repetitive strain, and social and psychological factors. NP is experienced by people of all ages and both genders and is an important cause of medical expenses, work absenteeism, and disability. Current management of NP includes a range of different treatments such as reassurance, education, promotion of a timely return to normal activities, appropriate use of painkillers, and exercises. There remains uncertainty about the efficacy of cognitive‐behavioural therapy (CBT) for these patients. CBT is a psychological technique that encompasses a wide set of interventions conducted by health professionals. It includes cognitive and behavioural modifications of specific activities to reduce the impact of pain as well as physical and psychosocial disability and to overcome dangerous barriers to physical and psychosocial recovery. Review Question We therefore reviewed the evidence about the effect of CBT on pain, disability, psychological factors, and quality of life among patients with subacute and chronic NP. Specifically, we compared CBT versus no treatment, CBT versus other types of interventions, and CBT in addition to another intervention (e.g. physiotherapy) versus the other intervention alone. We included 10 randomised trials (836 participants). Two studies included subjects with subacute NP (337 participants), while the other eight studies included participants with chronic NP (499 participants). CBTwas compared to no treatment (225 participants) or to other types of treatments (506 participants), or combined with another intervention (e.g. physiotherapy) and compared to the other intervention alone (200 participants). The interventions were carried out at primary and secondary health care centres. With regard to chronic NP, CBT was statistically significantly better than no treatment at improving pain, disability, and quality of life, but these effects could not be considered clinically meaningful. No differences between CBT and other types of interventions (e.g. medication, education, physiotherapy, manual therapy, and exercises) were found in terms of pain and disability; there was moderate quality evidence that CBT was better than other interventions in improving fear of movement. No difference was found in terms of disability and fear of movement. | Although research on non‐surgical treatments for neck pain (NP) is progressing, there remains uncertainty about the efficacy of cognitive‐behavioural therapy (CBT) for this population. Addressing cognitive and behavioural factors might reduce the clinical burden and the costs of NP in society. Objectives To assess the effects of CBT among individuals with subacute and chronic NP. Specifically, the following comparisons were investigated: (1) cognitive‐behavioural therapy versus placebo, no treatment, or waiting list controls; (2) cognitive‐behavioural therapy versus other types of interventions; (3) cognitive‐behavioural therapy in addition to another intervention (e.g. physiotherapy) versus the other intervention alone. Search methods We searched CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, SCOPUS, Web of Science, and PubMed, as well as ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform up to November 2014. Reference lists and citations of identified trials and relevant systematic reviews were screened. Selection criteria We included randomised controlled trials that assessed the use of CBT in adults with subacute and chronic NP. Data collection and analysis Two review authors independently assessed the risk of bias in each study and extracted the data. If sufficient homogeneity existed among studies in the pre‐defined comparisons, a meta‐analysis was performed. We determined the quality of the evidence for each comparison with the GRADE approach. We included 10 randomised trials (836 participants) in this review. Four trials (40%) had low risk of bias, the remaining 60% of trials had a high risk of bias. The quality of the evidence for the effects of CBT on patients with chronic NP was from very low to moderate. There was low quality evidence that CBT was better than no treatment for improving pain (standard mean difference (SMD) ‐0.58, 95% confidence interval (CI) ‐1.01 to ‐0.16), disability (SMD ‐0.61, 95% CI ‐1.21 to ‐0.01), and quality of life (SMD ‐0.93, 95% CI ‐1.54 to ‐0.31) at short‐term follow‐up, while there was from very low to low quality evidence of no effect on various psychological indicators at short‐term follow‐up. Both at short‐ and intermediate‐term follow‐up, CBT did not affect pain (SMD ‐0.06, 95% CI ‐0.33 to 0.21, low quality, at short‐term follow‐up; MD ‐0.89, 95% CI ‐2.73 to 0.94, low quality, at intermediate‐term follow‐up) or disability (SMD ‐0.10, 95% CI ‐0.40 to 0.20, moderate quality, at short‐term follow‐up; SMD ‐0.24, 95% CI‐0.54 to 0.07, moderate quality, at intermediate‐term follow‐up) compared to other types of interventions. There was moderate quality evidence that CBT was better than other interventions for improving kinesiophobia at intermediate‐term follow‐up (SMD ‐0.39, 95% CI ‐0.69 to ‐0.08, I 2 = 0%). Finally, there was very low quality evidence that CBT in addition to another intervention did not differ from the other intervention alone in terms of effect on pain (SMD ‐0.36, 95% CI ‐0.73 to 0.02) and disability (SMD ‐0.10, 95% CI ‐0.56 to 0.36) at short‐term follow‐up. For patients with subacute NP, there was low quality evidence that CBT was better than other interventions at reducing pain at short‐term follow‐up (SMD ‐0.24, 95% CI ‐0.48 to 0.00), while no difference was found in terms of effect on disability (SMD ‐0.12, 95% CI ‐0.36 to 0.12) and kinesiophobia. None of the included studies reported on adverse effects. With regard to chronic neck pain, CBT was found to be statistically significantly more effective for short‐term pain reduction only when compared to no treatment, but these effects could not be considered clinically meaningful. When comparing both CBT to other types of interventions and CBT in addition to another intervention to the other intervention alone, no differences were found. For patients with subacute NP, CBT was significantly better than other types of interventions at reducing pain at short‐term follow‐up, while no difference was found for disability and kinesiophobia. Further research is recommended to investigate the long‐term benefits and risks of CBT including for the different subgroups of subjects with NP. |
t182 | Raynaud's phenomenon is a disorder whereby blood vessels in the fingers and toes constrict and reduce blood flow, causing pain and discolouration. This is usually in response to cold exposure or emotional stress. In a small number of cases, Raynaud's phenomenon is associated with an underlying disease but, for most people, it is idiopathic (of uncertain cause, or 'primary'). Primary Raynaud's phenomenon is extremely common (especially in women), with one UK study suggesting that over 15% of the population are affected. For people with primary Raynaud's phenomenon who do not respond to conservative measures (e.g. keeping warm), calcium channel blockers represent the first line in drug treatment. Calcium channel blockers (sometimes called calcium antagonists) are drugs that affect the way calcium passes into certain muscle cells and they are the most commonly prescribed medication for primary Raynaud's phenomenon. Although overall all the trials were classed as being at low or unclear risk of bias, the sample size of the included trials was small and there was unclear reporting of outcomes. Two different calcium channel blockers were included: nifedipine and nicardipine. Comparisons in six trials were with placebo and in one trial with both placebo and another type of drug (although only data relating to the calcium channel blocker and placebo were used in this case). Treatment with oral calcium channel blockers was found to be minimally effective in primary Raynaud's phenomenon, reducing the frequency of attacks by around 1.7 attacks per person per week. One trial provided information on duration of attacks reporting no difference between the calcium channel blocker and placebo groups . Oral calcium channel blockers had no effect on severity scores in the two trials in which these were assessed. Only two trials reported preference scores (whereby participants are asked which treatment they prefer) specifically in those with primary Raynaud's phenomenon, and in only one of these was there a between‐treatment group difference (participants preferred nifedipine to placebo). Physiological measurements (for example measurement of finger blood flow) were performed in five trials, data could not be combined as the methods were too different, no differences found between calcium channel blocker and placebo treatment were seen in any trial. Treatment with calcium channel blockers was associated with a number of adverse events including headaches, flushing and ankle swelling. | Calcium channel blockers are the most commonly prescribed drugs for people with primary Raynaud's phenomenon. Primary Raynaud's phenomenon is a common condition characterised by an exaggerated vasospastic response to cold or emotion: classically the digits (fingers and toes) turn white, then blue, then red. This is an update of the review first published in 2014. Objectives To assess the effects of different calcium channel blockers for primary Raynaud's phenomenon as determined by attack rates, severity scores, participant‐preference scores and physiological measurements. Search methods For this update the Cochrane Vascular Trial Search Co‐ordinator searched the Specialised Register (last searched January 2016) and the Cochrane Register of Studies (CENTRAL) (2015, Issue 12). In addition the TSC searched clinical trials databases. Selection criteria Randomised controlled trials evaluating the effects of oral calcium channel blockers for the treatment of primary Raynaud's phenomenon. Data collection and analysis Three review authors independently assessed the trials for inclusion and their quality, and extracted the data. Data extraction included adverse events. We contacted trial authors for missing data. We included seven randomised trials with 296 participants. Four trials examined nifedipine and the remainder nicardipine. Comparisons were with placebo in six trials and with both dazoxiben and placebo in one trial (only the nifedipine versus placebo data were used within this review). Treatment with oral calcium channel blockers was minimally effective in primary Raynaud's phenomenon at decreasing the frequency of attacks (standardised mean difference of 0.23; 95% confidence interval (CI) 0.08 to 0.38, P = 0.003). This translates to 1.72 (95% CI 0.60 to 2.84) fewer attacks per week on calcium channel blockers compared to placebo. One trial provided details on duration of attacks reporting no statistically significant difference between the nicardipine and placebo groups (no P value reported). Only two trials provided any detail of statistical comparisons of (unvalidated) severity scores between treatment groups: one of these trials (60 participants) reported a mean severity score of 1.55 on placebo and 1.36 on nicardipine, difference 0.2 (95% CI of difference 0 to 0.4, no P value reported) and the other trial (three participants only with primary Raynaud's phenomenon) reported a median severity score of 2 on both nicardipine and placebo treatment (P > 0.999) suggesting little effect on severity. Participant‐preference scores were included in four trials, but in only two were results specific to participants with primary Raynaud's phenomenon, and scoring systems differed between trials: scores differed between treatments in only one trial, in which 33% of participants on placebo and 73% on nifedipine reported improvement in symptoms (P < 0.001). Physiological measurements were included as outcome measures in five trials (different methodologies were used in each): none of these trials found any statistically significant between‐treatment group differences. Treatment with calcium channel blockers appeared to be associated with a number of adverse reactions, including headaches, flushing and oedema (swelling). Overall, the trials were classed as being at low or unclear risk of bias; and the quality of the evidence presented was moderate for number of attacks, very low for duration of attacks, high for severity scores and low for patient preference scores. The randomised controlled trials included in this review provide moderate quality evidence that oral calcium channel blockers are minimally effective in the treatment of primary Raynaud's phenomenon as measured by the frequency of attacks and high‐quality evidence that they have little effect on severity. We are unable to comment on duration of attacks or on patient preference due to the very low and low quality of evidence as a result of small sample sizes in the included studies and the variable data quality of outcome measures. |
t183 | Modern technologies have created new platforms for advancing medical education. E‐learning has gained popularity due to the potential benefits of personalised instruction, allowing learners to tailor the pace and content of courses to their individual needs, increasing the accessibility of information to remote learners, decreasing costs and facilitating frequent content updates. Previous reviews have not identified differences, but they were limited by the type of participants included (mix of licensed health professionals and medical students) and study types evaluated (randomised together with non‐randomised trials). The review authors identified 16 relevant studies from 10 different countries, providing data on 5679 participants (4759 mixed health professionals, 587 nurses, 300 doctors and 33 childcare health consultants). Companies funded three studies, whereas government agencies financed six. One study with 847 health professionals found little or no difference between e‐learning and traditional learning on patient outcomes at one year, and two studies with 950 health professionals suggested little to no difference in health professionals' behaviours at 3 to 12 months, as the certainty of the evidence was low. We are uncertain whether e‐learning improves or reduces health professionals' skills at 0 to 12 weeks' follow‐up, based on the results of six studies with 2912 participants and very low certainty of evidence. E‐learning may also make little or no difference on health professionals' knowledge, based on the results from 11 studies with 3236 participants at 0 to 12 weeks follow‐up, as the certainty of the evidence was low. | The use of e‐learning, defined as any educational intervention mediated electronically via the Internet, has steadily increased among health professionals worldwide. Several studies have attempted to measure the effects of e‐learning in medical practice, which has often been associated with large positive effects when compared to no intervention and with small positive effects when compared with traditional learning (without access to e‐learning). However, results are not conclusive. Objectives To assess the effects of e‐learning programmes versus traditional learning in licensed health professionals for improving patient outcomes or health professionals' behaviours, skills and knowledge. Search methods We searched CENTRAL, MEDLINE, Embase, five other databases and three trial registers up to July 2016, without any restrictions based on language or status of publication. We examined the reference lists of the included studies and other relevant reviews. If necessary, we contacted the study authors to collect additional information on studies. Selection criteria Randomised trials assessing the effectiveness of e‐learning versus traditional learning for health professionals. We excluded non‐randomised trials and trials involving undergraduate health professionals. Data collection and analysis Two authors independently selected studies, extracted data and assessed risk of bias. We graded the certainty of evidence for each outcome using the GRADE approach and standardised the outcome effects using relative risks (risk ratio (RR) or odds ratio (OR)) or standardised mean difference (SMD) when possible. We included 16 randomised trials involving 5679 licensed health professionals (4759 mixed health professionals, 587 nurses, 300 doctors and 33 childcare health consultants). When compared with traditional learning at 12‐month follow‐up, low‐certainty evidence suggests that e‐learning may make little or no difference for the following patient outcomes: the proportion of patients with low‐density lipoprotein (LDL) cholesterol of less than 100 mg/dL (adjusted difference 4.0%, 95% confidence interval (CI) −0.3 to 7.9, N = 6399 patients, 1 study) and the proportion with glycated haemoglobin level of less than 8% (adjusted difference 4.6%, 95% CI −1.5 to 9.8, 3114 patients, 1 study). At 3‐ to 12‐month follow‐up, low‐certainty evidence indicates that e‐learning may make little or no difference on the following behaviours in health professionals: screening for dyslipidaemia (OR 0.90, 95% CI 0.77 to 1.06, 6027 patients, 2 studies) and treatment for dyslipidaemia (OR 1.15, 95% CI 0.89 to 1.48, 5491 patients, 2 studies). It is uncertain whether e‐learning improves or reduces health professionals' skills (2912 health professionals; 6 studies; very low‐certainty evidence), and it may make little or no difference in health professionals' knowledge (3236 participants; 11 studies; low‐certainty evidence). Due to the paucity of studies and data, we were unable to explore differences in effects across different subgroups. Owing to poor reporting, we were unable to collect sufficient information to complete a meaningful 'Risk of bias' assessment for most of the quality criteria. We evaluated the risk of bias as unclear for most studies, but we classified the largest trial as being at low risk of bias. Missing data represented a potential source of bias in several studies. When compared to traditional learning, e‐learning may make little or no difference in patient outcomes or health professionals' behaviours, skills or knowledge. Even if e‐learning could be more successful than traditional learning in particular medical education settings, general claims of it as inherently more effective than traditional learning may be misleading. |
t184 | Women have different lengths of labour, with first labours lasting on average eight hours (and unlikely to last more than 18 hours) and second and subsequent labours lasting an average of five hours and unlikely to last more than 12 hours. Assessment of progress in labour takes into account not just cervical dilatation, but also descent and rotation of the fetal head and the strength, duration and frequency of contractions. Some evidence suggests that up to one‐third of women in their first labour experience delay. They are often given a synthetic version of the hormone oxytocin to increase uterine contractions and shorten labour. Surprisingly for such a routine treatment, the ideal dose at which it should be given is not known, although some comparisons suggest that higher‐dose regimens of oxytocin could shorten labour and reduce the chance of caesarean section with an increase in the numbers of women having a spontaneous vaginal birth compared with lower‐dose regimens. However, there are potentially harmful side effects as oxytocin may cause the uterus to contract too quickly, and the baby to become distressed. Clinicians attempt to mitigate these side effects by adjusting the dose of oxytocin with the contractions to reduce the chances of the baby being distressed in labour. From the four randomised controlled trials involving 644 pregnant women that we included in this review, results indicate that a higher dose of oxytocin (4‐7 mU per minute, compared with 1‐2 mU per minute) reduced the length of labour and the rate of caesarean sections with increased spontaneous vaginal births, but the studies did not provide enough evidence on possible differences between the high‐ and low‐dose regimens on adverse events including hyperstimulation of the uterus, and outcomes for the newborn infant. Only one trial reported on the possible effect on women. While the current evidence is promising and suggests that the high‐dose regimens reduce the length of labour and the rate of caesarean sections, this evidence is not strong enough to recommend that high‐dose regimens are used routinely for women delayed in labour. | A major cause of failure to achieve spontaneous vaginal birth is delay in labour due to presumed inefficient uterine action. Oxytocin is given to increase contractions and high‐dose regimens may potentially increase the number of spontaneous vaginal births, but as oxytocin can cause hyperstimulation of the uterus, there is a possibility of increased adverse events. Objectives To compare starting dose and increment dose of oxytocin for augmentation for women delayed in labour to determine whether augmentation by high‐dose regimens of oxytocin improves labour outcomes and to examine the effect on both maternal/neonatal outcomes and women's birth experiences. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2013) and reference lists of retrieved studies. Selection criteria We included all randomised and quasi‐randomised controlled trials for women in delayed labour requiring augmentation by oxytocin comparing high‐dose regimens (defined as starting dose and increment of equal to or more than 4 mU per minute) with low‐dose regimens (defined as starting dose and an increment of less than 4 mU per minute). Increase interval: between 15 and 40 minutes. The separation of low‐ and high‐dose regimens is based on an arbitrary decision. Data collection and analysis Four review authors undertook assessment of trial eligibility, risk of bias, and data extraction independently. We included four studies involving 644 pregnant women. Three studies were randomised controlled trials and one trial was a quasi‐randomised study. A higher dose of oxytocin was associated with a significant reduction in length of labour reported from one trial (mean difference (MD) ‐3.50 hours; 95% confidence interval (CI) ‐6.38 to ‐0.62; one trial, 40 women). There was a decrease in the rate of caesarean section (risk ratio (RR) 0.62; 95% CI 0.44 to 0.86 four trials, 644 women) and an increase in the rate of spontaneous vaginal birth in the high‐dose group (RR 1.35; 95% CI 1.13 to 1.62, three trials, 444 women), although for both of these outcomes there were inconsistencies between studies in the size of effect. When we carried out sensitivity analysis (temporarily removing a study at high risk of bias) the differences between groups were no longer statistically significant There were no significant differences between high‐ and low‐dose regimens for instrumental vaginal birth, epidural analgesia, hyperstimulation, postpartum haemorrhage, chorioamnionitis or women's perceptions of experiences. For neonatal outcomes, there was no significant difference between groups for Apgar scores, umbilical cord pH, admission to special care baby unit, or neonatal mortality. The following outcomes were not evaluated in the included studies: perinatal mortality, uterine rupture, abnormal cardiotocography, women's pyrexia, dystocia and neonatal neurological morbidity. Higher‐dose regimens of oxytocin (4 mU per minute or more) were associated with a reduction in the length of labour and in caesarean section, and an increase in spontaneous vaginal birth. However, there is insufficient evidence to recommend that high‐dose regimens are advised routinely for women with delay in the first stage of labour. Further research should evaluate the effect of high‐dose regimens of oxytocin for women delayed in labour and should include maternal and neonatal outcomes as well as the effects on women. |
t185 | Body dysmorphic disorder (BDD) is a condition characterised by a distressing and disabling preoccupation with an imagined or slight defect in appearance. This causes people with this disorder either significant distress or disrupts their daily functioning (or both). There has been a growing recognition that BDD is common, and is associated with significant illness and disability. There is also some evidence that it may respond to pharmacotherapy and psychotherapy. Our systematic review of randomised controlled trials assesses the effects of drug treatment or psychotherapy when used on their own or in combination. We found five eligible trials, including three of psychotherapy (cognitive behavioural therapy (CBT) and exposure and response prevention (ERP)) and two of medication (the serotonin reuptake inhibitors (SRIs) fluoxetine and clomipramine). In the only placebo‐controlled medication trial included in our review, people with BDD treated with fluoxetine were more likely to respond (56%, 19 out of 34) than those allocated placebo (18%, 6 out of 33). Symptoms became less severe after treatment with both medication and psychotherapy. Adverse events were mild to moderate in severity and none of the people in the active treatment groups were reported to have dropped out of the studies because of treatment‐emergent adverse events. There is preliminary evidence from one trial of CBT that the effects of CBT may persist once treatment has ended. Treatment response in the medication trials was not effected by the degree to which people had insight into their condition. Although few controlled trials have been done, and those that have been conducted were small, indicating that our findings should be used with caution unless confirmed by larger studies (some of which are ongoing), the results suggest that treatment with both medication or psychotherapy can be effective in treating the symptoms of body dysmorphic disorder. | Body dysmorphic disorder (BDD) is a prevalent and disabling preoccupation with a slight or imagined defect in appearance. Trials have investigated the use of serotonin reuptake inhibitors (SRIs) and cognitive behaviour therapy (CBT) for BDD. Objectives To assess the efficacy of pharmacotherapy, psychotherapy or a combination of both treatment modalities for body dysmorphic disorder. Search methods We searched the Cochrane Depression, Anxiety and Neurosis Trial Register (December 2007), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2007), MEDLINE (January 1966 to December 2007), and PsycINFO (1967 to December 2007). Ongoing and unpublished trials were located through searching the metaRegister of Controlled Trials, the CRISP and WHO ICTRP search portals (databases searched in December 2007), and through contacting key researchers and pharmaceutical companies. Additional studies were located through study reference lists. Selection criteria Randomised controlled trials (RCTs) of patients meeting DSM or ICD diagnostic criteria for BDD, in which the trials compare pharmacotherapy, psychotherapy or multi‐modal treatment groups with active or non‐active control groups. Short or long‐term trials were eligible. Data collection and analysis Two review authors independently assessed RCTs for inclusion in the review, collated trial data, and assessed trial quality. Investigators were contacted to obtain missing data. Summary effect sizes for dichotomous and continuous outcomes were calculated using a random effects model and heterogeneity was assessed. Two pharmacotherapy and three psychotherapy trials were eligible for inclusion in the review, with data from four short‐term RCTs (169 participants) available for analysis. Response data from a single placebo‐controlled trial of fluoxetine suggested overall superiority of medication relative to placebo (relative risk (RR) 3.07, 95% CI 1.4 to 6.72, n = 67). Symptom severity was also significantly reduced in the RCTs of fluoxetine and clomipramine (relative to desipramine), as well as in the two CBT trials (WMD ‐44.96, 95% CI ‐54.43 to ‐35.49, n = 73). A low relapse rate (4/22) was demonstrated in one trial of CBT. Results from the small number of available RCTs suggest that SRIs and CBT may be useful in treating patients with BDD. The findings of these studies need to be replicated. In addition, future controlled studies in other samples, such as adolescents, and using other selective SRIs, as well as a range of psychological therapy approaches and modalities (alone and in combination), are essential in supplementing the sparse data currently available. |
t186 | Allogeneic hematopoietic stem cell transplantation is a procedure in which a portion of a healthy donor's stem cells (cells that can develop into various types of blood cells) or bone marrow is obtained and prepared for intravenous infusion. Hematopoietic stem cells are taken from a healthy donor and transplanted into the patient (recipient). People undergoing allogeneic hematopoietic stem cell transplantation are at risk of developing graft‐versus‐host disease (GVHD). GVHD results when the transplanted cells from the donor (graft) attack the recipient's (host) body cells because they perceive the recipient's body as foreign. Mycophenolate mofetil and methotrexate are two drugs often used to suppress the human body's reaction against the graft (immune response) and prevent GVHD. We conducted a systematic review of three randomized controlled trials (RCTs, which are clinical studies where people are randomly put into one of two or more treatment groups) that compared mycophenolate mofetil versus methotrexate for use in preventing GVHD among 174 participants. All participants in these RCTs received a drug aimed at suppressing the immune response (cyclosporine or tacrolimus). Our results show no clinically meaningful difference between mycophenolate mofetil and methotrexate on length of survival, incidence of GVHD, disease relapse, or treatment‐related death. People treated with mycophenolate mofetil had a shorter time to make new platelets (cells that help the blood to clot) from the donor cells compared with people treated with methotrexate. In addition, in terms of side effects, people treated with mycophenolate mofetil were less likely to have severe mucositis (inflammation of the mucus membranes), require parenteral nutrition (feeding through a vein), or pain medication. In summary, mycophenolate mofetil and methotrexate both remain acceptable medications for the prevention of GVHD; however, mycophenolate mofetil seems to be associated with a smaller incidence of harms such as severe mucositis and related supportive care. | Allogeneic hematopoietic stem cell transplantation (allo‐HCT) is associated with improved outcomes for people with various hematologic diseases; however, the morbidity and mortality resulting from acute and subsequently chronic graft‐versus‐host disease (GVHD) pose a serious challenge to wider applicability of allo‐HCT. Intravenous methotrexate in combination with a calcineurin inhibitor, cyclosporine or tacrolimus, is a widely used regimen for the prophylaxis of acute GVHD, but the administration of methotrexate is associated with a number of adverse events. Mycophenolate mofetil, in combination with a calcineurin inhibitor, has been used extensively in people undergoing allo‐HCT. Conflicting results regarding various clinical outcomes following allo‐HCT have been observed when comparing mycophenolate mofetil‐based regimens against methotrexate‐based regimens for acute GVHD prophylaxis. Objectives Primary objective: to assess the effect of mycophenolate mofetil versus methotrexate for prevention of acute GVHD in people undergoing allo‐HCT. Secondary objectives: to evaluate the effect of mycophenolate mofetil versus methotrexate for overall survival, prevention of chronic GVHD, incidence of relapse, treatment‐related harms, nonrelapse mortality, and quality of life. Search methods We searched Cochrane Central Register of Controlled Trials (CENTRAL) and MEDLINE from inception to March 2014. We handsearched conference abstracts from the last two meetings (2011 and 2012) of relevant societies in the field. We searched ClinicalTrials.gov, Novartis clinical trials database (www.novctrd.com), Roche clinical trial protocol registry (www.roche‐trials.com), Australian New Zealand Clinical Trials Registry (ANZCTR), and the metaRegister of Controlled Trials for ongoing trials. Selection criteria Two review authors independently reviewed all titles/abstracts and selected full‐text articles for inclusion. We included all references that reported results of randomized controlled trials (RCTs) of mycophenolate mofetil versus methotrexate for the prophylaxis of GVHD among people undergoing allo‐HCT in this review. Data collection and analysis Two review authors independently extracted data on outcomes from all studies and compared prior to data entry and analysis. We expressed results as risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes and hazard ratios (HR) and 95% CIs for time‐to‐event outcomes. We pooled the individual study effects using the random‐effects model. Estimates lower than one indicate that mycophenolate mofetil was favored over methotrexate. We included three trials enrolling 177 participants (174 participants analyzed). All participants in the trials by Keihl et al. and Bolwell et al. received cyclosporine while all participants enrolled in the trial by Perkins et al. received tacrolimus. However, the results did not differ by the type of calcineurin inhibitor employed (cyclosporine versus tacrolimus). There was no evidence for a difference between mycophenolate mofetil versus methotrexate for the outcomes of incidence of acute GVHD (RR 1.25; 95% CI 0.75 to 2.09; P value = 0.39, very low quality evidence), overall survival (HR 0.73; 95% CI 0.45 to 1.17; P value = 0.19, low‐quality evidence), median days to neutrophil engraftment (HR 0.77; 95% CI 0.51 to 1.17; P value = 0.23, low‐quality evidence), incidence of relapse (RR 0.84; 95% CI 0.52 to 1.38; P value = 0.50, low‐quality evidence), non‐relapse mortality (RR 1.21; 95% CI 0.62 to 2.36; P value = 0.57, low‐quality evidence), and incidence of chronic GVHD (RR 0.92; 95% CI 0.65 to 1.30; P value = 0.62, low‐quality evidence). There was low‐quality evidence that mycophenolate mofetil compared with methotrexate improved platelet engraftment period (HR 0.87; 95% CI 0.81 to 0.93; P value < 0.0001, low‐quality evidence). There was low‐quality evidence that mycophenolate mofetil compared with methotrexate resulted in decreased incidence of severe mucositis (RR 0.48; 95% CI 0.32 to 0.73; P value = 0.0006, low‐quality evidence), use of parenteral nutrition (RR 0.48; 95% CI 0.26 to 0.91; P value = 0.02, low‐quality evidence), and medication for pain control (RR 0.76; 95% CI 0.63 to 0.91; P value = 0.002, low‐quality evidence). Overall heterogeneity was not detected in the analysis except for the outcome of neutrophil engraftment. None of the included studies reported any outcomes related to quality of life. Overall quality of evidence was low. The use of mycophenolate mofetil compared with methotrexate for primary prevention of GVHD seems to be associated with a more favorable toxicity profile, without an apparent compromise on disease relapse, transplant‐associated mortality, or overall survival. The effects on incidence of GVHD between people receiving mycophenolate mofetil compared with people receiving methotrexate were uncertain. There is a need for additional high‐quality RCTs to determine the optimal GVHD prevention strategy. Future studies should take into account a comprehensive view of clinical benefit, including measures of morbidity, symptom burden, and healthcare resource utilization associated with interventions. |
t187 | Depression in physical illness is common. Antidepressants have been shown to improve depression in people who are physically healthy, but there has been doubt about whether they are appropriate for people who are physically ill. This review examined clinical trials of antidepressants in physically ill people to determine whether antidepressants help these patients, and in particular if they lessen depression. We used standard methods recommended by Cochrane to identify and select studies and to collect and analyse the information. Our results found that antidepressants are better than a placebo (inactive) drug in treating depression in physically ill people. Both the two main classes of antidepressant, tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), were shown to be more effective than a placebo. Antidepressants improved depressive symptoms within 4‐5 weeks of treatment, and this benefit persisted after 18 weeks. However, patients taking an antidepressant were more likely to experience sexual dysfunction and dry mouth, and were more likely to stop taking their medication after 6‐8 weeks of treatment. There are no grounds to recommend one antidepressant over another on the basis of this review. We conclude that antidepressants appear to be useful in treating depression and should be considered for physically ill patients. The decision to prescribe antidepressants should take account of patients' preferences, symptoms, and possible interactions with other medicines they are taking. | There is an increased risk of depression in people with a physical illness. Depression is associated with reduced treatment adherence, poor prognosis, increased disability and higher mortality in many physical illnesses. Antidepressants are effective in the treatment of depression in physically healthy populations, but there is less clarity regarding their use in physically ill patients. This review updates Gill’s Cochrane review (2000), which found that antidepressants were effective for depression in physical illness. Since Gill there have been a number of larger trials assessing the efficacy of antidepressants in this context. Objectives To determine the efficacy of antidepressants in the treatment of depression in patients with a physical illness. Search methods Electronic searches of the Cochrane Depression, Anxiety and Neurosis Review Group (CCDAN) trial registers were conducted together with supplementary searches of The Cochrane Central Register of Controlled Trials (CENTRAL) and the standard bibliographic databases, MEDLINE, EMBASE and PsycINFO. Reference lists of included studies were scanned and trials registers were searched to identify additional unpublished data. Last searches were run in December 2009. Selection criteria Randomised controlled trials comparing the efficacy of antidepressants and placebo in the treatment of depression in adults with a physical illness. Depression included diagnoses of Major Depression, Adjustment Disorder and Dysthymia based on standardised criteria. Data collection and analysis The primary outcome was efficacy 6‐8 weeks after randomisation. Data were also extracted at three additional time‐points (4‐5 weeks, 9‐18 weeks, >18 weeks). Acceptability and tolerability were assessed by comparing the number of drop‐outs and adverse events. Odds ratios with 95% confidence intervals were calculated for dichotomous data (response to treatment). Standardised mean differences with 95% CI were calculated for continuous data (mean depression score). Data were pooled using a random effects model. Fifty‐one studies including 3603 participants were included in the review. Forty‐four studies including 3372 participants contributed data towards the efficacy analyses. Pooled efficacy data for the primary outcome provided an OR of 2.33, CI 1.80‐3.00, p<0.00001 (25 studies, 1674 patients) favouring antidepressants. Antidepressants were also more efficacious than placebo at the other time‐points. At 6‐8 weeks, fewer patients receiving placebo dropped out compared to patients treated with an antidepressant. Dry mouth and sexual dysfunction were more common in patients treated with an antidepressant. This review provides evidence that antidepressants are superior to placebo in treating depression in physical illness. However, it is likely that publication and reporting biases exaggerated the effect sizes obtained. Further research is required to determine the comparative efficacy and acceptability of particular antidepressants in this population. |
t188 | We assessed the effectiveness in women and the safety in men of concurrent antibiotic treatment for the sexual partners of women treated for bacterial vaginosis (BV). Bacterial vaginosis (BV) is an infection that has a prevalence between 10% to 50% worlwide. BV results in an imbalance of the normal vaginal flora. Microorganisms associated with BV have been isolated from the normal flora of the male genital tract, and their presence could be related to the recurrence of infection after antibiotic treatment. Therefore, the treatment of sexual partners could offer the advantages of decreasing the recurrence of infection and possibly reducing the burden of the disease. The trials included sexually‐active non‐pregnant women between 17 and 56 years of age, either single or married, with symptomatic BV. Four studies only included women involved into a monogamous heterosexual relationship and there was no information about this for the remaining trials. Six trials used 5‐nitroimidazoles to treat the sexual partner, four trials used metronidazole and two trials used tinidazole; only one study used a lincosamide for treatment. Five trials compared antibiotic versus placebo (854 participants) and two trials compared antibiotic treatment with no intervention (172 participants). Pharmaceutical companies funded four of the included trials. Compared with placebo, antibiotic treatment for the sexual partners of women treated for BV had no effects on clinical or symptomatic improvement in women, regardless of the time period over which the trials assessed these outcomes (during the first, between the first and fourth, or after the fourth week). Furthermore, antibiotic treatment of the sexual partner may have no effect on the recurrence of BV up to 12 weeks after treatment, but may increase the frequency of minor adverse events reported by sexual partners. Compared with no intervention, treatment of sexual partners of women with BV may have no effect on decreasing the recurrence rate or over the frequency of clinical or symptomatic improvement between the first and fourth or after the fourth week, respectively. | Bacterial vaginosis (BV) is an infection that has a prevalence between 10% to 50% worlwide. BV results in an imbalance of the normal vaginal flora. Microorganisms associated with BV have been isolated from the normal flora of the male genital tract, and their presence could be related to the recurrence of BV after antibiotic treatment. Therefore, the treatment of sexual partners could decrease the recurrence of infection and possibly the burden of the disease. Objectives To assess the effectiveness in women and the safety in men of concurrent antibiotic treatment for the sexual partners of women treated for BV. Search methods We searched the Cochrane Sexually Transmitted Infections Group Specialized Register (23 July 2016), CENTRAL (1991 to 23 July 2016), MEDLINE (1946 to 23 July 2016), Embase (1974 to 23 July 2016), LILACS (1982 to 23 July 2016), the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) (23 July 2016), ClinicalTrials.gov (23 July 2016) and the Web of Science™ (2001 to 23 July 2016). We also handsearched conference proceedings, contacted trial authors and reviewed the reference lists of retrieved studies. Selection criteria Randomized controlled trials (RCTs) that compared the concurrent use of any antibiotic treatment with placebo, no intervention or any other intervention by the sexual partners of women treated for BV. Data collection and analysis Three review authors independently assessed trials for inclusion, extracted data and assessed the risk of bias in the included studies. We resolved any disagreements through consensus. Seven RCTs (1026 participants) met our inclusion criteria, and pharmaceutical industry funded four of these trials. Five trials (854 patients) compared any antibiotic treatment of sexual partners with placebo. Based on high quality evidence, antibiotic treatment does not increase the rate of clinical or symptomatic improvement in women during the first week (risk ratio (RR) 0.99, 95% confidence interval (CI) 0.96 to 1.03; 712 participants, four studies; RR 1.06, 95% CI 1.00 to 1.12; 577 patients, three studies, respectively), between the first and fourth week (RR 1.02, 95% CI 0.94 to 1.11; 590 participants, three studies; RR 0.93, 95% CI 0.84 to 1.03; 444 participants, two studies; respectively) or after the fourth week (RR 0.98, 95% CI 0.90 to 1.07; 572 participants, four studies; RR 1.03, 95% CI 0.90 to 1.17; 296 participants, two studies; respectively). Antibiotic treatment does not led to a lower recurrence during the first and fourth week (RR 1.28, 95% CI 0.68 to 2.43; 218 participants, one study; low quality evidence) or after the fourth week of treatment (RR 1.00, 95% CI 0.67 to 1.52; 372 participants, three studies; low quality evidence) in women, but increases the frequency of adverse events (most frequently gastrointestinal symptoms) reported by sexual partners (RR 2.55, 95% CI 1.55 to 4.18; 477 participants, three studies; low quality evidence). Two trials (172 participants) compared any antibiotic treatment for sexual partners with no intervention. When we compared it with no intervention, the effects of antibiotic treatment on recurrence rate after the fourth week (RR 1.71, 95% CI 0.65 to 4.55; 51 participants, one study), clinical improvement between the first and fourth week (RR 0.93, 95% CI 0.70 to 1.25; 152 participants, two studies) and symptomatic improvement after the fourth week (RR 0.66, 95% CI 0.39 to 1.11; 70 participants, one study) were imprecise and there were no differences between groups. High quality evidence shows that antibiotic treatment for sexual partners of women with BV, compared with placebo, does not increase the rate of clinical or symptomatic improvement during the first, between the first and fourth or after the fourth week into the women. Low quality evidence suggests that antibiotic treatment does not led to a lower recurrence rate during the first and fourth or after the fourth week of treatment into the women, but increases the frequency of adverse events reported by sexual partners. Finally, compared with no intervention, antibiotic treatment does not decrease the recurrence rate after the fourth week and does not increase the frequency of clinical or symptomatic improvement between the first and fourth or after the fourth week into the women, respectively. |
t189 | This review update assessed evidence from 2641 participants in 20 randomised, double blind, placebo‐controlled clinical trials of oxycodone, with or without paracetamol, in adults with moderate to severe acute postoperative pain. Oral oxycodone 10 mg plus paracetamol 650 mg provided effective analgesia. About half of those treated experienced at least half pain relief over 4 to 6 hours, and the effects lasting up to 10 hours. Higher doses gave more effect. Associated adverse events (predominantly nausea, vomiting, dizziness and somnolence) were more frequent with oxycodone or oxycodone plus paracetamol than with placebo, but studies of this type are of limited use for studying adverse effects. Limited information about oxycodone on its own suggests that it provided analgesia at doses greater than 5 mg, and that addition of paracetamol made it more effective. | Oxycodone is a strong opioid agonist used to treat severe pain. It is commonly combined with milder analgesics such as paracetamol. This review updates a previous review that concluded, based on limited data, that all doses of oxycodone exceeding 5 mg, with or without paracetamol, provided analgesia in postoperative pain, but with increased incidence of adverse events compared with placebo. Additional new studies provide more reliable estimates of efficacy and harm. Objectives To assess efficacy, duration of action, and associated adverse events of single dose oral oxycodone, with or without paracetamol, in acute postoperative pain in adults. Search methods Cochrane CENTRAL, MEDLINE, EMBASE and Oxford Pain Relief Database, searched in May 2009. Selection criteria Randomised, double blind, placebo‐controlled trials of single dose orally administered oxycodone, with or without paracetamol, in adults with moderate to severe acute postoperative pain. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Pain relief or pain intensity data were extracted and converted into the dichotomous outcome of number of participants with at least 50% pain relief over 4 to 6 hours, from which relative risk and number‐needed‐to‐treat‐to‐benefit (NNT) were calculated. Numbers of participants remedicating over specified time periods, and time‐to‐use of rescue medication, were sought as additional measures of efficacy. Adverse events and withdrawals information was collected. This updated review includes 20 studies, with 2641 participants. For oxycodone 15 mg alone compared with placebo, the NNT for at least 50% pain relief was 4.6 (95% Confidence Interval 2.9 to 11). For oxycodone 10 mg plus paracetamol 650 mg, the NNT was 2.7 (2.4 to 3.1). A dose response was demonstrated for this outcome with combination therapy. Duration of effect was 10 hours with oxycodone 10 mg plus paracetamol 650 mg, and 4 hours with half that dose. Fewer participants needed rescue medication over 6 hours at the higher dose. Adverse events occurred more frequently with combination therapy than placebo, but were generally described as mild to moderate in severity and rarely led to withdrawal. Single dose oxycodone is an effective analgesic in acute postoperative pain at doses over 5 mg; oxycodone is two to three times stronger than codeine. Efficacy increases when combined with paracetamol. Oxycodone 10 mg plus paracetamol 650 mg provides good analgesia to half of those treated, comparable to commonly used non‐steroidal anti‐inflammatory drugs, with the benefit of longer duration of action. |
t190 | We investigated if giving drugs before surgery for uterine fibroids improves outcomes. Uterine fibroids are smooth muscle tumours of the uterus (womb) that can cause fertility problems, heavy menstrual bleeding, repeated pregnancy loss and pelvic pain. Fibroids are usually treated by surgery. Some drugs, particularly gonadotropin‐releasing hormone analogues (GnRHa), have been used to temporarily control bleeding and reduce fibroid and uterine size before surgery. They are unsuitable for long‐term use because they may cause bone loss. Other drugs, including progestins, dopamine agonists, selective progesterone receptor modulators (SPRMs), oestrogen receptor antagonists and selective oestrogen receptor modulators (SERMs), may also provide benefits used short‐term. However, such therapies tend to be expensive. We included 38 studies that involved 3623 women with fibroids that caused symptoms and who were scheduled for surgery to remove the fibroids. Surgeries were either hysterectomy (uterus removal) or myomectomy or resection (removal of fibroids from the uterus wall). Many women were anaemic (had low red blood cell or haemoglobin levels). The studies compared GnRHa with no treatment or sham treatment, GnRHa with other medical treatments, and SPRMs with sham treatment. GnRHa increased haemoglobin levels before surgery and decreased uterine and fibroid size, compared with no treatment or placebo. Blood loss, need for blood transfusion, operation time during hysterectomy and postoperative complications were reduced. However, women were more likely to experience hot flushes during treatment. An SPRM drug (ulipristal acetate) had similar benefits, particularly reduced bleeding. | Uterine fibroids occur in up to 40% of women aged over 35 years. Some are asymptomatic, but up to 50% cause symptoms that warrant therapy. Symptoms include anaemia caused by heavy menstrual bleeding, pelvic pain, dysmenorrhoea, infertility and low quality of life. Surgery is the first choice of treatment. In recent years, medical therapies have been used before surgery to improve intraoperative and postoperative outcomes. However, such therapies tend to be expensive. Fibroid growth is stimulated by oestrogen. Gonadotropin‐hormone releasing analogues (GnRHa) induce a state of hypo‐oestrogenism that shrinks fibroids , but has unacceptable side effects if used long‐term. Other potential hormonal treatments, include progestins and selective progesterone‐receptor modulators (SPRMs). This is an update of a Cochrane Review published in 2000 and 2001; the scope has been broadened to include all preoperative medical treatments. Objectives To assess the effectiveness and safety of medical treatments prior to surgery for uterine fibroids. Search methods We searched the Cochrane Gynaecology and Fertility Group specialised register, CENTRAL, MEDLINE, Embase, PsycINFO and CINAHL in June 2017. We also searched trials registers (ClinicalTrials.com; WHO ICTRP), theses and dissertations and the grey literature, handsearched reference lists of retrieved articles and contacted pharmaceutical companies for additional trials. Selection criteria We included randomised comparisons of medical therapy versus placebo, no treatment, or other medical therapy before surgery, myomectomy, hysterectomy or endometrial resection, for uterine fibroids. Data collection and analysis We used standard methodological procedures expected by The Cochrane Collaboration. We included a total of 38 RCTs (3623 women); 19 studies compared GnRHa to no pretreatment (n = 19), placebo (n = 8), other medical pretreatments (progestin, SPRMs, selective oestrogen receptor modulators (SERMs), dopamine agonists, oestrogen receptor antagonists) (n = 7), and four compared SPRMs with placebo. Most results provided low‐quality evidence due to limitations in study design (poor reporting of randomisation procedures, lack of blinding), imprecision and inconsistency. GnRHa versus no treatment or placebo GnRHa treatments were associated with reductions in both uterine (MD ‐175 mL, 95% CI ‐219.0 to ‐131.7; 13 studies; 858 participants; I² = 67%; low‐quality evidence) and fibroid volume (heterogeneous studies, MD 5.7 mL to 155.4 mL), and increased preoperative haemoglobin (MD 0.88 g/dL, 95% CI 0.7 to 1.1; 10 studies; 834 participants; I² = 0%; moderate‐quality evidence), at the expense of a greater likelihood of adverse events, particularly hot flushes (OR 7.68, 95% CI 4.6 to 13.0; 6 studies; 877 participants; I² = 46%; moderate‐quality evidence). Duration of hysterectomy surgery was reduced among women who received GnRHa treatment (‐9.59 minutes, 95% CI 15.9 to ‐3.28; 6 studies; 617 participants; I² = 57%; low‐quality evidence) and there was less blood loss (heterogeneous studies, MD 25 mL to 148 mL), fewer blood transfusions (OR 0.54, 95% CI 0.3 to 1.0; 6 studies; 601 participants; I² = 0%; moderate‐quality evidence), and fewer postoperative complications (OR 0.54, 95% CI 0.3 to 0.9; 7 studies; 772 participants; I² = 28%; low‐quality evidence). GnRHa appeared to reduce intraoperative blood loss during myomectomy (MD 22 mL to 157 mL). There was no clear evidence of a difference among groups for other primary outcomes after myomectomy: duration of surgery (studies too heterogeneous for pooling), blood transfusions (OR 0.85, 95% CI 0.3 to 2.8; 4 studies; 121 participants; I² = 0%; low‐quality evidence) or postoperative complications (OR 1.07, 95% CI 0.43 to 2.64; I² = 0%; 5 studies; 190 participants; low‐quality evidence). No suitable data were available for analysis of preoperative bleeding. GnRHa versus other medical therapies GnRHa was associated with a greater reduction in uterine volume (‐47% with GnRHa compared to ‐20% and ‐22% with 5 mg and 10 mg ulipristal acetate) but was more likely to cause hot flushes (OR 12.3, 95% CI 4.04 to 37.48; 5 studies; 183 participants; I² = 61%; low‐quality evidence) compared with ulipristal acetate. There was no clear evidence of a difference in bleeding reduction (ulipristal acetate 5 mg: OR 0.71, 95% CI 0.3 to 1.7; 1 study; 199 participants; moderate‐quality evidence; ulipristal acetate 10 mg: OR 0.39, 95% CI 0.1 to 1.1; 1 study; 203 participants; moderate‐quality evidence) or haemoglobin levels (MD ‐0.2, 95% CI ‐0.6 to 0.2; 188 participants; moderate‐quality evidence). There was no clear evidence of a difference in fibroid volume between GnRHa and cabergoline (MD 12.71 mL, 95% CI ‐5.9 to 31.3; 2 studies; 110 participants; I² = 0%; low‐quality evidence). The included studies did not report usable data for any other primary outcomes. SPRMs versus placebo SPRMs (mifepristone, CDB‐2914, ulipristal acetate and asoprisnil) were associated with greater reductions in uterine or fibroid volume than placebo (studies too heterogeneous to pool) and increased preoperative haemoglobin levels (MD 0.93 g/dL, 0.5 to 1.4; 2 studies; 173 participants; I² = 0%; high‐quality evidence). Ulipristal acetate and asoprisnil were also associated with greater reductions in bleeding before surgery (ulipristal acetate 5 mg: OR 41.41, 95% CI 15.3 to 112.4; 1 study; 143 participants; low‐quality evidence; ulipristal acetate 10 mg: OR 78.83, 95% CI 24.0 to 258.7; 1 study; 146 participants; low‐quality evidence; asoprisnil: MD ‐166.9 mL; 95% CI ‐277.6 to ‐56.2; 1 study; 22 participants; low‐quality evidence). There was no evidence of differences in preoperative complications. No other primary outcomes were measured. A rationale for the use of preoperative medical therapy before surgery for fibroids is to make surgery easier. There is clear evidence that preoperative GnRHa reduces uterine and fibroid volume, and increases preoperative haemoglobin levels, although GnRHa increases the incidence of hot flushes. During hysterectomy, blood loss, operation time and complication rates were also reduced. Evidence suggests that ulipristal acetate may offer similar advantages (reduced fibroid volume and fibroid‐related bleeding and increased haemoglobin levels) although replication of these studies is advised before firm conclusions can be made. Future research should focus on cost‐effectiveness and distinguish between groups of women with fibroids who would most benefit. |
t191 | Blockages in the arteries to the legs ‐ peripheral arterial disease ‐ affect 20% of people over 70 years of age and 4% to 12% of the population aged 55 to 70 years. Approximately 40% of those affected with peripheral arterial disease complain of pain in the legs on walking, this is known as intermittent claudication. Intermittent claudication is characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. The symptoms of intermittent claudication are an indicator for the development of blocked arteries elsewhere in the body. Compared with age‐matched controls, people with intermittent claudication have a three‐ to six‐fold increased chance of dying as a result of cardiovascular events. The majority of patients with intermittent claudication are treated with best medical management. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, which includes smoking cessation and a structured exercise programme. Further cardiovascular risk modification includes treatment for hypertension, diabetes and cholesterol reduction. In practice, compliance with best medical treatment is poor and most people continue to have symptoms of intermittent claudication. Some drug therapies are used specifically to help improve walking distance in intermittent claudication and cilostazol is one of these. We have looked at the evidence supporting cilostazol in improving the symptoms of intermittent claudication. This review included fifteen double‐blind, randomised controlled trials, with a total of 3718 participants. The risk of bias was poor over all of the studies but the results from this review suggest that cilostazol improves walking distances and ankle‐brachial pressure (blood pressure in the legs) for people with intermittent claudication. | Peripheral arterial disease (PAD) affects between 4% and 12% of people aged 55 to 70 years, and 20% of people over 70 years. A common complaint is intermittent claudication, characterised by pain in the legs or buttocks that occurs with exercise and which subsides with rest. Compared with age‐matched controls, people with intermittent claudication have a three‐ to six‐fold increase in cardiovascular mortality. Symptoms of intermittent claudication, walking distance, and quality of life can be improved by risk factor modification, smoking cessation, and a structured exercise programme. Antiplatelet treatment is beneficial in patients with intermittent claudication for the reduction of vascular events but has not previously been shown to influence claudication distance. This is an update of a review first published in 2007. Objectives To determine the effect of cilostazol (an antiplatelet treatment) on improving initial and absolute claudication distances, and in reducing mortality and vascular events in patients with stable intermittent claudication. Search methods For this update, the Cochrane Peripheral Vascular Diseases Group Trials Search Co‐ordinator searched the Specialised Register (last searched October 2013) and CENTRAL (2013, Issue 9). Selection criteria Double‐blind, randomised controlled trials (RCTs) of cilostazol versus placebo, or versus other antiplatelet agents in patients with stable intermittent claudication. Data collection and analysis Two authors independently assessed trials for selection and independently extracted data. Disagreements were resolved by discussion. We performed the meta‐analysis as a fixed‐effect model with weighted mean differences (WMDs) and 95% confidence intervals (CIs) for continuous data, and odds ratios (ORs) with 95% CIs for dichotomous data. We included fifteen double‐blind, RCTs comparing cilostazol with placebo, or medications currently known to increase walking distance e.g. pentoxifylline. There were a total of 3718 randomised participants with treatment durations ranging from six to 26 weeks. All participants had intermittent claudication secondary to PAD. Comparisons included cilostazol twice daily, with dosages of 50 mg, 100 mg and 150 mg compared with placebo, and cilostazol 100 mg, twice daily, compared with pentoxifylline 400 mg, three times daily. The methodological quality of the trials was generally low, with the majority being at an unclear risk for selection bias, performance bias, detection bias and other bias. Attrition bias was generally low, but reporting bias was high or unclear in the majority of the studies. For eight studies data were compatible for comparison by meta‐analysis, but data for seven studies were too heterogenous to be pooled. For the studies included in the meta‐analysis, for initial claudication distance (ICD ‐ the distance walked on a treadmill before the onset of calf pain) there was an improvement in the cilostazol group for the 100 mg and 50 mg twice daily, compared with placebo (WMD 31.41 metres, 95% CI 22.38 to 40.45 metres; P < 0.00001) and WMD 19.89 metres, 95% CI 9.44 to 30.34 metres; P = 0.0002), respectively. ICD was improved in the cilostazol group for the comparison of cilostazol 150 mg versus placebo and cilostazol 100 mg versus pentoxifylline, but only single studies were used for these analyses. Absolute claudication distance (ACD ‐ the maximum distance walked on a treadmill) was significantly increased in participants taking cilostazol 100 mg and 50 mg twice daily, compared with placebo (WMD 43.12 metres, 95% CI 18.28 to 67.96 metres; P = 0.0007) and WMD 32.00 metres, 95% CI 14.17 to 49.83 metres; P = 0.0004), respectively. As with ICD, ACD was increased in participants taking cilostazol 150 mg versus placebo, but with only one study an association cannot be clearly determined. Two studies comparing cilostazol to pentoxifylline had opposing findings, resulting in an imprecise CI (WMD 13.42 metres (95% CI ‐43.51 to 70.35 metres; P = 0.64). Ankle brachial index (ABI) was lowered in the cilostazol 100 mg group compared with placebo (WMD 0.06, 95% CI 0.04 to 0.08; P < 0.00001). The single study evaluating ABI for the comparison of cilostazol versus pentoxifylline found no change in ABI. There was no association between treatment type and all‐cause mortality for any of the treatment comparisons, but there were very few events, and therefore larger, adequately powered studies will be needed to assess if there is a relationship. Only one study evaluated individual cardiovascular events, and from this study there is no clear evidence of a difference between any of the treatment groups and risk of myocardial infarction or stroke. We evaluated adverse side effects, and in general cilostazol was associated with a higher odds of headache, diarrhoea, abnormal stool, dizziness and palpitations. We only reported quality of life measures descriptively as there was insufficient statistical detail within the studies to combine the results, although there was a possible indication in improvement of quality of life in the cilostazol treatment groups. Cilostazol has been shown to be of benefit in improving walking distance in people with intermittent claudication secondary to PAD. Although there is an increase in adverse side effects, they are generally mild and treatable. There is currently insufficient data on whether taking cilostazol results in a reduction of all‐cause mortality and cardiovascular events or an improvement in quality of life. Future research into the effect of cilostazol on intermittent claudication should carefully consider comparability, sample size and homogeneity when designing a study. |
t192 | Not taking enough physical activity leads to an increased risk of a number of chronic diseases including coronary heart disease. Regular physical activity can reduce this risk and also provide other physical and possibly mental health benefits. The majority of adults are not active at recommended levels. The findings of this review indicate that professional advice and guidance with continued support can encourage people to be more physically active in the short to mid‐term. More research is needed to establish which methods of exercise promotion work best in the long‐term to encourage specific groups of people to be more physically active. | Little is known about the effectiveness of strategies to enable people to achieve and maintain recommended levels of physical activity. Objectives To assess the effectiveness of interventions designed to promote physical activity in adults aged 16 years and older, not living in an institution. Search methods We searched The Cochrane Library ( issue 1 2005), MEDLINE, EMBASE, CINAHL, PsycLIT, BIDS ISI, SPORTDISCUS, SIGLE, SCISEARCH (from earliest dates available to December 2004). Reference lists of relevant articles were checked. No language restrictions were applied. Selection criteria Randomised controlled trials that compared different interventions to encourage sedentary adults not living in an institution to become physically active. Studies required a minimum of six months follow up from the start of the intervention to the collection of final data and either used an intention‐to‐treat analysis or, failing that, had no more than 20% loss to follow up. Data collection and analysis At least two reviewers independently assessed each study quality and extracted data. Study authors were contacted for additional information where necessary. Standardised mean differences and 95% confidence intervals were calculated for continuous measures of self‐reported physical activity and cardio‐respiratory fitness. For studies with dichotomous outcomes, odds ratios and 95% confidence intervals were calculated. The effect of interventions on self‐reported physical activity (19 studies; 7598 participants) was positive and moderate (pooled SMD random effects model 0.28 95% CI 0.15 to 0.41) as was the effect of interventions (11 studies; 2195 participants) on cardio‐respiratory fitness (pooled SMD random effects model 0.52 95% CI 0.14 to 0.90). There was significant heterogeneity in the reported effects as well as heterogeneity in characteristics of the interventions. The heterogeneity in reported effects was reduced in higher quality studies, when physical activity was self‐directed with some professional guidance and when there was on‐going professional support. Our review suggests that physical activity interventions have a moderate effect on self‐reported physical activity, on achieving a predetermined level of physical activity and cardio‐respiratory fitness. Due to the clinical and statistical heterogeneity of the studies, only limited conclusions can be drawn about the effectiveness of individual components of the interventions. Future studies should provide greater detail of the components of interventions. |
t193 | Ingrowing toenails are a common problem and occur when the edge of the nail grows into flesh at the side of the nail, causing a painful injury. This punctured skin can become inflamed and infected. This is an update of the Cochrane review 'Surgical treatments for ingrowing toenails'. We have broadened the scope of this review to include all types of treatment for ingrowing toenails. As well as including non‐surgical treatments for ingrowing toenails, we have also looked at surgical interventions with pre‐ and postoperative interventions to reduce postoperative complications. We included 24 randomised controlled trials, with a total of 2826 participants, and our aim was to determine which is the most effective treatment. By comparison with non‐surgical interventions, surgical interventions are more effective in preventing the recurrence of an ingrowing toenail. We found that none of postoperative treatments used, such as antibiotics or manuka honey; povidone‐iodine with paraffin; hydrogel with paraffin; or paraffin gauze, reduced the risk of postoperative infection or postoperative pain, or gave a shorter healing time. Different non‐surgical and surgical interventions for ingrowing toenails are available, but there is no agreement about a standard first‐choice treatment. | Ingrowing toenails are a common problem in which part of the nail penetrates the skinfold alongside the nail, creating a painful area. Different non‐surgical and surgical interventions for ingrowing toenails are available, but there is no consensus about a standard first‐choice treatment. Objectives To evaluate the effects of non‐surgical and surgical interventions in a medical setting for ingrowing toenails, with the aim of relieving symptoms and preventing regrowth of the nail edge or recurrence of the ingrowing toenail. Search methods We updated our searches of the following databases to January 2010: the Cochrane Skin Group Specialised Register, CENTRAL in The Cochrane Library , MEDLINE, and EMBASE. We also updated our searches of CINAHL, WEB of SCIENCE, ongoing trials databases, and reference lists of articles. Selection criteria Randomised controlled trials of non‐surgical and surgical interventions for ingrowing toenails, which are also known by the terms 'unguis incarnatus' and 'onychocryptosis', and those comparing postoperative treatment options. Studies must have had a follow‐up period of at least one month. Data collection and analysis Two authors independently selected studies, assessed methodological quality, and extracted data from selected studies. We analysed outcomes as risk ratios (RR) with 95% confidence intervals (CI). This is an update of the Cochrane review 'Surgical treatments for ingrowing toenails'. In this update we included 24 studies, with a total of 2826 participants (of which 7 were also included in the previous review). Five studies were on non‐surgical interventions, and 19 were on surgical interventions. The risk of bias of each included study was assessed; this is a measure of the methodological quality of several characteristics in these studies. It was found to be unclear for several items, due to incomplete reporting. Participants were not blinded to the treatment they received because of the nature of the interventions, e.g. surgery or wearing a brace on the toe. Outcome assessors were reported to be blinded in only 9 of the 24 studies. None of the included studies addressed our primary outcomes of 'relief of symptoms' or 'regrowth', but 16 did address 'recurrence'. Not all of the included studies addressed all of our secondary outcomes (healing time, postoperative complications ‐ infection and haemorrhage, pain of operation/postoperative pain, participant satisfaction), and two studies did not address any of the secondary outcomes. Surgical interventions were better at preventing recurrence than non‐surgical interventions with gutter treatment (or gutter removal), and they were probably better than non‐surgical treatments with orthonyxia (brace treatment). In 4 of the 12 studies in which a surgical intervention with chemical ablation (e.g. phenol) was compared with a surgical intervention without chemical ablation, a significant reduction of recurrence was found. The surgical interventions on both sides in these comparisons were not equal, so it is not clear if the reduction was caused by the addition of the chemical ablation. In only one study, a comparison was made of a surgical intervention known as partial nail avulsion with matrix excision compared to the same surgical intervention with phenol. In this study of 117 participants, the surgical intervention with phenol was significantly more effective in preventing recurrence than the surgical intervention alone (14% compared to 41% respectively, RR 0.34, 95% CI 0.17 to 0.69). None of the postoperative interventions described, such as the use of antibiotics or manuka honey; povidone‐iodine with paraffin; hydrogel with paraffin; or paraffin gauze, showed any significant difference when looking at infection rates, pain, or healing time. Surgical interventions are more effective than non‐surgical interventions in preventing the recurrence of an ingrowing toenail. In the studies comparing a surgical intervention to a surgical intervention with the application of phenol, the addition of phenol is probably more effective in preventing recurrence and regrowth of the ingrowing toenail. Because there is only one study in which the surgical interventions in both study arms were equal, more studies have to be done to confirm these outcomes. Postoperative interventions do not decrease the risk of postoperative infection, postoperative pain, or healing time. |
t194 | Uterine fibroids are also known as uterine leiomyoma, myoma or fibromyoma and are non‐cancerous benign growths in the uterus. Fibroids are the most common benign tumours in females and are typically found during the middle and later reproductive years. Common symptoms include heavy bleeding, menstrual pain, pressure in lower abdomen, infertility or miscarriage. Fibroids can be treated with surgery using either myomectomy (removal of fibroids leaving the uterus in place) or hysterectomy (removal of uterus). Drugs such as mifepristone have been suggested as a therapeutic option. This review includes three trials and 112 women with uterine fibroids under mifepristone treatment. These clinical trials included a small number of participants and show limited methodological quality. The studies included in this review show that mifepristone had a moderate effect in relief of bleeding and showed an improvement in fibroid‐specific quality of life. Determination of the effects of mifepristone on uterine fibroid volume requires much larger trials to draw a confident conclusion for mifepristone in clinical use. | Uterine fibroids are the most common benign uterine tumours present in women of reproductive age. Mifepristone (RU‐486) competitively binds and inhibits progesterone receptors. Studies have suggested that fibroid growth depends on the sexual steroids. Mifepristone has been shown to decrease fibroid size. This review summarises the effects of mifepristone treatment on fibroids and the associated adverse effects as described in randomised controlled trials. Objectives To determine the efficacy and safety of mifepristone for the management of uterine fibroids in pre‐menopausal women. Search methods We searched the specialised register of the Cochrane Menstrual Disorders and Subfertility (Cochrane Menstrual Disorders and subfertility Review Group), the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library 2011, Issue 4), MEDLINE, EMBASE, PsycINFO, and CINAHL (to November 2011). We handsearched a number of journals, and searched reference lists, databases of ongoing trials and the Internet. There were no language restrictions. Selection criteria Only truly randomised controlled trials of mifepristone versus other forms of medical therapy or placebo in pre‐menopausal women with confirmed uterine fibroids were included. Data collection and analysis Four authors independently extracted data and assessed trial quality. Data were analysed using the Peto odds ratios (OR) for dichotomous data and the weighted mean differences for continuous data, with 95% confidence intervals (CI). Meta‐analyses were performed using the fixed‐effect model. Three studies involving 112 participants were included. Comparison interventions included different dosages of mifepristone, placebo and vitamin B tablets. There is evidence that treatment with mifepristone relieves heavy menstrual bleeding compared with placebo (Peto OR 17.84; 95% CI 6.72 to 47.38; 2 RCTs, 77 women, I 2 = 0%). Three studies ( Bagaria 2009 ; Engman 2009 ; Fiscella 2006 ) were included in the meta‐analysis of this comparison. There was no evidence of an effect of mifepristone on the fibroid volume (standardised mean difference (SMD) ‐0.02; 95% CI ‐0.38 to 0.41; 99 women). Two studies ( Bagaria 2009 ; Fiscella 2006 ) were included in the meta‐analysis of this comparison. There was no evidence of an effect of mifepristone on uterine volume (mean difference (MD) ‐77.24; 95% CI ‐240.62 to 86.14; 72 women). The pooled data suggest an increased adverse event (abnormal endometrial histology) in the mifepristone group compared to placebo (OR 31.65; 95% CI 4.83 to 207.35; 2 RCTs; 54 women; I 2 = 0%). Only one study ( Bagaria 2009 ) reported endometrial hyperplasia at the end of the therapy (12/19 women in the mifepristone group versus 0/16 in the placebo group; OR 55.0; 95% CI 2.86 to 105.67). Engman 2009 found a significantly higher rate of cystic glandular dilatation in women in the mifepristone group (5/8 women biopsied) compared with the placebo group (1/11 women biopsied) (OR 16.67; 95% CI 1.36 to 204.03). One study ( Fiscella 2006 ) suggested significant improvements (P < 0.001) for specific quality of life outcomes. Mifepristone reduced heavy menstrual bleeding and improved fibroid‐specific quality of life. However, it was not found to reduce fibroid volume. Further well‐designed, adequately powered RCTs are needed before a recommendation can be made on the use of mifepristone for the treatment of uterine fibroids. |
t195 | For low‐ and middle‐income families, in‐work tax credit for families (IWTC) interventions to reduce poverty and unemployment (both of which are thought to harm health) could be expected to improve health status in adults. This review sought to assess the effects of IWTCs on health outcomes in working‐age adults (18 to 64 years). The review included randomised and quasi‐randomised controlled trials and cohort, controlled before‐and‐after and interrupted time series studies of IWTCs in working‐age adults. We looked for studies which reported adult self rated general health; mental health/psychological distress; mental illness; overweight/obesity; alcohol use and tobacco use. Five studies comprising a total of 5,677,383 participants (all women) were included in the review. Because all of these non‐experimental studies had considerable systematic errors in the way they conducted their analysis, we judged this body of evidence to have very low overall quality. This review found weak evidence that in‐work tax credit for families interventions had no effect on health status, except for mixed evidence for tobacco use in adult women, where some studies suggested that rates of smoking reduced. | By improving two social determinants of health (poverty and unemployment) in low‐ and middle‐income families on or at risk of welfare, in‐work tax credit for families (IWTC) interventions could impact health status and outcomes in adults. Objectives To assess the effects of IWTCs on health outcomes in working‐age adults (18 to 64 years). Search methods We searched 16 electronic academic databases, including the Cochrane Public Health Group Specialised Register, Cochrane Database of Systematic Reviews ( The Cochrane Library 2012, Issue 7), MEDLINE and EMBASE, as well as six grey literature databases between July and September 2012 for records published between January 1980 and July 2012. We also searched key organisational websites, handsearched reference lists of included records and relevant journals, and contacted academic experts. Selection criteria We included randomised and quasi‐randomised controlled trials and cohort, controlled before‐and‐after (CBA) and interrupted time series (ITS) studies of IWTCs in working‐age adults. Included primary outcomes were: self rated general health; mental health/psychological distress; mental illness; overweight/obesity; alcohol use and tobacco use. Data collection and analysis Two review authors independently extracted data and assessed the risk of bias in included studies. We contacted study authors to obtain missing information. Five studies (one CBA and four ITS) comprising a total of 5,677,383 participants (all women) fulfilled the inclusion criteria and were synthesised narratively. The in‐work tax credit intervention assessed in all included studies is the permanent Earned Income Tax Credit in the United States, established in 1975. This intervention distributed nearly USD 62 billion to over 27 million individuals in 2011, and its administration costs were less than one per cent of its total costs. All included studies carried a high risk of bias (especially from confounding and insufficient control for underlying time trends). Due to the small number of (observational) studies and their high risk of bias, we judged this body of evidence to have very low overall quality. One study found that IWTC had no detectable effect on self rated general health and mental health/psychological distress five years after its implementation (i.e. a considerable change in the generosity of the permanent IWTC) and on overweight/obesity eight years after implementation. One study found no effect of IWTC on tobacco use five years after implementation, one a moderate reduction in tobacco use one year after implementation (odds ratio 0.95, 95% confidence interval (CI) 0.94 to 0.96), and one differential effects, with no effect in African‐Americans and a large reduction in European‐Americans two years after implementation (risk difference ‐11.1%, 95% CI ‐20.9% to ‐1.3%). No evidence was available for the effect of IWTC on mental illness and alcohol use. No adverse effects of IWTC were identified. One study also found no detectable effect of IWTC on the number of bad physical health days and of risky biomarkers for inflammation, cardiovascular disease and metabolic conditions eight years after implementation. One study found that IWTC had a large, positive effect on income from wages or salaries one year after implementation. Two studies found no effect on employment two and five years after implementation, whereas two found a moderate increase five and eight years after implementation and one a large increase in employment due to IWTC one year after implementation. No differences in outcomes between groups with different educational status were found for self rated health and mental health/psychological distress. In one study European‐American women with lower levels of education were more likely to reduce tobacco use, while tobacco use did not change among African‐American women with lower levels of education. However, no differences in tobacco use by educational status were observed in a second study. Two studies found that the intervention may have reduced inequity with respect to employment, where women with less education were more likely to move into employment (although one did not establish whether this difference was statistically significant), while two studies found no such difference and no studies found differences by ethnic group on employment rates. In summary, the small and methodologically limited existing body of evidence with a high risk of bias provides no evidence for an effect of in‐work tax credit for families interventions on health status (except for mixed evidence for tobacco smoking) in adults. |
t196 | Cancer patients develop neutropenia, a decrease in the neutrophil subset of the white blood cells, as a result of chemotherapy. Neutropenia exposes patients to infections, mainly bacterial. Without antibiotic treatment these infections may be fatal, therefore antibiotic treatment is administered when a patient with neutropenia develops fever. The objective of this review was to compare antibiotic treatments currently recommended in consensus guidelines for the initial treatment of cancer patients with fever and neutropenia. We identified 44 studies comparing different antibiotics. Cefepime resulted in significantly higher mortality compared to all other antibiotics combined, at the end of patients' hospital stay or 30 days after entry into the study. The risk was 39% higher with cefepime, ranging from 4 to 86% increased risk. We did not find an explanation for this when looking into other outcomes reported in the primary studies. Piperacillin‐tazobactam resulted in lower mortality than other antibiotics. The other antibiotics (ceftazidime, imipenem and meropenem) showed comparable efficacy, with a lower rate of antibiotic changes for imipenem or meropenem and a higher rate of severe diarrhea with these two antibiotics. We conclude that piperacillin‐tazobactam might be the preferred antibiotic for the treatment of cancer patients with fever and neutropenia and that cefepime should not be used. Antibiotic selection (other than cefepime) depends on the individual patient and the type of bacteria prevalent in the specific hospital. | Several beta‐lactams are recommended as single agents for the treatment of febrile neutropenia. Objectives To compare the effectiveness of different anti‐pseudomonal beta‐lactams as single agents in the treatment of febrile neutropenia. To compare the development of bacterial resistance, bacterial and fungal superinfections during or following treatment with the different beta‐lactams. Search methods We searched the Cochane Register of Controlled Trials (CENTRAL), Issue 3, 2010. MEDLINE, EMBASE, LILACS, FDA drug applications, conference proceedings and ongoing clinical trial databases up to August 2010. References of included studies were scanned. Selection criteria Randomised controlled trials (RCTs) comparing an antipseudomonal beta‐lactam to another antipseudomonal beta‐lactam antibiotic, both given alone or with the addition of the same glycopeptide to both study arms, for the initial treatment of fever and neutropenia among cancer patients. Data collection and analysis Two review authors applied inclusion criteria and extracted the data independently. Missing data were sought. Risk ratios (RR) were calculated with 95% confidence intervals (CI), and pooled using the fixed effect model. The primary outcome was all‐cause mortality. Risk of bias was assessed using a domain‐based evaluation and its effect of results was assessed through sensitivity analyses. Forty‐four trials were included. The antibiotics assessed were cefepime, ceftazidime, piperacillin‐tazobactam, imipenem and meropenem. Adequate allocation concealment and generation were reported in about half of the trials and only two trials were double‐blinded. The risk for all‐cause mortality was significantly higher with cefepime compared to other beta‐lactams (RR 1.39, 95% CI 1.04 to 1.86, 21 trials, 3471 participants), without heterogeneity and with higher RRs in trials at low risk for bias. There were no differences in secondary outcomes but for a non‐significantly higher rate of bacterial superinfections with cefepime. Mortality was significantly lower with piperacillin‐tazobactam compared to other antibiotics (RR 0.56, 95% CI 0.34 to 0.92, 8 trials, 1314 participants), without heterogeneity. Carbapenems resulted in similar all‐cause mortality and a lower rate of clinical failure and antibiotic modifications as compared to other antibiotics, but a higher rate of diarrhea caused by Clostridium difficile . Current evidence supports the use of piperacillin‐tazobactam in locations where antibiotic resistance profiles do not mandate empirical use of carbapenems. Carbapenems result in a higher rate of antibiotic‐associated and Clostridium difficile ‐associated diarrhea. There is a high level of evidence that all‐cause mortality is higher with cefepime compared to other beta‐lactams and it should not be used as monotherapy for patients with febrile neutropenia. |
t197 | Multiple myeloma (also known as myeloma or plasma cell myeloma) is a B‐cell malignancy or, more precisely, plasma cell neoplasm. This cancer grows inside or outside of bones. The bone damage, or osteolytic lesions, may lead to fractures of the long bones or compression fractures in the spine. The mechanism of bone destruction appears to be related to increased bone resorption by cells called osteoclasts. Bisphosphonates are drugs that can inhibit bone resorption by reducing the number and activity of osteoclasts. Use of bisphosphonates in participants with multiple myeloma did not improve overall survival or disease progression‐free survival. Use of bisphosphonates in participants with multiple myeloma reduces overall fractures, fractures of the vertebra but not the non‐vertebral fractures. Bisphosphonates also alleviates pain without many side effects except a significant increase in reduced blood flow to bones of the jaw resulting in decay of the bone also called osteonecrosis. Overall, for every 1000 participants treated with bisphosphonates, about one patient will suffer from the osteonecrosis of the jaw. Zoledronate was found to be better than etidronate and placebo, but not superior to pamidronate or clodronate for improving overall survival and other outcomes such as fractures in general or specifically fractures of vertebra. There was no evidence of superiority of any specific aminobisphosphonate (zoledronate, pamidronate or ibandronate) or non‐aminobisphosphonate (etidronate or clodronate) for any outcome. | Bisphosphonates are specific inhibitors of osteoclastic activity and are used in the treatment of patients with multiple myeloma (MM). While bisphosphonates are shown to be effective in reducing vertebral fractures and pain, their role in improving overall survival (OS) remains unclear. This is an update of a Cochrane review first published in 2002 and previously updated in 2010 and 2012. Objectives To assess the evidence related to benefits and harms associated with use of various types of bisphosphonates (aminobisphosphonates versus non‐aminobisphosphonates) in the management of patients with MM. Our primary objective was to determine whether adding bisphosphonates to standard therapy in MM improves OS and progression‐free survival (PFS), and decreases skeletal‐related morbidity. Our secondary objectives were to determine the effects of bisphosphonates on pain, quality of life, incidence of hypercalcemia, incidence of bisphosphonate‐related gastrointestinal toxicities, osteonecrosis of jaw (ONJ) and hypocalcemia. Search methods We searched MEDLINE, Embase (September 2011 to July 2017) and the CENTRAL (2017, Issue 7) to identify all randomized controlled trial (RCT) in MM up to July 2017 using a combination of text and MeSH terms. Selection criteria Any randomized controlled trial (RCT) comparing bisphosphonates versus placebo/no treatment/bisphosphonates and observational studies or case reports examining bisphosphonate‐related ONJ in patients with MM were eligible for inclusion. Data collection and analysis Two review authors extracted the data. Data were pooled and reported as hazard ratio (HR) or risk ratio (RR) using a random‐effects model. We used meta‐regression to explore statistical heterogeneity. Network meta‐analysis using Bayesian approach was conducted. In this update, we included four new studies (601 participants), resulting in a total of 24 included studies. Twenty RCTs compared bisphosphonates with either placebo or no treatment and four RCTs involved another bisphosphonate as a comparator. The 24 included RCTs enrolled 7293 participants. Pooled results showed that there was moderate‐quality evidence of a reduction in mortality with on OS from 41% to 31%, but the confidence interval is consistent with a larger reduction and small increase in mortality compared with placebo or no treatment (HR 0.90, 95% CI 0.76 to 1.07; 14 studies; 2706 participants). There was substantial heterogeneity among the included RCTs (I 2 = 65%) for OS. To explain this heterogeneity we performed a meta‐regression assessing the relationship between bisphosphonate potency and improvement in OS, which found an OS benefit with zoledronate but limited evidence of an effect on PFS. This provided a further rationale for performing a network meta‐analyses of the various types of bisphosphonates that were not compared head‐to‐head in RCTs. Results from network meta‐analyses showed evidence of a benefit for OS with zoledronate compared with etidronate (HR 0.56, 95% CI 0.29 to 0.87) and placebo (HR 0.67, 95% CI 0.46 to 0.91). However, there was no evidence for a difference between zoledronate and other bisphosphonates. The effect of bisphosphonates on disease progression (PFS) is uncertain. Based on the HR of 0.75 (95% CI 0.57 to 1.00; seven studies; 908 participants), 47% participants would experience disease progression without treatment compared with between 30% and 47% with bisphosphonates (low‐quality evidence). There is probably a similar risk of non‐vertebral fractures between treatment groups (RR 1.03, 95% CI 0.68 to 1.56; six studies; 1389 participants; moderate‐quality evidence). Pooled analysis demonstrated evidence for a difference favoring bisphosphonates compared with placebo or no treatment on prevention of pathological vertebral fractures (RR 0.74, 95% CI 0.62 to 0.89; seven studies; 1116 participants; moderate‐quality evidence) and skeletal‐related events (SREs) (RR 0.74, 95% CI 0.63 to 0.88; 10 studies; 2141 participants; moderate‐quality evidence). The evidence for less pain with bisphosphonates was of very low quality (RR 0.75, 95% CI 0.60 to 0.95; eight studies; 1281 participants). Bisphosphonates may increase ONJ compared with placebo but the confidence interval is very wide (RR 4.61, 95% CI 0.99 to 21.35; P = 0.05; six studies; 1284 participants; low‐quality evidence). The results from the network meta‐analysis did not show any evidence for a difference in the incidence of ONJ (eight RCTs, 3746 participants) between bisphosphonates. Data from nine observational studies (1400 participants) reported an incidence of 5% to 51% with combination of pamidronate and zoledronate, 3% to 11% with zoledronate alone, and 0% to 18% with pamidronate alone. The pooled results showed no evidence for a difference in increase in frequency of gastrointestinal symptoms with the use of bisphosphonates compared with placebo or no treatment (RR 1.23, 95% CI 0.95 to 1.59; seven studies; 1829 participants; low‐quality evidence).The pooled results showed no evidence for a difference in increase in frequency of hypocalcemia with the use of bisphosphonates compared with placebo or no treatment (RR 2.19, 95% CI 0.49 to 9.74; three studies; 1090 participants; low‐quality evidence). The results from network meta‐analysis did not show any evidence for differences in the incidence of hypocalcemia, renal dysfunction and gastrointestinal toxicity between the bisphosphonates used. Use of bisphosphonates in participants with MM reduces pathological vertebral fractures, SREs and pain. Bisphosphonates were associated with an increased risk of developing ONJ. For every 1000 participants treated with bisphosphonates, about one patient will suffer from the ONJ. We found no evidence of superiority of any specific aminobisphosphonate (zoledronate, pamidronate or ibandronate) or non‐aminobisphosphonate (etidronate or clodronate) for any outcome. However, zoledronate was found to be better than placebo and first‐generation bisposphonate (etidronate) in pooled direct and indirect analyses for improving OS and other outcomes such as vertebral fractures. Direct head‐to‐head trials of the second‐generation bisphosphonates are needed to settle the issue if zoledronate is truly the most efficacious bisphosphonate currently used in practice. |
t198 | Ventilators are machines that breathe for patients. The ventilator tube goes into the mouth and through the windpipe. Sometimes there are bacteria on the ventilator tube that infect the patient's lungs, leading to a disease called ventilator‐associated pneumonia. Ventilator‐associated pneumonia can cause significant harmful effects, and can sometimes lead to death. When treating people with ventilator‐associated pneumonia, doctors must decide which antibiotic therapy to prescribe, usually without knowing the particular type of bacterial infection. This decision is important because inappropriate initial treatment may increase risk of harmful effects and longer hospital stays. We looked at studies involving adults aged over 18 years who were treated in intensive care units for ventilator‐associated pneumonia and needed antibiotic treatment. We analysed 12 studies with 3571 participants. All included studies looked at the use of one antibiotic treatment plan versus another, but these varied among studies. There was potential for bias because some studies did not report outcomes for all participants, and funding for many was provided by pharmaceutical companies and study authors were affiliated with these companies. We used statistical techniques to evaluate our results. For single versus multiple antibiotics, we found no difference in rates of death or cure, or adverse events. For our comparison of combination therapies with optional adjunctives we were only able to analyse clinical cure for one the antibiotics Tigecycline and imipenem‐cilastatin for which imipenem‐cilastatin was found to have higher clinica cure. We also looked at carbapenem (antibiotics used to treat infections caused by multidrug‐resistant bacteria) versus non‐carbapenem treatment; we found no difference in death rate or adverse effects, but we found that carbapenems are associated with an increase in clinical cure. We did not find differences between single and combination therapy, lending support to use of a single‐antibiotic treatment plan for people with ventilator‐associated pneumonia. This may not be applicable to all patients because studies did not identify patients who are at risk of exposure to harmful types of bacteria. | Ventilator‐associated pneumonia (VAP) is a significant cause of morbidity and mortality, complicating the medical course of approximately 10% of mechanically‐ventilated patients, with an estimated attributable mortality of 13%. To treat VAP empirically, the American Thoracic Society currently recommends antibiotic therapy based on the patients' risk of colonisation by an organism with multidrug resistance. The selection of initial antibiotic therapy in VAP is important, as inappropriate initial antimicrobial treatment is associated with higher mortality and longer hospital stay in intensive care unit (ICU) patients. While guidelines exist for the antibiotic treatment of hospital‐acquired pneumonia (HAP) from the American Thoracic Society and the British Society for Antimicrobial Chemotherapy, there are many limitations in the quality of available evidence. This systematic review aimed to summarise the results of all randomised controlled trials (RCTs) that compare empirical antibiotic regimens for VAP. Objectives The primary objective of this review was to assess the effect of different empirical antimicrobial therapies on the survival and clinical cure of adult patients with ventilator‐associated pneumonia (VAP). Secondary objectives included reporting the incidence of adverse events, new superinfections, length of hospital stay, and length of intensive care unit (ICU) stay associated with these therapies. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, CINAHL and Web of Science to December 2015; we searched ClinicalTrials.gov to September 2016. Selection criteria Two review authors independently assessed RCTs comparing empirical antibiotic treatments of VAP in adult patients, where VAP was defined as new‐onset pneumonia that developed more than 48 hours after endotracheal intubation. Physicians and researchers were not required to be blinded for inclusion in this review. Data collection and analysis Two review authors independently extracted study data. We pooled studies and analysed them in two ways. We examined monotherapy, or a single experimental antimicrobial drug, versus combination therapy, or multiple experimental antimicrobial drugs. We also examined carbapenem therapy versus non‐carbapenem therapy. We included 12 studies with 3571 participants. All included studies examined the empiric use of one antimicrobial regimen versus another for the treatment of adults with VAP, but the particular drug regimens examined by each study varied. There was potential for bias because some studies did not report outcomes for all participants. All but one study reported sources of funding or author affiliations with pharmaceutical companies. We found no statistical difference in all‐cause mortality between monotherapy and combination therapy (N = 4; odds ratio (OR) monotherapy versus combination 0.97, 95% confidence interval (CI) 0.73 to 1.30), clinical cure (N = 2; OR monotherapy versus combination 0.88, 95% CI 0.56 to 1.36), length of stay in ICU (mean difference (MD) 0.65, 95% CI 0.07 to 1.23) or adverse events (N = 2; OR monotherapy versus combination 0.93, 95% CI 0.68 to 1.26). We downgraded the quality of evidence for all‐cause mortality, adverse events, and length of ICU stay to moderate for this comparison. We determined clinical cure for this comparison to be of very low‐quality evidence. For our second comparison of combination therapy with optional adjunctives only one meta‐analysis could be performed due to a lack of trials comparing the same antibiotic regimens. Two studies compared tigecycline versus imipenem‐cilastatin for clinical cure in the clinically evaluable population and there was a statistically significant increase in clinical cure for imipenem‐cilastatin (N = 2; OR tigecycline versus imipenem‐cilastatin 0.44, 95% CI 0.23 to 0.84). Of importance, this effect was due to a single study. We found no statistical difference in all‐cause mortality between carbapenem and non‐carbapenem therapies (N = 1; OR carbapenem versus non‐carbapenem 0.59, 95% CI 0.30 to 1.19) or adverse events (N = 3; OR carbapenem versus non‐carbapenem 0.78, 95% CI 0.56 to 1.09), but we found that carbapenems are associated with a statistically significant increase in the clinical cure (N = 3; OR carbapenem versus non‐carbapenem 1.53, 95% CI 1.11 to 2.12 for intention‐to‐treat (ITT) analysis and N = 2; OR carbapenem versus non‐carbapenem 2.29, 95% CI 1.19 to 4.43 for clinically evaluable patients analysis). For this comparison we downgraded the quality of evidence for mortality, and clinical cure (ITT and clinically evaluable populations) to moderate. We determined the quality of evidence for adverse events to be low. We did not find a difference between monotherapy and combination therapy for the treatment of people with VAP. Since studies did not identify patients with increased risk for multidrug‐resistant bacteria, these data may not be generalisable to all patient groups. However, this is the largest meta‐analysis comparing monotherapy to multiple antibiotic therapies for VAP and contributes further evidence to the safety of using effective monotherapy for the empiric treatment of VAP. Due to lack of studies, we could not evaluate the best antibiotic choice for VAP, but carbapenems as a class may result in better clinical cure than other tested antibiotics. |
t199 | Acute respiratory infection (including pneumonia) is one of the leading causes of morbidity and mortality in children under five years of age in developing countries. Antibiotics are needed when a bacterial infection is suspected. When children are hospitalised they often receive injectable antibiotics. This has disadvantages: pain, risk of other infections and cost. There are studies that show that oral antibiotics are effective when children are treated as outpatients. The objective of this review was to determine the effectiveness and safety of oral antibiotics compared to parenteral antibiotics in the treatment of pneumonia in children less than five years old. Oral therapy appears to be an effective and safe alternative to parenteral antibiotics in hospitalised children with severe pneumonia who do not have any serious signs or symptoms. There is currently insufficient evidence to determine the relative benefits and harms of oral antibiotics in children with severe pneumonia if serious signs and symptoms are present or in children with severe pneumonia associated with bacterial confirmation or lobar consolidation on chest X‐ray. | Acute respiratory infection (ARI) is one of the leading causes of morbidity and mortality in children under five years of age in developing countries. When hospitalisation is required, the usual practice includes administering parenteral antibiotics if a bacterial infection is suspected. This has disadvantages as it causes pain and discomfort to the children, which may lead to treatment refusal or reduced compliance. It is also associated with needle‐related complications. In some settings this equipment is in short supply or unavailable necessitating transfer of the child, which increases risks and healthcare costs. Objectives To determine the equivalence in effectiveness and safety of oral antibiotic compared to parenteral antibiotic therapies in the treatment of severe pneumonia in children between three months and five years of age. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL) ( The Cochrane Library, 2005, issue 2) which contains the Acute Respiratory Infections Group's specialized register; MEDLINE (January 1966 to July 2005); EMBASE (January 1990 to July 2005) and LILACS (February 2005). Selection criteria The review included published or unpublished randomised controlled trials (RCTs) and quasi‐RCTs comparing any oral antibiotic therapy with any parenteral antibiotic therapy for the treatment of severe pneumonia in children from three months to five years of age. Data collection and analysis The search yielded more than 1300 titles. Only three studies met all criteria for eligibility. One of the identified trials is yet to publish its results. We did not perform a meta‐analysis because of clinical heterogeneity of therapies compared in the included trials. Campbell 1988 compared oral co‐trimoxazole versus intramuscular procaine penicillin followed by oral ampicillin in 134 children. At the seventh day of follow up, treatment failure occurred in 6/66 (9.1%) in the oral co‐trimoxazole group and 7/68 (10.2%) in the combined‐treatment group. The risk difference was ‐0.01% (95% confidence interval (CI) ‐0.11 to 0.09). The APPIS Group 2004 evaluated 1702 patients comparing oral amoxicillin versus intravenous penicillin for two days followed by oral amoxicillin. After 48 hours, treatment failure occurred in 161/845 (19%) in the amoxicillin group and 167/857 (19%) in the parenteral penicillin group. The risk difference was ‐0.4% (95% CI ‐4.2 to 3.3). The authors reported similar recovery in both groups at 5 and 14 days. Oral therapy appears to be an effective and safe alternative to parenteral antibiotics in hospitalised children with severe pneumonia who do not have any serious signs or symptoms. |
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