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Clinical NLP Lab 23

CochranePLS1200

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 29 studies in the review, 21 of which were included in at least one meta-analysis. Non-legislative interventions increased observed helmet wearing (11 studies: OR 2.08, 95% CI 1.29 to 3.34). The effect was most marked amongst community-based interventions (four studies: OR 4.30, 95% 2.24 to 8.25) and those providing free helmets (two studies: OR 4.35, 95% CI 2.13 to 8.89). Significant effects were also found amongst school-based interventions (eight studies: OR 1.73, CI 95% 1.03 to 2.91), with a smaller effect found for interventions providing education only (three studies: OR 1.43, 95% CI 1.09 to 1.88). No significant effect was found for providing subsidised helmets (seven studies: OR 2.02, 95% CI 0.98 to 4.17). Interventions provided to younger children (aged under 12) may be more effective (five studies: OR 2.50, 95% CI 1.17 to 5.37) than those provided to children of all ages (five studies: OR 1.83, 95% CI 0.98 to 3.42). Interventions were only effective in increasing self reported helmet ownership where they provided free helmets (three studies: OR 11.63, 95% CI 2.14 to 63.16). Interventions were effective in increasing self reported helmet wearing (nine studies: OR 3.27, 95% CI 1.56 to 6.87), including those undertaken in schools (six studies: OR 4.21, 95% CI 1.06 to 16.74), providing free helmets (three studies: OR 7.27, 95% CI 1.28 to 41.44), providing education only (seven studies: OR 1.93, 95% CI 1.03 to 3.63) and in healthcare settings (two studies: OR 2.78, 95% CI 1.38 to 5.61). Non-legislative interventions appear to be effective in increasing observed helmet use, particularly community-based interventions and those providing free helmets. Those set in schools appear to be effective but possibly less so than community-based interventions. Interventions providing education only are less effective than those providing free helmets. There is insufficient evidence to recommend providing subsidised helmets at present. Interventions may be more effective if provided to younger rather than older children. There is evidence that interventions offered in healthcare settings can increase self reported helmet wearing. Further high-quality studies are needed to explore whether non-legislative interventions increase helmet wearing, and particularly the effect of providing subsided as opposed to free helmets, and of providing interventions in healthcare settings as opposed to in schools or communities. Alternative interventions (e.g. those including peer educators, those aimed at developing safety skills including skills in decision making and resisting peer pressure or those aimed at improving self esteem or self efficacy) need developing and testing, particularly for 11 to 18 year olds. The effect of interventions in countries with existing cycle helmet legislation and in low and middle-income countries also requires investigation. Output:

This review focused on encouraging children to wear helmets, as distinct from compelling them to do so through laws. The authors wanted to find out which sort of helmet programmes work best, particularly with children from poor families who are less likely to own helmets. They found 29 helmet promotion programmes that had been studied. The programmes varied widely with regard to where they were carried out, age of the children, programme methods, etc. The results were also very varied but overall 11 studies found that after a helmet programme children were more likely to be observed wearing helmets than other children. More research is still needed but it seems likely that the best schemes are based in the community and involve both education and providing free helmets. Promotion of helmets in schools also seems to be effective. Promoting helmets appears to be more effective for younger children (aged 12 years and under) than for older children and young people. The studies reviewed did not look at the impact of helmet programmes on injury rates, or assess whether programmes had any negative effects such as reducing cycling. Most of the studies were undertaken in higher-income countries and the additional effect of helmet promotion above existing legislation was not explored. More research is needed to understand more about whether providing subsidised helmets is as effective as providing free helmets and whether programmes in healthcare settings are as effective as those in schools or communities. Other types of helmet programmes (e.g. those including peer educators, those developing skills such as decision making and resisting peer pressure, or improving self esteem or self efficacy) need developing and testing, particularly for 11 to 18 year olds. The effect of helmet programmes in countries with existing cycle helmet legislation and in low and middle-income countries also requires investigation.

CochranePLS1201

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: No differences were found in contraceptive effectiveness for the 13 COC pairs for which this outcome was reported. Compared to the higher-estrogen pills, several COCs containing 20 μg EE resulted in higher rates of early trial discontinuation (overall and due to adverse events such as irregular bleeding) as well as increased risk of bleeding disturbances (both amenorrhea or infrequent bleeding and irregular, prolonged, frequent bleeding, or breakthrough bleeding or spotting). While COCs containing 20 μg EE may be theoretically safer, this review did not focus on the rare events required to assess this hypothesis. Data from existing randomized controlled trials are inadequate to detect possible differences in contraceptive effectiveness. Low-dose estrogen COCs resulted in higher rates of bleeding pattern disruptions. However, most trials compared COCs containing different progestin types, and changes in bleeding patterns could be related to progestin type as well as estrogen dose. Higher follow-up rates are essential for meaningful interpretation of results. Output:

In July 2013, we did computer searches for randomized trials of pills with 20 µg estrogen versus more estrogen. We did not find any new trials. For the initial review, we also wrote to researchers and makers of birth control pills to find other trials. Studies had to be written in the English language, include at least three cycles, and focus on birth control. The trials had to report on pregnancy, bleeding problems, or stopping the pills early. We also looked at side effects. More women taking the pills with less estrogen quit the studies early. The women on less estrogen also had more bleeding problems than those taking pills with more estrogen. Pregnancy rates seemed to be the same between groups, but the studies may not have been large enough to know for sure. This review did not focus on the rare events needed to test whether birth control pills with 20 µg estrogen were safer. Also, most trials compared pills with different types of the hormone progestin, which could also affect bleeding patterns. The high losses in many trials make the results hard to interpret.

CochranePLS1202

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 12 studies reporting data on 1642 participants (intervention = 833, control = 809). Eight studies targeted adults with epilepsy, one study included participants of all ages, one study included participants older than two years, one study targeted caregivers of children with epilepsy, and one study targeted families of children with epilepsy. We identified six ongoing trials. Follow-up time was generally short in most trials, ranging from one to 12 months. The trials examined three main types of interventions: educational interventions, behavioural interventions and mixed interventions. All studies compared treatment versus usual care or 'no intervention', except for two studies. Due to heterogeneity between studies in terms of interventions, methods used to measure adherence and the way the studies were reported, we did not pool the results and these findings were inappropriate to be included in a meta-analysis. Education and counselling of participants with epilepsy resulted in mixed success (moderate-quality evidence). Behavioural interventions such as use of intensive reminders provided more favourable effects on adherence (moderate-quality evidence). The effect on adherence to antiepileptic drugs described by studies of mixed interventions showed improved adherence in the intervention groups compared to the control groups (high-quality evidence). Behavioural interventions such as intensive reminders and the use of mixed interventions demonstrate some positive results; however, we need more reliable evidence on their efficacy, derived from carefully-designed randomised controlled trials before we can draw a firm conclusion. Since the last version of this review, none of the new relevant studies have provided additional information that would lead to significant changes in our conclusions. This current update includes 12 studies, of which six came from the latest searches. Output:

We searched scientific databases for clinical trials looking at ways of improving adherence to drug treatment in people with epilepsy. We limited our search to randomised controlled trials involving people with a clinical diagnosis of epilepsy of any age and treated with antiepileptic drugs in a primary care, outpatient or other community setting. The results are up-to-date to February 2016. We identified twelve trials (1642 participants). The trials were conducted in different countries with the majority from the United States. The trials examined three main types of interventions: i) education and counselling of participants about topics such as epilepsy and medication used to control epilepsy, ii) behavioural interventions such as asking epileptic patients to link the intention of taking their medication with a particular time, place and other routine activity and iii) the use of more than one intervention (mixed interventions). Behavioural interventions and mixed interventions resulted in an improved adherence in the intervention groups compared to the control groups. Four trials showed that when adherence improved in the intervention groups, seizure frequency or seizure severity was decreased. Many of the included trials are of moderate quality and have limitations in the design. Therefore, it is difficult to draw firm conclusions. We need carefully-designed randomised controlled trials involving more people with longer follow-up periods to identify the best intervention to improve adherence to antiepileptic medication.

CochranePLS1203

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 98 studies (147 articles). There were 88 core studies: 37 focused on advocates (4 survey-based, 3 instrument development, 30 qualitative focus) and seven on abused women (6 qualitative studies, 1 survey); 44 were experimental intervention studies (some including qualitative evaluations). Ten further studies (3 randomised controlled trials (RCTs), 1 intervention process evaluation, 1 qualitative study, 2 mixed methods studies, 2 surveys of women, and 1 mixed methods study of women and staff) did not fit the original criteria but added useful information, as befitting a realist approach. Two studies are awaiting classification and three are ongoing. Advocacy interventions varied considerably in contact hours, profession delivering and setting. We constructed a conceptual model from six essential principles based on context-mechanism-outcome (CMO) patterns. We have moderate and high confidence in evidence for the importance of considering both women's vulnerabilities and intersectionalities and the trade-offs of abuse-related decisions in the contexts of individual women's lives. Decisions should consider the risks to the woman's safety from the abuse. Whether actions resulting from advocacy increase or decrease abuse depends on contextual factors (e.g. severity and type of abuse), and the outcomes the particular advocacy intervention is designed to address (e.g. increasing successful court orders versus decreasing depression). We have low confidence in evidence regarding the significance of physical dependencies, being pregnant or having children. There were links between setting (high confidence), and potentially also theoretical underpinnings of interventions, type, duration and intensity of advocacy, advocate discipline and outcomes (moderate and low confidence). A good therapeutic alliance was important (high confidence); this alliance might be improved when advocates are matched with abused women on ethnicity or abuse experience, exercise cultural humility, and remove structural barriers to resource access by marginalised women. We identified significant challenges for advocates in inter-organisational working, vicarious traumatisation, and lack of clarity on how much support to give a woman (moderate and high confidence). To work effectively, advocates need ongoing training, role clarity, access to resources, and peer and institutional support. Our provisional model highlights the complex way that factors combine and interact for effective advocacy. We confirmed the core ingredients of advocacy according to both women and advocates, supported by studies and theoretical considerations: education and information on abuse; rights and resources; active referral and liaising with other services; risk assessment and safety planning. We were unable to confirm the impact of complexity of the intervention (low confidence). Our low confidence in the evidence was driven mostly by a lack of relevant studies, rather than poor-quality studies, despite the size of the review. Results confirm the core ingredients of advocacy and suggest its use rests on sound theoretical underpinnings. We determined the elements of a good therapeutic alliance and how it might be improved, with a need for particular considerations of the factors affecting marginalised women. Women's goals from advocacy should be considered in the contexts of their personal lives. Women's safety was not necessarily at greatest risk from staying with the abuser. Potentially, if undertaken for long enough, advocacy should benefit an abused woman in terms of at least one outcome providing the goals are matched to each woman's needs. Some outcomes may take months to be determined. Where abuse is severe, some interventions may increase abuse. Advocates have a challenging role and must be supported emotionally, through provision of resources and through professional training, by organisations and peers. Future research should consider the different principles identified in this review, and study outcomes should be considered in relation to the mechanisms and contexts elucidated. More longitudinal evidence is needed. Single-subject research designs may help determine exactly when effect no longer increases, to determine the duration of longitudinal work, which will likely differ for vulnerable and marginalised women. Further work is needed to ascertain how to tailor advocacy interventions to cultural variations and rural and resource-poor settings. The methods used in the included studies may, in some cases, limit the applicability and completeness of the data reported. Economic analyses are required to ascertain if resources devoted to advocacy interventions are cost-effective in healthcare and community settings. Output:

We found 98 studies from 15 countries. Of the 88 core studies, 37 asked advocates about their views and experiences and seven asked abused women about advocacy (two of these also asked staff). The other 44 core studies helped us understand the way advocacy works and how effective it is. We included 10 additional studies that did not fit the original criteria but added useful information, as befitting a realist approach. Of these, three were randomised controlled trials (RCTs; a type of experiment in which participants are randomly allocated to two or more interventions), one was an intervention process evaluation, one was a qualitative (e.g. focus groups, interviews) study, two studies used mixed methods (a combination of qualitative and quantitative research) to explore women's experiences, two were surveys of women, and one was a mixed methods study of women and staff. We were unable to obtain the full texts of two studies that we thought might be core and three further relevant studies are still ongoing. Advocacy interventions varied considerably in duration, participating staff (e.g. nurses, psychologists, social workers), and setting (e.g. healthcare settings, domestic violence refuges or shelters). In the studies, women and advocates agreed that the following were all important parts of advocacy: education and information on abuse and on women's rights and sources of help (resources); active referral to, and help in accessing other services; assessment of risk of repeat abuse; and safety planning to avoid it. Trust in the advocate is important and more likely when the advocate and the woman share an ethnic background or the advocate was also abused. Advocates must help women consider their best options, depending on things like ethnicity, immigration status, where they live, the severity and type of the abuse experienced and finances. There are trade-offs when making decisions to reduce the abuse and women's safety was not necessarily at greatest risk from staying with the abuser. Advocacy could potentially have some benefits for abused women, if undertaken for long enough, but its goals need to match each woman's needs. It may take months to have an effect. Two studies (one involving the police and one in an antenatal clinic) found that where abuse is severe to start with, some interventions may possibly prompt the abuser to increase the abuse. Advocates want to help women and can get stressed if they do not feel helpful enough, so they need support from organisations and other advocates, including repeat training, debriefs, and funding to do their job well. Our confidence in the key findings varied between moderate and high. However, some themes (the effect on outcomes of women being physically dependent on their abuser, being pregnant or having children) were less well supported by evidence and further, good-quality research is needed to confirm findings. Researchers should be careful when choosing how to measure abuse so that measures have more meaning for advocates and abused women, thus increasing the usefulness of future reviews. Further evidence from studies where participants are followed up for years would be helpful. More economic analyses are needed to establish if current advocacy interventions are the best way of spending money for abused women.

CochranePLS1204

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 34 studies evaluating 1614 women and approximately 2396 groins. The overall methodological quality of included studies was moderate. The studies included in this review used the following traceable techniques to identify sentinel nodes in their participants: blue dye only (three studies), technetium only (eight studies), blue dye plus technetium combined (combined tests; 13 studies) and various inconsistent combinations of these three techniques (mixed tests; 10 studies). For studies of mixed tests, we obtained separate test data where possible. Most studies used haematoxylin and eosin (H&E) stains for the histological examination. Additionally an immunohistochemical (IHC) stain with and without ultrastaging was employed by 14 and eight studies, respectively. One study used reverse transcriptase polymerase chain reaction analysis (CA9 RT-PCR), whilst three studies did not describe the histological methods used. The pooled sensitivity estimate for studies using blue dye only was 0.94 (68 women; 95% confidence interval (CI) 0.69 to 0.99), for mixed tests was 0.91 (679 women; 95% CI 0.71 to 0.98), for technetium only was 0.93 (149 women; 95% CI 0.89 to 0.96) and for combined tests was 0.95 (390 women; 95% CI 0.89 to 0.97). Negative predictive values (NPVs) for all index tests were > 95%. Most studies also reported sentinel node detection rates (the ability of the test to identify a sentinel node) of the index test. The mean detection rate for blue dye alone was 82%, compared with 95%, 96% and 98% for mixed tests, technetium only and combined tests, respectively. We estimated the clinical consequences of the various tests for 100 women undergoing the sentinel node procedure, assuming the prevalence of groin metastases to be 30%. For the combined or technetium only tests, one and two women with groin metastases might be 'missed', respectively (95% CI 1 to 3); and for mixed tests, three women with groin metastases might be 'missed' (95% CI 1 to 9). The wide CIs associated with the pooled sensitivity estimates for blue dye and mixed tests increased the potential for these tests to 'miss' women with groin metastases. There is little difference in diagnostic test accuracy between the technetium and combined tests. The combined test may reduce the number of women with 'missed' groin node metastases compared with technetium only. Blue dye alone may be associated with more 'missed' cases compared with tests using technetium. Sentinel node assessment with technetium-based tests will reduce the need for IFL by 70% in women with early vulval cancer. It is not yet clear how the survival of women with negative sentinel nodes compares to those undergoing standard surgery (IFL). A randomised controlled trial of sentinel node dissection and IFL has methodological and ethical issues, therefore more observational data on the survival of women with early vulval cancer are needed. Output:

We included 34 studies (1614 women) that evaluated three techniques: blue dye only, technetium (a radioactive substance) only, or blue dye and technetium combined. Ten studies used all three techniques during the course of the study (one technique per participant). There are two attributes to a test: the ability to identify or detect the sentinel node, and the ability to identify the cancer in the sentinel node. We found that all tests can identify cancer in the groin nodes with good accuracy (more than 90% of nodes with cancer will be accurately identified with any of the tests), although the combined test was the most accurate (95%). The ability of the tests to detect sentinel nodes varied, with the blue dye test only detecting sentinel nodes in 82% of women, compared with 98% for the combined test. If sentinel nodes are not detected, they cannot be examined for cancer cells; therefore, women in whom sentinel nodes are not detected will usually need to undergo IFL. The combined and technetium only tests are able to predict accurately which women have cancerous spread to the groin. For a group of 100 women undergoing assessment, the findings mean that approximately one or fewer women having the combined or technetium only tests will undergo an unnecessary IFL, compared with approximately 11 women having the blue dye only test. This is mainly because the blue dye only test is not as good as technetium in identifying sentinel nodes. Fewer women with spread to the groin will be missed with the combined or technetium only tests (1 to 3 out of 30) compared with the blue dye only test (1 to 8 out of 30). It is not clear whether women with negative sentinel nodes (i.e. no spread of cancer to the groin lymph nodes) who do not undergo IFL will live as long as those who undergo IFL. The current best data on survival come from a Dutch study that followed up 259 women with negative sentinel nodes and reported a three-year survival of 97%.

CochranePLS1205

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: One randomised trial was identified and included in the review. It was of low methodological quality. The trial compared D-penicillamine versus placebo in 70 patients with primary sclerosing cholangitis. Compared with placebo, D-penicillamine therapy had no significant effect on mortality (RR 1.14, 95% CI 0.49 to 2.64), liver transplantation (RR 1.11, 95% CI 0.39 to 3.17), hepatic histologic progression (RR 1.17, 95% CI 0.79 to 1.74), or cholangiographic deterioration (RR 0.87, 95% CI 0.43 to 1.79). D-penicillamine led to a significant improvement in the serum aspartate aminotransferase (WMD -23.00 U/L; 95% CI -30.66 to -15.34), but not in serum bilirubin level (WMD 0.40 mg/L; 95% CI -0.19 to 0.99) and serum alkaline phosphatases activity (WMD 44.00 U/L; 95% CI -37.89 to 125.89). There were significantly more adverse events in patients receiving D-penicillamine (P = 0.013). There is not sufficient evidence to support or refute the use of D-penicillamine for patients with primary sclerosing cholangitis. We do not recommend the use of D-penicillamine for patients with primary sclerosing cholangitis outside randomised trials. Output:

The only identified randomised clinical trial did not demonstrate any beneficial effect of D-penicillamine on the course, complications, and survival of patients with primary sclerosing cholangitis. In addition, its use was associated with a number of adverse events. Therefore, we cannot recommend the use of D-penicillamine outside randomised trials.

CochranePLS1206

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Of 15440 identified citations, 7387 unique citations, 15 RCTs fulfilled the eligibility criteria. These trials enrolled 1615 participants with cancer and VTE: 13 compared LMWH with UFH enrolling 1025 participants, one compared fondaparinux with UFH and LMWH enrolling 477 participants, and one compared dalteparin with tinzaparin enrolling 113 participants. The meta-analysis of mortality at three months included 418 participants from five studies and that of recurrent VTE included 422 participants from 3 studies. The findings showed that LMWH likely decreases mortality at three months compared to UFH (risk ratio (RR) 0.66, 95% confidence interval (CI) 0.40 to 1.10; risk difference (RD) 57 fewer per 1000, 95% CI 101 fewer to 17 more; moderate certainty evidence), but did not rule out a clinically significant increase or decrease in VTE recurrence (RR 0.69, 95% CI 0.27 to 1.76; RD 30 fewer per 1000, 95% CI 70 fewer to 73 more; moderate certainty evidence). The study comparing fondaparinux with heparin (UFH or LMWH) did not exclude a beneficial or detrimental effect of fondaparinux on mortality at three months (RR 1.25, 95% CI 0.86 to 1.81; RD 43 more per 1000, 95% CI 24 fewer to 139 more; moderate certainty evidence), recurrent VTE (RR 0.93, 95% CI 0.56 to 1.54; RD 8 fewer per 1000, 95% CI 52 fewer to 63 more; moderate certainty evidence), major bleeding (RR 0.82, 95% CI 0.40 to 1.66; RD 12 fewer per 1000, 95% CI 40 fewer to 44 more; moderate certainty evidence), or minor bleeding (RR 1.53, 95% CI 0.88 to 2.66; RD 42 more per 1000, 95% CI 10 fewer to 132 more; moderate certainty evidence) The study comparing dalteparin with tinzaparin did not exclude a beneficial or detrimental effect of dalteparin on mortality (RR 0.86, 95% CI 0.43 to 1.73; RD 33 fewer per 1000, 95% CI 135 fewer to 173 more; low certainty evidence), recurrent VTE (RR 0.44, 95% CI 0.09 to 2.16; RD 47 fewer per 1000, 95% CI 77 fewer to 98 more; low certainty evidence), major bleeding (RR 2.19, 95% CI 0.20 to 23.42; RD 20 more per 1000, 95% CI 14 fewer to 380 more; low certainty evidence), or minor bleeding (RR 0.82, 95% CI 0.30 to 2.21; RD 24 fewer per 1000, 95% CI 95 fewer to 164 more; low certainty evidence). LMWH is possibly superior to UFH in the initial treatment of VTE in people with cancer. Additional trials focusing on patient-important outcomes will further inform the questions addressed in this review. The decision for a person with cancer to start LMWH therapy should balance the benefits and harms and consider the person's values and preferences. Output:

We searched scientific databases for clinical trials comparing different blood thinners in people with cancer with a confirmed diagnosis of deep vein thrombosis (a blood clot in the limbs) or pulmonary thrombosis (a blood clot in the lungs). We included trials of adults and children with either solid tumors or blood cancer irrespective of the type of cancer treatment. The trials looked at death, recurrent blood clots, and bleeding. The evidence is current to January 2018. We included 15 trials. In this systematic review, data from five studies with 422 participants suggested that the effect of low molecular weight heparin on death compared with unfractionated heparin was uncertain, but if anything of small size. There was not enough evidence to prove superiority in reducing recurrence of blood clots or risk of bleeding. We found no data to compare the safety profile of these two medications. Also, fondaparinux did not prove or exclude any important effect compared to heparins, on death, blood clots, or bleeding. Similarly,the available evidence did not show any difference between dalteparin and tinzaparin for all tested outcomes. We judged the certainty of evidence for low molecular weight heparin versus unfractionated heparin to be moderate for all assessed outcomes. We judged the certainty of evidence for fondaparinux versus heparin to be moderate for all tested outcomes. We judged the certainty of evidence for tinzaparin versus dalteparin to be low for all tested outcomes.

CochranePLS1207

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Searches identified 5116 unique papers; we retrieved 827 for full screening. In this review, we included 105 studies from 115 papers, in which 10,302 participants were randomized. Mainly as a result of updating the search in July 2015, 38 papers are awaiting classification. Sixty-one of the 105 studies measured the outcome pain, 14 behavioural recovery, 58 length of stay and 49 negative affect. Participants underwent a wide range of surgical procedures, and a range of psychological components were used in interventions, frequently in combination. In the 105 studies, appropriate data were provided for the meta-analysis of 38 studies measuring the outcome postoperative pain (2713 participants), 36 for length of stay (3313 participants) and 31 for negative affect (2496 participants). We narratively reviewed the remaining studies (including the 14 studies with 1441 participants addressing behavioural recovery). When pooling the results for all types of intervention there was low quality evidence that psychological preparation techniques were associated with lower postoperative pain (SMD -0.20, 95% confidence interval (CI) -0.35 to -0.06), length of stay (mean difference -0.52 days, 95% CI -0.82 to -0.22) and negative affect (SMD -0.35, 95% CI -0.54 to -0.16) compared with controls. Results tended to be similar for all categories of intervention, although there was no evidence that behavioural instruction reduced the outcome pain. However, caution must be exercised when interpreting the results because of heterogeneity in the types of surgery, interventions and outcomes. Narratively reviewed evidence for the outcome behavioural recovery provided very low quality evidence that psychological preparation, in particular behavioural instruction, may have potential to improve behavioural recovery outcomes, but no clear conclusions could be reached. Generally, the evidence suffered from poor reporting, meaning that few studies could be classified as having low risk of bias. Overall,we rated the quality of evidence for each outcome as ‘low’ because of the high level of heterogeneity in meta-analysed studies and the unclear risk of bias. In addition, for the outcome behavioural recovery, too few studies used robust measures and reported suitable data for meta-analysis, so we rated the quality of evidence as `very low'. The evidence suggested that psychological preparation may be beneficial for the outcomes postoperative pain, behavioural recovery, negative affect and length of stay, and is unlikely to be harmful. However, at present, the strength of evidence is insufficient to reach firm conclusions on the role of psychological preparation for surgery. Further analyses are needed to explore the heterogeneity in the data, to identify more specifically when intervention techniques are of benefit. As the current evidence quality is low or very low, there is a need for well-conducted and clearly reported research. Output:

We included studies of adults who received planned surgery with general anaesthesia. We looked at seven psychological preparation techniques: procedural information (information about what, when and how processes will happen); sensory information (what the experience will feel like and what other sensations they may have, e.g. taste, smell); behavioural instruction (telling patients what they need to do); cognitive intervention (techniques that aim to change how people think); relaxation techniques; hypnosis; and emotion-focused interventions (techniques that aim to help people to manage their feelings). The psychological preparation had to be delivered before surgery for the study to be included in the review. We included studies that looked at the effect of psychological preparation on pain, behavioural recovery, length of stay and negative emotion after surgery (within one month). Studies were included in the review up to the search date of 4 May 2014. We updated the search on 7 July 2015 and will incorporate the 38 studies found in this later search when the review is updated. We included 105 studies from 115 papers, with 10,302 participants taking part. Sixty-one studies measured the outcome pain, 14 behavioural recovery, 58 length of stay and 49 negative emotion. In accordance with the review protocol, we did not record details about funding sources. In this review we included 105 studies, which were reported in 115 papers. A total of 10,302 participants were randomized in these studies. For pain, length of stay and negative emotion we combined numerical findings from the studies. We found that psychological preparation before surgery seemed to reduce pain and negative emotion after the operation and may reduce the time spent in hospital by around half a day but the quality of the evidence was low. Also, the studies used many different psychological preparation techniques (often in different combinations) so it was not possible to discover which techniques were better. We could not statistically combine numerical findings for behavioural recovery because few studies provided sufficient details and studies used different ways of measuring how quickly people returned to usual activities. In reviewing the studies, we found that psychological preparation, in particular behavioural instruction, may have the potential to improve behavioural recovery. However, the quality of this evidence was very low. We looked at the effect of psychological preparation on pain, behavioural recovery, length of stay and negative emotion in this review and did not find evidence to suggest that psychological preparation might lead to harm in these outcomes. However, as we did not look at other outcomes it is possible that we did not identify potential harm. Many studies were poorly reported, so we could not be confident that findings were reliable. For this reason and because of the large variation in psychological techniques, types of surgery and measures used, we graded the quality of the evidence as `low' for the outcomes pain, negative emotion and length of stay; we cannot be confident that these techniques help patients to recover from surgery. For behavioural recovery, we further downgraded the quality of the evidence to `very low' because of problems with measurement and reporting of the outcome.

CochranePLS1208

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Forty-one RCTs with a total of 2732 participants (1564 cell therapy, 1168 controls) were eligible for inclusion. Cell treatment was not associated with any changes in the risk of all-cause mortality (34/538 versus 32/458; RR 0.93, 95% CI 0.58 to 1.50; 996 participants; 14 studies; moderate quality evidence), cardiovascular mortality (23/277 versus 18/250; RR 1.04, 95% CI 0.54 to 1.99; 527 participants; nine studies; moderate quality evidence) or a composite measure of mortality, reinfarction and re-hospitalisation for heart failure (24/262 versus 33/235; RR 0.63, 95% CI 0.36 to 1.10; 497 participants; six studies; moderate quality evidence) at long-term follow-up. Statistical heterogeneity was low (I2 = 0% to 12%). Serious periprocedural adverse events were rare and were generally unlikely to be related to cell therapy. Additionally, cell therapy had no effect on morbidity, quality of life/performance or LVEF measured by magnetic resonance imaging. Meta-analyses of LVEF measured by echocardiography, single photon emission computed tomography and left ventricular angiography showed evidence of differences in mean LVEF between treatment groups although the mean differences ranged between 2% and 5%, which are accepted not to be clinically relevant. Results were robust to the risk of selection, performance and attrition bias from individual studies. The results of this review suggest that there is insufficient evidence for a beneficial effect of cell therapy for AMI patients. However, most of the evidence comes from small trials that showed no difference in clinically relevant outcomes. Further adequately powered trials are needed and until then the efficacy of this intervention remains unproven. Output:

Randomised trials comparing bone marrow-derived cells with no cells in patients diagnosed with acute myocardial infarction were eligible for this review. We searched databases to March 2015. This review was supported by the National Institute of Health Research (NIHR) through its Cochrane Incentive Award programme. In this updated systematic review we analysed data from a total of 41 trials with over 2700 patients. Evaluation of the currently available evidence indicates that this treatment may not lead to improvement when compared to standard treatment, as measured by the frequency of deaths, heart attacks and/or heart failure requiring re-hospitalisation following treatment, as well as tests of heart function, in the short and long term. The evidence in this review is of moderate quality due to the small number of events.

CochranePLS1209

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We identified two new studies, giving a total of 10 studies, involving 3655 participants. The medication adherence interventions studied were all provided in addition to standard behavioural support.They typically provided further information on the rationale for, and emphasised the importance of, adherence to medication or supported the development of strategies to overcome problems with maintaining adherence (or both). Seven studies targeted adherence to NRT, two to bupropion and one to varenicline. Most studies were judged to be at high or unclear risk of bias, with four of these studies judged at high risk of attrition or detection bias. Only one study was judged to be at low risk of bias. Meta-analysis of all 10 included studies (12 comparisons) provided moderate-certainty evidence that adherence interventions led to small improvements in adherence (i.e. the mean amount of medication consumed; SMD 0.10, 95% CI 0.03 to 0.18; I² = 6%; n = 3655), limited by risk of bias. Subgroup analyses for the primary outcome identified no significant subgroup effects, with effect sizes for subgroups imprecisely estimated. However, there was a very weak indication that interventions focused on the 'practicalities' of adhering to treatment (i.e. capabilities, resources, levels of support or skills) may be effective (SMD 0.21, 95% CI 0.03 to 0.38; I² = 39%; n = 1752), whereas interventions focused on treatment 'perceptions' (i.e. beliefs, cognitions, concerns and preferences; SMD 0.10, 95% CI –0.03 to 0.24; I² = 0%; n = 839) or on both (SMD 0.04, 95% CI –0.08 to 0.16; I² = 0%; n = 1064), may not be effective. Participant-centred interventions may be effective (SMD 0.12, 95% CI 0.02 to 0.23; I² = 20%; n = 2791), whereas those that are clinician-centred may not (SMD 0.09, 95% CI –0.05 to 0.23; I² = 0%; n = 864). Five studies assessed short-term smoking abstinence (five comparisons), while an overlapping set of five studies (seven comparisons) assessed long-term smoking abstinence of six months or more. Meta-analyses resulted in low-certainty evidence that adherence interventions may slightly increase short-term smoking cessation rates (RR 1.08, 95% CI 0.96 to 1.21; I² = 0%; n = 1795) and long-term smoking cessation rates (RR 1.16, 95% CI 0.96 to 1.40; I² = 48%; n = 3593). In both cases, the evidence was limited by risk of bias and imprecision, with CIs encompassing minimal harm as well as moderate benefit, and a high likelihood that further evidence will change the estimate of the effect. There was no evidence that interventions to increase adherence to medication led to any adverse events. Studies did not report on factors plausibly associated with increases in adherence, such as self-efficacy, understanding of and attitudes toward treatment, and motivation and intentions to quit. In people who are stopping smoking and receiving behavioural support, there is moderate-certainty evidence that enhanced behavioural support focusing on adherence to smoking cessation medications can modestly improve adherence. There is only low-certainty evidence that this may slightly improve the likelihood of cessation in the shorter or longer-term. Interventions to increase adherence can aim to address the practicalities of taking medication, change perceptions about medication, such as reasons to take it or concerns about doing so, or both. However, there is currently insufficient evidence to confirm which approach is more effective. There is no evidence on whether such interventions are effective for people who are stopping smoking without standard behavioural support. Output:

We searched for studies up to September 2018, and we found 10 studies, including 3655 people. All of these people were smokers, over 18 years of age. Studies tested different ways of helping people use their stop-smoking medicines properly. Typically this meant providing additional information about the medicine or helping people to overcome problems they had with taking the medicine. One study delivered support by telephone, and the rest provided at least some face-to-face support. All included studies measured the amount that people used their medicines and all but one measured how many people quit smoking. People who received help to improve their use of medicines to stop smoking used their medicines slightly more than people who did not receive this help. There was some evidence that this also led to slightly more people quitting smoking. The evidence that helping people improve their use of stop-smoking medicines can successfully boost the use of these medicines is of moderate quality, meaning that more evidence could make us feel more certain of this effect. This is because there were problems with the methods of some of the included studies. The evidence suggesting that approaches to improve the use of stop-smoking medicines can help more people to quit smoking is of low quality, which means that we are not confident that they do actually help more people to quit and further evidence may or may not strengthen our confidence in this effect. This is because there were problems with some of the study methods and because it is unclear whether providing extra support to encourage people to use their medicines leads to more or fewer people successfully quitting smoking.

CochranePLS1210

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Only one trial, involving 256 children, met the inclusion criteria for this review. This study was assessed as having high risk of bias because of non-random allocation, incomplete outcome data and insufficient control of confounding factors. Results from this study suggest that centre-based day care may have a positive effect on child cognitive ability compared with no treatment (care at home) (assessed using a modified version of the British Ability Scale-II (BAS-II) (standardised mean difference (SMD) 0.74, 95% confidence interval (CI) 0.48 to 1.00, 256 participants, 1 study, very low-quality evidence). This study did not measure other variables relevant to this review. The single study included in this review provides limited evidence on the effects of centre-based day care for children younger than five years of age in low- and middle-income countries. This study was at high risk of bias and may have limited generalisability to other low- and middle-income countries. Many of the studies excluded from this review paired day care attendance with co-interventions that are unlikely to be provided in normal day care centres. Effectiveness studies on centre-based day care without these co-interventions are few, and the need for such studies is significant. In future studies, comparisons might include home visits or alternative day care arrangements. Output:

We included studies that assessed the effects of centre-based day care for children younger than five years of age in low- and middle-countries. To isolate the effects of day care, we excluded interventions that involved medical, psychological or non–child-focused co-interventions. Of the 34,902 citations identified through electronic searches, we found only one study that met our inclusion criteria. This study was based in Kenya, Uganda and Tanzania/Zanzibar and included 256 children. Evidence is current to April 2014. The one included study reported positive effects of centre-based day care on the cognitive development of children. It did not report the effects of centre-based day care on children's psychosocial development, the incidence or prevalence of infectious diseases, parental employment or household income. This review includes only one trial. This study did not assign participants to the intervention by chance, so the comparison groups may have differed in important ways. Therefore results must be interpreted with caution. Although current studies do not now allow for conclusive judgements regarding the effects of centre-based day care on the development of children and the economic situation of parents, this does not imply that these services are not important in low- and middle-income countries. Effectiveness studies of centre-based day care without co-interventions are few, and the need for such studies is significant. This review is one of a pair of reviews; researchers and practitioners may find evidence from the high-income country review to be informative also (Van Urk 2014).

CochranePLS1211

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: 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 main results and quality of evidence should be verified once all trials are fully published. Output:

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. If 1000 people were treated with ranibizumab for one or two years, 34 would die. If treated instead with bevacizumab, between 27 and 53 of them would die. If 1000 people were treated with ranibizumab, 222 would experience one or more SSAEs. If 1000 people were treated instead with bevacizumab, between 200 and 291 would experience such an event. Deaths are likely to be unrelated to the administration of drugs. We could not fully assess the quality of three unpublished studies. We rated the overall quality of the evidence as low to moderate because we could not be certain that one drug was better than the other one on many of our outcomes. Another limitation of the studies was the participants who were recruited into them, and the fact that studies may have missed measuring the outcomes of interest in a few individuals that might have experienced a SSAE. Missing information was equally common in participants treated with bevacizumab and those treated with ranibizumab.

CochranePLS1212

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Thirty-four separate RCTs studying roflumilast (20 trials with 17,627 participants) or cilomilast (14 trials with 6457 participants) met the inclusion criteria, with a duration of between six weeks and one year. These included people across international study centres with moderate to very severe COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades II-IV), with a mean age of 64 years. We considered that the methodological quality of the 34 published and unpublished trials was acceptable overall. Treatment with a PDE4 inhibitor was associated with a significant improvement in forced expiratory volume in one second (FEV1) over the trial period compared with placebo (MD 51.53 mL, 95% confidence interval (CI) 43.17 to 59.90, 27 trials with 20,585 participants, moderate-quality evidence due to moderate levels of heterogeneity and risk of reporting bias). There were small improvements in quality of life (St George's Respiratory Questionnaire (SGRQ), MD -1.06 units, 95% CI -1.68 to -0.43, 11 trials with 7645 participants, moderate-quality evidence due to moderate levels of heterogeneity and risk of reporting bias) and COPD-related symptoms, but no significant change in exercise tolerance. Treatment with a PDE4 inhibitor was associated with a reduced likelihood of COPD exacerbation (OR 0.78, 95% CI 0.73 to 0.83; 23 trials with 19,948 participants, high-quality evidence). For every 100 people treated with PDE4 inhibitors, five more remained exacerbation-free during the study period compared with placebo (number needed to treat for an additional beneficial outcome (NNTB) 20, 95% CI 16 to 26). More participants in the treatment groups experienced non-serious adverse events compared with controls, particularly a range of gastrointestinal symptoms such as diarrhoea, nausea, vomiting or dyspepsia. For every 100 people treated with PDE4 inhibitors, seven more suffered from diarrhoea during the study period compared with placebo (number needed to treat for an additional harmful outcome (NNTH) 15, 95% CI 13 to 17). Roflumilast in particular was associated with weight loss during the trial period and an increase in insomnia and depressive mood symptoms. There was no significant effect of treatment on non-fatal serious adverse events (OR 0.99, 95% CI 0.91 to 1.07) or mortality (OR 0.97, 95% CI 0.76 to 1.23), although mortality was a rare event during the trials. Participants treated with PDE4 inhibitors were more likely to withdraw from the trials because of adverse effects; on average 14% in the treatment groups withdrew compared with 8% in the control groups. In people with COPD, PDE4 inhibitors offered benefit over placebo in improving lung function and reducing the likelihood of exacerbations; however, they had little impact on quality of life or symptoms. Gastrointestinal adverse effects and weight loss were common, and safety data submitted to the US Food and Drug Administration (FDA) have raised concerns over psychiatric adverse events with roflumilast. The findings of this review give cautious support to the use of PDE4 inhibitors in COPD. They may be best used as add-on therapy in a subgroup of people with persistent symptoms or exacerbations despite optimal COPD management. This is in accordance with the GOLD 2017 guidelines. Longer-term trials are needed to determine whether or not PDE4 inhibitors modify FEV1 decline, hospitalisation or mortality in COPD. Output:

Compared with placebo, these medicines provide a small improvement in lung function measurements and reduce the likelihood of an exacerbation of COPD. Based on these results, we would expect that out of 100 people who took PDE4 inhibitors every day for a year, 28 would experience at least one exacerbation which is five fewer than for others who did not receive these medicines. However, people reported that these medicines only provided a small effect on levels of breathlessness and quality of life. Furthermore, around 5% to 10% of people in trials who received roflumilast or cilomilast reported side effects such as diarrhoea, nausea and vomiting. We would expect that out of 100 people who took PDE4 inhibitors every day for a year, 11 would experience diarrhoea, which is seven more than for others who did not receive these medicines. There was also a two- to three-fold increase in the risk of sleep or mood disturbance for the roflumilast 500 μg dose, although overall the total number of reported incidents was still small. There was no effect on rates of hospitalisation and deaths. The effects were the same regardless of the severity of COPD, or whether other medicines for COPD were being taken. The studies were generally well designed, as people did not know if they were receiving this new treatment or a placebo medicine. Overall we rated the evidence as being of moderate to high quality. It is of concern that results seen in trials published in journals by pharmaceutical companies showed a greater benefit of these medicines than those which were unpublished. Therefore, this relies on unpublished trial data being made accessible and up to date. The psychiatric adverse effects data remain unpublished. Longer-term trials are necessary to get a more accurate estimate of the benefits and safety of these medicines over time, including whether they slow COPD disease progression.

CochranePLS1213

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 17 RCTs (9975 participants, mean age 63.3 years). We found very limited (or no) data to inform most planned comparisons. Summary data were used to inform comparison of ranolazine versus placebo. Overall, risk of bias was assessed as unclear. For add-on ranolazine compared to placebo, no data were available to estimate cardiovascular and non-cardiovascular mortality. We found uncertainty about the effect of ranolazine on: all-cause mortality (1000 mg twice daily, RR 0.83, 95% CI 0.26 to 2.71; 3 studies, 2053 participants; low quality evidence); quality of life (any dose, SMD 0.25, 95% CI -0.01 to 0.52; 4 studies, 1563 participants; I² = 73%; moderate quality evidence); and incidence of non-fatal acute myocardial infarction (AMI) (1000mg twice daily, RR 0.40, 95% CI 0.08 to 2.07; 2 studies, 1509 participants; low quality evidence). Add-on ranolazine 1000 mg twice daily reduced the fervour of angina episodes (MD -0.66, 95% CI -0.97 to -0.35; 3 studies, 2004 participants; I² = 39%; moderate quality evidence) but increased the risk of non-serious adverse events (RR 1.22, 95% CI 1.06 to 1.40; 3 studies, 2053 participants; moderate quality evidence). For ranolazine as monotherapy compared to placebo, we found uncertain effect on cardiovascular mortality (1000 mg twice daily, RR 1.03, 95% CI 0.56 to 1.88; 1 study, 2604 participants; low quality evidence). No data were available to estimate non-cardiovascular mortality. We also found an uncertain effect on all-cause mortality for ranolazine (1000 mg twice daily, RR 1.00, 95% CI 0.81 to 1.25; 3 studies, 6249 participants; low quality evidence), quality of life (1000 mg twice daily, MD 0.28, 95% CI -1.57 to 2.13; 3 studies, 2254 participants; moderate quality evidence), non-fatal AMI incidence (any dose, RR 0.88, 95% CI 0.69 to 1.12; 3 studies, 2983 participants; I² = 50%; low quality evidence), and frequency of angina episodes (any dose, MD 0.08, 95% CI -0.85 to 1.01; 2 studies, 402 participants; low quality evidence). We found an increased risk for non-serious adverse events associated with ranolazine (any dose, RR 1.50, 95% CI 1.12 to 2.00; 3 studies, 947 participants; very low quality evidence). We found very low quality evidence showing that people with stable angina who received ranolazine as monotherapy had increased risk of presenting non-serious adverse events compared to those given placebo. We found low quality evidence indicating that people with stable angina who received ranolazine showed uncertain effect on the risk of cardiovascular death (for ranolazine given as monotherapy), all-cause death and non-fatal AMI, and the frequency of angina episodes (for ranolazine given as monotherapy) compared to those given placebo. Moderate quality evidence indicated that people with stable angina who received ranolazine showed uncertain effect on quality of life compared with people who received placebo. Moderate quality evidence also indicated that people with stable angina who received ranolazine as add-on therapy had fewer angina episodes but increased risk of presenting non-serious adverse events compared to those given placebo. Output:

We included 17 studies that involved a total of 9975 adult participants and lasted between 1 and 92 weeks. We only compared ranolazine and placebo because there were few data for other comparisons. The evidence was uncertain about the effect of ranolazine 1000 mg given alone twice daily to people with stable angina pectoris on the chance of dying from heart-related causes. There was no evidence about whether ranolazine changed the risk of dying from causes that were not heart-related. Although the evidence was uncertain about the effect of ranolazine 1000 mg twice daily on the chance of dying from any cause, quality of life, the possibility of heart attack or the frequency of angina attacks (for ranolazine taken alone), ranolazine did modestly reduce the numbers of angina attacks per week when given with other anti-angina drugs. Ranolazine 1000 mg twice daily increased the risk for experiencing dizziness, nausea and constipation from taking the drug (mild adverse events). Overall, evidence quality was assessed as very low for the chance of mild adverse events (for people who took ranolazine alone). Evidence was also low for estimating the chance of death from heart-related (when ranolazine is taken alone) or any causes, having a heart attack, and how often angina attacks occur (when ranolazine is taken alone). We found moderate quality evidence about quality of life, frequency of angina attacks and the chance of experiencing mild adverse events (for people who took ranolazine together with other anti-angina drugs), Low evidence quality related to problems and reporting of study methods and too few data to calculate precise estimates.

CochranePLS1214

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included five RCTs (with 264 women) comparing gonadotrophins plus metformin versus gonadotrophins. The gonadotrophin used was recombinant FSH in four studies and highly purified FSH in one study. Evidence was of low quality: The main limitations were serious risk of bias due to poor reporting of study methods and blinding of participants and outcome assessors. Live birth Metformin plus FSH was associated with a higher cumulative live birth rate when compared with FSH (odds ratio (OR) 2.31, 95% confidence interval (CI) 1.23 to 4.34; two RCTs, n = 180; I2 = 0%; low-quality evidence). This suggests that if the chance of live birth after FSH is assumed to be 27%, then the chance after addition of metformin would be between 32% and 60%. Other pregnancy outcomes Metformin use was associated with a higher ongoing pregnancy rate (OR 2.46, 95% CI 1.36 to 4.46; four RCTs, n = 232; I2 = 0%; low-quality evidence) and a higher clinical pregnancy rate (OR 2.51, 95% CI 1.46 to 4.31; five RCTs, n = 264; I2 = 0%; low-quality evidence). Multiple pregnancy Results showed no evidence of a difference in multiple pregnancy rates between metformin plus FSH and FSH (OR 0.55, 95% CI 0.15 to 1.95; four RCTs, n = 232; I2 = 0%; low-quality evidence) and no evidence of a difference in rates of miscarriage or OHSS. Other adverse effects Evidence was inadequate as the result of limited available data on adverse events after metformin compared with after no metformin (OR 1.78, 95% CI 0.39 to 8.09; two RCTs, n = 91; I2 = 0%; very low-quality evidence). Preliminary evidence suggests that metformin may increase the live birth rate among women undergoing ovulation induction with gonadotrophins. At this moment, evidence is insufficient to show an effect of metformin on multiple pregnancy rates and adverse events. Additional trials are necessary before we can provide further conclusions that may affect clinical practice. Output:

We included five randomised controlled trials of women with PCOS undergoing gonadotrophin treatment for ovulation induction. This review of trials compared metformin or placebo added to gonadotrophins for ovulation induction. Evidence is current to July 2016. We were able to include only five trials with a total of 264 women. We graded the quality of the evidence as low. We found no evidence of a difference in risk of multiple pregnancy between metformin and placebo, but we noted higher rates of live birth, ongoing pregnancy and clinical pregnancy with metformin. Evidence was of low quality for live birth, ongoing pregnancy, clinical pregnancy and multiple pregnancy. Limitations of the evidence included inadequate reporting of study methods and blinding of participants and outcome assessors.

CochranePLS1215

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included four studies in this review (251 participants), and found few significant differences between treatment and comparison groups for the outcomes of interest. Blood phenylalanine levels were significantly lower in participants with phenylketonuria following a low-phenylalanine diet compared to those on a less restricted diet, mean difference (MD) at three months -698.67 (95% confidence interval (CI) -869.44 to -527.89). Intelligence quotient was significantly higher in participants who continued the diet than in those who stopped the diet, MD after 12 months 5.00 (95% CI 0.40 to 9.60). However, these results came from a single study. The results of non-randomised studies have concluded that a low-phenylalanine diet is effective in reducing blood phenylalanine levels and improving intelligence quotient and neuropsychological outcomes. We were unable to find any randomised controlled studies that have assessed the effect of a low-phenylalanine diet versus no diet from diagnosis. In view of evidence from non-randomised studies, such a study would be unethical and it is recommended that low-phenylalanine diet should be commenced at the time of diagnosis. There is uncertainty about the precise level of phenylalanine restriction and when, if ever, the diet should be relaxed. This should be addressed by randomised controlled studies. Output:

Other studies suggest that a low-phenylalanine diet can reduce blood phenylalanine levels. The review includes four studies, but we were not able to combine many results. Results from one study showed that blood phenylalanine levels were lower and intelligent quotient higher for people on a special diet. We recommend that a low-phenylalanine diet should be followed from the time of diagnosis. More research is needed to show if it is safe to relax this diet later on.

CochranePLS1216

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Thirty-one studies involving 9571 participants, described in 33 articles, met the inclusion criteria. All were published in English. Fifteen studies were randomized controlled trials, nine were controlled before-and-after studies, four were non-equivalent controlled studies with a historical control, one was a non-equivalent controlled study with a post-test only and two were non-equivalent controlled studies with pre- and post-test findings for the intervention group and post-test for the control group. Twenty-one studies assessed the effects of interventions related to plagiarism and 10 studies assessed interventions in research integrity/ethics. Participants included undergraduates, postgraduates and academics from a range of research disciplines and countries, and the studies assessed different types of outcomes. We judged most of the included randomized controlled trials to have a high risk of bias in at least one of the assessed domains, and in the case of non-randomized trials there were no attempts to alleviate the potential biases inherent in the non-randomized designs. We identified a range of interventions aimed at reducing research misconduct. Most interventions involved some kind of training, but methods and content varied greatly and included face-to-face and online lectures, interactive online modules, discussion groups, homework and practical exercises. Most studies did not use standardized or validated outcome measures and it was impossible to synthesize findings from studies with such diverse interventions, outcomes and participants. Overall, there is very low quality evidence that various methods of training in research integrity had some effects on participants' attitudes to ethical issues but minimal (or short-lived) effects on their knowledge. Training about plagiarism and paraphrasing had varying effects on participants' attitudes towards plagiarism and their confidence in avoiding it, but training that included practical exercises appeared to be more effective. Training on plagiarism had inconsistent effects on participants' knowledge about and ability to recognize plagiarism. Active training, particularly if it involved practical exercises or use of text-matching software, generally decreased the occurrence of plagiarism although results were not consistent. The design of a journal's author contribution form affected the truthfulness of information supplied about individuals' contributions and the proportion of listed contributors who met authorship criteria. We identified no studies testing interventions for outcomes at the organizational level. The numbers of events and the magnitude of intervention effects were generally small, so the evidence is likely to be imprecise. No adverse effects were reported. The evidence base relating to interventions to improve research integrity is incomplete and the studies that have been done are heterogeneous, inappropriate for meta-analyses and their applicability to other settings and population is uncertain. Many studies had a high risk of bias because of the choice of study design and interventions were often inadequately reported. Even when randomized designs were used, findings were difficult to generalize. Due to the very low quality of evidence, the effects of training in responsible conduct of research on reducing research misconduct are uncertain. Low quality evidence indicates that training about plagiarism, especially if it involves practical exercises and use of text-matching software, may reduce the occurrence of plagiarism. Output:

Some studies showed positive effects on researchers' attitudes to plagiarism. Practical training, such as using computer programs that can detect plagiarism, or writing exercises, sometimes decreased plagiarism by students but not all studies showed positive effects. We did not find any studies on fabrication or falsification. Two studies showed that the way in which journals ask authors for details about who did each part of a study can affect their responses. Many of the studies included in this review had problems such as small sample sizes or had used methods that might produce biased results. The training methods tested in the studies (which included online courses, lectures and discussion groups) were often not clearly described. Most studies tested effects over short time periods. Many studies involved university students rather than active researchers. In summary, the available evidence is of very low quality, so the effect of any intervention for preventing misconduct and promoting integrity in research and publication is uncertain. However, practical training about how to avoid plagiarism may be effective in reducing plagiarism by students, although we do not know whether it has long-term effects.

CochranePLS1217

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Four trials, enrolling a total of 614 infants, compared low (restrictive) to high (liberal) haemoglobin thresholds. Restrictive thresholds tended to be similar, but one trial used liberal thresholds much higher than the other three. There were no statistically significant differences in the combined outcomes of death or serious morbidity at first hospital discharge (typical risk ratio (RR) 1.19; 95% confidence interval (CI) 0.95 to 1.49) or in component outcomes. Only the largest trial reported follow-up at 18 to 21 months corrected gestational age; in this study there was no statistically significant difference in a composite of death or adverse neurodevelopmental outcome (RR 1.06; 95% CI 0.95 to 1.19). One additional trial comparing transfusion for clinical signs of anaemia versus transfusion at a set level of haemoglobin or haematocrit, reported no deaths and did not address disability. The use of restrictive as compared to liberal haemoglobin thresholds in infants of very low birth weight results in modest reductions in exposure to transfusion and in haemoglobin levels. Restrictive practice does not appear to have a significant impact on death or major morbidities at first hospital discharge or at follow-up. However, given the uncertainties of these conclusions, it would be prudent to avoid haemoglobin levels below the lower limits tested here. Further trials are required to clarify the impact of transfusion practice on long term outcome. Output:

This review of five studies compares the effects of blood transfusion at low levels of haemoglobin to transfusion at high levels. Within the levels tested, there were no differences seen in survival, in the serious complications of prematurity, or in longer term development as measured at 18 to 21 months past the baby's due date. Allowing the baby to become a little more anaemic did not affect the baby's weight gain or breathing patterns. These conclusions are not firm, because too few babies have been studied. Our overall recommendation is not to exceed the higher levels of haemoglobin used in these trials, and thus diminish the risks of over-transfusion, but not to allow the level of haemoglobin to fall below the lower limits tested in these studies until further studies are completed.

CochranePLS1218

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Thirty randomized controlled studies (21 blinded, four open and five active control) with a total of 3682 subjects were included. For each outcome, there were few studies with available data. For the proportion of patients with pain relief (eight studies) pooled data showed benefits for the treatment group, with an NNT at 4 weeks of 11[95% CI 6-36] and at 12 weeks of 7 [95% CI 5-12]. In terms of adverse drug reactions, the NNH was 16 [95% CI 12-27] for discontinuation of therapy. Nausea and vomiting were reported in 24 studies with a non-significant trend for greater risk in the treatment group. One study showed a small improvement in quality of life for the treatment group at 4 weeks. The small number of studies in each subgroup with relevant data limited our ability to explore the most effective bisphosphonates and their relative effectiveness for different primary neoplasms. There is evidence to support the effectiveness of bisphosphonates in providing some pain relief for bone metastases. There is insufficient evidence to recommend bisphosphonates for immediate effect; as first line therapy; to define the most effective bisphosphonates or their relative effectiveness for different primary neoplasms. Bisphosphonates should be considered where analgesics and/or radiotherapy are inadequate for the management of painful bone metastases. Output:

This review looked at the effect of bisphosphonates on pain caused by bone metastases. Bisphosphonates do have some effect but are not as useful as either strong analgesics (such as morphine) or radiotherapy. However, where other methods of pain relief are inadequate, the addition of bisphosphonates can be beneficial. Bisphosphonates can cause nausea and vomiting.

CochranePLS1219

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: A total of 16,558 patients from four trials contributed to the analyses. The methodological quality was high in all four trials. The anticoagulants tested were unfractionated heparin (UFH) and low molecular-weight heparin. Aspirin was used as control in all trials. Overall, there was no evidence that anticoagulants were superior to aspirin in reducing 'death or dependency' at long-term follow-up (odds ratio (OR) 1.07, 95% confidence interval (CI) 0.98 to 1.15). Compared with aspirin, anticoagulants were associated with a small but significant increase in the number of deaths at the end of follow-up (OR 1.10, 95% CI 1.01 to 1.29), equivalent to 20 more deaths (95% CI 0 to 30) per 1000 patients treated; a significant increased risk of symptomatic intracranial haemorrhage (OR 2.35, 95% CI 1.49 to 3.46); and a non-significant increased risk of 'any recurrent stroke' during treatment (OR 1.20, 95% CI 0.99 to 1.46). These neutral or adverse effects outweighed a small, but significant effect on symptomatic deep vein thrombosis (OR 1.20, 95% CI 0.07 to 0.58), equivalent to 10 fewer (95% CI 0 to 30) DVTs by 14 days per 1000 patients treated with anticoagulants instead of aspirin. Subgroup analysis could not identify any type, dose, or route of administration of anticoagulants associated with net benefit, or any benefit in patients with atrial fibrillation. Overall, the combination of UFH and aspirin did not appear to be associated with a net advantage over aspirin alone. A subgroup analysis showed that, compared with aspirin, the combination of low-dose UFH and aspirin was associated with a marginally significant reduced risk of 'any recurrent stroke' (OR 0.75, 95% CI 0.56 to 1.03) and a marginally significant reduced risk of death at 14 days (OR 0.84, 95% CI 0.69 to 1.01), and with no clear adverse effect on death at end of follow-up (OR 0.98, 95% CI 0.85 to 1.12). Anticoagulants offered no net advantages over antiplatelet agents in acute ischaemic stroke. The combination of low-dose UFH and aspirin appeared in a subgroup analysis to be associated with net benefits compared with aspirin alone, and this merits further research. Output:

This review aimed to test whether any anticoagulant regimen offers net advantages over antiplatelet agents, overall, or in specific categories of patients. There was no evidence that anticoagulants are superior to antiplatelet agents (in fact, anticoagulants caused a small increase in the number of deaths at long-term follow-up). However, the combination of low-dose anticoagulant and aspirin seemed to offer benefits over aspirin alone, and the combination should be investigated further.

CochranePLS1220

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: The electronic search located 62 studies. We included two RCTs of oral aspirin (300 mg/daily) given in addition to compression compared with compression and placebo, or compression alone. To date, the impact of aspirin on VLUs has been examined by only two randomised clinical trials, both with a small number of participants. The first RCT was conducted in the United Kingdom (n=20) and reported that daily administration of aspirin (300mg) in addition to compression bandages increased both the rate of healing, and the number of participants healed when compared to placebo in addition to compression bandaging over a four month period. Thirty-eight per cent of the participants given aspirin reported complete healing compared with 0% in the placebo group . Improvement (assessed by reduction in wound size) occurred in 52% of the participants taking aspirin compared with 26% in those taking placebo). The study identified potential benefits of taking aspirin as an adjunct to compression but the sample size was small, and neither the mechanism by which aspirin improved healing nor its effects on recurrence were investigated. In 2012 an RCT in Spain (n=51) compared daily administration of aspirin (300mg) in addition to compression bandages with compression alone over a five month period. There was little difference in complete healing rates between groups (21/28 aspirin and 17/23 compression bandages alone) but the average time to healing was shorter (12 weeks in the treated group vs 22 weeks in the compression only group) and the average time for recurrence was longer in the aspirin group (39 days: [SD 6.0] compared with 16.3 days [SD 7.5] in the compression only group). Although this trial provides some limited data about the potential use of aspirin therapy, the sample size (only 20 patients) was too small for us to draw meaningful conclusions. In addition, patients were only followed up for 4 months and no information on placebo was reported. Low quality evidence from two trials indicate that there is currently insufficient evidence for us to draw definitive conclusions about the benefits and harms of oral aspirin on the healing and recurrence of venous leg ulcers. We downgraded the evidence to low quality due to potential selection bias and imprecision due to the small sample size. The small number of participants may have a hidden real benefit, or an increase in harm. Due to the lack of reliable evidence, we are unable to draw conclusions about the benefits and harms of oral daily aspirin as an adjunct to compression in VLU healing or recurrence. Further high quality studies are needed in this area. Output:

We identified only two randomised controlled trials that compared oral aspirin (300mg daily) plus compression with compression and placebo, or compression alone. One study conducted in UK included 20 participants (ten in the aspirin group and ten in the control group) and followed people for four months. This trial reported that the ulcer area had reduced (by 6.5 cm², a 39.4% reduction) in the aspirin group compared with no reduction in ulcer area in the control group, and that a higher proportion of the ulcers (38%) in the aspirin group had completely healed compared with none in the control group. Recurrence was not investigated in this study. Another study conducted in Spain included 51 participants (23 in the aspirin group and 28 in the control group) and followed people until their ulcers had healed. The study reported that the average time for healing was 12 weeks in the aspirin group and 22 weeks in the control group, and that there was no real difference between the proportion of people with ulcers healed (17 (74%) out 23 people in the aspirin group and 21 (75%) out 28 people in the control group). The average time for recurrence was longer in the aspirin group (39 days) compared with (16.3 days) in group of compression alone. Adverse events were not reported in either trial. We considered these two studies too small and low quality for us to draw definitive conclusions about the benefits and harms of oral aspirin on the healing and recurrence of venous leg ulcers. The UK study provides only limited data about the potential benefits of daily oral aspirin therapy with compression due to a small sample size of only 20 participants and short follow up. The Spanish study provides limited data on 51 participants comparing aspirin and compression to a control group. The fact that no information was reported regarding placebo in the control group means the estimate of effect is uncertain. Further high quality studies are needed in this area. This plain language summary is up to date as of 27 May 2015.

CochranePLS1221

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Individual participant data were obtained for five studies, which recruited a total of 635 participants, representing 80% of 798 individuals from all seven identified eligible trials. For remission outcomes, an HR of less than 1 indicates an advantage for phenytoin and for first seizure and treatment failure outcomes an HR of less than 1 indicates an advantage for phenobarbitone. Results for the primary outcome of the review were: time to treatment failure for any reason related to treatment (pooled HR adjusted for seizure type for 499 participants: 1.61, 95% CI 1.22 to 2.12, low-certainty evidence), time to treatment failure due to adverse events (pooled HR adjusted for seizure type for 499 participants: 1.99, 95% CI 1.37 to 2.87, low-certainty evidence), time to treatment failure due to lack of efficacy (pooled HR adjusted for seizure type for 499 participants: 1.87, 95% CI 1.32 to 2.66, moderate-certainty evidence), showing a statistically significant advantage for phenytoin compared to phenobarbitone. For our secondary outcomes, we did not find any statistically significant differences between phenytoin and phenobarbitone: time to first seizure post-randomisation (pooled HR adjusted for seizure type for 624 participants: 0.85, 95% CI 0.69 to 1.06, moderate-certainty evidence), time to 12-month remission (pooled HR adjusted for seizure type for 588 participants: 0.90, 95% CI 0.69 to 1.19, moderate-certainty evidence), and time to six-month remission pooled HR adjusted for seizure type for 588 participants: 0.91, 95% CI 0.71 to 1.15, moderate-certainty evidence). For individuals with focal onset seizures (73% of individuals contributing to analysis), numerical results were similar and conclusions the same as for analyses of all individuals and for individuals with generalised onset seizures (27% of individuals contributing to analysis), results were imprecise and no clear differences between the drugs were observed. Several confounding factors, most notably the differences in design of the trials with respect to blinding, were likely to have impacted on the results of the primary outcome 'time to treatment failure', and in turn, the treatment failure rates may have impacted on the secondary efficacy outcomes of time to first seizure and time to 12-month and six-month remission. Low-certainty evidence from this review suggests that phenytoin may be a more effective drug than phenobarbitone in terms of treatment retention (treatment failures due to lack of efficacy or adverse events or both). Moderate-certainty evidence from this review also indicates no differences between the drugs in terms of time to seizure recurrence and seizure remission. However, the trials contributing to the analyses had methodological inadequacies and methodological design differences that may have impacted upon the results of this review. Therefore, we do not suggest that results of this review alone should form the basis of a treatment choice for a patient with newly onset seizures. We recommend that future trials should be designed to the highest quality possible with consideration of masking, choice of population, classification of seizure type, duration of follow-up, choice of outcomes and analysis, and presentation of results. Output:

The last search for trials was in August 2018. We assessed the evidence from seven clinical trials in which people received either phenobarbitone or phenytoin and their treatment was decided randomly. We were able to combine data for 635 people from five of the seven trials; for the remaining 163 people from two trials, data were not available to use in this review Key results This review found no evidence to suggest a difference between phenobarbitone and phenytoin in terms of the time to seizure recurrence and time to seizure remission (seizure free period of six or 12 months). Phenobarbitone treatment was more likely to be withdrawn than phenytoin treatment, however, this may have been influenced by the design of the included studies (whether the people and the clinicians treating them knew which treatment the person was receiving). Quality of the evidence Some of the trials contributing data to the review had methodological problems, which may have introduced bias and inconsistent results into this review. Also, we believe that the difference in study design with regards to whether the treatment was masked from the patients and clinicians (e.g. with a placebo tablet) had an impact on the rates of withdrawal from the study treatments, which also is likely to have impacted on the outcomes related to seizure control These problems may have affected the results of this review and we judged the quality of the evidence provided by this review to be moderate to low quality. We do not suggest using the results of this review alone for making a choice between phenytoin or phenobarbitone for the treatment of epilepsy. Future trials comparing these drugs or any other antiepileptic drugs should be designed using high-quality methods to ensure results are also of high quality.

CochranePLS1222

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We identified five studies that met the inclusion criteria for this review: four RCTs and one cluster-RCT. The study characteristics differed in terms of healthcare settings, the nature of the interventions studied and outcome measures reported. The cluster-RCT, and two of the RCTs, explored the effectiveness of education delivered to healthcare staff within residential or nursing home settings, or nursing home and hospital wards, compared to no intervention, or usual practices. Educational intervention in one of these studies was embedded within a broader, quality improvement bundle. The other two individually randomised controlled trials explored the effectiveness of educational intervention, delivered in two formats, to nursing staff cohorts. Due to the heterogeneity of the studies identified, pooling was not appropriate and we have presented a narrative overview. We explored a number of comparisons (1) education versus no education (2) components of educational intervention in a number of combinations and (3) education delivered in different formats. There were three primary outcomes: change in healthcare professionals' knowledge, change in healthcare professionals' clinical behaviour and incidence of new pressure ulcers. We are uncertain whether there is a difference in health professionals' knowledge depending on whether they receive education or no education on pressure ulcer prevention (hospital group: mean difference (MD) 0.30, 95% confidence interval (CI) -1.00 to 1.60; 10 participants; nursing home group: MD 0.30, 95% CI -0.77 to 1.37; 10 participants). This was based on very low-certainty evidence from one study, which we downgraded for serious study limitations, indirectness and imprecision. We are uncertain whether there is a difference in pressure ulcer incidence with the following comparisons: training, monitoring and observation, versus monitoring and observation (risk ratio (RR) 0.63, 95% CI 0.37 to 1.05; 345 participants); training, monitoring and observation, versus observation alone (RR 1.21, 95% CI 0.60 to 2.43; 325 participants) or, monitoring and observation versus observation alone (RR 1.93, 95% CI 0.96 to 3.88; 232 participants). This was based on very low-certainty evidence from one study, which we downgraded for very serious study limitations and imprecision. We are uncertain whether multilevel intervention versus attention control makes any difference to pressure ulcer incidence. The report presented insufficient data to enable further interrogation of this outcome. We are uncertain whether education delivered in different formats such as didactic education versus video-based education (MD 4.60, 95% CI 3.08 to 6.12; 102 participants) or e-learning versus classroom education (RR 0.92, 95% CI 0.80 to 1.07; 18 participants), makes any difference to health professionals' knowledge of pressure ulcer prevention. This was based on very low-certainty evidence from two studies, which we downgraded for serious study limitations and study imprecision. None of the included studies explored our other primary outcome: change in health professionals' clinical behaviour. Only one study explored the secondary outcomes of interest, namely, pressure ulcer severity and patient and carer reported outcomes (self-assessed quality of life and functional dependency level respectively). However, this study provided insufficient information to enable our independent assessment of these outcomes within the review. We are uncertain whether educating healthcare professionals about pressure ulcer prevention makes any difference to pressure ulcer incidence, or to nurses' knowledge of pressure ulcer prevention. This is because the included studies provided very low-certainty evidence. Therefore, further information is required to clarify the impact of education of healthcare professionals on the prevention of pressure ulcers. Output:

In June 2017 we searched for studies evaluating the effect of the education of healthcare professionals on pressure ulcer prevention, and found five relevant studies. Two studies explored the impact of education on the prevention of pressure ulcers. We are uncertain whether education of healthcare professionals makes any difference to the number of new pressure ulcers that develop. This is because the certainty of the evidence within the studies was very low. Three studies explored the impact of education on staff knowledge of pressure ulcer prevention. The studies compared: education versus no education; components of educational intervention in a number of combinations; and education delivered in different formats. We are uncertain whether education makes any difference to staff knowledge of pressure ulcer prevention, or to the number of new pressure ulcers that develop. This is because the certainty of the evidence within the studies was very low. No study explored the impact of education on the treatment provided by health professionals. Only one study explored the secondary outcomes of interest: pressure ulcer severity, patients' views on their quality of life and carers' views on the patients' ability to carry out daily tasks independently. However, there was not enough information provided within the study to enable our independent assessment of these outcomes. We examined the certainty of the evidence using the GRADE approach and concluded that all of the evidence was of very low certainty. Therefore we are unable to determine whether education can prevent pressure ulcers. We are also unable to determine whether education affects the knowledge that healthcare staff possess about preventing pressure ulcers. The evidence of this review is up-to-date as of 12 June 2017.

CochranePLS1223

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Twelve trials on artificial or bioartificial support systems versus standard medical therapy (483 patients) and two trials comparing different artificial support systems (105 patients) were included. Most trials had unclear methodological quality. Compared to standard medical therapy, support systems had no significant effect on mortality (RR 0.86; 95% CI 0.65 to 1.12) or bridging to liver transplantation (RR 0.87; 95% CI 0.73 to 1.05), but a significant beneficial effect on hepatic encephalopathy (RR 0.67; 95% CI 0.52 to 0.86). Meta-regression indicated that the effect of support systems depended on the type of liver failure (P = 0.03). In subgroup analyses, artificial support systems appeared to reduce mortality by 33% in acute-on-chronic liver failure (RR 0.67; 95% CI 0.51 to 0.90), but not in acute liver failure (RR 0.95; 95% CI 0.71 to 1.29). Two trials comparing artificial support systems showed significant mortality reductions with intermittent versus continuous haemofiltration (RR 0.58; 95% CI 0.36 to 0.94) and no significant difference between five versus ten hours of charcoal haemoperfusion (RR 1.03; 95% CI 0.65 to 1.62). The incidence of adverse events was inconsistently reported. This Review indicates that artificial support systems may reduce mortality in acute-on-chronic liver failure. Artificial and bioartificial support systems did not appear to affect mortality in acute liver failure. However, considering the strength of the evidence additional randomised clinical trials are needed before any support system can be recommended for routine use. Output:

Evidence from twelve small randomised trials were combined. Most trials had unclear methodologic quality. Overall, support systems did not appear to affect mortality or bridging to transplantation, but had a beneficial effect on hepatic encephalopathy. The risk of adverse events could not be established. Further evidence is needed before support systems can be recommended for routine use.

CochranePLS1224

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Seven RCTs (1205 patients) were included in the review. Stone-free rates were lower in patients who underwent ESWL (7 studies, 1205 participants: RR 0.84, 95% CI 0.73 to 0.96) but re-treatment rates were lower in ureteroscopy patients (6 studies, 1049 participants: RR 6.18, 95% CI 3.68 to 10.38. ESWL-treated patients had less need for auxiliary treatment (5 studies, 751 participants: RR 0.43, 95% CI 0.25 to 0.74; fewer complications (7 studies, 1205 participants: RR 0.54, 95% CI 0.33 to 0.88); and shorter length of hospital stay (2 studies, 198 participants: MD -2.55 days, 95% CI -3.24 to -1.86). Three studies adequately described the randomisation sequence, three studies were unclear on how they randomised, while one study had a high risk of selection bias. All the studies had an unclear risk of performance bias and detection bias, while all had a low risk of attrition bias, reporting bias, or other sources of bias identified. Compared with ESWL, ureteroscopic removal of ureteral stones achieves a greater stone-free state, but with a higher complication rate and longer hospital stay. Output:

We analysed reports from seven randomised controlled trials of 1205 patients and found that ureteroscopy provided a better stone-free rate after treatment, but patients had to stay in hospital longer, and there was a higher risk of complications. We found that there were many variations among the seven studies in their design, duration, and data collected which made comparison and evaluation challenging. We recommend that further evaluation and research is conducted to ensure that new and improved treatments and studies are considered to inform clinical practice.

CochranePLS1225

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 53 studies primarily describing the experiences of LHWs, programme recipients, and other health workers. LHWs in high income countries mainly offered promotion, counselling and support. In low and middle income countries, LHWs offered similar services but sometimes also distributed supplements, contraceptives and other products, and diagnosed and treated children with common childhood diseases. Some LHWs were trained to manage uncomplicated labour and to refer women with pregnancy or labour complications. Many of the findings were based on studies from multiple settings, but with some methodological limitations. These findings were assessed as being of moderate certainty. Some findings were based on one or two studies and had some methodological limitations. These were assessed have low certainty. Barriers and facilitators were mainly tied to programme acceptability, appropriateness and credibility; and health system constraints. Programme recipients were generally positive to the programmes, appreciating the LHWs’ skills and the similarities they saw between themselves and the LHWs. However, some recipients were concerned about confidentiality when receiving home visits. Others saw LHW services as not relevant or not sufficient, particularly when LHWs only offered promotional services. LHWs and recipients emphasised the importance of trust, respect, kindness and empathy. However, LHWs sometimes found it difficult to manage emotional relationships and boundaries with recipients. Some LHWs feared blame if care was not successful. Others felt demotivated when their services were not appreciated. Support from health systems and community leaders could give LHWs credibility, at least if the health systems and community leaders had authority and respect. Active support from family members was also important. Health professionals often appreciated the LHWs’ contributions in reducing their workload and for their communication skills and commitment. However, some health professionals thought that LHWs added to their workload and feared a loss of authority. LHWs were motivated by factors including altruism, social recognition, knowledge gain and career development. Some unsalaried LHWs wanted regular payment, while others were concerned that payment might threaten their social status or lead recipients to question their motives. Some salaried LHWs were dissatisfied with their pay levels. Others were frustrated when payment differed across regions or institutions. Some LHWs stated that they had few opportunities to voice complaints. LHWs described insufficient, poor quality, irrelevant and inflexible training programmes, calling for more training in counselling and communication and in topics outside their current role, including common health problems and domestic problems. LHWs and supervisors complained about supervisors’ lack of skills, time and transportation. Some LHWs appreciated the opportunity to share experiences with fellow LHWs. In some studies, LHWs were traditional birth attendants who had received additional training. Some health professionals were concerned that these LHWs were over-confident about their ability to manage danger signs. LHWs and recipients pointed to other problems, including women’s reluctance to be referred after bad experiences with health professionals, fear of caesarean sections, lack of transport, and cost. Some LHWs were reluctant to refer women on because of poor co-operation with health professionals. We organised these findings and the outcome measures included in the review of LHW programme effectiveness in a logic model. Here we proposed six chains of events where specific programme components lead to specific intermediate or long-term outcomes, and where specific moderators positively or negatively affect this process. We suggest how future updates of the LHW effectiveness review could explore whether the presence of these components influences programme success. Rather than being seen as a lesser trained health worker, LHWs may represent a different and sometimes preferred type of health worker. The close relationship between LHWs and recipients is a programme strength. However, programme planners must consider how to achieve the benefits of closeness while minimizing the potential drawbacks. Other important facilitators may include the development of services that recipients perceive as relevant; regular and visible support from the health system and the community; and appropriate training, supervision and incentives. Output:

A LHW is a lay person who has received some training to deliver healthcare services but is not a health professional. In most of the studies in this review, LHWs offered health care to people who were on low incomes living in wealthy countries or to people living in poor countries. The LHWs in wealthy countries offered health promotion, counselling and support. The LHWs in poor countries offered similar services but they sometimes also distributed food supplements, contraceptives and other products, treated children with common childhood diseases, or managed women in uncomplicated labour. What the research says The studies described the experiences of LHWs, mothers, programme managers, and other health workers with LHW programmes. Many of our findings were based on studies from different settings and had some methodological problems. We judged these findings to have moderate certainty. Some findings were only based on one or two studies that had some methodological problems and were judged to be of low certainty. Mothers were generally positive about the programmes. They appreciated the LHWs’ skills and the similarities they saw between themselves and the LHWs. However, some mothers were concerned about confidentiality when receiving home visits. Others saw LHW services as not relevant or not sufficient, particularly when LHWs only offered promotional services. LHWs and mothers emphasised the importance of trust, respect, kindness and empathy. However, LHWs sometimes found it difficult to manage emotional relationships and boundaries with mothers. Some LHWs feared blame if health care was not successful. Others felt demotivated when their services were not appreciated. Support from health systems and community leaders could give LHWs credibility if these health systems and community leaders had authority and respect. Active support from family members was also important. Health professionals often appreciated the LHWs' contributions to reducing their workload, and their communication skills and commitment. However, some health professionals thought that LHWs added to their own workloads and feared a loss of authority. LHWs were motivated by altruism, social recognition, knowledge gain and career development. Some unsalaried LHWs wanted regular payment. Others were concerned that payment might threaten their social status or lead people to question their motives. Some salaried LHWs were dissatisfied with their pay levels. Others were frustrated when other LHWs had higher salaries. Some LHWs said that they had few opportunities to voice complaints. Some LHWs described insufficient, poor quality and irrelevant training programmes. They called for more training in counselling and communication and in topics outside their current role, including common health problems and domestic problems. LHWs and supervisors complained about supervisors’ lack of skills, time and transportation. Some LHWs appreciated the opportunity to share experiences with other LHWs. Some LHWs were traditional birth attendants who had received additional training. Some health professionals were concerned that these LHWs were over-confident about their ability to manage danger signs. LHWs and mothers identified women’s reluctance to be referred after bad experiences with health professionals, fear of caesarean sections, lack of transport, and costs. Some LHWs were also reluctant to refer women on because of poor co-operation with health professionals. We organized these findings into chains of events where we have proposed how certain LHW programme elements might lead to greater programme success. Authors’ conclusions Rather than being seen as a lesser trained health worker, LHWs represent a different and sometimes preferred type of health worker. The often close relationship between LHWs and their recipients is a strength of such programmes. However, programme planners must consider how to achieve the benefits of closeness while avoiding the problems. It may also be important to offer services that recipients perceive as relevant; to ensure regular and visible support from other health workers and community leaders; and to offer appropriate training, supervision and incentives.

CochranePLS1226

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: No additional studies were identified in this 2015 review update, in total leading to no studies meeting the criteria for inclusion in this review. The efficacy of ECP in the treatment of chronic GvHD in paediatric patients after haematopoietic stem cell transplantation based on RCTs cannot be evaluated since the original version of this review and the first review update found no RCTs. Current recommendations are based on retrospective or observational studies only. Thus, ideally, ECP should be applied in the context of controlled trials only. However, performing RCTs in this patient population will be challenging due to the limited number of patients, the variable disease presentation and the lack of well-defined response criteria. International collaboration, multicentre trials and appropriate funding for such trials will be needed. If treatment decisions based on clinical data are made in favour of ECP, patients should be carefully monitored for beneficial and harmful effects. In addition, efforts should be made to share this information with other clinicians, for example by setting up registries for paediatric patients that are treated with ECP. Output:

We searched scientific databases for randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) that were designed to evaluate the effectiveness and safety of ECP for the management of chronic graft-versus-host disease in children and adolescents (under 18 years of age) after HSCT. The original version of this review and this 2015 review update found no RCTs that analysed the efficacy of ECP for paediatric patients with chronic graft-versus-host disease after HSCT. Current recommendations are based on retrospective (a study in which the outcomes have occurred to the participants before the study began) or observational (a study in which the investigators do not seek to intervene, and simply observed the course of events) studies only. Thus, ideally, ECP should be applied in paediatric patients in the context of RCTs only. ECP may be considered in people with steroid-refractory chronic GvHD, keeping in mind that such a treatment is not supported by high-level evidence. If treatment decisions based on clinical data in favour of ECP are made, patients should be carefully monitored for beneficial and harmful effects and efforts should be made to share this information with other clinicians, for example by setting up registries for paediatric patients that are treated with ECP.

CochranePLS1227

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included three RCTs that enrolled a total of 139 eyes of 136 participants and analysed 123 (88%) eyes. Two RCTs randomised eyes into either the endothelial keratoplasty (EK) group or penetrating keratoplasty (PKP) group and one RCT randomised eyes into either the femtosecond laser-assisted endothelial keratoplasty (FLEK) group or PKP group. The RCTs comparing EK with PKP did not show any significant differences between procedures with respect to best corrected visual acuity (BCVA) at two years (mean difference (MD) 0.14 logMAR; 95% confidence interval (CI) -0.08 to 0.36; P = 0.23) or at one year (MD 0.09 logMAR; 95% CI -0.05 to 0.23; P = 0.22), whereas the trial comparing FLEK with PKP showed significantly better BCVA after PKP (MD 0.20 logMAR; 95% CI 0.10 to 0.30; P = 0.0001). Only one RCT reported on irregular astigmatism (higher-order aberration), which was less with EK than PKP (MD -1.20 µm; 95% CI -1.53 to -0.87; P < 0.001). Only one RCT reported on endothelial cell counts (lower after FLEK than PKP: MD -969 cells/mm²; 95% CI -1161 to -777; P < 0.001), primary graft failure (higher after FLEK than PKP: RR 7.76; 95% CI 0.41 to 145.22; P = 0.10), and graft rejection (more after FLEK than PKP: RR 1.11; 95% CI 0.07 to 17.12; P = 0.94). Only one RCT reported that 27.8% of participants had graft dislocation, 2.8% had epithelial ingrowth and postoperative pupillary block, and 13.9% had intraocular pressure (IOP)-related problems in the FLEK group compared with the PKP group, in whom 10% had suture-related problems, 5% had wound dehiscence and 10% had suture revision to correct astigmatism. Overall, the adverse events in the FLEK group appeared to be more frequent than in the PKP group. No trials reported information about quality of life or economic data. The overall methodological quality of the three trials was not satisfactory as most did not perform allocation concealment or masking of participants and outcome assessors, and all trials had a small sample size. The rapid growth of endothelial keratoplasty as the treatment of choice for FED is based upon the belief that visual recovery is more rapid, surgically induced astigmatism (regular and irregular) is less and rates of transplant rejection are lower with EK. This change in practice also assumes that the rates of long term transplant survival are equal for the two procedures. The practical differences between the surgical procedures mean that visual recovery is inherently more rapid following EK, but this review found no strong evidence from RCTs of any difference in the final visual outcome between EK and PKP for people with FED. This review also found that higher order aberrations are fewer following EK but endothelial cell loss is greater following EK. The RCTs that we included employed different EK techniques, which may have a bearing on these findings. EK procedures have evolved over the years and can be performed using different techniques, for example deep lamellar endothelial keratoplasty, Descemets stripping endothelial keratoplasty (DSEK), Descemets stripping automated endothelial keratoplasty (DSAEK), femtosecond laser-assisted endothelial keratoplasty and Descemet membrane endothelial keratoplasty (DMEK). More RCTs are needed to compare PKP with commonly performed EK procedures such as DSEK, DSAEK and DMEK in order to determine the answers to two key questions, whether there is any difference in the final visual outcome between these techniques and whether there are differences in the rates of graft survival in the long term? Output:

We found three randomised controlled trials that compared EK with PKP, one of which used the FLEK method. The evidence was current to January 2014. The three trials enrolled a total of 139 eyes of 136 participants, of which 123 eyes were included in the final analyses. The trial on FLEK and PKP was conducted from 2005 to 2007 in the Netherlands; the other two trials were conducted in the United States and were reported in 2008 and 2009 but the study dates were not specified. Over 70% of the included participants were diagnosed with FED, and the remaining participants had other ocular conditions. There was no difference in best corrected visual acuity (BCVA) between the two groups in one study at 12 months and another at 24 months. Chances of having an irregular shape of the front of the cornea (astigmatism) was less but endothelial cell loss was higher following EK procedures than after PKP. Only one trial reported harms of the interventions, and indicated that FLEK may result in slightly more complications than PKP (for example, 8% graft failure in the FLEK group versus none in the PKP group; and 3% graft rejection in the FLEK group versus 2% in the PKP group). No trials reported information about quality of life or economic data. The quality of the evidence was not high due to some limitations with the study designs and because all trials had small numbers of participants with FED.

CochranePLS1228

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Eight RCTs were included with a total of 3610 PAD patients. Four studies compared a recognised class of anti-hypertensive treatment with placebo and four studies compared two anti-hypertensive treatments with each other. Studies were not pooled due to the variation of the comparisons and the outcomes presented. Overall the quality of the available evidence was unclear, primarily as a result of a lack of detail in the study reports on the randomisation and blinding procedures and incomplete outcome data. Two studies compared angiotensin converting enzyme (ACE) inhibitors against placebo. In one study there was a significant reduction in the number of cardiovascular events in patients receiving ramipril (odds ratio (OR) 0.72, 95% confidence interval (CI) 0.58 to 0.91; n = 1725). In the second trial using perindopril (n = 52) there was a marginal increase in claudication distance but no change in ABI and a reduction in maximum walking distance. A trial comparing the calcium antagonist verapamil versus placebo in patients undergoing angioplasty (n = 96) suggested that verapamil reduced restenosis (per cent diameter stenosis (± SD) 48.0% ± 11.5 versus 69.6% ± 12.2; P < 0.01), although this was not reflected in the maintenance of a high ABI (0.76 ± 0.10 versus 0.72 ± 0.08 for verapamil versus placebo). Another study (n = 80) demonstrated no significant difference in arterial intima-media thickness (IMT) in men receiving the thiazide diuretic hydrochlorothiazide (HCTZ) compared to those receiving the alpha-adrenoreceptor blocker doxazosin (-0.12 ± 0.14 mm and -0.08 ± 0.13 mm, respectively; P = 0.66). A study (n = 36) comparing telmisartan to placebo found a significant improvement in maximum walking distance at 12 months with telmisartan (median (interquartile range (IQR)) 191 m (157 to 226) versus 103 m (76 to 164); P < 0.001) but no differences in ABI (median (IQR) 0.60 (0.60 to 0.77) versus 0.52 (0.48 to 0.67)) or arterial IMT (median (IQR) 0.08 cm (0.07 to 0.09) versus 0.09 cm (0.08 to 0.10)). Two studies compared the beta-adrenoreceptor blocker nebivolol with either the thiazide diuretic HCTZ or with metoprolol. Both studies found no significant differences in intermittent or absolute claudication distance, ABI, or all-cause mortality between the anti-hypertensives. A subgroup analysis of PAD patients (n = 2699) in a study which compared a calcium antagonist-based strategy (verapamil slow release (SR) ± trandolapril) to a beta-adrenoreceptor blocker-based strategy (atenolol ± hydrochlorothiazide) found no significant differences in the composite endpoints of death, non-fatal myocardial infarction or non-fatal stroke with or without revascularisation (OR 0.90, 95% CI 0.76 to 1.07 and OR 0.96, 95% CI 0.82 to 1.13, respectively). Evidence on the use of various anti-hypertensive drugs in people with PAD is poor so that it is unknown whether significant benefits or risks accrue. However, lack of data specifically examining outcomes in PAD patients should not detract from the overwhelming evidence on the benefit of treating hypertension and lowering blood pressure. Output:

We identified eight RCTs with a total of 3610 people with symptomatic PAD where participants were randomised to receive an anti-hypertensive treatment for at least one month or placebo or no treatment. Four studies compared an anti-hypertensive treatment with placebo and four studies compared two anti-hypertensive treatments with each other. The studies were not combined due to the variation of comparisons and the outcomes presented. One trial with 1725 participants showed that the angiotensin converting enzyme (ACE) inhibitor ramipril was effective in reducing the number of cardiovascular events by 28% compared to placebo. In one other study using an ACE inhibitor (n = 52) the perindopril group showed a small increase in claudication distance but no change in ABI and a reduction in maximal walking distance (MWD). In patients undergoing peripheral arterial angioplasty (a procedure to open narrowed or blocked blood vessels) the results from a trial with 96 participants suggested that the calcium channel blocker verapamil reduced restenosis (new blockage of the artery) at six months. In one small study (n = 80) peripheral arterial wall thickness was similar whether men received the thiazide diuretic hydrochlorothiazide (HCTZ) or the alpha-adrenoreceptor blocker doxazosin. In another small study (n = 36) MWD was improved at 12 months in the angiotensin-II receptor antagonist telmisartan group compared to the placebo group but there were no significant differences in ABI or arterial wall thickness. Another study (n = 163) found no significant differences in intermittent or absolute claudication distance, ABI, all-cause mortality or non-fatal cardiovascular events after 24 weeks of treatment in the beta-adrenoreceptor blocker nebivolol group and the HCTZ group. A study comparing two beta-adrenoreceptor blockers, nebivolol and metoprolol, found no clear differences in intermittent or absolute claudication distance, ABI, all-cause mortality or revascularisation after 36 weeks of treatment. A subgroup analysis of PAD patients (n = 2699) in the final study revealed no significant differences in the combined endpoints of death, non-fatal myocardial infarction or non-fatal stroke with or without revascularisation between the calcium antagonist-based strategy (verapamil slow release (SR) with or without trandolapril) compared to the beta-adrenoreceptor blocker strategy (atenolol with or without HCTZ). The evidence on the use of various anti-hypertensive drugs in people with PAD is poor so that it is not known whether significant benefits or risks accrue. However, lack of data specifically examining outcomes in hypertensive PAD patients should not detract from the overwhelming evidence on the benefit of treating hypertension and lowering blood pressure.

CochranePLS1229

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included eight randomised studies encompassing 850 participants. Five studies compared titanium clips versus ligature, two studies compared an endoscopic stapler device versus ligature, and one study compared an endoscopic stapler device, titanium clips, and ligature. In our analyses of primary outcomes, we found no differences in total complications (OR 0.97, 95% CI 0.27 to 3.50, 8 RCTs, very low-quality evidence), intraoperative complications (OR 0.93, 95% CI 0.34 to 2.55, 8 RCTs, very low-quality evidence), or postoperative complications (OR 0.80, 95% CI 0.21 to 3.13, 8 RCTs, very low-quality evidence) between ligature and all types of mechanical devices. However, our analyses of secondary outcomes revealed that use of mechanical devices saved approximately nine minutes of total operating time when compared with use of a ligature (mean difference (MD) -9.04 minutes, 95% CI -12.97 to -5.11 minutes, 8 RCTs, very low-quality evidence). However, this finding did not translate into a clinically or statistically significant reduction in inpatient hospital stay (MD 0.02 days, 95% CI -0.12 to 0.17 days, 8 RCTs, very low-quality evidence). Available information was insufficient for reliable comparison of total hospital costs and postoperative pain/quality of life between the two approaches. Overall, evidence across all analyses was of very low quality, with substantial potential for confounding factors. Given the limitations of all studies in terms of bias and the low quality of available evidence, a clear conclusion regarding superiority of any one particular type of mechanical device over another is not possible. Evidence is insufficient at present to advocate omission of conventional ligature-based appendix stump closure in favour of any single type of mechanical device over another in uncomplicated appendicitis. Output:

We searched for all relevant randomised controlled trials up to 14 June 2017. This systematic review included eight randomised controlled trials involving a total of 850 participants. All trials compared mechanical devices versus ligatures for appendix stump closure. Five of the eight trials compared use of clips versus ligature, two trials compared an automated stapler versus ligature, and one trial compared all three methods. Use of mechanical devices to close the appendix stump during laparoscopic appendectomy did not make a significant difference in the rate of overall complications when compared with use of a ligature, or in the rate of complications that happened during or after the appendectomy procedure. However, mechanical devices did make the operation nine minutes quicker when compared with ligatures. Mechanical devices did not make a substantial difference in overall hospital stay. We did not have enough information to reliably evaluate hospital costs, pain, or quality of life for either of these comparisons. As a result, we have not found enough evidence at present that would lead us to strongly recommend any particular method over another. More research should be undertaken to better compare available newer methods. The evidence used to derive our conclusions was generally of low quality. The studies we included for each analysis were vulnerable to different types of bias and contained inconsistencies and imprecision in their results due to small numbers of participants and events in each included study arm. It is likely that future research will substantially change our conclusions; further studies in this field are needed.

CochranePLS1230

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 13 trials in this Cochrane review. Ten studies were at 'low' risk of bias. Six studies compared NSAIDs with placebo, and included 1354 participants in total. There is low quality evidence that NSAIDs are more effective than placebo, with a mean difference in pain intensity score from baseline of -6.97 (95% CI −10.74 to −3.19) on a 0 to 100 visual analogue scale (VAS) with a median follow-up of 56 days (interquartile range (IQR) 13 to 91 days). Four studies measured disability using the Roland Morris Disability Questionnaire. There is low quality evidence that NSAIDs are more effective than placebo on disability, with a mean difference from baseline of −0.85 (95% CI −1.30 to −0.40) on a scale from 0 to 24 with a median follow-up of 84 days (IQR 42 to 105 days). All six placebo controlled studies also reported adverse events, and suggested that adverse events are not statistically significant more frequent in participants using NSAIDs compared to placebo (RR 1.04, 95% CI 0.92 to 1.17). Due to the relatively small sample size and relatively short follow-up in most included trials, it is likely that the proportion of patients experiencing an adverse event is underestimated. Two studies compared different types of non-selective NSAIDs, namely ibuprofen versus diclofenac and piroxicam versus indomethacin. The trials did not find any differences between these NSAID types, but both trials had small sample sizes. One trial reported no differences in pain intensity between treatment groups that used selective or non-selective NSAIDs. One other trial compared diflunisal with paracetamol and showed no difference in improvement from baseline on pain intensity score. One trial showed a better global improvement in favour of celecoxib versus tramadol. One included trial compared NSAIDs with 'home-based exercise'. Disability improved more in participants who did exercises versus participants receiving NSAIDs, but pain scores were similar. Six of the 13 included RCTs showed that NSAIDs are more effective than placebo regarding pain intensity. NSAIDs are slightly more effective than placebo regarding disability. However, the magnitude of the effects is small, and the level of evidence was low. When we only included RCTs at low risk of bias, differences in effect between NSAIDs and placebo were reduced. We identified no difference in efficacy between different NSAID types, including selective versus non-selective NSAIDs. Due to inclusion of RCTs only, the relatively small sample sizes and relatively short follow-up in most included trials, we cannot make firm statements about the occurrence of adverse events or whether NSAIDs are safe for long-term use. Output:

We collected all published randomized controlled trials evaluating the efficacy of NSAIDs until 24 June 2015. We included 13 trials which compared NSAIDs with placebo, other NSAIDs, other drugs or other treatment in people with chronic low back pain. Six trials compared NSAIDs with placebo, and included 1354 participants in total. Follow-up was between nine days and 16 weeks. NSAIDs reduced pain and disability in people with chronic low back pain compared to placebo. However, the differences were small: 7 points on a 100-point scale for pain intensity. Regarding disability, people receiving NSAIDs scored 0.9 points better on a 0 to 24 disability scale. The number of adverse events was not significantly different between the people receiving NSAIDs and people receiving placebo, but larger studies of longer duration would be needed to identify rare or delayed adverse events, important drug interactions and adverse events occurring with prolonged use. Different types of NSAIDs did not show significantly different effects. Three of the 13 included studies compared two different types of NSAIDs and none found any differences. NSAIDs were also compared to other drug types: paracetamol, tramadol and pregabalin. There were no differences found between NSAIDs and paracetamol and pregabalin in either effect or adverse events. A single study comparing celecoxib with tramadol showed a better global improvement in peoples using celecoxib. One trial compared NSAIDs with 'home-based exercise'. Regarding disability, people who did exercise improved more than people receiving NSAIDs, but pain scores were not statistically different. There was low quality evidence that NSAIDs are slightly more effective than placebo in chronic low back pain. The magnitude of the difference was small, and when we only accounted for trials of higher quality, these differences reduced.

CochranePLS1231

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 36 trials involving 1472 participants in this review update. Electromechanical-assisted gait training in combination with physiotherapy increased the odds of participants becoming independent in walking (odds ratio (random effects) 1.94, 95% confidence interval (CI) 1.39 to 2.71; P < 0.001; I² = 8%; moderate-quality evidence) but did not significantly increase walking velocity (mean difference (MD) 0.04 m/s, 95% CI 0.00 to 0.09; P = 0.08; I² = 65%; low-quality evidence) or walking capacity (MD 5.84 metres walked in 6 minutes, 95% CI -16.73 to 28.40; P = 0.61; I² = 53%; very low-quality evidence). The results must be interpreted with caution because 1) some trials investigated people who were independent in walking at the start of the study, 2) we found variations between the trials with respect to devices used and duration and frequency of treatment, and 3) some trials included devices with functional electrical stimulation. Our planned subgroup analysis suggested that people in the acute phase may benefit, but people in the chronic phase may not benefit from electromechanical-assisted gait training. Post hoc analysis showed that people who are non-ambulatory at intervention onset may benefit, but ambulatory people may not benefit from this type of training. Post hoc analysis showed no differences between the types of devices used in studies regarding ability to walk, but significant differences were found between devices in terms of walking velocity. People who receive electromechanical-assisted gait training in combination with physiotherapy after stroke are more likely to achieve independent walking than people who receive gait training without these devices. We concluded that seven patients need to be treated to prevent one dependency in walking. Specifically, people in the first three months after stroke and those who are not able to walk seem to benefit most from this type of intervention. The role of the type of device is still not clear. Further research should consist of large definitive pragmatic phase III trials undertaken to address specific questions about the most effective frequency and duration of electromechanical-assisted gait training as well as how long any benefit may last. Output:

We included 36 studies involving a total of 1472 participants over the age of 18 years with acute, postacute, or chronic ischaemic or haemorrhagic stroke. The mean age in the included studies ranged from 48 years to 76 years. The majority of studies were conducted in an inpatient setting. We found moderate-quality evidence that electromechanical-assisted gait training combined with physiotherapy when compared with physiotherapy alone may improve recovery of independent walking in people after stroke. We determined that for every seven patients treated with electromechanical- and robotic-assisted gait training devices, just one prevention of dependency in walking occurs. Specifically, people in the first three months after stroke and those who are not able to walk appear to benefit most from this type of intervention. The importance of the type of device is still not clear. Further research should address what frequency or duration of walking training might be most effective and how long the benefit lasts. It also remains unclear how such devices should be used in routine rehabilitation. The quality of the evidence for automated electromechanical- and robotic-assisted gait-training devices for improving walking after stroke was moderate. The quality of evidence was low for walking speed, very low for walking capacity, and low for adverse events and people discontinuing treatment.

CochranePLS1232

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Six RCTs ranging from 8 to 26 weeks investigating 1450 participants met the inclusion criteria. Overall, the risk of bias of these trials was unclear or high. All RCTs compared the effects of colesevelam with or without other antidiabetic drug treatments with placebo only (one study) or combined with antidiabetic drug treatments. Colesevelam with add-on antidiabetic agents demonstrated a statistically significant reduction in fasting blood glucose with a mean difference (MD) of -15 mg/dL (95% confidence interval (CI) -22 to - 8), P < 0.0001; 1075 participants, 4 trials, no trial with low risk of bias in all domains. There was also a reduction in glycosylated haemoglobin A1c (HbA1c) in favour of colesevelam (MD -0.5% (95% CI -0.6 to -0.4), P < 0.00001; 1315 participants, 5 trials, no trial with low risk of bias in all domains. However, the single trial comparing colesevelam to placebo only (33 participants) did not reveal a statistically significant difference between the two arms - in fact, in both arms HbA1c increased. Colesevelam with add-on antidiabetic agents demonstrated a statistical significant reduction in low-density lipoprotein (LDL)-cholesterol with a MD of -13 mg/dL (95% CI -17 to - 9), P < 0.00001; 886 participants, 4 trials, no trial with low risk of bias in all domains. Non-severe hypoglycaemic episodes were infrequently observed. No other serious adverse effects were reported. There was no documentation of complications of the disease, morbidity, mortality, health-related quality of life and costs. Colesevelam added on to antidiabetic agents showed significant effects on glycaemic control. However, there is a limited number of studies with the different colesevelam/antidiabetic agent combinations. More information on the benefit-risk ratio of colesevelam treatment is necessary to assess the long-term effects, particularly in the management of cardiovascular risks as well as the reduction in micro- and macrovascular complications of type 2 diabetes mellitus. Furthermore, long-term data on health-related quality of life and all-cause mortality also need to be investigated. Output:

A total of 1450 patients took part in six studies investigating colesevelam. These studies lasted 8 to 26 weeks. Only one small study compared colesevelam directly to placebo, the other five studies investigated a combination of colesevelam with other antidiabetic agents versus a combination of placebo with other antidiabetic agents. There were no two studies with the same intervention and comparison group. When added to other antidiabetic agents colesevelam showed improvements in the control of blood glucose and blood lipids. However, it is difficult to disentangle the effects of colesevelam from the other antidiabetic agents used because only one study compared colesevelam to placebo. The same is true for adverse effects: three studies reported on just a few non-severe hypoglycaemic episodes, no other serious side effects were observed. No study investigated mortality; complications of type 2 diabetes such as eye disease, kidney disease, heart attack and stroke; health-related quality of life; functional outcomes and costs of treatment. Therefore, long-term data on the efficacy and safety of colesevelam are necessary.

CochranePLS1233

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Six trials involving a total of 2128 people were included in this review. We did not combine the results quantitatively because the interventions and patient populations were so diverse. Early versus delayed fluid administration Three trials reported mortality and two reported coagulation data. In the first trial (n = 598) the relative risk (RR) for death with early fluid administration was 1.26 (95% confidence interval (CI) 1.00 to 1.58). The weighted mean differences (WMD) for prothrombin time and partial thromboplastin time were 2.7 (95% CI 0.9 to 4.5) and 4.3 (95% CI 1.74 to 6.9) seconds, respectively. In the second trial (n = 50) the RR for death with early blood transfusion was 5.4 (95% CI 0.3 to 107.1). The WMD for partial thromboplastin time was 7.0 (95% CI 6.0 to 8.0) seconds. In the third trial (n = 1309) the RR for death with early fluid administration was 1.06 (95% CI 0.77 to 1.47). Larger versus smaller volume of fluid administration Three trials reported mortality and one reported coagulation data. In the first trial (n = 36) the RR for death with a larger volume of fluid resuscitation was 0.80 (95% CI 0.28 to 22.29). Prothrombin time and partial thromboplastin time were 14.8 and 47.3 seconds in those who received a larger volume of fluid, as compared to 13.9 and 35.1 seconds in the comparison group. In the second trial (n = 110) the RR for death with a high systolic blood pressure resuscitation target (100 mm Hg) maintained with a larger volume of fluid as compared to a low systolic blood pressure resuscitation target (70 mm Hg) maintained with a smaller volume of fluid was 1.00 (95% CI 0.26 to 3.81). In the third trial (n = 25) there were no deaths. We found no evidence from randomised controlled trials for or against early or larger volume of intravenous fluid administration in uncontrolled haemorrhage. There is continuing uncertainty about the best fluid administration strategy in bleeding trauma patients. Further randomised controlled trials are needed to establish the most effective fluid resuscitation strategy. Output:

The authors searched for relevant medical research reports and found six randomised controlled trials involving a total of 2128 people. In each study, people with uncontrolled bleeding were randomly assigned to receive one treatment or another. Three studies were about the amount of fluid given (more or less), and three studies were about giving fluid at different times following injury (sooner or later). The authors were interested in finding out which treatments were better, to reduce deaths and to enable blood clotting. Blood clotting was measured by prothrombin time and partial thromboplastin time during fluid administration. The review of trials found that there is uncertainty about the best time to give fluid and what volume of fluid should be given. While increasing fluids will maintain blood pressure, it may also worsen bleeding by diluting clotting factors in the blood. The first version of this review was published in 2000 and included these six trials. The authors searched for new, relevant studies in 2003, 2008 and 2014 but none were found. The authors will look for studies in 2020, and any new information will be incorporated into the review.

CochranePLS1234

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Three trials involving a total of 79 participants were included. All three trials, which compared topical nasal steroids against placebo for perennial rhinitis, provided some, albeit limited data, relevant to our primary outcomes; but in two of the trials the data analysis was flawed and in the third trial it was incomprehensible. None of the trials provided data relevant to our secondary outcomes. There were no adverse events reported from any of the interventions. The three included trials provided some weak and unreliable evidence for the effectiveness of Beconase® and flunisolide used topically intranasally for the treatment of intermittent and persistent allergic rhinitis in children. The reduction of severity in symptoms as assessed by the trialists could not be confirmed with the data provided and decisions on the use of these medications should, until such time as more robust evidence is available, be guided by the physician's clinical experience and patients' individual circumstances and preferences. Output:

The three included trials provided some weak and unreliable evidence for the effectiveness of Beconase® and flunisolide used topically in the nose for the treatment of intermittent and persistent allergic rhinitis in children. The review authors concluded that until more research is available, decisions on the use of topical steroids should be guided by the physician's clinical experience and patients' individual circumstances and preferences.

CochranePLS1235

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We did not find any fully-published, completed RCTs of angiogenesis inhibitors that met our inclusion criteria. We identified five abstracts of completed RCTs of four different angiogenesis-inhibiting agents, with a total of 3701 participants. Meta-analysis of two trials found no statistically significant difference in overall survival (OS) between women with newly-diagnosed advanced ovarian cancer who received concurrent and maintenance bevacizumab compared to those who received chemotherapy (carboplatin and paclitaxel) alone. However, women who received concurrent and maintenance bevacizumab had their risk of disease progression reduced by a quarter (hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.68 to 0.83; P < 0.001); they also had a significantly increased risk of severe gastrointestinal adverse events, moderate or severe hypertension and severe bleeding. One trial also compared chemotherapy to concurrent (but not maintenance bevacizumab), and found no statistically significant difference in OS or progression-free survival (PFS).  However, the women who received bevacizumab had a significantly higher risk of moderate or severe hypertension. A three-armed RCT, of paclitaxel alone or with low- or high-dose AMG 386, in women with recurrent ovarian cancer, found no statistically significant difference in OS. However, women who received low-dose AMG 386 had a third less risk of disease progression than those who received placebo (HR 0.57, 95% CI 0.36 to 0.91; P = 0.02). The trial found no evidence of increased adverse events in the intervention arms. Two relatively small RCTs (one of VEGF-Trap, the other of BIBF 1120) found no evidence of either significant survival benefit or increased severe adverse events, compared to placebo, but they both lacked statistical power. All five trials had unclear risk of bias, largely because they have only been published in abstract form, and thus many methodological details are unclear. We identified twelve suitable ongoing trials. There is, as yet, no fully-published RCT evidence for the efficacy or safety of angiogenesis inhibitors for the treatment of ovarian cancer, but some preliminary results are available from five trials. There is some evidence from a meta-analysis of two trials that the addition of concurrent and maintenance bevacizumab to standard chemotherapy may reduce the risk of disease progression, in women with newly-diagnosed advanced ovarian cancer. There is also some evidence from a single trial that low-dose AMG 386 may reduce the risk of disease progression in women with recurrent ovarian cancer. However, there is currently no evidence that angiogenesis inhibitors improve OS, nor is there enough evidence to justify the routine use of angiogenesis inhibitors in treating women with ovarian cancer. We eagerly await both the more detailed results of these five completed trials, and the preliminary results of the several ongoing trials. Output:

Two trials looked at the effect of adding bevacizumab to conventional chemotherapy in women who had just been diagnosed with ovarian cancer and had debulking surgery. Bevacizumab was given both alongside the chemotherapy, and then continued afterwards (called maintenance therapy). Taking the results of these two trials together, there was no significant benefit from adding bevacizumab to standard chemotherapy in terms of survival time, but there was fairly strong evidence that it might slow the growth of the cancer (increased progression-free survival (PFS)). However, the trials also showed that there were worse side effects in women who received bevacizumab in addition to chemotherapy (particularly high blood pressure, serious bowel problems and bleeding). One of these two trials also looked at the effect of giving bevacizumab concurrently with chemotherapy (not continuing afterwards), and found no significant improvement in either survival time or slowing cancer growth, but did find a significant increase in moderate and severe high blood pressure (hypertension). A third trial looked at adding a different agent, AMG 386, to paclitaxel chemotherapy in women with recurrent ovarian cancer. The trial compared the addition of either a higher or lower dose of AMG 386 to placebo. It found no improvement in survival with either the higher or lower dose of AMG 386, but there were suggestions that it might slow cancer growth. It did not seem to increase side effects. We identified two other trials; one comparing placebo to BIBF 1120, and the other comparing placebo to VEGF (vascular endothelial growth factor)-Trap. Neither study found evidence of slowing cancer growth/prolonging survival, or worsening side effects. However, these were both relatively small studies, which made them less likely to detect an effect that may or may not have been present. All of the included trials that we identified reported only preliminary results, which had been presented at conferences, but not yet published in full. It is thus difficult to be sure of the specific details of how these trials were performed, and therefore to assess their risk of bias. We found 12 other on-going studies that fulfilled our inclusion criteria, and some of these are expected to release preliminary results soon.

CochranePLS1236

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Eighteen randomised trials with 50,623 participants provided data for the analyses. All trials came from high-income countries. Most of the trials had a high risk of bias, mainly for-profit bias. Most trials included elderly community-dwelling women (aged 47 to 97 years). Vitamin D was administered for a weighted mean of six years. Fourteen trials tested vitamin D₃, one trial tested vitamin D₂, and three trials tested calcitriol supplementation. Cancer occurrence was observed in 1927/25,275 (7.6%) recipients of vitamin D versus 1943/25,348 (7.7%) recipients of control interventions (RR 1.00 (95% confidence interval (CI) 0.94 to 1.06); P = 0.88; I² = 0%; 18 trials; 50,623 participants; moderate quality evidence according to the GRADE instrument). Trial sequential analysis (TSA) of the 18 vitamin D trials shows that the futility area is reached after the 10th trial, allowing us to conclude that a possible intervention effect, if any, is lower than a 5% relative risk reduction. We did not observe substantial differences in the effect of vitamin D on cancer in subgroup analyses of trials at low risk of bias compared to trials at high risk of bias; of trials with no risk of for-profit bias compared to trials with risk of for-profit bias; of trials assessing primary prevention compared to trials assessing secondary prevention; of trials including participants with vitamin D levels below 20 ng/mL at entry compared to trials including participants with vitamin D levels of 20 ng/mL or more at entry; or of trials using concomitant calcium supplementation compared to trials without calcium. Vitamin D decreased all-cause mortality (1854/24,846 (7.5%) versus 2007/25,020 (8.0%); RR 0.93 (95% CI 0.88 to 0.98); P = 0.009; I² = 0%; 15 trials; 49,866 participants; moderate quality evidence), but TSA indicates that this finding could be due to random errors. Cancer occurrence was observed in 1918/24,908 (7.7%) recipients of vitamin D₃ versus 1933/24,983 (7.7%) in recipients of control interventions (RR 1.00 (95% CI 0.94 to 1.06); P = 0.88; I² = 0%; 14 trials; 49,891 participants; moderate quality evidence). TSA of the vitamin D₃ trials shows that the futility area is reached after the 10th trial, allowing us to conclude that a possible intervention effect, if any, is lower than a 5% relative risk reduction. Vitamin D₃ decreased cancer mortality (558/22,286 (2.5%) versus 634/22,206 (2.8%); RR 0.88 (95% CI 0.78 to 0.98); P = 0.02; I² = 0%; 4 trials; 44,492 participants; low quality evidence), but TSA indicates that this finding could be due to random errors. Vitamin D₃ combined with calcium increased nephrolithiasis (RR 1.17 (95% CI 1.03 to 1.34); P = 0.02; I² = 0%; 3 trials; 42,753 participants; moderate quality evidence). TSA, however, indicates that this finding could be due to random errors. We did not find any data on health-related quality of life or health economics in the randomised trials included in this review. There is currently no firm evidence that vitamin D supplementation decreases or increases cancer occurrence in predominantly elderly community-dwelling women. Vitamin D₃ supplementation decreased cancer mortality and vitamin D supplementation decreased all-cause mortality, but these estimates are at risk of type I errors due to the fact that too few participants were examined, and to risks of attrition bias originating from substantial dropout of participants. Combined vitamin D₃ and calcium supplements increased nephrolithiasis, whereas it remains unclear from the included trials whether vitamin D₃, calcium, or both were responsible for this effect. We need more trials on vitamin D supplementation, assessing the benefits and harms among younger participants, men, and people with low vitamin D status, and assessing longer duration of treatments as well as higher dosages of vitamin D. Follow-up of all participants is necessary to reduce attrition bias. Output:

The aim of this systematic review was to analyse the benefits and harms of the different forms of vitamin D especially on cancer occurrence. A total of 18 trials provided data for this review; 50,623 participants were randomly assigned to either vitamin D or placebo or no treatment. All trials were conducted in high-income countries. The age range of the participants was 47 to 97 years and on average 81% were women. The majority of the included participants did not have vitamin D deficiency. Vitamin D administration lasted on average six years and most trial investigators used vitamin D₃ (cholecalciferol). We did not find firm evidence that vitamin D supplementation decreases or increases cancer occurrence in predominantly elderly community-dwelling women. We observed decreases in all-cause mortality and cancer-related mortality among the vitamin D/D₃ treated participants in comparison with the participants in the control groups. However, using trial sequential analysis, a statistical approach to reconfirm or question these findings, we conclude that these results could be due to random errors (play of chance). We also found evidence that combined vitamin D₃ and calcium supplements increased renal stone occurrence, but it remains unclear from the included trials whether vitamin D₃, calcium, or both were responsible for this effect. Moreover, these results could also be due to random errors (play of chance). A large number of the study participants left the trials before completion, and this raises concerns regarding the validity of the results. Most of the trials were judged not to be well and fairly conducted so that the results were likely to be biased (that is, possibly an overestimation of benefits and underestimation of harms). This evidence is up to date as of February 2014.

CochranePLS1237

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Twenty-eight studies (reporting a total of thirty-two comparisons) were included. Computer reminders achieved a median improvement in process adherence of 4.2% (interquartile range (IQR): 0.8% to 18.8%) across all reported process outcomes, 3.3% (IQR: 0.5% to 10.6%) for medication ordering, 3.8% (IQR: 0.5% to 6.6%) for vaccinations, and 3.8% (IQR: 0.4% to 16.3%) for test ordering. In a sensitivity analysis using the best outcome from each study, the median improvement was 5.6% (IQR: 2.0% to 19.2%) across all process measures and 6.2% (IQR: 3.0% to 28.0%) across measures of medication ordering. In the eight comparisons that reported dichotomous clinical endpoints, intervention patients experienced a median absolute improvement of 2.5% (IQR: 1.3% to 4.2%). Blood pressure was the most commonly reported clinical endpoint, with intervention patients experiencing a median reduction in their systolic blood pressure of 1.0 mmHg (IQR: 2.3 mmHg reduction to 2.0 mmHg increase). Point of care computer reminders generally achieve small to modest improvements in provider behaviour. A minority of interventions showed larger effects, but no specific reminder or contextual features were significantly associated with effect magnitude. Further research must identify design features and contextual factors consistently associated with larger improvements in provider behaviour if computer reminders are to succeed on more than a trial and error basis. Output:

This review found 28 studies that evaluated the effects of different on-screen computer reminders. The studies tested reminders to prescribe specific medications, to warn about drug interactions, to provide vaccinations, or to order tests.  The review found small to moderate benefits. The reminders improved physician practices by a median of 4%. In eight of the studies, patients' health improved by a median of 3%. Although some studies showed larger benefits than these median effects, no specific reminders or features of how they worked were consistently associated with these larger benefits. More research is needed to identify what types of reminders work and when.

CochranePLS1238

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 18 RCTs with a total of 2738 participants. Fourteen studies had participants with nasal polyps and four studies had participants without nasal polyps. Only one study was conducted in children. Intranasal corticosteroids versus placebo or no intervention Only one study (20 adult participants without polyps) measured our primary outcome disease-specific HRQL using the Rhinosinusitis Outcome Measures-31 (RSOM-31). They reported no significant difference (numerical data not available) (very low quality evidence). Our second primary outcome, disease severity , was measured using the Chronic Sinusitis Survey in a second study (134 participants without polyps), which found no important difference (mean difference (MD) 2.84, 95% confidence interval (CI) -5.02 to 10.70; scale 0 to 100). Another study (chronic rhinosinusitis with nasal polyps) reported an increased chance of improvement in the intranasal corticosteroids group (RR 2.78, 95% CI 1.76 to 4.40; 109 participants). The quality of the evidence was low. Six studies provided data on at least two of the individualsymptoms used in the EPOS 2012 criteria to define chronic rhinosinusitis (nasal blockage, rhinorrhoea, loss of sense of smell and facial pain/pressure). When all four symptoms in the EPOS criteria were available on a scale of 0 to 3 (higher = more severe symptoms), the average MD in change from baseline was -0.26 (95% CI -0.37 to -0.15; 243 participants; two studies; low quality evidence). Although there were more studies and participants when only nasal blockage and rhinorrhoea were considered (MD -0.31, 95% CI -0.38 to -0.24; 1702 participants; six studies), the MD was almost identical to when loss of sense of smell was also considered (1345 participants, four studies; moderate quality evidence). When considering the results for the individual symptoms, benefit was shown in the intranasal corticosteroids group. The effect size was larger for nasal blockage (MD -0.40, 95% CI -0.52 to -0.29; 1702 participants; six studies) than for rhinorrhoea (MD -0.25, 95% CI -0.33 to -0.17; 1702 participants; six studies) or loss of sense of smell (MD -0.19, 95% CI -0.28 to -0.11; 1345 participants; four studies). There was heterogeneity in the analysis for facial pain/pressure (MD -0.27, 95% CI -0.56 to 0.02; 243 participants; two studies). The quality of the evidence was moderate for nasal blockage, rhinorrhoea and loss of sense of smell, but low for facial pain/pressure. There was an increased risk of epistaxis with intranasal corticosteroids (risk ratio (RR) 2.74, 95% CI 1.88 to 4.00; 2508 participants; 13 studies; high quality evidence). Considering our secondary outcome, general HRQL, one study (134 participants without polyps) measured this using the SF-36 and reported a statistically significant benefit only on the general health subscale. The quality of the evidence was very low. It is unclear whether there is a difference in the risk of local irritation (RR 0.94, 95% CI 0.53 to 1.64; 2124 participants; 11 studies) (low quality evidence). None of the studies treated or followed up patients long enough to provide meaningful data on the risk of osteoporosis or stunted growth (children). Other comparisons We identified no other studies that compared intranasal corticosteroids plus co-intervention A versus placebo plus co-intervention A. Most of the evidence available was from studies in patients with chronic rhinosinusitis with nasal polyps. There is little information about quality of life (very low quality evidence). For disease severity, there seems to be improvement for all symptoms (low quality evidence), a moderate-sized benefit for nasal blockage and a small benefit for rhinorrhoea (moderate quality evidence). The risk of epistaxis is increased (high quality evidence), but these data included all levels of severity; small streaks of blood may not be a major concern for patients. It is unclear whether there is a difference in the risk of local irritation (low quality evidence). Output:

We included 18 randomised controlled trials (RCTs) with a total of 2738 participants in this review. Most studies were relatively small, with as few as 9 or 10 patients per intervention arm. The largest study had 748 patients in total. Most were conducted in tertiary referral centres in northern Europe, the US and Canada. Fourteen studies only included participants with chronic rhinosinusitis with nasal polyps and four studies had participants without nasal polyps. Only one study was conducted in children. The studies looked at a range of types, doses and methods of administration (e.g. spray, drops) of intranasal corticosteroids. One study (20 participants) reported no statistically significant difference in disease-specific health-related quality of life. Another measured general health-related quality of life and reported a statistically significant benefit only on a subscale for general health. Both studies recruited participants with chronic rhinosinusitis without nasal polyps. The quality of the evidence was very low (we have very little confidence in the effect estimate: the true effect is likely to be substantially different from the estimate of effect). Disease severity was measured in one study (chronic rhinosinusitis without nasal polyps, 134 participants), which found no important difference. Another study (chronic rhinosinusitis with nasal polyps) reported an increased chance of improvement in the intranasal corticosteroids group. The quality of the evidence was low (our confidence in the effect estimate is limited: the true effect may be substantially different from the estimate of the effect). When each type of symptom was measured separately (nasal blockage, rhinorrhoea, loss of sense of smell, facial pain/pressure), benefit was shown in the intranasal corticosteroids group. The quality of the evidence was moderate for nasal blockage, rhinorrhoea and loss of sense of smell, but low for facial pain/pressure (moderate quality evidence means we are moderately confident in the effect estimate: the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different). There was an increased risk of nosebleeds (epistaxis) with intranasal corticosteroids (high quality evidence). However, it was unclear whether there was a difference in the risk of local (nose or throat) irritation (low quality evidence). None of the studies treated or followed up patients long enough to provide meaningful data on the risk of osteoporosis (fragile bones) or stunted growth (in children). Most of the evidence available was from studies in patients with chronic rhinosinusitis with nasal polyps. There is little information about quality of life and the quality of this evidence is very low. For disease severity, there seems to be improvement for all symptoms (low quality evidence), a moderate-sized benefit for nasal blockage and a small benefit for rhinorrhoea (moderate quality evidence). The risk of nosebleeds is increased (high quality evidence), but this included all levels of severity; for some patients small streaks of blood may not be a major concern. It is unclear whether there is a difference in the risk of local irritation (low quality evidence).

CochranePLS1239

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Eleven studies including a total of 422 participants contributed to data analyses. Most studies had a small population size (average 38 people per study) and were of short duration. We also detected a high risk of bias for selective outcome reporting in just under 50% of the trials. We therefore rated the overall methodological quality of the included studies as low. We considered seven main outcomes of interest: clinically important change in overall mental state, clinically important change in cognitive functioning, incidence of a clinically important adverse effect/event, clinically important change in global state, leaving the study early for any reason, clinically important change in quality of life, and hospital admission. All studies assessed the effects of adding modafinil to participants' usual antipsychotic treatment compared to adding placebo to usual antipsychotic treatment. Six studies found that adding modafinil to antipsychotic treatment may have little or no effect on overall mental state of people with schizophrenia, specifically the risk of worsening psychosis (RR 0.91, 95% CI 0.28 to 2.98; participants = 209; studies = 6, low-quality evidence). Regarding the effect of modafinil on cognitive function, the trials did not report clinically important change data, but one study reported endpoint scores on the MATRICS Consensus Cognitive Battery (MCCB): in this study we found no clear difference in scores between modafinil and placebo treatment groups (MD −3.10, 95% CI −10.9 to 4.7; participants = 48; studies = 1, very low-quality evidence). Only one study (N = 35) reported adverse effect/event data. In this study one serious adverse event occurred in each group (RR 0.84, 95% CI 0.06 to 12.42; participants = 35; studies = 1, very low-quality evidence). One study measured change in global state using the Clinical Global Impression - Improvement Scale. This study found that adding modafinil to antipsychotic treatment may have little or no effect on global state (RR 6.36, 95% CI 0.94 to 43.07, participants = 21; studies = 1, very low-quality evidence). Nine studies found that modafinil has no effect on numbers of participants leaving the study early (RR 1.26, 95% CI 0.63 to 2.52 participants = 357; studies = 9, moderate-quality evidence). None of the trials reported clinically important change in quality of life, but one study did report quality of life using endpoint scores on the Quality of Life Inventory, finding no clear difference between treatment groups (MD −0.2, 95% CI −1.18 to 0.78; participants = 20; studies = 1, very low-quality evidence). Finally, one study reported data for number of participants needing hospitalisation: one participant in each group was hospitalised (RR 0.84, 95% CI 0.06 to 12.42; participants = 35; studies = 1, very low-quality evidence). Due to methodological issues, low sample size, and short duration of the clinical trials as well as high risk of bias for outcome reporting, most of the evidence available for this review is of very low or low quality. For results where quality is low or very low, we are uncertain or very uncertain if the effect estimates are true effects, limiting our conclusions. Specifically, we found that modafinil is no better or worse than placebo at preventing worsening of psychosis; however, we are uncertain about this result. We have more confidence that participants receiving modafinil are no more likely to leave a trial early than participants receiving placebo. However, we are very uncertain about the remaining equivocal results between modafinil and placebo for outcomes such as improvement in global state or cognitive function, incidence of adverse events, and changes in quality of life. More high-quality data are needed before firm conclusions regarding the effects of modafinil for people with schizophrenia or related disorders can be made. Output:

We ran an electronic search of Cochrane Schizophrenia's register of trials in April 2015, May 2017, and October 2019 for trials that randomised (allocated participants to treatment groups using a random method) people with schizophrenia to receive add-on modafinil (modafinil added to their standard care) or to receive add-on placebo. We identified 67 records that referred to 25 studies. Eleven studies met the review requirements and reported data that could be used in analyses. However, the trials included small numbers of participants and were of short duration; schizophrenia is a long-term health problem that ideally requires studies of longer duration. Our analysis of the data showed there is no clear difference between add-on modafinil and add-on placebo for improving mental state or global state, changing cognitive functioning, causing participants to leave a study early, producing adverse effects, or affecting rates of hospitalisation. However, most of these results were based on very low- or low-quality data, therefore it is uncertain if these statistical effect sizes found by our data analyses are true effects. The results of this review indicate no clear difference in effectiveness and safety between add-on modafinil and add-on placebo, however these results are not conclusive as they are based low- or very low-quality evidence. Based on the current evidence we were unable to provide an answer to our review question as to whether modafinil is better than placebo for improving the symptoms of schizophrenia, or if it is safe to use for people with schizophrenia. More high-quality research is needed.

CochranePLS1240

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Thirty-five placebo-controlled trials (4060 participants) provided data in a form suitable for inclusion in the meta-analyses. When compared with placebo, the use of IS was shown to reduce ARTIs measured as the total numbers of ARTIs (MD -1.24; 95% CI -1.54 to -0.94) and the difference in ARTI rates (MD -38.84%; 95% CI -46.37% to -31.31%). Trial quality was generally poor and a high level of statistical heterogeneity was evident. The subgroup analysis of bacterial IS, D53 and OM-85 studies produced similar results, with lower heterogeneity. No difference in adverse events was evident between the placebo and IS groups. This review shows that IS reduce the incidence of ARTIs by 40% on average in susceptible children. Studies in healthy children are not available. Although the safety profile in the studies was good, some IS may be unsafe. ARTI-susceptible children may benefit from IS treatment. Further high-quality trials are needed and we encourage national health authorities to conduct large, multicentre, double-blind, placebo-controlled RCTs on the role of IS in preventing ARTIs in children. Output:

By combining results, immunostimulants reduced 1.24 ARTIs in a six-month period, equivalent to a 39% reduction in ARTIs compared to the placebo group. Only 20 studies provided adequate data on adverse events: the most frequent were rash, nausea, vomiting, abdominal pain and diarrhea. The main limitations of this review were the poor methodological quality and diverse trial results. We conclude that ARTI-susceptible children may benefit from immunostimulants, but more high-quality studies are needed. We suggest that national health authorities conduct high-quality randomized controlled trials to assess the true effects of immunostimulant preparations.

CochranePLS1241

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: With this current update, a total of five eligible studies (215 patients) were identified. Only one outcome, the proportion of patients with Expanded Disability Status Scale (EDSS) improvement at four weeks, was common to three trials, while two trials examined magnetic resonance imaging (MRI) outcomes. The results of this review shows there is no significant difference in relapse recovery at week four (MD -0.22, 95% confidence interval (95% CI), 0.71 to 0.26, P = 0.20) nor differences in magnetic resonance imaging (MRI) gadolinium enhancement activity based on oral versus intravenous steroid treatment. However, only two of the five studies employed more current and rigorous methodological techniques, so these results must be taken with some caution. The Oral Megadose Corticosteroid Therapy of Acute Exacerbations of Multiple Sclerosis (OMEGA) trial and the "Efficacy and Safety of Methylprednisolone Per os Versus IV for the Treatment of Multiple Sclerosis (MS) Relapses" (COPOUSEP) trial, designed to address such limitations, are currently underway. The analysis of the five included trials comparing intravenous versus oral steroid therapy for MS relapses do not demonstrate any significant differences in clinical (benefits and adverse events), radiological or pharmacological outcomes. Based on the evidence, oral steroid therapy may be a practical and effective alternative to intravenous steroid therapy in the treatment of MS relapses. Output:

The objective of this review was to assess if oral and intravenous steroids are equally effective and safe in aiding in the recovery from relapses. Among the pertinent literature, only five studies met the inclusion criteria, comprising a total of 215 participants. Despite some limitations in the methods used to conduct the studies (i.e. incomplete reporting of the participants who dropped out the studies and appropriateness of the sample size) and in the analysis of the data, all five studies found that there were no significant differences in term of benefits and adverse events and in the pharmacological and radiological outcomes in patients taking oral or intravenous steroids. Both treatments appear to be equally effective and safe. Based on this evidence, oral steroid therapy may be a practical and effective alternative to intravenous steroid therapy for the treatment of MS relapses.

CochranePLS1242

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We identified three trials that met the inclusion criteria for this review. In these, a total of 47 people with MRSA-positive diabetic foot infections were randomised to six different antibiotic regimens. While these trials included 925 people with multiple pathogens, they reported the information on outcomes for people with MRSA infections separately (MRSA prevalence: 5.1%). The only outcome reported for people with MRSA infection in these trials was the eradication of MRSA. The three trials did not report the review's primary outcomes (death and quality of life) and secondary outcomes (length of hospital stay, use of healthcare resources and time to complete wound healing). Two trials reported serious adverse events in people with infection due to any type of bacteria (i.e. not just MRSA infections), so the proportion of patients with serious adverse events was not available for MRSA-infected wounds. Overall, MRSA was eradicated in 31/47 (66%) of the people included in the three trials, but there were no significant differences in the proportion of people in whom MRSA was eradicated in any of the comparisons, as shown below. 1. Daptomycin compared with vancomycin or semisynthetic penicillin: RR of MRSA eradication 1.13; 95% CI 0.56 to 2.25 (14 people). 2. Ertapenem compared with piperacillin/tazobactam: RR of MRSA eradication 0.71; 95% CI 0.06 to 9.10 (10 people). 3. Moxifloxacin compared with piperacillin/tazobactam followed by amoxycillin/clavulanate: RR of MRSA eradication 0.87; 95% CI 0.56 to 1.36 (23 people). We found no trials comparing the use of antibiotics with no antibiotic for treating MRSA-colonised non-surgical wounds and therefore can draw no conclusions for this population. In the trials that compared different antibiotics for treating MRSA-infected non surgical wounds, there was no evidence that any one antibiotic was better than the others. Further well-designed RCTs are necessary. Output:

We identified three trials that provided some information on this topic. A total of 47 people with MRSA-infected diabetic foot infections were randomised to six different antibiotic treatments (choice of treatment determined by a method similar to coin tossing). The only outcome reported was the eradication of MRSA. The trials reported none of the other outcomes that are important for patients and healthcare funders, such as death, quality of life, length of hospital stay, use of healthcare resources and time to complete wound healing. Each trial compared different antibiotics, and in each comparison there was no difference in the effectiveness of the antibiotics in eradicating MRSA. The three trials were very small and had a number of design faults, so it is still not possible to say which antibiotic is the most effective in eradicating MRSA from non-surgical wounds. Because there were no trials at all comparing the use of antibiotics with no antibiotic we do not know whether using antibiotics at all makes a difference for people with MRSA-colonised non-surgical wounds. Further well-designed randomised controlled trials are necessary to determine the best treatment for non surgical wounds containing or infected with MRSA.

CochranePLS1243

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Fourteen studies met the inclusion criteria, randomly assigning 2313 people with acute asthma to the comparisons of interest in this review. Most studies were double-blinded trials comparing a single infusion of 1.2 g or 2 g IV MgSO4 over 15 to 30 minutes versus a matching placebo. Eleven were conducted at a single centre, and three were multi-centre trials. Participants in almost all of the studies had already been given at least oxygen, nebulised short-acting beta2-agonists and IV corticosteroids in the ED; in some studies, investigators also administered ipratropium bromide. Ten studies included only adults, and four included both adults and children; these were included because the mean age of participants was over 18 years. Intravenous MgSO4 reduced hospital admissions compared with placebo (odds ratio (OR) 0.75, 95% confidence interval (CI) 0.60 to 0.92; I2 = 28%, P value 0.18; n = 972; high-quality evidence). In absolute terms, this odds ratio translates into a reduction of seven hospital admissions for every 100 adults treated with IV MgSO4 (95% CI two to 13 fewer). The test for subgroup differences revealed no statistical heterogeneity between the three severity subgroups (I2 = 0%, P value 0.73) or between the four studies that administered nebulised ipratropium bromide as a co-medication and those that did not (I2 = 0%, P value 0.82). Sensitivity analyses in which unpublished data and studies at high risk for blinding were removed from the primary analysis did not change conclusions. Within the secondary outcomes, high- and moderate-quality evidence across three spirometric indices suggests some improvement in lung function with IV MgSO4. No difference was found between IV MgSO4and placebo for most of the non-spirometric secondary outcomes, all of which were rated as low or moderate quality (intensive care admissions, ED treatment duration, length of hospital stay, readmission, respiration rate, systolic blood pressure). Adverse events were inconsistently reported and were not meta-analysed. The most commonly cited adverse events in the IV MgSO4 groups were flushing, fatigue, nausea and headache and hypotension (low blood pressure). This review provides evidence that a single infusion of 1.2 g or 2 g IV MgSO4 over 15 to 30 minutes reduces hospital admissions and improves lung function in adults with acute asthma who have not responded sufficiently to oxygen, nebulised short-acting beta2-agonists and IV corticosteroids. Differences in the ways the trials were conducted made it difficult for the review authors to assess whether severity of the exacerbation or additional co-medications altered the treatment effect of IV MgSO4. Limited evidence was found for other measures of benefit and safety. Studies conducted in these populations should clearly define baseline severity parameters and systematically record adverse events. Studies recruiting participants with exacerbations of varying severity should consider subgrouping results on the basis of accepted severity classifications. Output:

Fourteen studies met the inclusion criteria, involving a total of 2313 people. These studies varied in terms of how bad exacerbations had to be for people to be included and in terms of what other treatments were provided before IV MgSO4was given, but almost all trials gave participants at least oxygen, nebulised short-acting medications and steroid tablets or injection. Overall, IV MgSO4 reduced the need for hospital admission compared with placebo (seven fewer per 100 treated; 95% confidence interval two to 13 fewer). Not enough information was available to show whether the reduction in hospital admissions was associated with severity of the asthma exacerbation, or whether it made a difference what other treatments were given. Evidence suggests that IV MgSO4 improved some lung function parameters, but for other measures such as heart rate, variation among study findings reduced our confidence in the results. We did not find a difference between IV MgSO4 and placebo in most other measures (including time spent in the ED, respiratory rate and blood pressure), and adverse events generally were poorly reported. This review showed that IV MgSO4reduces hospital admissions and improves lung function in adults with exacerbations of asthma when other first-line medications have not relieved the acute symptoms (i.e. oxygen, inhaled short-acting medications and IV steroids). Evidence for other measures of benefit and safety was limited. Researchers should clearly define the severity of the asthma condition among people in their studies while carefully recording adverse events. This plain language summary is current as of May 2014.

CochranePLS1244

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: 35 short-term (14 weeks or less) RCTs were included in the analysis (4597 participants). Symptom severity for 17 trials was significantly reduced in the medication groups, relative to placebo (weighted mean difference -5.76, 95% confidence intervals (CI) -8.16 to -3.36, number of participants (N) = 2507). Similarly, summary statistics for responder status from 13 trials demonstrated overall superiority of a variety of medication agents to placebo (relative risk 1.49, 95% CI 1.28 to 1.73, number needed to treat = 4.85, 95% CI 3.85 to 6.25, N = 1272). Medication and placebo response occurred in 59.1% (N = 644) and 38.5% (628) of patients, respectively. Of the medication classes, evidence of treatment efficacy was most convincing for the SSRIs. Medication was superior to placebo in reducing the severity of PTSD symptom clusters, comorbid depression and disability. Medication was also less well tolerated than placebo. A narrative review of 3 maintenance trials suggested that long term medication may be required in treating PTSD. Medication treatments can be effective in treating PTSD, acting to reduce its core symptoms, as well as associated depression and disability. The findings of this review support the status of SSRIs as first line agents in the pharmacotherapy of PTSD, as well as their value in long-term treatment. However, there remain important gaps in the evidence base, and a continued need for more effective agents in the management of PTSD. Output:

This was a systematic review of 35 short-term randomised controlled trials of pharmacotherapy for PTSD (4597 participants). A significantly larger proportion of patients responded to medication (59.1%) than to placebo (38.5%) (13 trials, 1272 participants). Symptom severity was significantly reduced in 17 trials (2507 participants). The largest trials showing efficacy were of the selective serotonin reuptake inhibitors, with long-term efficacy also observed for these medications.

CochranePLS1245

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 30 studies, which evaluated 3D exercise (Tai Chi and yoga), balance training or strength and resistance training. Two of these were cluster-randomised trials, two were cross-over trials and one was quasi-randomised. The studies included a total of 2878 participants with a mean age ranging from 68 to 85 years. Most studies included more women than men, with four studies recruiting women only. Twelve studies recruited participants at increased risk of falls; three of these recruited participants who also had fear of falling. Poor reporting of the allocation methods in the trials made it difficult to assess the risk of selection bias in most studies. All of the studies were at high risk of performance and detection biases as there was no blinding of participants and outcome assessors and the outcomes were self reported. Twelve studies were at high risk of attrition bias. Using GRADE criteria, we judged the quality of evidence to be 'low' for fear of falling immediately post intervention and 'very low' for fear of falling at short or long-term follow-up and all other outcomes. Exercise interventions were associated with a small to moderate reduction in fear of falling immediately post intervention (SMD 0.37 favouring exercise, 95% confidence interval (CI) 0.18 to 0.56; 24 studies; 1692 participants, low quality evidence). Pooled effect sizes did not differ significantly between the different scales used to measure fear of falling. Although none of the sensitivity analyses changed the direction of effect, the greatest reduction in the size of the effect was on removal of an extreme outlier study with 73 participants (SMD 0.24 favouring exercise, 95% CI 0.12 to 0.36). None of our subgroup analyses provided robust evidence of differences in effect in terms of either the study primary aim (reduction of fear of falling or other aim), the study population (recruitment on the basis of increased falls risk or not), the characteristics of the study exercise intervention or the study control intervention (no treatment or alternative intervention). However, there was some weak evidence of a smaller effect, which included no reduction, of exercise when compared with an alternative control. There was very low quality evidence that exercise interventions may be associated with a small reduction in fear of falling up to six months post intervention (SMD 0.17, 95% CI -0.05 to 0.38; four studies, 356 participants) and more than six months post intervention (SMD 0.20, 95% CI -0.01 to 0.41; three studies, 386 participants). Very low quality evidence suggests exercise interventions in these studies that also reported on fear of falling reduced the risk of falling measured either as participants incurring at least one fall during follow-up or the number of falls during follow-up. Very low quality evidence from four studies indicated that exercise interventions did not appear to reduce symptoms of depression or increase physical activity. The only study reporting the effects of exercise interventions on anxiety found no difference between groups. No studies reported the effects of exercise interventions on activity avoidance or costs. It is important to remember that our included studies do not represent the totality of the evidence of the effect of exercise interventions on falls, depression, anxiety or physical activity as our review only includes studies that reported fear of falling. Exercise interventions in community-dwelling older people probably reduce fear of falling to a limited extent immediately after the intervention, without increasing the risk or frequency of falls. There is insufficient evidence to determine whether exercise interventions reduce fear of falling beyond the end of the intervention or their effect on other outcomes. Although further evidence from well-designed randomised trials is required, priority should be given to establishing a core set of outcomes that includes fear of falling for all trials examining the effects of exercise interventions in older people living in the community. Output:

We searched the medical literature up to July 2013 for studies that tested the effects of exercise and reported fear of falling in community-dwelling people (i.e. who live either at home or in places of residence that do not provide nursing care or rehabilitation) aged 65 years and older. The studies compared exercise with no treatment or an alternative intervention, such as education. Summary of the evidence We included 30 studies in the review, with a total of 2878 participants whose average age ranged from 68 to 85 years. Most studies recruited mainly women. Twelve studies recruited participants at increased risk of falls and three of these recruited people who also had fear of falling. All of the studies were at some risk of bias mainly because the participants were aware what group they were in. This lack of blinding may have influenced the study results. We found low quality evidence from 24 studies that exercise interventions result in a small to moderate reduction in fear of falling immediately after the intervention. Some exploratory analyses did not enable us to determine whether this effect differed in different groups of people, such as those at high risk of falling, or with different exercise interventions, such as group or individual exercise. We are very unsure that the effect of exercise on fear of falling is maintained in the next few months after the end of the intervention. We only included studies that reported fear of falling, therefore the evidence on our other outcomes (occurrence of falls, depression, anxiety and physical activity) is only a small part of the total evidence of the effects of exercise on these outcomes. However, the evidence from nine studies included in our review showing that exercise reduced the risk and number of falls is consistent with the results of another Cochrane review testing the effects of exercise on preventing falls. The evidence on the other outcomes was far less and none of the included studies reported the effects of exercise interventions on activity avoidance or costs. Conclusion We concluded that exercise interventions in community-dwelling older people probably reduce fear of falling to a limited extent immediately after the intervention, without increasing the risk or frequency of falls. We also concluded that there is not enough evidence to determine whether exercise interventions reduce fear of falling beyond the end of the intervention or their effect on other outcomes. We encourage further research on this topic.

CochranePLS1246

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: One ongoing study (Pellicer 2003) was identified. One study comparing adrenaline with dopamine infusion was included but was published in abstract form only (Phillipos 1996). It enrolled hypotensive, predominately preterm infants in the first 24 hours. Only infants >1750g are included in this review (report for infants <=1750g appears incomplete). The study was reported as being randomised and double blinded, but methods were not reported. Both adrenaline and dopamine significantly increased heart rate and mean BP, with no statistically significant effect on left or right ventricular outputs. No other clinical outcomes were reported. No studies were identified that compared adrenaline to other inotropes, placebo or no treatment. There are insufficient data on the use of adrenaline infusions in preterm infants with cardiovascular compromise to make recommendations for practice. There is a need for larger trials to determine whether adrenaline is effective in reducing morbidity and mortality in preterm infants with cardiovascular compromise. Output:

Not enough evidence from trials on the use of adrenaline (epinephrine) for preterm babies with poor heart rates and circulation. Sustained poor blood flow in preterm babies can lead to complications, including impaired development. Inotrope drugs, particularly dopamine and dobutamine, are commonly used to increase heart rate and blood pressure in preterm babies with poor circulation. Adrenaline (epinephrine) is another inotrope drug that can be used. The review found that there is not enough evidence from trials to show the effects of adrenaline on preterm babies with poor circulation, and more research is needed.

CochranePLS1247

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: 24 studies met the inclusion for the review (3907 participants). In non-oral steroid treated, mild to moderately severe asthma, no clinically worthwhile differences in FEV1, morning PEFR, symptom scores or rescue beta2 agonist use were apparent across a dose range of 200-1600 mcg/d. However, in moderate to severe asthma a significant reduction in the likelihood of trial withdrawal due to asthma exacerbation was apparent when treating patients with BUD 800 mcg/d compared to 200 mcg/d: Relative Risk 3.93 (95% confidence interval, 1.4 to 10.9). This result was weighted largely by a single, large, high quality RCT. In severe asthma significant improvements favouring high dose BUD (1600 mcg/d) over low dose (200 mcg/d) were apparent for FEV1 but not morning PEFR. This finding was based on two large RCTs of good quality. In oral steroid treated asthmatics no dose dependent oral steroid sparing effect was apparent for BUD 1600 mcg/d v 800 or 400 mcg/d. Statistically significant, dose dependent suppression of 24 hour urinary free cortisol excretion and serum cortisol post synthetic ACTH infusion over the dose range 800-3200 mcg/d was apparent but the clinical significance of these findings is unclear. Budesonide exhibits a significant dose response effect between low and high dose for improvement in FEV1 in severe asthma and reduction of exacerbations in moderate to severe asthma. No significant dose dependent improvements in FEV1, PEFR or symptoms are evident in non-oral steroid treated asthmatics with mild to moderate disease. Dose dependent alterations in sensitive measures of hypothalamic-pituitary-adrenal function were evident but the clinical significance of these changes is unclear. Output:

This review presents the effects of budesonide at different doses for people with varying degrees of asthma. In patients with mild-moderate asthma no important differences were apparent between the lowest dose (200 mcg/d) and the highest dose (1600 mcg/d) for measures of airway opening and symptoms. However, patients with more severe asthma are less likely to experience an acute worsening of their asthma control when a higher dose (1600 mcg/d) is used regularly compared to a lower dose (200 mcg/d). Future research should report results more comprehensively, and should use quality of life questionnaires.

CochranePLS1248

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Seven RCTs, involving 1671 women were identified for inclusion. The review found that giving women information about the procedure prior to the mammogram may reduce pain and discomfort. Increasing women's control over breast compression could reduce pain experienced during the procedure, though mammogram image quality was only maintained if the technologist controlled the first compression. If the technologist reduced compression force of the mammogram, discomfort experienced was unchanged. The use of breast cushions reduced pain of mammography; however, image quality was impaired in 2% of women in the intervention group. Acetoaminophen as a premedication did not affect discomfort of mammography. Differences in interventions, and inconsistency in measures, validation of pain scales, and in assessment of mammogram quality, mean that results of these studies cannot be combined. All results are based on single studies. Further research is required. Currently there are very few proven interventions to reduce pain and discomfort of screening mammography, especially procedures that can be readily introduced to screening programmes. With mammography continuing as the preferred method for breast screening, more research on such interventions is needed. Output:

Each study included in this review looked at a different intervention to reduce pain in mammography. The trial results show that giving women written or verbal information about the procedure prior to the mammogram can reduce pain or discomfort of the examination. Also increasing women's control of breast compression could reduce the pain they experience, though there was no change in the pain women experienced when a mammography-technologist reduced the compression force. Use of breast cushions also reduced the pain; however, it caused a poor quality of X-ray in 2% of women screened, which meant that they would need to have a further mammogram. Paracetamol taken before the procedure did not change the pain the women experienced. Further research is needed on interventions to relieve the pain and discomfort of screening mammography.

CochranePLS1249

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 51 trials in the review: non-platinum single-agent therapy versus non-platinum combination therapy (seven trials) and non-platinum combination therapy versus platinum combination therapy (44 trials). Non-platinum single-agent versus non-platinum combination therapy Low-quality evidence suggests that these treatments have similar effects on overall survival (hazard ratio (HR) 0.92, 95% confidence interval (CI) 0.72 to 1.17; participants = 1062; five RCTs), 1yOS (risk ratio (RR) 0.88, 95% CI 0.73 to 1.07; participants = 992; four RCTs), and PFS (HR 0.94, 95% CI 0.83 to 1.07; participants = 942; four RCTs). Non-platinum combination therapy may better improve ORR compared with non-platinum single-agent therapy (RR 1.79, 95% CI 1.41 to 2.26; participants = 1014; five RCTs; low-quality evidence). Differences in effects on major adverse events between treatment groups were as follows: anemia: RR 1.10, 95% 0.53 to 2.31; participants = 983; four RCTs; very low-quality evidence; neutropenia: RR 1.26, 95% CI 0.96 to 1.65; participants = 983; four RCTs; low-quality evidence; and thrombocytopenia: RR 1.45, 95% CI 0.73 to 2.89; participants = 914; three RCTs; very low-quality evidence. Only two RCTs assessed quality of life; however, we were unable to perform a meta-analysis because of the paucity of available data. Non-platinum therapy versus platinum combination therapy Platinum combination therapy probably improves OS (HR 0.76, 95% CI 0.69 to 0.85; participants = 1705; 13 RCTs; moderate-quality evidence), 1yOS (RR 0.89, 95% CI 0.82 to 0.96; participants = 813; 13 RCTs; moderate-quality evidence), and ORR (RR 1.57, 95% CI 1.32 to 1.85; participants = 1432; 11 RCTs; moderate-quality evidence) compared with non-platinum therapies. Platinum combination therapy may also improve PFS, although our confidence in this finding is limited because the quality of evidence was low (HR 0.76, 95% CI 0.61 to 0.93; participants = 1273; nine RCTs). Effects on major adverse events between treatment groups were as follows: anemia: RR 2.53, 95% CI 1.70 to 3.76; participants = 1437; 11 RCTs; low-quality evidence; thrombocytopenia: RR 3.59, 95% CI 2.22 to 5.82; participants = 1260; nine RCTs; low-quality evidence; fatigue: RR 1.56, 95% CI 1.02 to 2.38; participants = 1150; seven RCTs; emesis: RR 3.64, 95% CI 1.82 to 7.29; participants = 1193; eight RCTs; and peripheral neuropathy: RR 7.02, 95% CI 2.42 to 20.41; participants = 776; five RCTs; low-quality evidence. Only five RCTs assessed QoL; however, we were unable to perform a meta-analysis because of the paucity of available data. In people over the age of 70 with advanced NSCLC who do not have significant co-morbidities, increased survival with platinum combination therapy needs to be balanced against higher risk of major adverse events when compared with non-platinum therapy. For people who are not suitable candidates for platinum treatment, we have found low-quality evidence suggesting that non-platinum combination and single-agent therapy regimens have similar effects on survival. We are uncertain as to the comparability of their adverse event profiles. Additional evidence on quality of life gathered from additional studies is needed to help inform decision making. Output:

We performed a systematic search (up to 31 October 2014) for trials that compared non-platinum single-agent therapy versus non-platinum combination therapy or non-platinum combination therapy versus platinum combination therapy in patients over 70 years of age who have advanced non-small cell lung cancer. We included in the review a total of 51 studies (seven studies in the non-platinum single-agent therapy vs non-platinum combination therapy group and 44 studies in the non-platinum combination therapy vs platinum combination therapy group); however, we were able to include only 19 studies in the meta-analysis. Non-platinum single-agent versus non-platinum combination therapy We analyzed five trials involving 1294 participants. We found that these regimens are equally effective for survival. However, combinations of non-platinum agents are associated with a greater chance of decreasing tumor size. We also found that these regimens are similar regarding chance of major toxicity such as low hemoglobin levels, platelets, and white cell counts (neutrophils). Only two trials assessed the impact of treatment on quality of life, and we were not able to combine these results because of lack of information. Non-platinum therapy versus platinum combination therapy We analyzed 14 trials involving 1705 elderly participants. We found that platinum therapy is associated with longer survival and greater chance of decreasing tumor size among elderly patients. However, we found that these regimens are more toxic than those based on non-platinum agents and provide greater risk of low hemoglobin and platelet levels, fatigue, nausea or vomiting, and numbness or tingling in the hands and feet. Only five trials assessed the impact of treatment on quality of life, and we were not able to combine these results because of lack of information. Non-platinum single-agent versus non-platinum combination therapy We downgraded to low the quality of evidence on survival because different results were reported across studies, and because three included trials were stopped early, which also influenced the quality of evidence for chance of decreasing tumor size and low hemoglobin, platelet, and white cell counts. For theses outcomes, issues with study design were also a matter of concern, leading to low quality of evidence. Non-platinum combination versus platinum combination therapy We downgraded to moderate the quality of evidence on the benefit of platinum combination therapy for survival based on inclusion of nine trials that were not specifically designed for older patients. Other issues with study design influenced the quality of evidence on interval to tumor growth after start of treatment, rate of tumor shrinkage, and toxicity. Regarding low hemoglobin and platelet levels, we further reduced the quality of evidence to low because of imprecision of reported results. We recognize that other limitations such as age alone might not be adequate criteria for selection of the best treatment. Older people can be very different from one another in terms of other health conditions associated with aging. Older patients included in randomized trials were selected through strict eligibility criteria that excluded most patients with other health problems. Therefore, we believe that these results must be interpreted with clinical judgement applied regarding selection of an appropriate treatment regimen.

CochranePLS1250

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We identified five new studies for this update, which now has information from 10,857 participants in 39 studies, a 41% increase in participants from the earlier review; 32 studies compared a topical NSAID with carrier. All studies examined topical NSAIDs for treatment of osteoarthritis, and for pooled analyses studies were generally of moderate or high methodological quality, although we considered some at risk of bias from short duration and small size. In studies lasting 6 to 12 weeks, topical diclofenac and topical ketoprofen were significantly more effective than carrier for reducing pain; about 60% of participants had much reduced pain. With topical diclofenac, the NNT for clinical success in six trials (2353 participants) was 9.8 (95% confidence interval (CI) 7.1 to 16) (moderate quality evidence). With topical ketoprofen, the NNT for clinical success in four trials (2573 participants) was 6.9 (5.4 to 9.3) (moderate quality evidence). There was too little information for analysis of other individual topical NSAIDs compared with carrier. Few trials compared a topical NSAID to an oral NSAID, but overall they showed similar efficacy (low quality evidence). These efficacy results were almost completely derived from people with knee osteoarthritis. There was an increase in local adverse events (mostly mild skin reactions) with topical diclofenac compared with carrier or oral NSAIDs, but no increase with topical ketoprofen (moderate quality evidence). Reporting of systemic adverse events (such as gastrointestinal upsets) was poor, but where reported there was no difference between topical NSAID and carrier (very low quality evidence). Serious adverse events were infrequent and not different between topical NSAID and carrier (very low quality evidence). Clinical success with carrier occurred commonly - in around half the participants in studies lasting 6 to 12 weeks. Both direct and indirect comparison of clinical success with oral placebo indicates that response rates with carrier (topical placebo) are about twice those seen with oral placebo. A substantial amount of data from completed, unpublished studies was unavailable (up to 6000 participants). To the best of our knowledge, much of this probably relates to formulations that have never been marketed. Topical diclofenac and topical ketoprofen can provide good levels of pain relief beyond carrier in osteoarthritis for a minority of people, but there is no evidence for other chronic painful conditions. There is emerging evidence that at least some of the substantial placebo effects seen in longer duration studies derive from effects imparted by the NSAID carrier itself, and that NSAIDs add to that. Output:

This review is an update of 'Topical NSAIDs for chronic musculoskeletal pain in adults', originally published in 2012. We found 39 generally high-quality studies with 10,857 participants where topical NSAID was used at least once a day. These studies tested a number of different topical drugs, mostly against a topical placebo. We were interested in participants having good pain reduction (by about half), ideally 6 to 12 weeks after treatment started. Studies that last longer are more representative of the real world, because in these chronic conditions the pain almost never goes away if untreated. We looked at individual NSAIDs to see how effective they were. Diclofenac and ketoprofen were the only two with good quality and longer duration studies, mostly in people aged over 40 years with painful knee arthritis. The comparison was between topical diclofenac or ketoprofen in a solution or gel, and the solution or gel without any drug in it (topical placebo). For diclofenac and ketoprofen, about 6 people out of 10 with osteoarthritis had much reduced pain after 6 to 12 weeks, compared with 5 out of 10 with topical placebo (moderate quality evidence). Skin reactions (mostly mild) were more common (20 in 100) with topical diclofenac than topical placebo (5 in 100); there was no difference between topical ketoprofen and topical placebo (moderate quality evidence). Other adverse events, like stomach upsets, were poorly reported in these studies, but were no different between topical diclofenac or ketoprofen and topical placebo (very low quality evidence). Serious adverse events were uncommon. We rated the quality of the evidence for topical diclofenac and topical ketoprofen compared with placebo as moderate for efficacy, and very low for harmful effects. Moderate quality evidence means that further research may change our estimate of the effect, and very low quality evidence means that we are very uncertain about the accuracy of our estimate.

CochranePLS1251

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Twenty papers describing 17 unique trials met the inclusion criteria. Analysis of data from nine trials (1737 participants) showed that topiramate reduced headache frequency by about 1.2 attacks per 28 days as compared to placebo (MD -1.20; 95% confidence interval (CI) -1.59 to -0.80). Data from nine trials (1190 participants) show that topiramate approximately doubled the proportion of responders relative to placebo (RR 2.02; 95% CI 1.57 to 2.60; NNT 4; 95% CI 3 to 6). Separate analysis of different topiramate doses produced similar MDs versus placebo at 50 mg (-0.95; 95% CI -1.95 to 0.04; three studies; 520 participants), 100 mg (-1.15; 95% CI -1.58 to -0.71; six studies; 1620 participants), and 200 mg (-0.94; 95% CI -1.53 to -0.36; five studies; 804 participants). All three doses significantly increased the proportion of responders relative to placebo; ORs were as follows: for 50 mg, 2.35 (95% CI 1.60 to 3.44; three studies; 519 participants); for 100 mg, 3.49 (95% CI 2.23 to 5.45; five studies; 852 participants); and for 200 mg, 2.49 (95% CI 1.61 to 3.87; six studies; 1025 participants). All three doses also significantly improved three or more domains of quality of life as compared to placebo. Meta-analysis of the three studies that included more than one dose of topiramate suggests that 200 mg is no more effective than 100 mg. With regard to mean headache frequency and/or responder rate, seven trials using active comparators found (a) no significant difference between topiramate and amitriptyline (one study, 330 participants); (b) no significant difference between topiramate and flunarizine (one study, 83 participants); (c) no significant difference between topiramate and propranolol (two studies, 342 participants); (d) no significant difference between topiramate and relaxation (one study, 61 participants); but (e) a slight significant advantage of topiramate over valproate (two studies, 120 participants). Relaxation improved migraine-specific quality of life significantly more than topiramate. In trials of topiramate against placebo, seven adverse events (AEs) were reported by at least three studies. These were usually mild and of a non-serious nature. Except for taste disturbance and weight loss, there were no significant differences in the frequency of AEs in general, or of the seven specific AEs, between placebo and topiramate 50 mg. AEs in general and all of the specific AEs except nausea were significantly more common on topiramate 100 mg than on placebo, with NNHs varying from 3 to 25, and the RDs versus placebo were even higher for topiramate 200 mg, with NNHs varying from 2 to 17. Meta-analysis demonstrates that topiramate in a 100 mg/day dosage is effective in reducing headache frequency and reasonably well-tolerated in adult patients with episodic migraine. This provides good evidence to support its use in routine clinical management. More studies designed specifically to compare the efficacy or safety of topiramate versus other interventions with proven efficacy in the prophylaxis of migraine are needed. Output:

For the present review, researchers in The Cochrane Collaboration reviewed the evidence about the effects of topiramate in adult patients (≥ 16 years of age) with 'episodic' migraine (headache on < 15 days per month). They examined research published up to 15 January 2013 and found 17 relevant studies. Compared with placebo, topiramate reduced the frequency of migraine headaches by approximately 1.2 per month (nine studies, 1737 participants). Patients were also about twice as likely to reduce the number of their migraine headaches by 50% or more with topiramate than with placebo (nine studies, 1190 participants). Side effects associated with topiramate were common but generally mild; topiramate can, however, cause birth defects and so should be used with caution in women of childbearing age. Further research is needed comparing topiramate with other active drugs used for preventing migraine attacks.

CochranePLS1252

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: 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. Output:

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. No side effects were reported in the included trials. 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. Further rigorous randomised controlled trials are required to evaluate the role of perineal HAase injection in vaginal deliveries.

CochranePLS1253

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included only one comparison of whole gland cryotherapy versus external beam radiotherapy, which was informed by two trials with a total of 307 randomised participants. The median age of the included studies was around 70 years. The median follow-up of included studies ranged from 100 to 105 months. Primary outcomes: we are uncertain about the effect of whole gland cryotherapy compared to radiation therapy on time to death from prostate cancer; hazard ratio (HR) of 1.00 (95% confidence interval (CI) 0.11 to 9.45; 2 trials, 293 participants; very low QoE); this would correspond to zero fewer death from prostate cancer per 1000 men (95% CI 85 fewer to 520 more). We are equally uncertain about the effect of quality of life-related urinary function and bowel function (QoL) at 36 months using the UCLA-Prostate Cancer Index score for which higher values (range: 0 to 100) reflect better quality of life using minimal clinically important differences (MCID) of 8 and 7 points, respectively; mean difference (MD) of 4.4 (95% CI −6.5 to 15.3) and 4.0 (95% CI −73.96 to 81.96), respectively (1 trial, 195 participants; very low QoE). We are also uncertain about sexual function-related QoL using a MCID of 8 points; MD of −20.7 (95% CI −36.29 to −5.11; 1 trial, 195 participants; very low QoE). Lastly, we are uncertain of the risk for major adverse events; risk ratio (RR): 0.91 (95% CI 0.47 to 1.78; 2 trials, 293 participants; very low QoE); this corresponds to 10 fewer major adverse events per 1000 men (95% CI 58 fewer to 86 more). Secondary outcomes: we are very uncertain about the effects of cryotherapy on time to death from any cause (HR 0.99, 95% CI 0.05 to 18.79; 2 trials, 293 participants; very low QoE), and time to biochemical failure (HR 2.15, 95% CI 0.07 to 62.12; 2 trials, 293 participants; very low QoE). Rates of secondary interventions for treatment failure and minor adverse events were either not reported in the trials, or the data could not be used for analyses. We found no trials that compared whole gland cryotherapy or focal cryotherapy to other treatment forms such as radical surgery, active surveillance, watchful waiting or other forms of radiotherapy. Based on very low quality evidence, primary whole gland cryotherapy has uncertain effects on oncologic outcomes, QoL, and major adverse events compared to external beam radiotherapy. Reasons for downgrading the QoE included serious study limitations, indirectness due to the use of lower doses of radiation in the comparison group than currently recommended, and serious or very serious imprecision. Output:

We searched the medical literature for evidence from trials up to 6 March 2018. We found two randomised trials that compared freezing of the whole prostate to radiation treatment. These included 307 randomised men with prostate cancer (cryotherapy 154 men, radiation 153 men). Their average age was around 70 years. These studies followed men for eight to nine years after treatment. We did not find any studies that compared freezing the prostate to surgery. Also, we did not find randomised trials that compared freezing of parts of the prostate (focal cryotherapy) to radiation, surgery or no treatment. We are uncertain of the effects of freezing of the whole prostate compared to radiation treatment on the time to death from prostate cancer, quality of life for urinary, bowel, and sexual function and serious unwanted treatment reactions. The quality of evidence was very low for all outcomes meaning that the real effect of whole gland cryotherapy may differ a lot from the findings in this review. Further research is very likely to change these findings.

CochranePLS1254

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Thirty four studies involving 4001 children were included. Interventions included; long-term low-dose antibiotics, surgical reimplantation of ureters, endoscopic injection treatment, probiotics, cranberry products, circumcision, and oxybutynin. Interventions were used alone and in combinations. The quality of conduct and reporting of these studies was variable, with many studies omitting crucial methodological information used to assess the risk of bias. Only four of the 34 studies were considered at low risk of bias across all fields of study quality. The majority of studies had many areas of uncertainty in the risk of bias fields, reflecting missing detail rather than stated poor design. Low-dose antibiotic prophylaxis compared to no treatment/placebo may make little or no difference to the risk of repeat symptomatic UTI (9 studies, 1667 children: RR 0.77, 95% CI 0.54 to 1.09; low certainty evidence) and febrile UTI (RR 0.83, 95% CI 0.56 to 1.21; low certainty evidence) at one to two years. At one to three years, antibiotic prophylaxis made little or no difference to the risk of new or progressive renal damage on DMSA scan (8 studies, 1503 children: RR 0.73, 95% CI 0.33 to 1.61; low certainty evidence). Adverse events were reported in four studies with little or no difference between treatment groups (1056 children: RR 0.94, 95% CI 0.81 to 1.08; ), but antibiotics increased the likelihood of bacterial drug resistance threefold (187 UTIs: RR 2.97, 95% CI 1.54 to 5.74; moderate certainty evidence). Seven studies compared long-term antibiotic prophylaxis alone with surgical reimplantation of ureters plus antibiotics, but only two reported the outcome febrile UTI (429 children). Surgery plus antibiotic treatment may reduce the risk of repeat febrile UTI by 57% (RR 0.43, 95% CI 0.27 to 0.70; moderate certainty evidence). There was little or no difference in the risk of new kidney defects detected using intravenous pyelogram at 4 to 5 years (4 studies, 572 children, RR 1.09, 95% CI 0.79 to 1.49; moderate certainty evidence) Four studies compared endoscopic injection with antibiotics alone and three reported the outcome febrile UTI. This analysis showed little or no difference in the risk of febrile UTI with endoscopic injection compared to antibiotics (RR 0.74, 95% CI 0.31 to 1.78; low certainty evidence). Four studies involving 425 children compared two different materials for endoscopic injection under the ureters (polydimethylsiloxane (Macroplastique) versus dextranomer/hyaluronic acid polymer (Deflux), glutaraldehyde cross-linked (GAX) collagen (GAX) 35 versus GAX 65 and Deflux versus polyacrylate polyalcohol copolymer (VANTRIS)) but only one study (255 children, low certainty evidence) had the outcome of febrile UTI and it reported no difference between the materials. All four studies reported rates of resolution of VUR, and the two studies comparing Macroplastique with Deflux showed that Macroplastique was probably superior to dextranomer/hyaluronic acid polymer (3 months: RR 0.50, 95% CI 0.33 to 0.78; 12 months: RR 0.54 95% CI 0.35 to 0.83; low certainty evidence) Two studies compared probiotic treatment with antibiotics and showed little or no difference in risk of repeat symptomatic UTI (RR 0.82 95% CI 0.56 to 1.21; low certainty evidence) Single studies compared circumcision with antibiotics, cranberry products with no treatment, oxybutynin with placebo, two different surgical techniques and endoscopic injection with no treatment. Compared with no treatment, the use of long-term, low-dose antibiotics may make little or no difference to the number of repeat symptomatic and febrile UTIs in children with VUR (low certainty evidence). Considerable variation in the study designs and subsequent findings prevented drawing firm conclusions on efficacy of antibiotic treatment. The added benefit of surgical or endoscopic correction of VUR over antibiotic treatment alone remains unclear since few studies comparing the same treatment and with relevant clinical outcomes were available for analysis. Output:

A total of 34 randomised studies, involving 4001 children were identified and underwent data extraction and analysis. The most frequent comparisons were for long-term, low-dose antibiotics with no treatment (8 studies) or placebo (4 studies) and antibiotics versus surgical reimplantation of ureters plus antibiotics (7 studies). Other treatments looked at endoscopic correction by injection compared with antibiotics (3 studies), different materials for endoscopic correction (2 studies) circumcision (1 study), probiotics (1 study), cranberry product (1 study), and oxybutynin (2 studies). Meta-analysis of similar studies found that long-term low-dose antibiotic treatment compared with no treatment may lead to little or no difference in the risk for repeat UTIs in children with VUR. Associated side effects were infrequent and minor, but prophylaxis was associated with a threefold increased risk of bacterial resistance to the treatment drug in later infections. Surgery decreased the number of repeat UTIs with fever, but did not change the number of children developing UTI with illness or kidney damage. Many studies did not contribute to the meta-analysis as they failed to report relevant outcomes or were single studies examining a treatment option not used by other studies or combinations of treatments. Long-term low-dose antibiotic treatment in children with VUR makes little or no difference to the risk of repeat UTI causing a person to be unwell. Surgery may reduce the risk of repeat UTI with fever however this is based on two studies of 429 children who may not represent the majority and may not bear true in a more general group of children with VUR. Complementary therapies such as probiotics and cranberry were trialled in single or two studies and do not provide evidence of sufficient certainty to support or deny their use.

CochranePLS1255

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: In total we have identified 43 studies examining 4265 participants. The original review included 938 patients from 25 studies. The updated search identified an additional 18 studies with a combined total of 3327 participants between 1997 and June 2015. The results of these studies did not change the conclusions of the original review. No firm conclusions can be drawn from the many retrospective case series so the role of surgery in malignant bowel obstruction remains controversial. Clinical resolution varies from 26.7% to over 68%, though it is often unclear how this is defined. Despite being an inadequate proxy for symptom resolution or quality of life, the ability to feed orally was a popular outcome measure, with success rates ranging from 30% to 100%. Rates of re-obstruction varied, ranging from 0% to 63%, though time to re-obstruction was often not included. Postoperative morbidity and mortality also varied widely, although again the definition of both of these surgical outcomes differed between many of the papers. There were no data available for quality of life. The reporting of adverse effects was variable and this has been described where available. Where discussed, surgical procedures varied considerably and outcomes were not reported by specific intervention. Using the 'Risk of bias' assessment tool, most included studies were at high risk of bias for most domains. The role of surgery in malignant bowel obstruction needs careful evaluation, using validated outcome measures of symptom control and quality of life scores. Further information could include re-obstruction rates together with the morbidity associated with the various surgical procedures. Currently, bowel obstruction is managed empirically and there are marked variations in clinical practice by different units. In order to compare outcomes in malignant bowel obstruction, there needs to be a greater degree of standardisation of management. Since the last version of this review none of the new included studies have provided additional information to change the conclusions. Output:

We first looked at the evidence in 2000 and this is an update of the original review. In total we found 43 studies examining 4265 people. We looked at adults with advanced gynaecological or gastrointestinal cancer who developed bowel obstruction and had either surgical or non-surgical treatment. The studies we found were of low quality and measured success and benefit in different ways. It was therefore not possible to compare these studies and conclude whether surgery was of benefit or harm in this situation. Research in this area is problematic and the type of study needed to answer this question would be very difficult to conduct.

CochranePLS1256

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included twelve randomised studies in this update of which five are additional studies. One trial compared fluspirilene and placebo and did not report important differences in the global improvement (n=60, 1 RCT, RR "no important improvement "0.97 CI 0.9 to 1.1). Though movement disorders (n=60, 1 RCT, RR 31.0 CI 1.9 to 495.6, NNH 4) were found only in the fluspirilene group, there were no convincing data showing the advantage of oral chlorpromazine or other depot antipsychotics over fluspirilene decanoate. We found no difference between depot fluspirilene and other oral antipsychotics with regard to relapses or to the number of people leaving the study early. Global state data (CGI) were not significantly different, in the short term when comparing fluspirilene with other depots (n=90, 2 RCTs, RR "no important improvement" 0.80 CI 0.2 to 2.8). No significant difference were apparent between fluspirilene and other depots with respect to the number of people leaving the trial early (n=83, 2 RCTs, RR 0.55 CI 0.1 to 2.3) or relapse rates (n=109, 3 RCTs, RR 0.55 CI 0.1 to 2.3). Extrapyramidal adverse effects were significantly less prevalent in the fluspirilene groups (n=164, 4 RCTs, RR 0.50 CI 0.3 to 0.8, NNH 5). Other adverse effects were not significantly different. Attrition in the one comparison between fluspirilene in weekly versus biweekly administration (n=34, RR 3.00 CI 0.1 to 68.8) and relapse rates (n=34 RR 3.18 CI 0.1 to 83.8) were not significantly different. There were no significant difference for movement disorders in one short term study. No study reported on hospital and service outcomes or commented on participants' overall satisfaction with care. Economic outcomes were not recorded by any of the included studies. Participant numbers in each comparison were small and we found no clear differences between fluspirilene and oral medication or other depots. The choice of whether to use fluspirilene as a depot medication and whether it has advantages over other depots cannot, at present, be informed by trial-derived data. Well-conducted and reported randomised trials are still needed to inform practice. Output:

Fluspirilene is a relatively long-acting injectable depot antipsychotic drug used for schizophrenia. We updated the original systematic review (David 1999) on Depot fluspirilene for schizophrenia with five additional studies. Twelve randomised trials are included. Study sizes are small and most were of short term duration. This cannot be very informative for a drug that is meant for long-term maintenance treatment. However, from the studies we were able to include, fluspirilene decanoate does not differ greatly from other depot antipsychotics (fluphenazine decanoate, fluphenazine enathate, perphenazine onanthat, pipotiazine undecylenate) with respect to treatment efficacy, response or tolerability. Outcomes suggest that fluspirilene does not differ significantly from oral antipsychotics or in different weekly regimens, although much cannot be inferred because of the shortage of trials.

CochranePLS1257

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Fourteen trials were included. None of the included 2269 patients were previously treated for chronic hepatitis C. Peginterferon (either 2a, 180 microgram, or 2b, 1.5 microgram/kg, once weekly) plus ribavirin was more effective in achieving end of treatment and sustained virological response compared with interferon plus ribavirin (5 trials, 1340 patients) or peginterferon (2 trials, 714 patients). The benefit of peginterferon plus ribavirin was seen irrespective of HCV genotype although patients with genotype 1 or 4 had lower response rates (27%) than patients with genotype 2 or 3 (56%). The remaining trials compared different treatment regimens in patients who were treatment naive or had no virological response after three months of treatment, but overall they had not enough power to show any effect of increasing the dose of interferon or adding both amantadine or ribavirin. The overall mortality was 23/2111 patients with no significant differences between treatment regimens. Treatment increased the risk of adverse events including anaemia and flu-like symptoms, and several serious adverse events occurred including fatal lactic acidosis, liver failure, and suicide due to depression. Peginterferon plus ribavirin may be considered a treatment for patients with chronic hepatitis C and stable HIV who have not received treatment for hepatitis C as the intervention may clear the blood of HCV RNA. Supporting evidence comes mainly from the analysis of this non-validated surrogate outcome assessed in comparisons against other antiviral treatments. There is no evidence on treatment of patients who have relapsed or did not respond to previous therapy. Careful monitoring of adverse events is warranted. Output:

Based on evidence from trials on HIV-negative patients with hepatitis C, the viral genotype, dose of treatment and duration of therapy may affect the treatment response. This review is the first to evaluate the antiviral effect of peginterferon, ribavirin or amantadine administered in different combinations for a patient group, which has not previously been treated for hepatitis C. A total of 14 randomised clinical trials with at total of 2269 patients have been included in this review.The present review suggests that peginterferon plus ribavirin may also be considered if patients have HIV. The dose of peginterferon was similar to that assessed in trials on patients without HIV (180 microgram or 1.5 microgram/kg once weekly), but the dose of ribavirin was somewhat lower in most trials (800 mg daily). There were considerable differences between the trials possibly related to the dose and duration of treatment or the proportion of patients with different hepatitis C virus genotypes. The benefit of treatment was seen when assessing the proportion of patients with a sustained loss of the hepatitis C virus from the blood and the proportion with improved liver biopsies. No significant differences were seen in clinical outcome measures, including mortality (1%, irrespective of treatment). There were several adverse events. Fatal lactic acidosis and liver failure occurred. Other adverse events included anaemia and flu-like symptoms that occurred more frequently among patients receiving peginterferon plus ribavirin. No significant differences were seen regarding the risk of depression, mortality, and progression to cirrhosis or to AIDS. Additional randomised trials are necessary to assess the effect in HIV and HCV co-infected patients of peginterferon plus ribavirin in relation to the duration of therapy, especially in patients with hepatitis C genotype 2 or 3. Additional trials comparing peginterferon plus ribavirin versus interferon plus ribavirin or peginterferon alone do not seem warranted.

CochranePLS1258

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 12 trials with 695 participants; five trials included participants awaiting elective cardiac surgery and seven trials included participants awaiting elective major abdominal surgery. All trials contained at least one domain judged to be at high or unclear risk of bias. Of greatest concern was the risk of bias associated with inadequate blinding, as it was impossible to blind participants due to the nature of the study designs. We could pool postoperative atelectasis in seven trials (443 participants) and postoperative pneumonia in 11 trials (675 participants) in a meta-analysis. Preoperative IMT was associated with a reduction of postoperative atelectasis and pneumonia, compared with usual care or non-exercise intervention (respectively; risk ratio (RR) 0.53, 95% confidence interval (CI) 0.34 to 0.82 and RR 0.45, 95% CI 0.26 to 0.77). We could pool all-cause mortality within postoperative period in seven trials (431 participants) in a meta-analysis. However, the effect of IMT on all-cause postoperative mortality is uncertain (RR 0.40, 95% CI 0.04 to 4.23). Eight trials reported the incidence of adverse events caused by IMT. All of these trials reported that there were no adverse events in both groups. We could pool the mean duration of hospital stay in six trials (424 participants) in a meta-analysis. Preoperative IMT was associated with reduced length of hospital stay (MD -1.33, 95% CI -2.53 to -0.13). According to the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) Working Group guidelines for evaluating the impact of healthcare interventions, the overall quality of studies for the incidence of pneumonia was moderate, whereas the overall quality of studies for the incidence of atelectasis, all-cause postoperative death, adverse events, and duration of hospital stay was low or very low. We found evidence that preoperative IMT was associated with a reduction of postoperative atelectasis, pneumonia, and duration of hospital stay in adults undergoing cardiac and major abdominal surgery. The potential for overestimation of treatment effect due to lack of adequate blinding, small-study effects, and publication bias needs to be considered when interpreting the present findings. Output:

We included 12 trials with 695 participants. Five of the 12 studies included participants awaiting planned heart surgery, and seven studies included participants awaiting planned major abdominal surgery. The evidence is current to October 2014. This review showed that training of breathing muscles before surgery reduced the risk of some lung complications (atelectasis and pneumonia) after surgery and the length of hospital stay, compared with usual care. However, the effect of this training on in-hospital death after surgery is unclear and needs further investigation. The trials did not report any undesirable effects associated with training of breathing muscles, and no study reported on costs resulting from breathing training using a device. Although the available evidence is insufficient in terms of the quality and size of trials, we can conclude that training of breathing muscles before surgery prevents lung complications after surgery. This training is easily performed at home under the supervision of a physiotherapist. The training of breathing muscles therefore appears to be a suitable option as one of the preparations for planned surgery, especially for adults awaiting high-risk heart and abdominal surgery. Other surgeries, such as oesophageal resection (removal of part of the gastrointestinal tract 'food pipe'), should be evaluated; cost-effectiveness and patient-reported outcomes should be reported. The potential for overestimation of treatment effect needs to be considered when interpreting the present findings, as the quality of evidence is low to moderate.

CochranePLS1259

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: For the primary outcome, pregnancy, two controlled studies of LAM users reported life table pregnancy rates at six months of 0.45% and 2.45%, one controlled study reported 5% pregnancies in the absence of life table rates per month, and eight uncontrolled studies of LAM users reported pregnancy rates of 0% to 7.5%. Life table pregnancy rates for fully breastfeeding women who were amenorrheic but not using any contraceptive method were 0.88% in one study and 0.9% to 1.2% (95% confidence interval 0.0 to 2.4) in a second study, depending on the definition of menstruation used. The life table menstruation rate at six months in all studies varied between 11.1% and 39.4%. We found no clear differences in life table pregnancy rates between women using LAM and being supported in doing so, and fully breastfeeding amenorrheic women not using any method. As the length of lactation amenorrhoea in women using LAM differed greatly between the populations studied, and was population specific, it is uncertain whether LAM extends lactational amenorrhoea. Output:

In this review we have studied the effectiveness of LAM as a contraceptive method in fully breastfeeding women in comparison to breastfeeding women without any support. We found no clear differences in effectiveness (pregnancy) between women using LAM and being supported in doing so, and fully breastfeeding amenorrheic women not using any method. Apart from this we recommend breastfeeding itself from a public health point of view.

CochranePLS1260

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included nine studies that involved 735 people in this review. Four studies compared probiotic with placebo, two compared probiotic with no treatment, two compared probiotics with antibiotics in patients with UTI, and one study compared probiotic with placebo in healthy women. All studies aimed to measure differences in rates of recurrent UTI. Our risk of bias assessment found that most studies had small sample sizes and reported insufficient methodological detail to enable robust assessment. Overall, there was a high risk of bias in the included studies which lead to inability to draw firm conclusions and suggesting that any reported treatment effects may be misleading or represent overestimates. We found no significant reduction in the risk of recurrent symptomatic bacterial UTI between patients treated with probiotics and placebo (6 studies, 352 participants: RR 0.82, 95% CI 0.60 to 1.12; I2 = 23%) with wide confidence intervals, and statistical heterogeneity was low. No significant reduction in the risk of recurrent symptomatic bacterial UTI was found between probiotic and antibiotic treated patients (1 study, 223 participants: RR 1.12, 95% CI 0.95 to 1.33). The most commonly reported adverse effects were diarrhoea, nausea, vomiting, constipation and vaginal symptoms. None of the included studies reported numbers of participants with at least one asymptomatic bacterial UTI, all-cause mortality or those with at least one confirmed case of bacteraemia or fungaemia. Two studies reported study withdrawal due to adverse events and the number of participants who experienced at least one adverse event. One study reported withdrawal occurred in six probiotic participants (5.2%), 15 antibiotic participants (12.2%), while the second study noted one placebo group participant discontinued treatment due to an adverse event. No significant benefit was demonstrated for probiotics compared with placebo or no treatment, but a benefit cannot be ruled out as the data were few, and derived from small studies with poor methodological reporting. There was limited information on harm and mortality with probiotics and no evidence on the impact of probiotics on serious adverse events. Current evidence cannot rule out a reduction or increase in recurrent UTI in women with recurrent UTI who use prophylactic probiotics. There was insufficient evidence from one RCT to comment on the effect of probiotics versus antibiotics. Output:

We conducted a literature search up to September 2015 and nine studies were eligible for inclusion according to our selection criteria. The nine studies reported data on 735 participants and investigated probiotics for preventing UTI: seven studies involved women or girls with recurrent UTIs, one looked at children with abnormal urinary tracts, and one investigated UTI in healthy women. Generally, studies were poor quality with high risk of bias. Aside from the different populations, there were also many different species of probiotics used, different dosage forms such as vaginal and oral, and probiotics were given for varying lengths of time. All of these factors may have affected our results. Most studies did not collect information on adverse effects so we were unable to estimate any harms associated with probiotic therapies. We found no significant reduction in the risk of recurrent symptomatic bacterial UTI between patients treated with probiotics and placebo and no significant reduction in the risk of recurrent symptomatic bacterial UTI was found between probiotic and patients treated with antibiotics. The currently available evidence shows no reduction in UTI using probiotics.

CochranePLS1261

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Forty studies (3764 patients) were included. Studies conducted earlier tended to have a higher risk of bias due to poor (or poorly reported) study design, broad inclusion criteria, less well developed disease definitions and low patient numbers. Later studies tend to have improved in all areas of quality, aided by the development of large international study groups. Induction therapy: Plasma exchange as adjunctive therapy may reduce the need for dialysis at three (2 studies: RR 0.43, 95% CI 0.23 to 0.78; I2 = 0%) and 12 months (6 studies: RR 0.45, 95% CI 0.29 to 0.72; I2 = 0%) (low certainty evidence). Plasma exchange may make little or no difference to death, serum creatinine (SCr), sustained remission or to serious or the total number of adverse events. Plasma exchange may increase the number of serious infections (5 studies: RR 1.26, 95% CI 1.03 to 1.54; I2 = 0%; low certainty evidence). Remission rates for pulse versus continuous cyclophosphamide (CPA) were equivalent but pulse treatment may increase the risk of relapse (4 studies: RR 1.79, 95% CI 1.11 to 2.87; I2 = 0%) (low certainty evidence) compared with continuous cyclophosphamide. Pulse CPA may make little or no difference to death at final follow-up, or SCr at any time point. More patients required dialysis in the pulse CPA group. Leukopenia was less common with pulse treatment; however, nausea was more common. Rituximab compared to CPA probably makes little or no difference to death, remission, relapse, severe adverse events, serious infections, or severe adverse events. Kidney function and dialysis were not reported. A single study reported no difference in the number of deaths, need for dialysis, or adverse events between mycophenolate mofetil (MMF) and CPA. Remission was reported to improve with MMF however more patients relapsed. A lower dose of steroids was probably as effective as high dose and may be safer, causing fewer infections; kidney function and relapse were not reported. There was little of no difference in death or remission between six and 12 pulses of CPA. There is low certainty evidence that there were less relapses with 12 pulses (2 studies: RR 1.57, 95% CI 0.96 to 2.56; I2 = 0%), but more infections (2 studies: RR 0.79, 95% CI 0.36 to 1.72; I2 = 45%). One study reported severe adverse events were less in patients receiving six compared to 12 pulses of CPA. Kidney function and dialysis were not reported. There is limited evidence from single studies about the effectiveness of intravenous immunoglobulin, avacopan, methotrexate, immunoadsorption, lymphocytapheresis, or etanercept. Maintenance therapy: Azathioprine (AZA) has equivalent efficacy as a maintenance agent to CPA with fewer episodes of leucopenia. MMF resulted in a higher relapse rate when tested against azathioprine in remission maintenance. Rituximab is an effective remission induction and maintenance agent. Oral co-trimoxazole did not reduce relapses in granulomatosis with polyangiitis. There were fewer relapses but more serious adverse events with leflunomide compared to methotrexate. There is limited evidence from single studies about the effectiveness of methotrexate versus CPA or AZA, cyclosporin versus CPA, extended versus standard AZA, and belimumab. Plasma exchange was effective in patients with severe AKI secondary to vasculitis. Pulse cyclophosphamide may result in an increased risk of relapse when compared to continuous oral use but a reduced total dose. Whilst CPA is standard induction treatment, rituximab and MMF were also effective. AZA, methotrexate and leflunomide were effective as maintenance therapy. Further studies are required to more clearly delineate the appropriate place of newer agents within an evidence-based therapeutic strategy. Output:

Forty studies (3764 patients) were identified. Plasma exchange reduces the risk of end-stage kidney disease in patients presenting with severe acute kidney failure (AKI). The use of pulse cyclophosphamide results in good remission rates but there was an increased risk of relapse. Other appropriate induction agents include rituximab and mycophenolate. Azathioprine is effective as maintenance therapy once remission has been achieved. A lower dose of steroids is just as effective as high dose and may be safer, causing fewer infections. One study shows that a new complement inhibitor can be used to replace steroids in the initial treatment of vasculitis. These are early data. The drug is likely to be very expensive so its place in treatment is not yet clearly defined. Mycophenolate mofetil has also been tested in maintenance treatment and was found to result in a higher rate of disease relapse, when compared to Azathioprine. Methotrexate and leflunomide are useful in maintenance therapy but their relative effectiveness are not clearly defined. Patients on immunosuppression for up to four years after diagnosis have a lowered relapse rate to those in whom treatment is ceased by three years. Plasma exchange was effective in patients with severe AKI. Pulse cyclophosphamide may result in an increased risk of relapse when compared to continuous oral use but a reduced total dose. Whilst cyclophosphamide is used as standard induction treatment, rituximab and mycophenolate mofetil were also effective. Lower dose steroids can now be safely used in initial treatment protocols. Azathioprine, rituximab, mycophenolate, methotrexate and leflunomide are effective maintenance therapy. More trials are required to understand these drugs and new therapies for quickly treating renal vasculitis.

CochranePLS1262

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 30 studies, analysing 14,835 participants, in this review. We assessed 10 studies (33%) as at low risk of bias, nine (30%) as at high risk of bias and 11 (37%) as unclear. Plaque Compared with control, after six to seven months of use, triclosan/copolymer toothpaste reduced plaque by 0.47 on a 0 to 5 scale (MD -0.47, 95% confidence interval (CI) -0.60 to -0.34, 20 studies, 2675 participants, moderate-quality evidence). The control group mean was 2.17, representing a 22% reduction in plaque. After six to seven months of use, it also reduced the proportion of sites scoring 3 to 5 on a 0 to 5 scale by 0.15 (MD -0.15, 95% CI -0.20 to -0.10, 13 studies, 1850 participants, moderate-quality evidence). The control group mean was 0.37, representing a 41% reduction in plaque severity. Gingivitis After six to nine months of use, triclosan/copolymer toothpaste reduced inflammation by 0.27 on a 0 to 3 scale (MD -0.27, 95% CI -0.33 to -0.21, 20 studies, 2743 participants, moderate-quality evidence). The control group mean was 1.22, representing a 22% reduction in inflammation. After six to seven months of use, it reduced the proportion of bleeding sites (i.e. scoring 2 or 3 on the 0 to 3 scale) by 0.13 (MD -0.13, 95% CI -0.17 to -0.08, 15 studies, 1998 participants, moderate-quality evidence). The control group mean was 0.27, representing a 48% reduction in bleeding. Periodontitis After 36 months of use, there was no evidence of a difference between triclosan/copolymer toothpaste and control in the development of periodontitis (attachment loss) (RR 0.92, 95% CI 0.67 to 1.27, one study, 480 participants, low-quality evidence). Caries After 24 to 36 months of use, triclosan/copolymer toothpaste slightly reduced coronal caries when using the decayed and filled surfaces (DFS) index (MD -0.16, 95% CI -0.31 to -0.02, four studies, 9692 participants, high-quality evidence). The control group mean was 3.44, representing a 5% reduction in coronal caries. After 36 months of use, triclosan/copolymer toothpaste probably reduced root caries (MD -0.31, 95% CI -0.39 to -0.23, one study, 1357 participants, moderate-quality evidence). Calculus After six months of use, triclosan/copolymer toothpaste may have reduced the mean total calculus per participant by 2.12 mm (MD -2.12 mm, 95% CI -3.39 to -0.84, two studies, 415 participants, low-quality evidence). The control group mean was 14.61 mm, representing a 15% reduction in calculus. Adverse effects There were no data available for meta-analysis regarding adverse effects, but 22 studies (73%) reported that there were no adverse effects caused by either the experimental or control toothpaste. There was considerable heterogeneity present in the meta-analyses for plaque, gingivitis and calculus. Plaque and gingivitis showed such consistent results that it did not affect our conclusions, but the reader may wish to interpret the results with more caution. There was moderate-quality evidence showing that toothpastes containing triclosan/copolymer, in addition to fluoride, reduced plaque, gingival inflammation and gingival bleeding when compared with fluoride toothpastes without triclosan/copolymer. These reductions may or may not be clinically important, and are evident regardless of initial plaque and gingivitis levels, or whether a baseline oral prophylaxis had taken place or not. High-quality evidence showed that triclosan/copolymer toothpastes lead to a small reduction in coronal caries. There was weaker evidence to show that triclosan/copolymer toothpastes may have reduced root caries and calculus, but insufficient evidence to show whether or not they prevented periodontitis. There do not appear to be any serious safety concerns regarding the use of triclosan/copolymer toothpastes in studies up to three years in duration. Output:

Authors from the Cochrane Oral Health Group carried out this review of existing studies and the evidence is current up to 19 August 2013. It includes 30 studies published from 1990 to 2012 in which 14,835 participants were randomised to receive a triclosan/copolymer containing fluoride toothpaste or a fluoride toothpaste that did not include triclosan/copolymer. The toothpaste that was used in most of the studies is sold by the manufacturer Colgate. The evidence produced shows benefits in using a triclosan/copolymer fluoride toothpaste when compared with a fluoride toothpaste (without triclosan/copolymer). There was a 22% reduction in plaque, a 22% reduction in gingivitis, a 48% reduction in bleeding gums and a 5% reduction in tooth decay. There was insufficient evidence to show a difference between either toothpaste in preventing periodontitis. There was no evidence of any harmful effects associated with the use of triclosan/copolymer toothpastes in studies up to three years in length. The evidence relating to plaque and gingivitis was considered to be of moderate quality. The evidence on tooth decay was high quality, while the evidence on periodontitis was low quality.

CochranePLS1263

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Four trials were identified for inclusion in this review. All the trials were at high risk of bias. Three trials provided information for this review. Overall, this review included 280 people undergoing planned surgery. Participants were randomised to early dressing removal (removal of the wound dressing within the 48 hours following surgery) (n = 140) or delayed dressing removal (continued dressing of the wound beyond 48 hours) (n = 140) in the three trials. There were no statistically significant differences between the early dressing removal group and delayed dressing removal group in the proportion of people who developed superficial surgical site infection within 30 days (RR 0.64; 95% CI 0.32 to 1.28), superficial wound dehiscence within 30 days (RR 2.00; 95% CI 0.19 to 21.16) or serious adverse events within 30 days (RR 0.83; 95% CI 0.28 to 2.51). No deep wound infection or deep wound dehiscence occurred in any of the participants in the trials that reported this outcome. None of the trials reported quality of life. The hospital stay was significantly shorter (MD -2.00 days; 95% CI -2.82 to -1.18) and the total cost of treatment significantly less (MD EUR -36.00; 95% CI -59.81 to -12.19) in the early dressing removal group than in the delayed dressing removal group in the only trial that reported these outcomes. The early removal of dressings from clean or clean contaminated surgical wounds appears to have no detrimental effect on outcomes. However, it should be noted that the point estimate supporting this statement is based on very low quality evidence from three small randomised controlled trials, and the confidence intervals around this estimate were wide. Early dressing removal may result in a significantly shorter hospital stay, and significantly reduced costs, than covering the surgical wound with wound dressings beyond the first 48 hours after surgery, according to very low quality evidence from one small randomised controlled trial. Further randomised controlled trials of low risk of bias are necessary to investigate whether dressings are necessary after 48 hours in different types of surgery and levels of contamination and investigate whether antibiotic therapy influences the outcome Output:

We reviewed the medical literature up to July 2013 and identified four randomised controlled trials that investigated early (permanent removal of dressings within 48 hours of surgery) versus delayed removal of dressings (permanent removal of dressings after 48 hours of surgery with interim changes of dressing allowed) in people with surgical wounds. The levels of bias across the studies were mostly high or unclear, i.e. flaws in the conduct of these trials could have resulted in the production of incorrect results. A total of 280 people undergoing planned surgery were included in this review. One-hundred and forty people had their dressings removed within 48 hours following surgery and 140 people had their wounds dressed beyond 48 hours. The choice of whether the dressing was removed early (within 48 hours) or retained for more 48 hours was made randomly by a method similar to the toss of a coin. No significant differences were reported between the two groups in terms of superficial surgical site infection (infection of the wound), superficial wound dehiscence (partial disruption of the wound that results in it reopening at the skin surface) or the number of people experiencing serious adverse events. There were no deep wound infections or complete wound dehiscence (complete disruption of wound healing, when the wound reopens completely) in the studies that reported these complications. However, the studies were not large enough to identify small differences in complication rates. None of the studies reported quality of life. Participants in the group that had early removal of dressings had significantly shorter hospital stays and incurred significantly lower treatment costs than those in the delayed removal of dressings group, but these results were based on very low quality evidence from one small randomised controlled trial. We recommend further randomised controlled trials are performed to investigate whether dressing of wounds beyond 48 hours after surgery is necessary, since the current evidence is based on very low quality evidence from three small randomised controlled trials.

CochranePLS1264

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We identified 4 RCTs (1,194 adolescents). No RCT reported enough detail to assess whether a strong  randomisation method was used or allocation was concealed. Blinding was not possible as the intervention was mentoring. Three RCTs provided complete data. No selective reporting. Three RCTs provided evidence about mentoring and preventing alcohol use. We pooled two RCTs (RR for mentoring compared to no intervention = 0.71 (95% CI = 0.57 to 0.90, P value = 0.005). A third RCT found no significant differences. Three RCTs provided evidence about mentoring and preventing drug use, but could not be pooled. One found significantly less use of “illegal" drugs," one did not, and one assessed only marijuana use and found no significant differences. One RCT measured “substance use” without separating alcohol and drugs, and found no difference for mentoring. All four RCTs were in the US, and included “deprived” and mostly minority adolescents. Participants were young (in two studies age 12, and in two others 9-16). All students at baseline were non-users of alcohol and drugs. Two RCTs found mentoring reduced the rate of initiation of alcohol, and one of drug usage. The ability of the interventions to be effective was limited by the low rates of commencing alcohol and drug use during the intervention period in two studies (the use of marijuana in one study increased to 1% in the experimental and to 1.6% in the control group, and in another study drug usage rose to 6% in the experimental and 11% in the control group). However, in a third study there was scope for the intervention to have an effect as alcohol use rose to 19% in the experimental and 27% in the control group. The studies assessed structured programmes and not informal mentors. Output:

Four randomised controlled trials (RCTs) were identified. All four RCTs were in the US and with adolescents described as deprived, and most were minority group adolescents. Two RCTs tested the "Across Ages" mentoring programme, one the Big Brothers/Big Sisters mentoring programme, and one an intervention with adolescents whose parents were HIV+. Two RCTs found that mentoring reduced rates of initiation of use of alcohol, and one reduced initiation of use of drugs. No adverse effects were identified. The relative youth of three of the samples made it unlikely that the interventions would be effective due to low baseline rates of usage. The studies assessed formal programmes, and as most mentors are informal their work remains un assessed.

CochranePLS1265

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: The original review included six studies on tension-type headache. We now include eight studies with a total of 412 participants with chronic forms of tension-type headache. These studies evaluated five SSRIs (citalopram, sertraline, fluoxetine, paroxetine, fluvoxamine) and one SNRI (venlafaxine). The two new studies included in this update are placebo controlled trials, one evaluated sertraline and one venlafaxine. Six studies, already included in the previous version of this review, compared SSRIs to other antidepressants (amitriptyline, desipramine, sulpiride, mianserin). Most of the included studies had methodological and/or reporting shortcomings and lacked adequate power. Follow-up ranged between two and four months. Six studies explored the effect of SSRIs or SNRIs on tension-type headache frequency, the primary endpoint. At eight weeks of follow-up, we found no difference when compared to placebo (two studies, N = 127; mean difference (MD) -0.96, 95% confidence interval (CI) -3.95 to 2.03; I2= 0%) or amitriptyline (two studies, N = 152; MD 0.76, 95% CI -2.05 to 3.57; I2= 44%). When considering secondary outcomes, SSRIs reduce the symptomatic/analgesic medication use for acute headache attacks compared to placebo (two studies, N = 118; MD -1.87, 95% CI -2.09 to -1.65; I2= 0%). However, amitriptyline appeared to reduce the intake of analgesic more efficiently than SSRIs (MD 4.98, 95% CI 1.12 to 8.84; I2= 0%). The studies supporting these findings were considered at unclear risk of bias. We found no differences compared to placebo or other antidepressants in headache duration and intensity. SSRIs or SNRI were generally more tolerable than tricyclics. However, the two groups did not differ in terms of number of participants who withdrew due to adverse events or for other reasons (four studies, N = 257; odds ratio (OR) 1.04; 95% CI 0.41 to 2.60; I2= 25% and OR 1.55, 95% CI 0.71 to 3.38; I2= 0%). We did not find any study comparing SSRIs or SNRIs with pharmacological treatments other than antidepressants (e.g. botulinum toxin) or non-drug therapies (e.g. psycho-behavioural treatments, manual therapy, acupuncture). Since the last version of this review, the new included studies have not added high quality evidence to support the use of SSRIs or venlafaxine (a SNRI) as preventive drugs for tension-type headache. Over two months of treatment, SSRIs or venlafaxine are no more effective than placebo or amitriptyline in reducing headache frequency in patients with chronic tension-type headache. SSRIs seem to be less effective than tricyclic antidepressants in terms of intake of analgesic medications. Tricyclic antidepressants are associated with more adverse events; however, this did not cause a greater number of withdrawals. No reliable information is available at longer follow-up. Our conclusion is that the use of SSRIs and venlafaxine for the prevention of chronic tension-type headache is not supported by evidence. Output:

This is an update of a previous review that included studies on migraine and tension-type headache. The original review has been split into two separate reviews: this update addresses only studies on tension-type headache, while a second focuses on migraine. When we updated this review (November 2014), we identified two new studies. Six studies were already included in the previous version of the review. Overall, we analysed a total of 412 adults participants. All the studies had a small number of participants and were conducted over a period of two to four months. Only a few were of high quality. Results suggest that SSRIs or SNRIs are no better than placebo (sugar pill) in reducing the number of days with tension-type headache. There were no differences in minor side effects between participants treated with SSRIs or SNRIs versus those treated with placebo. SSRIs and SNRIs do not seem to offer advantages when compared to other active treatments, specifically the tricyclic antidepressant, amitriptyline. The participants treated with SSRIs or SNRIs suffered fewer minor side effects than those who took amitriptyline, however the number of people who stopped taking one drug or the other due to side effects was approximately equal. These results are based on poor quality, small, short-term trials (no more than four months). We did not find a study comparing SSRIs or SNRIs with other medications (e.g. botulinum toxin) or non-drug therapies (e.g. psycho-behavioural treatments, manual therapy, acupuncture).

CochranePLS1266

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 41 randomised clinical trials with 6193 patients with chronic hepatitis C. All trials had high risk of bias. All included trials compared amantadine versus placebo or no intervention. Standard antiviral therapy was administered equally to the intervention and the control groups in 40 trials. The standard antiviral therapy, which was administered to both intervention groups, was interferon-alpha, interferon-alpha plus ribavirin, and peg interferon-alpha plus ribavirin, depending on the time when the trial was conducted. When we meta-analysed all trials together, the overall results demonstrated no significant effects of amantadine, when compared with placebo or no intervention, on our all-cause mortality or liver-related morbidity composite outcome (5/2353 (0.2%) versus 6/2264 (0.3%); RR 0.90, 95% CI 0.38 to 2.17; I² = 0%; 32 trials; very low quality). There was also no significant effect on adverse events (288/2869 (10%) versus 293/2777 (11%); RR 0.98, 95% CI 0.84 to 1.14; I² = 0%; 35 trials; moderate quality). We used both fixed-effect and random-effects meta-analyses. Amantadine, when compared with placebo or no intervention, did not significantly influence the number of patients who failed to achieve a sustained virological response (1821/2861 (64%) versus 1737/2721 (64%); RR 0.98, 95% CI 0.95 to 1.02; I² = 35%; 35 trials; moderate quality). However, in the subgroup using interferon plus ribavirin, amantadine decreased the number of patients who failed to achieve a sustained virological response (422/666 (63%) versus 447/628 (71%); RR 0.89, 95% CI 0.83 to 0.96; I² = 41%; 11 trials; low quality). Similar results were found for failure to achieve an end of treatment virological response. Amantadine, when compared with placebo or no intervention, significantly decreased the number of patients without normalisation of alanine aminotransferase (ALT) serum levels at the end of treatment (671/1141 (59%) versus 732/1100 (67%); RR 0.88, 95% CI 0.83 to 0.94; I² = 47%; 19 trials; low quality). Amantadine, when compared with placebo or no intervention, did not significantly influence the end of follow-up biochemical response (1133/1896 (60%) versus 1151/1848 (62%); RR 0.95, 95% CI 0.91 to 1.00; I² = 49%; 21 trials; low quality). The observed beneficial effects could be true effects but could also be due to both systematic errors (bias) and random errors (play of chance). The latter is due to the fact that trial sequential analyses could not confirm or refute our findings. We were not able to perform meta-analyses for failure of histological improvement or quality of life due to a lack of valid data. This systematic review does not demonstrate any significant effects of amantadine on all-cause mortality or liver-related morbidity composite outcome and on adverse events in patients with hepatitis C; however, the median trial duration was 12 months, with a median follow-up of six months, which is not long enough to assess the composite outcome sufficiently. Overall, we did not see an effect of amantadine on failure to achieve a sustained virological response. Subgroup analyses demonstrated that the combination of amantadine plus interferon-alpha and ribavirin seems to increase the number of patients achieving a sustained virological response. This finding may be caused by both systematic errors (bias) and risks of random errors (play of chance), but it could also be real. Based on the results of the overall evidence, it appears less likely that future trials assessing amantadine for patients with chronic hepatitis C will show strong benefits. Therefore, it is probably advisable to wait for the results of trials assessing other direct-acting antiviral drugs. In the absence of convincing evidence of benefit, the use of amantadine is justified in the context of randomised clinical trials assessing the effects of combination therapy. We found a lack of evidence on other aminoadamantanes than amantadine. Output:

Only amantadine has been tested in randomised clinical trials including participants with chronic hepatitis C. The main goal of these trials was to investigate whether amantadine as a single therapy or amantadine in combination with other antiviral therapy, compared with placebo or no intervention (with or without antiviral therapy), could increase the proportion of patients with virus eradication from the blood. This review evaluates whether amantadine has any beneficial or harmful effect in patients with chronic hepatitis C. The primary outcomes were all-cause mortality or liver-related morbidity (combined outcome) and adverse events. The review includes 41 randomised clinical trials with a total of 6193 patients. This review shows that there seems to be no significant benefit of amantadine on hepatitis C-infected patients regarding all-cause mortality or liver-related morbidity. We were unable to assess the effect of amantadine on quality of life due to lack of data from the trials. Furthermore, amantadine did not increase the proportion of patients with a sustained virological response which is clearance of the virus from the blood six months after treatment. We considered all the included trials to have a high risk of bias. Accordingly, the evidence from this review does not support the routine clinical use of amantadine. There is some justification for amantadine to be used in future randomised clinical trials. We found no randomised clinical trials assessing other aminoadamantanes, for example rimantadine.

CochranePLS1267

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Eighteen trials are included in the review. The majority were in family care settings. For fourteen studies, FA was just one aspect of a broad multi-component programme of care. Assessing the effect of FA was compromised by ill-defined protocols for the duration of component parts of these programmes (i.e. frequency of the intervention or actual time spent). Therefore, establishing the real effect of the FA component was not possible. Overall, positive effects were noted at post-intervention for the frequency of reported challenging behaviour (but not for incidence or severity) and for caregiver reaction (but not burden or depression). These effects were not seen at follow-up. The delivery of FA has been incorporated within wide ranging multi-component programmes and study designs have varied according to setting - i.e. family care, care homes and hospital, with surprisingly few studies located in care homes. Our findings suggest potential beneficial effects of multi-component interventions, which utilise FA. Whilst functional analysis for challenging behaviour in dementia care shows promise, it is too early to draw conclusions about its efficacy. Output:

In this review we analysed the effectiveness of functional analysis-based interventions for challenging behaviour in dementia. We found eighteen randomised controlled trials suitable for analysis in all four types of care settings. The majority were in family care settings and there were surprisingly few care home based studies. Most evaluated broad programmes of care, where FA was just one component of a wide range of other interventions. This made it hard to determine the real effect of FA for the management of challenging behaviour in dementia. However, positive results were noted in the frequency of the person’s reported problem behaviours and the caregiver’s reaction to them. No significant effects were found for incidence or severity of mood and other problem behaviours. Similarly, no significant effects were found for caregiver mood or burden. Whilst it is too early to reach a firm conclusion on the evidence for FA in the management of challenging behaviour in dementia, we note emerging beneficial effects on challenging behaviour where multi-component psychosocial interventions have used FA as part of the programme of care.

CochranePLS1268

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Four trials (with a combined total of 528 adult participants) were included, but almost none of the data from these studies could be aggregated in a meta-analysis. One trial (with 88 participants) compared bromhexine versus placebo. Compared with placebo, high doses of bromhexine with antibiotics eased difficulty in expectoration (mean difference (MD) -0.53, 95% confidence interval (CI) -0.81 to -0.25 at 16 days); the quality of the evidence was rated as low. A reduction in sputum production was noted with bromhexine (MD -21.5%, 95% CI -38.9 to -4.1 at day 16); again the quality of the evidence was rated as low. No significant differences between bromhexine and placebo were observed with respect to reported adverse events (odds ratio (OR) 2.93; 95% CI 0.12 to 73.97), and again the quality of the evidence was rated as low. In a single small, blinded but not placebo-controlled trial of older (> 55 years) participants with stable bronchiectasis and mucus hypersecretion, erdosteine combined with physiotherapy over a 15-day period improved spirometry and sputum purulence more effectively compared with physiotherapy alone. The spirometric improvement was small (MD 200 mL in forced expiratory volume in one second (FEV1) and 300 mL in forced vital capacity (FVC)) and was apparent only at day 15, not at earlier time points. The remaining two studies (with a combined total of 410 participants) compared recombinant human DNase (RhDNase) versus placebo. These two studies were very different (one was a two-week study of 61 participants, and the other ran for 24 weeks and included 349 participants), and the opportunity for combining data from the two studies was very limited. Compared with placebo, recombinant human DNase showed no difference in FEV1 or FVC in the smaller study but showed a significant negative effect on FEV1 in the larger and longer study. For reported adverse events, no significant differences between recombinant human DNase and placebo were noted. In all of the above comparisons of recombinant human DNase versus placebo, the quality of the evidence was judged to be low. Given the harmful effects of recombinant human DNase in one trial and no evidence of benefit, this drug should be avoided in non–cystic fibrosis bronchiectasis, except in the context of clinical trials. Evidence is insufficient to permit evaluation of the routine use of other mucolytics for bronchiectasis. High doses of bromhexine coupled with antibiotics may help with sputum production and clearance, but long-term data and robust clinical outcomes are lacking. Similarly, erdosteine may be a useful adjunct to physiotherapy in stable patients with mucus hypersecretion, but robust longer-term trials are required. Generally, clinical trials in children on the use of various mucolytic agents are lacking. As the number of agents available on the market, such as RhDNase, acetylcysteine and bromhexine, is increasing, improvement of the evidence base is needed. Output:

Four studies (with a total of 528 participants) were identified that met the inclusion criterion of comparing mucolytic treatment versus no mucolytic treatment. All studies were conducted in adults. One study considered bromhexine versus placebo, two compared RhDNase versus placebo (one for a period of two weeks and the other over a period of 24 weeks) and the fourth compared erdosteine with physiotherapy versus physiotherapy alone in elderly patients. The small number of studies available for review and their different designs meant that only descriptions of the individual studies were possible with very limited opportunities for combining the studies in single analyses. No strong evidence is available to support the use of these drugs in people with bronchiectasis (from causes other than cystic fibrosis); however it is not possible to draw any clear conclusions, as so few studies have been reported. Details of the way patients were allocated to receive or not receive mucolytics were not clearly described in any of the four studies. This was considered carefully in the review in relation to our level of uncertainty in interpreting the results. When this is taken into account, together with the imprecision of the results, estimates of the usefulness of mucolytics as treatment were generally judged to be of low quality in relation to (non–cystic fibrosis) bronchiectasis.

CochranePLS1269

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Two randomized trials were included, enrolling 722 HIV-positive pregnant women from Malawi and Zambia. Both compared monthly regimens of sulfadoxine-pyrimethamine (SP) to the standard 2-dose regimen given in the second and third trimesters. In women in their first or second pregnancy, monthly SP may reduce both maternal parasitaemia (two trials, 463 participants, RR 0.25, 95% CI 0.14 to 0.43, low quality evidence), and placental parasitaemia at delivery (two trials, 459 participants, RR 0.38, 95% CI 0.21 to 0.70, low quality evidence). Monthly SP may have a small effect on the prevalence of maternal anaemia at delivery (two trials, 447 participants, RR 0.93, 95% CI 0.72 to 1.20, low quality evidence), and the number of babies born with low birth weight (two trials, 469 participants, RR 0.80, 95% CI 0.52 to 1.23, low quality evidence), but larger trials are necessary to reliably prove or exclude clinically important benefits on these outcomes. There is currently insufficient evidence to make conclusions regarding an effect on neonatal mortality (one study, 253 participants, very low quality evidence). In women in their third or higher pregnancy, there is insufficient evidence to make any conclusions on the benefits of monthly SP compared to the two dose regimen (one trial, 166 participants, very low quality evidence). There were no trials that assessed other treatment regimens for intermittent preventive treatment in HIV-positive pregnant women. Three or more doses of SP may have some advantages over the standard two doses in HIV-positive pregnant women, but larger trials would be necessary to confirm an effect on patient important outcomes. However, since SP cannot be administered concurrently with co-trimoxazole - a drug often recommended for infection prophylaxis in HIV-positive pregnant women, new drugs and research is needed to address needs of HIV-positive pregnant women. Output:

This review only identified two trials which compared the impact of using three or more doses of sulphadoxine-pyrimethamine to using only two doses. Using three or more doses was more effective at preventing the presence of malaria parasites in the placenta and in the peripheral blood of the pregnant woman than using the standard two doses only. Also, children born to HIV-positive pregnant women who used three or more doses of sulphadoxine-pyrimethamine weighed more than those born to mothers who used only the standard two doses. Although more frequent doses of this drug are effective in preventing malaria, HIV-positive pregnant women with low CD4 count can not use the drug since the current policy requires that they use co-trimoxazole (Bactrim®) to prevent opportunistic infections. There is need, therefore, to investigate alternative drugs and regimens in preventing malaria in HIV-positive pregnant women.

CochranePLS1270

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 11 studies that randomly assigned 509 people with schizophrenia, schizoaffective disorder or psychotic depression. No trials were conducted in patients at their first episode of psychotic illness and none included populations at high risk for developing psychosis. Our pre-stated outcomes of interest were mental state, global state, general functioning, adverse effects and quality of life. Two trials compared antiglucocorticoid drugs (mifepristone) versus placebo as sole treatment. Limited data from one trial showed no difference in the proportion responding to mifepristone when mental state was assessed immediately post intervention using the Brief Psychiatric Rating Scale (BPRS) (n = 5, 1 RCT, MD -5.20, 95% CI -17.91 to 7.51; very low-quality evidence); depressive symptoms (Hamilton Rating Scale for Depression (HAMD) total) were also similar between groups (n = 5, 1 RCT, MD 1.67, 95% CI -16.44 to 19.78; very low-quality evidence). However, a significant difference favoured treatment at short-term follow-up for global state (30% reduction in total BPRS, n = 221, 1 RCT, RR 0.58, 95% CI 0.38 to 0.89; low-grade quality evidence). This effect was also seen for short-term positive psychotic symptoms (50% reduction in BPRS positive symptom subscale, n = 221, 1 RCT, RR 0.60, 95% CI 0.43 to 0.84; low-grade quality evidence). Participants receiving mifepristone experienced a similar overall number of adverse effects as those receiving placebo (n = 226, 2 RCTs, RR 0.92, 95% CI 0.77 to 1.09; moderate-quality evidence). No data on general functioning or quality of life were available. One trial compared an antiglucocorticoid, dehydroepiandrosterone (DHEA), as an adjunct to atypical antipsychotic treatment to adjunctive placebo. Data for main outcomes of interest were of low quality, and analysis of useable data showed no significant effects of treatment on mental state or adverse effects. Data on global state, general functioning and quality of life were not available. Data from six trials comparing antiglucocorticoid drugs as an adjunct to combination treatment versus adjunctive placebo showed no significant differences between groups in mean endpoint scores for overall psychotic symptoms (n = 171, 6 RCTs, SMD 0.01, 95% CI - 0.29 to 0.32) or positive psychotic symptoms (n = 151, 5 RCTs, SMD -0.07, 95% CI - 0.40 to 0.25). Data from three trials showed no differences between groups in mean endpoint scores for negative symptoms (n = 94, 3 RCTs, MD 2.21, 95% CI -0.14 to 4.55). One study found improvements in global state that were similar between groups (n = 30, 1 RCT, RR 0.58, 95% CI 0.32 to 1.06; very low-quality evidence). In this comparison, pooled results showed that antiglucorticoids caused a greater overall number of adverse events (n = 199, 7 RCTs, RR 2.66, 95% CI 1.33 to 5.32; moderate quality evidence), but no quality of life data were available. Good evidence is insufficient to conclude whether antiglucocorticoid drugs provide effective treatment for psychosis. Some global state findings suggest a favourable effect for mifepristone, and a few overall adverse effect findings favour placebo. Additional large randomised controlled trials are needed to justify findings. Output:

Eleven studies (involving 509 participants) were included in this review. Several antiglucocorticoid-related drugs were examined, including dehydroepiandrosterone (DHEA) (n = 5), mifepristone (n = 4), dexamethasone (n = 1) and ketoconazole (n = 1). All participants were adults with a diagnosis of schizophrenia, schizoaffective disorder or psychotic depression. Most trials examined giving antiglucocorticoid drugs as an additional part of regular treatment. Available data from these trials revealed no effects for overall psychotic symptoms, 'positive' symptoms or 'negative' symptoms. One large trial comparing mifepristone versus placebo as the sole treatment revealed a significant difference in the proportion of people responding to treatment with mifepristone versus placebo. This effect was not seen immediately but 21 days after the intervention was begun. Adverse effect data varied. When individual anticorticoids such as mifepristone and DHEA were compared with placebo, the incidence of side effects was similar between groups; however, pooled data on various antiglucorticoids given as an adjunct to combination treatment showed that antiglucocorticoids increased incidence of side effects than placebo. In summary, very few trials are under way, and most involve a small number of people. Limited available data do not provide enough evidence to support the use of antiglucocorticoid treatments for psychosis; additional trials are needed.

CochranePLS1271

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included one single blind study (total n = 24). The overall risk of bias in the study was considered to be unclear although the randomisation was adequate. It compared a package of horticultural therapy which consisted of one hour per day of horticultural activity plus standard care with standard care alone over two weeks (10 consecutive days) with no long-term follow-up. Only two people were lost to follow-up in the study, both in the horticultural therapy group (1 RCT n = 24,RR 5.00 95% CI 0.27 to 94.34, very low quality evidence). There was no clear evidence of a difference in Personal Wellbeing Index (PWI-C) change scores between groups, however confidence intervals were wide (1 RCT n = 22, MD -0.90 95% CI -10.35 to 8.55, very low quality evidence). At the end of treatment, the Depression Anxiety Stress Scale (DASS21) change scores in horticultural therapy group were greater than that in the control group (1 RCT n = 22, MD -23.70 CI -35.37 to - 12.03, very low quality evidence). The only included study did not report on adverse effects of interventions. Based on the current very low quality data, there is insufficient evidence to draw any conclusions on benefits or harms of horticultural therapy for people with schizophrenia. This therapy remains unproven and more and larger randomised trials are needed to increase high quality evidence in this area. Output:

This review focuses on the effects of horticultural therapy for people with schizophrenia. An electronic search for relevant randomised trials was run in January 2013. Only one trial was included, it randomised a total of 24 people with schizophrenia to received either their standard care plus horticultural therapy or standard care only. The trial only lasted 2 weeks (10 consecutive days) with no long-term follow-up. There are few results and the quality of evidence was rated by the review authors to be very low quality. Some of the information from this one study favoured horticultural therapy but there is insufficient evidence to draw any conclusions on benefits or harms of horticultural therapy for people with schizophrenia. More large, better conducted and reported trials are required to determine the effectiveness and benefits of horticultural therapy. This plain language summary has been written by a consumer Ben Gray, Service User and Service User Expert, Rethink Mental Illness.

CochranePLS1272

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Fifty studies met the inclusion criteria. Six additional studies were identified since the original review. Only 31 of these studies involving 7104 participants were judged to have used a sufficiently robust measure of fatigue and thus were deemed suitable for detailed analysis. The drugs were still analysed by class (psychostimulants; haemopoietic growth factors; antidepressants and progestational steroids). Methylphenidate showed a small but significant improvement in fatigue over placebo (Z = 2.83; P = 0.005). Since the publication of the original review increased safety concerns have been raised regarding erythropoietin and this cannot now be recommended in practice.There was a very high degree of statistical and clinical heterogeneity in the trials and the reasons for this are discussed. There is increasing evidence that psychostimulant trials provide evidence for improvement in CRF at a clinically meaningful level. There is still a requirement for a large scale RCT of methylphenidate to confirm the preliminary results from this review. There is new safety data which indicates that the haemopoietic growth factors are associated with increased adverse outcomes. These drugs can no longer be recommended in the treatment of CRF. Readers of the first review should re-read the document in full. Output:

This review has examined drug treatment for fatigue as it represents one of the ways this problem can be tackled. The review authors looked at trials in all types of cancer and at all stages of treatment. Fifty studies met the inclusion criteria but only 31 (7104 participants) were deemed suitable for detailed analysis as they explored fatigue in sufficient detail. They found mixed results with some drugs showing an effect on fatigue - most notably drugs that stimulate red blood cell production and also drugs that improve levels of concentration. Methylphenidate, a stimulant drug that improves concentration, is effective for the management of cancer-related fatigue but the small samples used in the available studies mean more research is needed to confirm its role. Erythropoietin and darbopoetin, drugs that improve anaemia, are effective in the management of cancer-related fatigue. However safety concerns and side effects from these drugs mean that they can no longer be recommended to treat cancer fatigue.

CochranePLS1273

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Only two RCTs were eligible. One was a cross-over trial with 18 participants. The other randomised 400 participants to one of four treatments, of which two (L-carnitine and placebo) were relevant to this review, but the exact numbers of participants in these two treatment groups was not reported. All participants were young adults. Methodological details were poorly reported, and we considered the risk of bias in both studies to be unclear. The trials assessed different cognitive outcomes. We could extract cognitive data on approximately 200 participants from one trial. We found no evidence that L-carnitine has any effect on reaction time, vigilance, immediate memory, or delayed recall after three days of treatment. This trial report stated that there was a small number of adverse effects, none of which were serious. The small cross-over trial also reported no effect of L-carnitine on cognition, but did not provide data; no information was provided on adverse effects. We considered the available evidence to be of very low quality for all reported outcomes. Due to the limited number of included trials, short-term treatment, and inadequate reporting, we were unable to draw any conclusions about the efficacy or safety of L-carnitine for cognitive enhancement in healthy adults. Well-designed, randomised, placebo-controlled trials of L-carnitine for cognition enhancement in cognitively healthy people, with large samples and relatively long-term follow-up, are still needed. Output:

It was difficult to properly assess the quality of the included trials because of poor reporting. We considered there to be a serious risk of bias due to poor study methods, and further uncertainty about the results because the studies were so small. We also considered the studies to be too short to adequately address our research question. Due to these factors, we considered the quality of the evidence to be very low. Given the limited amount of evidence of very low quality, we were not able to draw any conclusions about the effect of L-carnitine on cognitive function or its safety in healthy people. Larger, better-quality studies conducted over a longer period of time are needed to answer our review question.

CochranePLS1274

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 18 studies involving 549 relevant participants, of which 14 (421 participants) were included in the analysis (one within both comparisons). Four of the 14 studies compared the effects of bilateral training with usual care. Primary outcomes: results were not statistically significant for performance in ADL (standardised mean difference (SMD) 0.25, 95% confidence interval (CI) -0.14 to 0.63); functional movement of the arm (SMD -0.07, 95% CI -0.42 to 0.28) or hand (SMD -0.04, 95% CI -0.50 to 0.42). Secondary outcomes: no statistically significant results. Eleven of the 14 studies compared the effects of bilateral training with other specific upper limb (arm) interventions. Primary outcomes: no statistically significant results for performance of ADL (SMD -0.25, 95% CI -0.57 to 0.08); functional movement of the arm (SMD -0.20, 95% CI -0.49 to 0.09) or hand (SMD -0.21, 95% CI -0.51 to 0.09). Secondary outcomes: one study reported a statistically significant result in favour of another upper limb intervention for performance in extended ADL. No statistically significant differences were found for motor impairment outcomes. There is insufficient good quality evidence to make recommendations about the relative effect of simultaneous bilateral training compared to placebo, no intervention or usual care. We identified evidence that suggests that bilateral training may be no more (or less) effective than usual care or other upper limb interventions for performance in ADL, functional movement of the upper limb or motor impairment outcomes. Output:

This review of 18 studies with 549 relevant participants looked at whether performing identical activities with both arms at the same time (simultaneous bilateral training) could improve performance in daily (or extended daily) activities, movement of the arm and/or reduce arm impairments. In comparison with usual care, bilateral training had no effect on performance in activities of daily living, functional movement of the arm or hand, performance in extended activities of daily living or motor impairment outcomes. In comparison with other arm interventions, bilateral training had no effect on performance in activities of daily living, functional movement of the arm or hand or motor impairment outcomes. One study found that people who undertook bilateral training showed less improvement in performance in extended activities of daily living than people doing another arm intervention. The evidence in this area is limited. Further research is needed to determine the effects of bilateral training.

CochranePLS1275

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Six studies with a total of 1039 patients were eligible for inclusion. The two largest studies were rated as low risk of bias for all assessed items. Four studies were rated as unclear risk of bias for randomization and allocation concealment. Two studies were rated as high risk of bias for incomplete outcome data and selective reporting. There was a marginal significant benefit of n-3 therapy for maintenance of remission. Thirty-nine per cent of patients in the n-3 group relapsed at 12 months compared to 47% of placebo patients (6 studies, 1039 patients; RR 0.77, 95% CI 0.61 to 0.98). A GRADE analysis rated the overall quality of the evidence for the primary outcome (i.e. relapse) as very low due to unexplained heterogeneity (I2 = 58%), publication bias, and a high or unknown risk of bias in four studies in the pooled analysis. When two large studies at low risk of bias were considered the benefit was no longer statistically significant. Thirty-seven per cent of patients in the n-3 group relapsed at 12 months compared to 42% of placebo patients (2 studies, 738 patients; RR 0.88, 95% CI 0.74 to 1.05). No significant heterogeneity was identified for this pooled analysis ( I2 = 0%). A GRADE analysis indicated that the overall quality of the evidence supporting this outcome was moderate due to sparse data (294 events). No serious adverse events were recorded in any of the studies but in a pooled analyses there was a significantly higher rate of diarrhea (4 studies, 862 patients; RR 1.36 95% CI 1.01 to 1.84) and upper gastrointestinal tract symptoms (5 studies, 999 patients; RR 1.65, 95% CI 1.25 to 2.18) in the n-3 treatment group. Evidence from two large high quality studies suggests that omega 3 fatty acids are probably ineffective for maintenance of remission in CD. Omega 3 fatty acids appear to be safe although they may cause diarrhea and upper gastrointestinal tract symptoms. Output:

Randomized placebo-controlled studies that evaluated the effect of daily intake of capsules containing omega-3 fatty acids to maintain remission in Crohn's disease were reviewed. Six studies including 1039 patients were included in the review. A pooled analysis of six studies suggests a marginal benefit for omega 3 fatty acids over placebo (i.e. fake medicine) in preventing relapse of disease at one year. However, these results need to be interpreted with caution due to differences across the studies in terms of induction of remission regimens (e.g. surgical remission versus drug therapy) patients (e.g. adult versus pediatric patients) and medication regimens (e.g. some studies used different placebos), the possibility of publication bias (i.e. only studies with positive results are published) and low methodological quality in four studies in the pooled analysis. When the two largest and highest quality studies were pooled the results showed no benefit to omega-3 treatment over placebo. There were no serious side effects in any of the studies. Common side effects included unpleasant taste, bad breath, heartburn, nausea and diarrhea. Evidence from two large high quality studies suggests that omega 3 fatty acids are probably ineffective for maintenance of remission in CD. Omega 3 fatty acids appear to be safe although they may cause diarrhea and upper gastrointestinal tract symptoms.

CochranePLS1276

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Overall, more than 3500 references were considered and 19 original reports with a total of 3599 patients were included. There were 9 trials analysing antibiotics versus placebo/no treatment, with all outcomes significantly favouring antibiotic use (P < 0.05) (I2 = 0%), including bacteriuria (risk ratio (RR) 0.25 (95% confidence interval (CI) 0.15 to 0.42), bacteremia (RR 0.67, 95% CI 0.49 to 0.92), fever (RR 0.39, 95% CI 0.23 to 0.64), urinary tract infection (RR 0.37, 95% CI 0.22 to 0.62), and hospitalization (RR 0.13, 95% CI 0.03 to 0.55). Several classes of antibiotics were effective prophylactically for TRPB, while the quinolones, with the highest number of studies (5) and patients (1188), were the best analysed. For 'antibiotics versus enema', we analysed four studies with a limited number of patients. The differences between groups for all outcomes were not significant. For 'antibiotic versus antibiotic + enema', only the risk of bacteremia (RR 0.25, 95% CI 0.08 to 0.75) was diminished in the 'antibiotic + enema group'. Seven trials reported the effects of short-course (1 day) versus long-course (3 days) antibiotics. Long course was significantly better than short-course treatment only for bacteriuria (RR 2.09, 95% CI 1.17 to 3.73). For 'single versus multiple dose', there was significantly greater risk of bacteriuria for single-dose treatment (RR 1.98, 95% CI 1.18 to 3.33). Comparing oral versus systemic administration - intramuscular injection (IM), or intravenous (IV) - of antibiotics, there were no significant differences in the groups for bacteriuria, fever, UTI and hospitalization. Antibiotic prophylaxis is effective in preventing infectious complications following TRPB. There is no definitive data to confirm that antibiotics for long-course (3 days) are superior to short-course treatments (1 day), or that multiple-dose treatment is superior to single-dose. Output:

In nine trials we observed that antibiotic prophylaxis is effective in preventing infectious complications (bacteriuria, bacteremia, fever, urinary tract infection, sepsis) and hospitalization following prostate biopsy. Several classes of antibiotics are effective for prophylaxis in prostate biopsy, with the quinolones the best analysed class. There are no definitive data to confirm that antibiotic for long-course is superior to short-course treatment, or that multiple-dose treatment is superior to single-dose treatment.

CochranePLS1277

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Fifteen studies met the inclusion criteria, enrolling 1926 participants. The trial size varied from 20 to 598 patients. Most studies compared corticosteroids, particularly dexamethasone, to standard therapy. We included six studies with data at one week in the meta-analysis for pain intensity; no data were available at that time point for the remaining studies. Corticosteroid therapy resulted in less pain (measured on a scale of 0 to 10 with a lower score indicating less pain) compared to control at one week (MD 0.84 lower pain, 95% CI 1.38 to 0.30 lower; low quality evidence). Adverse events were poorly documented. Factors limiting statistical analysis included the lack of standardised measurements of pain and the use of different agents, dosages, comparisons and routes of drug delivery. Subgroup analysis according to type of cancer was not possible. The quality of this evidence was limited by the risk of bias of the studies and small sample size. The results were also compromised by attrition, with data missing for the enrolled patients. The evidence for the efficacy of corticosteroids for pain control in cancer patients is weak. Significant pain relief was noted in some studies, albeit only for a short period of time. This could be important for patients with poor clinical status. Further trials, with increased numbers of participants, are needed to evaluate the safety and effectiveness of corticosteroids for the management cancer pain in adults, and to establish an ideal dose, duration of therapy and route of administration. Output:

Study characteristics: We found 15 relevant studies with 1926 participants. The trial size varied from 20 to 598 patients and the duration of the included studies ranged from seven days to 42 weeks. Most studies compared corticosteroids, particularly dexamethasone, to standard therapy. Key results and quality of the evidence: Overall, we found that the current evidence is based on studies that contain only a small number of patients. The following conclusions can be made from the available evidence: 1) the evidence for the efficacy of corticosteroids for pain control in cancer patients is weak (GRADE quality of evidence for pain outcome was low); 2) significant pain relief was noted in some studies, albeit only for a short period of time; this could be important for patients who have only a short time to live; 3) overall, more studies found corticosteroids not to be of benefit; 4) it was not possible to determine whether steroids are more effective for pain in specific cancers; and 5) the side effect profile of steroids, especially in the longer term, is not well described.

CochranePLS1278

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included four randomised trials (257 participants). The overall risk of bias in the included studies was low. Two trials compared the addition of intravenous acyclovir to a steroid (prednisolone). One included 43 participants, the other 70 patients. Neither demonstrated any hearing improvement with ISSHL. Another (84 patients) did not show any statistically significant difference between groups with the addition of valacyclovir to prednisolone (compared to steroid plus placebo) with respect to change in pure-tone audiogram. Comparing the addition of intravenous acyclovir to hydrocortisone with hydrocortisone alone, the final trial did not show any statistically significant difference between groups (60 patients). No trial documented any serious adverse effects related to the use of antiviral treatment. One study reported slight to moderate nausea equally in the acyclovir and placebo groups (one patient in each). Another reported insomnia, nervousness and weight gain with valacyclovir (number not specified). Even though no meta-analysis was possible, evidence from the four RCTs has demonstrated no statistically significant advantage in the use of antivirals in the treatment of ISSHL. There is currently no evidence to support the use of antiviral drugs in the treatment of ISSHL. The four trials included in this review were, however, small and with a low risk of bias. Further randomised controlled trials with larger patient populations, using standardised inclusion criteria, antiviral regimes and outcome measures, are needed in order for adequate meta-analysis to be performed to reach definitive conclusions. A uniform definition of ISSHL should also be established, together with what constitutes adequate recovery. Output:

Antiviral drugs are often used, usually in conjunction with steroids, to treat sudden hearing loss of unknown cause, based on the theory that the deafness is caused by a viral infection. We searched for randomised controlled trials (RCTs) which compared treatment of sudden hearing loss with antiviral drugs (either alone or in combination with another treatment) with placebo or no antiviral drug, in patients of any age. We found four RCTs (257 patients). The overall risk of bias in the studies was low. All four trials compared steroid treatment (either alone or plus a placebo drug) with steroid plus antiviral treatment. None of the trials found a statistically significant difference between groups. No trial documented any serious adverse effects related to using antiviral treatments. One study reported slight to moderate nausea equally in the acyclovir and placebo groups (one patient in each), both attributable to the steroid treatment. Another reported insomnia, nervousness and weight gain with valacyclovir (number not specified). The effectiveness of antiviral drugs in the treatment of sudden hearing loss of unknown origin is questionable. Certainly, this review of the clinical trials did not identify any substantial evidence to support their use. Further research is required with larger patient numbers and standardised inclusion criteria, antiviral regimes and outcome measures.

CochranePLS1279

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We found no RCTs or quasi-RCTs in the original review or updates in 20011 and 2012. Cure or improvement have been described in high quality observational studies: (1) A single study describes spontaneous improvement of meralgia paraesthetica in 20 (69%) of 29 cases. (2) Four studies evaluating the injection of corticosteroid and local anaesthetic found cure or improvement in 130 (83%) out of a combined total of 157 cases. (3) Surgical treatments have been found to be beneficial in 264 (88%) out of 300 cases treated with decompression (nine studies); and 45 (94%) out of 48 cases treated with neurectomy (three studies). (4) Ninety-nine (97%) out of 102 patients with iatrogenic meralgia paraesthetica recovered completely (three studies). In the absence of any published RCTs or quasi-RCTs, the objective evidence base for treatment choices in meralgia paraesthetica is weak. High quality observational studies report comparable high improvement rates for meralgia paraesthetica following local injection of corticosteroid and surgical interventions (either nerve decompression or neurectomy). However, a similar outcome has been reported without any intervention in a single natural history study. Output:

We found no randomised controlled trials (RCTs) in the original review or when searches were updated in 2010 and 2012. Local injections of corticosteroid and surgical operations were found to be effective treatments in observational studies. However, a single observational study also showed that meralgia paraesthetica improved spontaneously in the majority of cases. RCTs of treatments for meralgia paraesthetica are needed.

CochranePLS1280

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: No studies comparing CTG monitoring during labour with an ES to intermittent auscultation were identified. Two randomised controlled trials comparing CTG monitoring during labour with an ES versus CTG without an ES were identified and included in the qualitative synthesis of results, but only one trial (n = 220) provided data for quantitative analysis. Both trials were classified as low risk of bias. There was no strong evidence that CTG with an ES has an effect on the incidence of caesarean delivery (risk ratio (RR) 0.61; 95% confidence interval (CI) 0.35 to 1.04) when compared with CTG with fetal blood sampling.There was no strong evidence supporting a reduction in the incidence of neonatal seizures (RR 0.33; 95% CI 0.01 to 8.09) or fetal acidaemia (RR 0.50; 95% CI 0.09 to 2.67) in women monitored using a CTG with an ES versus a CTG without an ES. Overall perinatal mortality could not be ascertained for this trial since data on early neonatal deaths were unavailable. Although fetal deaths were recorded, no fetal deaths occurred in either arm of the trial, and thus no risk estimates could be derived. There was no strong evidence supporting a reduction in the incidence of forceps-assisted vaginal birth (RR 0.50; 95% CI 0.05 to 5.43), hypoxic ischaemic encephalopathy (RR 0.33; 95% CI 0.01 to 8.09), admission to the neonatal intensive care unit (RR 0.40; 95% CI 0.08 to 2.02) or an Apgar less than seven at five minutes (RR 0.50; 95% CI 0.13 to 1.95). The trial did not report on artificial rupture of amniotic membranes,oxytocin augmentation of labour ormaternal satisfaction with labour. Two trials met the inclusion criteria for this review but one trial did not provide data for any of this review's outcomes. The single trial that did contribute data was underpowered to evaluate the association between CTG monitoring with an ES and the primary outcomes of interest. No recommendations for clinical practice can be made at this time. Adequately powered trials are necessary before the impact of ESs for fetal assessment in labour can be determined. Output:

However, we did identify two randomised controlled trials looking at birth-related outcomes among women who were monitored using a CTG with an ES compared to women who were monitored using CTG without an ES. Although the review identified two eligible randomised controlled trials that were at a low risk of bias, only one trial (involving 220 women) examined the outcomes of interest in this review. Data relating to death of the baby within the first 28 days of life (early neonatal death) was unavailable but the study reported that none of the babies died before being born (fetal deaths). There was no strong evidence that CTG with an ES reduces the likelihood of caesarean delivery, forceps-assisted vaginal birth or adverse baby outcomes (such as fetal acidaemia, neonatal seizures, brain injury due to lack of oxygen (hypoxic ischaemic encephalopathy), Apgar score less than seven at five minutes or admission to the neonatal intensive care unit). These results should be interpreted with caution since the trial was underpowered as too few women were included in the trial to detect modest differences in adverse outcomes. Larger randomised controlled trials are necessary to see if CTG with an ES reduces adverse outcomes for women and their babies during the birth.

CochranePLS1281

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 21 trials (2588 patients). The drugs did not reduce mortality significantly (relative risk 0.97, 95% confidence interval (CI) 0.75 to 1.25, for the trials with a low risk of bias, and 0.80, 95% CI 0.63 to 1.01, for the other trials). Units of blood transfused were 0.7 (0.2 to 1.1) less with drugs in the trials with a low risk of bias and 1.5 (0.9 to 2.0) less in the other trials. Number of patients failing initial haemostasis was reduced, relative risk 0.68 (0.54 to 0.87). Number of patients with rebleeding was not significantly reduced for the trials with a low risk of bias, relative risk 0.84 (0.52 to 1.37) while it was substantially reduced in the other trials, relative risk 0.36 (0.19 to 0.68). Use of balloon tamponade was rarely reported. The need for blood transfusions corresponded to one half unit of blood saved per patient. It is doubtful whether this effect is worthwhile. The findings do not suggest a need for further placebo-controlled trials of the type reviewed here. A large placebo controlled trial enrolling thousands of patients is needed if one wishes to rule out the possibility that a worthwhile effect on mortality might have been overlooked. Output:

The review of 21 trials (2588 patients) found that the tested drugs did not reduce deaths. There was a small reduction in the need for blood transfusions, corresponding to one half unit of blood saved per patient. It is doubtful whether this effect is worthwhile.

CochranePLS1282

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Of twenty eligible studies, ten evaluated breastfeeding and ten evaluated supplemental breast milk. Sixteen studies analysed used heel lance and four used venepuncture as procedure. We noted marked heterogeneity in control intervention and pain assessment measures among the studies. Neonates in the breastfeeding group had statistically a significantly lower increase in heart rate, reduced proportion of crying time and reduced duration of first cry and total crying time compared to positioning (swaddled and placed in a crib), holding by mother, placebo, pacifier use, no intervention or oral sucrose group, or both. Premature Infant Pain Profile (PIPP) scores were significantly lower in the breastfeeding group compared to positioning, placebo or oral sucrose group, or both. However, there was no statistically significant difference in PIPP scores when compared to no intervention. Douleur Aigue Nouveau-ne scores (DAN) were significantly lower in the breastfeeding group compared to the placebo group and the group held in mother's arms, but not when compared to the glucose group. Neonatal Infant Pain Scale (NIPS) was significantly lower in the breastfeeding group compared to the no intervention group, but there was no difference when compared to the oral sucrose group. The Neonatal Facial Coding System (NFCS) was significantly lower in the breastfeeding group when compared to oral glucose, pacifier use, holding by mother and no intervention, but no difference was found when compared to formula feeding. Supplemental breast milk yielded variable results. Neonates in the supplemental breast milk group had a significantly lower increase in heart rate, a reduction in duration of crying and a lower NFCS compared to the placebo group. Neonates in the supplemental breast milk group had a significantly higher increase in heart rate changes when compared to the sucrose group. Sucrose (in any concentration, i.e. 12.5%, 20%, 25%) was found to reduce the duration of cry when compared to breast milk, as did glycine, pacifier use, rocking, or no intervention. Breast milk was found not to be effective in reducing validated and non-validated pain scores such as NIPS, NFCS, and DAN; only being significantly better when compared to placebo (water) or massage. We did not identify any study that has evaluated safety/effectiveness of repeated administration of breastfeeding or supplemental breast milk for pain relief. If available, breastfeeding or breast milk should be used to alleviate procedural pain in neonates undergoing a single painful procedure rather than placebo, positioning or no intervention. Administration of glucose/sucrose had similar effectiveness as breastfeeding for reducing pain. The effectiveness of breast milk for painful procedure should be studied in the preterm population, as there are currently a limited number of studies in the literature that have assessed it's effectiveness in this population. Output:

Different studies done in babies have shown that breastfeeding is a good way to reduce the pain babies feel when subjected to minor painful procedures. These studies have been done in full-term babies and they have shown that breastfeeding is effective by demonstrating that it reduces babies' crying time and reduces different pain scores that have been validated for babies. Breast milk given by syringe has not shown the same efficacy as breastfeeding itself. No studies have been done in premature babies, and so new studies are needed to determine if the use of supplemental breast milk in these small babies is effective in reducing their pain.

CochranePLS1283

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: A total of 770 participants were involved in the 11 included studies. Data from five included randomised double-blind studies showed beneficial effects of antipsychotics in the treatment of acute and chronic pain. Quantitative analysis of these studies showed a significant reduction of mean pain intensity after administration of the antipsychotic compared to placebo or another active compound, weighted mean difference (WMD) -1.78 (95% CI -2.71 to -0.85) for the continuous data; and relative risk (RR) 0.43 (95% CI 0.25 to 0.73), number needed to treat to benefit (NNT) 2.6 for the dichotomous data. Nevertheless, the test for heterogeneity was significant for both the continuous data (P = 0.0007) and the dichotomous data (P = 0.04). Obviously this makes the calculated NNT less reliable and caution is warranted when interpreting these results. The most frequently reported adverse effects were extrapyramidal (that is involuntary movements, parkinsonism and akathisia) and sedating effects. The recent search found five new studies which were all excluded, so the review remains the same as previously. Antipsychotics might be used as an add-on therapy in the treatment of painful conditions. Nevertheless, extrapyramidal and sedating side effects have to be considered before using antipsychotics for treating painful conditions. Results for antipsychotics in the treatment of different painful conditions are mixed and most sample sizes in the reviewed RCTs are small. Further studies on atypical antipsychotics in larger double-blind placebo-controlled studies that include standardised pain assessment and documentation are warranted. Output:

The review authors assessed the effect of these medicines on pain and their side effects. Based on 5 out of 11 included trials there were some beneficial effects of antipsychotics in the treatment of acute and chronic pain. Analysis of these studies showed a significant reduction in pain after administration of the antipsychotic compared to placebo or another medicine, however these results were based on small studies and therefore they may be unreliable. It is also important to consider the unwanted effects that these medicines might cause.

CochranePLS1284

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Two studies fitting the selection criteria were found for computer aided prescribing and one study for computer aided physiological monitoring. Computer-aided prescribing: one study (Cade 1997) examined the effects of computerised prescribing of parenteral nutrition ordering. No significant effects on short-term outcomes were found and longer term outcomes were not studied. The second study (Balaguer 2001) investigated the effects of a database program in aiding the calculation of neonatal drug dosages. It was found that the time taken for calculation was significantly reduced and there was a significant reduction in the number of calculation errors. Computer-aided physiological monitoring: one eligible study (Cunningham 1998) was found which examined the effects of computerised cot side physiological trend monitoring and display. There were no significant effects on mortality, volume of colloid infused, frequency of blood gases sampling (samples per day) or severe intraventricular haemorrhage (Papile Grade IV). Published data did not permit us to analyse effects on long-term neurodevelopmental outcome. There are very limited data from randomised trials on which to assess the effects of clinical decision support systems in neonatal care. Further evaluation of CDSS using randomised controlled trials is warranted. Output:

The review authors searched the medical literature and contacted experts to find studies on CDSS used with newborns. They identified three randomised controlled studies that met the criteria for the review. Two of these three studies were on computer-aided drug prescribing and one was on computerized physiological monitoring of newborns. One of the studies on computer-aided prescribing showed that the CDSS used resulted in fewer drug dosage errors. The studies found no other benefits. The studies did not consider long-term outcomes in the newborns, just short-term effects. Also, with rapid changes in computer technology, current CDSS are more advanced than those used in the three studies. The Cochrane review authors conclude that there is not enough data to determine whether or not CDSS are beneficial for newborn care.

CochranePLS1285

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 12 studies with a total of 1121 women. Ten studies enrolled healthy nulliparous women only and two studies enrolled healthy parous women at term as well. All studies excluded women with complicated pregnancies. There were variations in the technique of initiation of epidural analgesia. Seven studies utilized the combined spinal epidural (CSE) technique, and the other five studies only placed an epidural catheter without any intrathecal injection. Seven studies utilized ropivacaine: six with fentanyl and one with sufentanil. Two studies used levobupivacaine: one with sufentanil and one with fentanyl. Three used bupivacaine with or without fentanyl. The overall risk of bias of the studies was low. AMB probably reduces the risk of breakthrough pain compared with BI for maintaining epidural analgesia for labour (from 33% to 20%; risk ratio (RR) 0.60; 95% confidence interval (CI) 0.39 to 0.92, 10 studies, 797 women, moderate-certainty evidence). AMB may make little or no difference to the risk of caesarean delivery compared to BI (15% and 16% respectively; RR 0.92; 95% CI 0.70 to 1.21, 11 studies, 1079 women, low-certainty evidence). AMB may make little or no difference in the risk of instrumental delivery compared to BI (12% and 9% respectively; RR 0.75; 95% CI 0.54 to 1.06, 11 studies, 1079 women, low-certainty evidence). There is probably little or no difference in the mean duration of labour with AMB compared to BI (mean difference (MD) −10.38 min; 95% CI −26.73 to 5.96, 11 studies, 1079 women, moderate-certainty evidence). There is probably a reduction in the hourly consumption of local anaesthetic with AMB compared to BI for maintaining epidural analgesia during labour (MD −1.08 mg/h; 95% CI −1.78 to −0.38, 12 studies, 1121 women, moderate-certainty evidence). Five out of seven studies reported an increase in maternal satisfaction with AMB compared to BI for maintaining epidural analgesia for labour; however, we did not pool these data due to their ordinal nature. Seven studies reported Apgar scores, though there was significant heterogeneity in reporting. None of the studies showed any significant difference between Apgar scores between groups. There is predominantly moderate-certainty evidence that AMB is similar to BI for maintaining epidural analgesia for labour for all measured outcomes and may have the benefit of decreasing the risk of breakthrough pain and improving maternal satisfaction while decreasing the amount of local anaesthetic needed. Output:

The evidence is current to January 2018. We found 12 studies involving 1121 women with uncomplicated pregnancies. We did not specifically assess the impact of the funding sources on the studies. The people taking part in the trials we looked for (known as randomized controlled trials) are randomly assigned to either the group receiving the treatment under investigation or to a group receiving standard treatment as the control. This is to reduce any bias that either the investigators or the participants of the trial may have. We found that automated mandatory bolus decreases the risk of breakthrough pain (pain requiring medical intervention from an anaesthesiologist) compared with basal infusion during childbirth. It does this without increasing the risk of a caesarean section; the risk of instrumental delivery (whether the obstetrician intervenes to assist delivery using an obstetric forceps or vacuum device); or the duration of childbirth. It may also reduce the dose of medication required on a per hourly basis. In addition, five of seven studies found that mothers preferred the automated mandatory bolus over basal infusion. The evidence was of moderate-certainty for all the outcomes we measured, with the exception of the risk of caesarean delivery and risk of instrumental delivery, which had only low-certainty evidence.

CochranePLS1286

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: The searches identified 161 records; after de-duplication and title and abstract screening 90 full-text articles were retrieved. From these we included three RCTs with a combined total of 613 participants. One study compared prophylactic dactinomycin to no prophylaxis (60 participants); the other two studies compared prophylactic methotrexate to no prophylaxis (420 and 133 participants). All participants were diagnosed with CMs. We considered the latter two studies to be of poor methodological quality. P-Chem reduced the risk of GTN occurring in women following a CM (3 studies, 550 participants; risk ratio (RR) 0.37, 95% confidence interval (CI) 0.24 to 0.57; I² = 0%; P < 0.00001; low-quality evidence). However, owing to the poor quality (high risk of bias) of two of the included studies, we performed sensitivity analyses excluding these two studies. This left only one small study of high-risk women to contribute data for this primary outcome (59 participants; RR 0.28, 95% CI 0.10 to 0.73; P = 0.01); therefore we consider this evidence to be of low quality. The time to diagnosis was longer in the P-Chem group than the control group (2 studies, 33 participants; mean difference (MD) 28.72, 95% CI 13.19 to 44.24; P = 0.0003; low-quality evidence); and the P-Chem group required more courses to cure subsequent GTN (1 poor-quality study, 14 participants; MD 1.10, 95% CI 0.52 to 1.68; P = 0.0002; very low quality evidence). There were insufficient data to perform meta-analyses for toxicity, overall survival, drug resistance and reproductive outcomes. P-Chem may reduce the risk of progression to GTN in women with CMs who are at a high risk of malignant transformation; however, current evidence in favour of P-Chem is limited by the poor methodological quality and small size of the included studies. As P-Chem may increase drug resistance, delays treatment of GTN and may expose women toxic side effects, this practice cannot currently be recommended. Output:

We found three randomised studies (randomised controlled trials (RCTs) where people are allocated at random i.e. by chance alone) involving a total of 613 women. Two studies tested methotrexate in all women with a CM and one study tested dactinomycin in women with a CM who were at a high risk of getting GTN. The two methotrexate studies are older studies that used relatively poor research methods, therefore their findings cannot be relied upon. Overall the review findings suggest that P-Chem reduces the number of women developing cancer after molar pregnancy; however, this is probably only true for women with high-risk moles (i.e. CM). In addition, P-Chem might make the time to diagnose the cancer longer and might increase the number of anti-cancer treatments needed to cure the cancer if it develops. We were unable to assess the short- and long-term side-effects of P-Chem in this review because there were not enough available data; however, we are concerned that the five- and eight-day courses of P-Chem used by researchers in these studies are too toxic to be given to women routinely. We consider this evidence to be of a low to very low quality. This conclusion is based on our assessment that two of the included studies were of poor methodological quality and at a high risk of bias; the third study was of a good quality but consisted of only 60 participants. Currently there is insufficient evidence to support giving anti-cancer drugs to women with molar pregnancies. However, GTN is almost always cured with modern care and P-Chem for molar pregnancy would only reduce the risk of needing full-scale chemotherapy, but would not remove that risk. In addition, it would not change the need for careful monitoring and follow-up of women with hydatidiform moles.

CochranePLS1287

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Nine studies were included in this review which analysed 634 participants. Study duration ranged from 4 to 24 weeks. The interventions included calcium-enriched bread, low phosphorus intake, low protein intake, very low protein intake, post haemodialysis supplements and hypolipaemic diet. Only one study reported death; none of the included studies reported cardiovascular events or fractures. There was insufficient reporting of design and methodological aspects among the included studies to enable robust assessment of risk of bias. There was limited and low-quality evidence to indicate that calcium-enriched bread increased serum calcium (1 study, 53 participants: MD -0.16 mmol/L, 95% CI -0.51 to -0.31), decreased serum phosphorus (53 participants: MD -0.41 mmol/L, 95% CI -0.51 to -0.31) and decreased the calcium × phosphate product (53 participants: MD -0.62 mmol²/L², 95% CI -0.77 to -0.47). Very low protein intake was not superior to conventional low protein intake in terms of effect on serum phosphorus (2 studies, 41 participants: MD -0.12 mmol/L, 95% CI -0.50 to 0.25), serum calcium (MD 0.00 mmol/L, 95% CI -0.17 to 0.17), or alkaline phosphatase (MD -22.00 U/L, 95% CI -78.25 to 34.25). PTH was significantly lower in the very low protein intake group (2 studies, 41 participants: MD -69.64 pmol/L, 95% CI -139.83 to 0.54). One study reported no significant difference in the number of deaths between low phosphorus intake and normal diet (279 participants: RR 0.18, 95% CI 0.01 to 3.82). Low phosphorus intake decreased serum phosphorus (2 studies, 359 participants: MD -0.18 mmol/L, 95% CI -0.29 to -0.07; I2 = 0%). One study reported post-haemodialysis supplements did not increase serum phosphorus compared to normal diet (40 participants: MD 0.12 mmol/L, 95% CI -0.24 to 0.49). One study reported low phosphorus intake plus lanthanum carbonate significantly decreased FGF-23 (19 participants: MD -333.80 RU/mL, 95% CI -526.60 to -141.00), but did not decrease serum phosphorus (19 participants: MD -0.10 mg/dL, 95% CI -0.38 to 0.58) or PTH (19 participants: MD 31.60 pg/mL, 95% CI -29.82 to 93.02). There was limited low quality evidence to indicate that dietary interventions (calcium-enriched bread or low phosphorus/protein intake) may positively affect CKD-MBD by increasing serum calcium, decreasing serum phosphorus, the calcium × phosphate product and FGF-23. Large and well-designed RCTs are needed to evaluate the effects of various interventions for people with CKD-MBD. Output:

We searched the literature to August 2015 and included nine studies that analysed 634 participants; durations of studies ranged from 4 and 24 weeks. The interventions included calcium-enriched bread, low phosphorus intake, low protein intake, very low protein intake, post-haemodialysis supplements and low lipid diet. Only one study reported death; none of the included studies reported cardiovascular events or fractures. One study reported adverse events. There was insufficient reporting of design and methodological aspects among the included studies to enable robust assessment of risk of bias. We found scant evidence to suggest that restricting protein or phosphorus in the diet may have positive effects for people with CKD. Evidence from one small, low quality study suggested that calcium-enriched bread may help to increase calcium and decrease phosphorus and the calcium × phosphate product. Evidence was assessed as low quality, and was insufficient to inform clinical decision-making about the value of dietary modification for people with CKD-MBD. None of the included studies reported our primary outcomes of cardiovascular events or fracture; only one study reported adverse events.

CochranePLS1288

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included eight studies, involving 809 participants, comparing oral dipyrone 500 mg (143 participants), oral dipyrone 1000 mg (57 participants), and intramuscular dipyrone 2000 mg (35 participants) with placebo (236 participants). In addition to placebo, all studies used active controls (ibuprofen, paracetamol, aspirin, flurbiprofen, ketoprofen; 338 participants). Seven studies used the oral route of administration, and one study used the intramuscular route. The mean age ranged from 23 to 62 years. Six studies included both men and women, and two studies included only women. All the studies were small, but were otherwise of moderate to good quality. Over 70% of participants experienced our primary outcome of at least 50% pain relief over four to six hours with oral dipyrone 500 mg compared to 30% with placebo (five studies, 288 participants; NNT 2.4 (95% CI 1.8 to 3.1)) (moderate quality evidence). There were insufficient data to assess other doses or routes of administration of dipyrone. Fewer participants needed rescue medication within four to six hours with dipyrone 500 mg than with placebo (7% with dipyrone versus 34% with placebo; four studies, 248 participants) (low quality evidence). The data on numbers of participants experiencing any adverse event was inconsistently reported and no analysis was possible. No serious adverse events or adverse event withdrawals were reported (very low quality evidence). There were too few data to compare dipyrone directly with other active treatments. Based on very limited information, a single dose of dipyrone 500 mg provides good pain relief to about 70% of people treated, compared to about 30% with placebo. For every five people given dipyrone 500 mg, two people would experience this level of pain relief over four to six hours who would not have done with placebo, and fewer people would need rescue medication. We were unable to compare dipyrone directly with other active treatments, or to assess the effects of different doses or routes of administration, or the number of participants experiencing adverse events, because of insufficient data and inadequate reporting. Output:

We searched medical databases for studies of dipyrone used to treat pain following surgery in adults and compared with placebo (a pretend treatment). The medicines could be given by mouth, into a vein, into a muscle, or into the rectum. The evidence is current to 11 August 2015. We found eight studies, involving 809 participants treated with dipyrone, placebo, and various other painkillers. The studies were all small, but otherwise of moderate to good quality. A single 500 mg dose of dipyrone provided effective pain relief (50% or more reduction in pain over four to six hours) for 7 in 10 (70%) participants, compared with 3 in 10 (30%) with placebo (five studies, 288 participants in the comparison; moderate quality evidence), and fewer participants need additional painkillers within four to six hours (7% with dipyrone, 34% with placebo; four studies, 248 participants; low quality evidence). There were too few data to compare dipyrone directly with other painkillers. There was too little information available to draw any conclusions about other doses and ways of giving dipyrone used in these studies, or about the number of people who had side effects. The studies reported no serious side effects or people withdrawing from the studies because of side effects, although not all studies provided information on these outcomes.

CochranePLS1289

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Treatment with naftidrofuryl tended to show reduction of pain evaluated by both analogue score and analgesic consumption, but the effect was statistically non-significant (mean difference (MD): 0.42; 95% confidence interval (CI)1.19 to 0.35). Similarly, improvement in rest pain or skin necrosis occurred, but these effects were also non-significant. The effect on mean ankle systolic pressure was inconclusive. Based on the results of these trials, it cannot be confirmed that intravenous naftidrofuryl is effective in the treatment of people with critical limb ischaemia. However, these results were based on trials of generally low methodological quality which had only a small number of participants, the duration of treatment was extremely short, and the methods varied between the trials. The wide range of endpoints effectively precluded any meaningful pooling of the results. Intravenous naftidrofuryl was withdrawn as a treatment for severe peripheral arterial disease in 1995 because of reported side effects. Output:

The review authors identified eight controlled trials that randomly allocated a total of 269 participants from five different countries to receive intravenous naftidrofuryl, other treatments, and placebo alone or with another treatment. There was no clear indication that short-term intravenous naftidrofuryl significantly improves either symptoms of ischaemic rest pain or skin necrosis. Treatment with naftidrofuryl tended to reduce pain, measured using a scale or with analgesic consumption, and improve rest pain and skin necrosis but the effects were not clear (statistically significant). The trials were generally of low methodological quality, included small numbers of predominantly elderly participants with varying levels of severity of critical limb ischaemia and used different measures of effect. The duration of treatment was short, from three to 42 days, most often seven days. Other treatments were haemodilution, anti-coagulant medication, prostaglandins, bed rest and reflex heating, and gingko biloba. Side effects included mild blood clotting (thrombophlebitis) at the injection site and in one trial two participants experienced renal insufficiency. Intravenous naftidrofuryl was withdrawn as a treatment for severe peripheral arterial disease in 1995 because of reported side effects.

CochranePLS1290

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We found no trials assessing the effect of visibility aids on pedestrian and cyclist-motor vehicle collisions and injuries. To date we have identified 42 trials assessing the effect of visibility aids on drivers' responses. Fluorescent materials in yellow, red and orange colours improve detection and recognition in the daytime. For night-time visibility, lamps, flashing lights and retroreflective materials in red and yellow colours increase detection and recognition. Retroreflective materials enhance recognition, in particular when arranged in a 'biomotion' configuration, taking advantage of the motion from a pedestrian's limbs. Substantial heterogeneity between and within the trials limited the possibility for meta-analysis. Summary statistics and descriptive summaries of the outcomes were presented for individual trials when appropriate. Visibility aids have the potential to increase visibility and enable drivers to detect pedestrians and cyclists earlier. Biomotion markings, which highlight the movement and form of the pedestrian, showed evidence of improving pedestrians' conspicuity at night. Public acceptability of various effective strategies which improve visibility would merit further development. However, the effect of visibility aids on pedestrian and cyclist safety remains unknown. A cluster randomised controlled trial involving large communities may provide an answer to this question. It would, however, be a challenging trial to conduct. Studies that collect data of road traffic injuries relating to the use of visibility aids also warrant consideration. Output:

The authors of this Cochrane review looked for studies which showed how effective visibility aids are for protecting pedestrians and cyclists. They focused their search on a type of study called a randomised controlled trial, which compares two similar groups of people who only differ on the issue being studied, for instance, the rate of crashes in communities with and without introduction of visibility aids. The authors found no studies that compared number of crashes but to date they have found 42 studies which compare driver detection of people with or without visibility aids. These studies showed that fluorescent materials in yellow, red and orange improved driver detection during the day; while lamps, flashing lights and retroreflective materials in red and yellow, particularly those with a 'biomotion' configuration (taking advantage of the motion from a pedestrian's limbs), improved pedestrian recognition at night. Although these visibility measures help drivers see pedestrians and cyclists, more research should be done to determine whether the increased visibility actually does prevent deaths and serious injuries.

CochranePLS1291

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Two prospective controlled clinical trials involving 167 patients were included. All of them were of low quality. Radioiodine treatment versus ATD showed benefits in achieving euthyroidism (relative risk (RR) 1.70, 95% confidence interval (CI) 1.29 to 2.24). Radioiodine treatment showed a higher incidence of hypothyroidism compared with ATD (RR 6.46, 95% CI 1.16 to 35.81). No significant differences in modifying Graves' opthalmopathy (worsening or appearance) between radioiodine treatment and ATD (RR 1.30, 95% CI 0.56 to 3.00) were observed. No trial evaluated mortality, health related quality of life, economic outcomes or compliance with treatments. The limited results in Chinese suggest that a gland specific lower dosage of radioiodine treatment is potentially effective for pediatric GD, but a significant higher incidence of hypothyroidism compared with ATD was observed. However, we could not identify a well-designed trial to provide strong evidence for radioiodine in the treatment of pediatric GD. High-quality randomised controlled clinical trials are needed to guide treatment choice. Output:

Two relevant trials with 167 patients were identified. The limited data suggest that a gland specific lower dosage of radioiodine treatment is potentially effective for pediatric GD, but a significant higher incidence of hypothyroidism compared with ATD was observed. However, all of the analysed studies were of low quality. No trial evaluated mortality, health related quality of life, economic outcomes or compliance with treatments.

CochranePLS1292

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Six studies compared optimal self-management allowing self-adjustment of medications according to an individualised written action plan to adjustment of medications by a doctor. These two styles of asthma management gave equivalent effects for hospitalisation, emergency room (ER) visits, unscheduled doctor visits and nocturnal asthma. Self-management using a written action plan based on peak expiratory flow (PEF) was found to be equivalent to self-management using a symptoms based written action plan in the six studies which compared these interventions. Three studies compared self-management options. In one, that provided optimal therapy but tested the omission of regular review, the latter was associated with more health centre visits and sickness days. In another, comparing high and low intensity education, the latter was associated with more unscheduled doctor visits. In a third, no difference in health care utilisation or lung function was reported between verbal instruction and written action plans. Optimal self-management allowing for optimisation of asthma control by adjustment of medications may be conducted by either self-adjustment with the aid of a written action plan or by regular medical review. Individualised written action plans based on PEF are equivalent to action plans based on symptoms. Reducing the intensity of self-management education or level of clinical review may reduce its effectiveness. Output:

Guidelines for the treatment of asthma recommend that patients be educated about their condition, obtain regular medical review, monitor their condition at home with either peak flow or symptoms and use a written action plan. This is known to improve health outcomes when compared to usual medical care. A number of variations on optimal self-management have now been described. This review examines the efficacy of some of these options. The results showed that self-adjustment of medications according to a written action plan gave a similar improvement in health outcomes to adjustment of medications by a doctor. Either symptom diaries or peak expiratory flow monitoring may be used for monitoring asthma and reducing the intensity of the education appears to dilute the effect.

CochranePLS1293

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Thirteen studies from six countries covering over 33,400 children and adults in rural, urban, and school settings met the review's inclusion criteria. In all studies the intervention was allocated at the community level. While the studies reported a wide range of effects, 11 of the 13 studies found the intervention was protective against diarrhoea. Differences in study populations and settings, in baseline sanitation levels, water, and hygiene practices, in types of interventions, study methodologies, compliance and coverage levels, and in case definitions and outcome surveillance limit the comparability of results of the studies included in this review. The validity of most individual study results are further compromised by the non-random allocation of the intervention among study clusters, an insufficient number of clusters, the lack of adjustment for clustering, unclear loss to follow-up, potential for reporting bias and other methodological shortcomings. This review provides some evidence that interventions to improve excreta disposal are effective in preventing diarrhoeal disease. However, this conclusion is based primarily on the consistency of the evidence of beneficial effects. The quality of the evidence is generally poor and does not allow for quantification of any such effect. The wide range of estimates of the effects of the intervention may be due to clinical and methodological heterogeneity among the studies, as well as to other important differences, including exposure levels, types of interventions, and different degrees of observer and respondent bias. Rigorous studies in multiple settings are needed to clarify the potential effectiveness of excreta disposal on diarrhoea. Output:

This review examined trials of interventions to improve the safe disposal of human faeces to prevent diarrhoea. In low-income settings, among the estimated 2.6 billion people who lack basic sanitation, this mainly consists of introducing or expanding the number and use of latrines and other facilities to contain or dispose of faeces. We identified 13 studies of such interventions involving more than 33,400 people in six countries. These trials provide some evidence that excreta disposal interventions are effective in preventing diarrhoeal diseases. However, major differences among the studies, including the conditions in which they were conducted and the types of interventions deployed, as well as methodological deficiencies in the studies themselves, makes it impossible to estimate with precision the protective effective of sanitation against diarrhoea. Further research, including randomized controlled trials, is necessary to understand the full impact of these interventions.

CochranePLS1294

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: Nine randomised trials studied 2119 women receiving primary treatment for ovarian cancer. We considered six trials to be of high quality. Women were less likely to die if they received an IP component to chemotherapy (eight studies, 2026 women; HR = 0.81; 95% confidence interval (CI): 0.72 to 0.90). Intraperitoneal component chemotherapy prolonged the disease-free interval (five studies, 1311 women; HR = 0.78; 95% CI: 0.70 to 0.86). There was greater serious toxicity with regard to gastrointestinal effects, pain, fever and infection but less ototoxicity with the IP than the IV route. Intraperitoneal chemotherapy increases overall survival and progression-free survival from advanced ovarian cancer. The results of this meta-analysis provide the most reliable estimates of the relative survival benefits of IP over IV therapy and should be used as part of the decision making process. However, the potential for catheter related complications and toxicity needs to be considered when deciding on the most appropriate treatment for each individual woman. The optimal dose, timing and mechanism of administration cannot be addressed from this meta-analysis. This needs to be addressed in the next phase of clinical trials. Output:

This review compared the effectiveness of IV chemotherapy to chemotherapy administered directly into the peritoneal cavity (intraperitoneal, or IP). The evidence suggests an improvement in survival if some of the chemotherapy is administered via the intraperitoneal route. The disadvantage is an increase in adverse effects principally relating to the presence of a peritoneal catheter, including pain, catheter blockage, gastrointestinal effects and infection.

CochranePLS1295

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included 11 studies (2635 women) in the review. Six trials compared carbetocin with oxytocin; four of these were conducted for women undergoing caesarean deliveries, one was for women following vaginal deliveries and one did not state the mode of delivery clearly. The carbetocin was administered as 100 µg intravenous dosage across the trials, while oxytocin was administered intravenously but at varied dosages. Four trials compared intramuscular carbetocin and intramuscular syntometrine for women undergoing vaginal deliveries. Three of the trials were on women with no risk factor for PPH, while one trial was on women with risk factors for PPH. One trial compared the use of intravenous carbetocin with placebo. Use of carbetocin resulted in a statistically significant reduction in the need for therapeutic uterotonics (risk ratio (RR) 0.62; 95% confidence interval (CI) 0.44 to 0.88; four trials, 1173 women) compared to oxytocin for those who underwent caesarean section, but not for vaginal delivery. Compared to oxytocin, carbetocin was associated with a reduced need for uterine massage following both caesarean delivery (RR 0.54; 95% CI 0.37 to 0.79; two trials, 739 women) and vaginal delivery (RR 0.70; 95% CI 0.51 to 0.94; one trial, 160 women). There were no statistically significant differences between carbetocin and oxytocin in terms of risk of any PPH (blood loss greater than 500 ml) or in risk of severe PPH (blood loss greater than 1000 ml). Comparison between carbetocin and syntometrine showed a lower mean blood loss in women who received carbetocin compared to syntometrine (mean difference (MD) -48.84 ml; 95% CI -94.82 to -2.85; four trials, 1030 women). There was no statistically significant difference in terms of the need for therapeutic uterotonic agents, but the risk of adverse effects such as nausea and vomiting were significantly lower in the carbetocin group: nausea (RR 0.24; 95% CI 0.15 to 0.40; four trials, 1030 women); vomiting (RR 0.21; 95% CI 0.11 to 0.39; four trials, 1030 women). The incidence of postpartum hypertension was also significantly lower in women who received carbetocin compared to those who received syntometrine. Cost-effectiveness of carbetocin was investigated by one study published as an abstract, with limited data. For women who undergo caesarean section, carbetocin resulted in a statistically significant reduction in the need for therapeutic uterotonics compared to oxytocin, but there is no difference in the incidence of postpartum haemorrhage. Carbetocin is associated with less blood loss compared to syntometrine in the prevention of PPH for women who have vaginal deliveries and is associated with significantly fewer adverse effects. Further research is needed to analyse the cost-effectiveness of carbetocin as a uterotonic agent. Output:

This review includes 11 randomised controlled trials involving 2635 women. The trials compared carbetocin against either oxytocin or syntometrine given after delivery, vaginally or by caesarean section. The comparison between intramuscular carbetocin and oxytocin showed that there was no difference in the risk of heavy bleeding, but that women who received carbetocin were less likely to require other medications to produce uterine contractions following caesarean sections. Comparisons between carbetocin and syntometrine showed that women who received carbetocin had less blood loss compared to women who received syntometrine after vaginal delivery, and were much less likely to experience side effects such as nausea and vomiting. The incidence of hypertension at 30 and 60 minutes post delivery was also significantly lower in women who received carbetocin compared to those who received syntometrine. Five of the 11 studies were known to be supported by a pharmaceutical company.

CochranePLS1296

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included three trials with 381 participants. We were unable to pool the data from the included studies due to the differences in interventions used; therefore we synthesised the trial findings narratively. Two trials were conducted in the USA and one was undertaken in Israel. All trials included participants who were admitted to hospital with myocardial infarction (MI), and one trial also included participants who had undergone coronary artery bypass grafting. All trials followed up participants for a minimum of three months post-intervention; the longest follow-up timepoint was five months. One trial (N = 92) tested an intensive (total five hours) psychotherapeutic sexual counselling intervention delivered by a sexual therapist. One trial (N = 115) used a 15-minute educational video plus written material on resuming sexual activity following a MI. One trial (N = 174) tested the addition of a component that focused on resumption of sexual activity following a MI within a hospital cardiac rehabilitation programme. The quality of the evidence for all outcomes was very low. None of the included studies reported any outcomes from partners. Two trials reported sexual function. One trial compared intervention and control groups on 12 separate sexual function subscales and used a repeated measures analysis of variance (ANOVA) test. They reported statistically significant differences in favour of the intervention. One trial compared intervention and control groups using a repeated measures analysis of covariance (ANCOVA), and concluded: "There were no significant differences between the two groups [for sexual function] at any of the time points". Two trials reported sexual satisfaction. In one trial, the authors compared sexual satisfaction between intervention and control and used a repeated measured ANOVA; they reported "differences were reported in favour of the intervention". One trial compared intervention and control with a repeated measures ANCOVA and reported: "There were no significant differences between the two groups [for sexual satisfaction] at any of the timepoints". All three included trials reported the number of patients returning to sexual activity following MI. One trial found some evidence of an effect of sexual counselling on reported rate of return to sexual activity (yes/no) at four months after completion of the intervention (relative risk (RR) 1.71, 95% confidence interval (CI) 1.26 to 2.32; one trial, 92 participants, very low quality of evidence). Two trials found no evidence of an effect of sexual counselling on rate of return to sexual activity at 12 week (RR 1.01, 95% CI 0.94 to 1.09; one trial, 127 participants, very low quality of evidence) and three month follow-up (RR 0.98, 95% CI 0.88 to 1.10; one trial, 115 participants, very low quality of evidence). Two trials reported psychological well-being. In one trial, no scores were reported, but the trial authors stated: "No treatment effects were observed on state anxiety as measured in three points in time". In the other trial no scores were reported but, based on results of a repeated measures ANCOVA to compare intervention and control groups, the trial authors stated: "The experimental group had significantly greater anxiety at one month post MI". They also reported: "There were no significant differences between the two groups [for anxiety] at any other time points". One trial reporting relationship satisfaction and one trial reporting quality of life found no differences between intervention and control. No trial reported on satisfaction in how sexual issues were addressed in cardiac rehabilitation services. We found no high quality evidence to support the effectiveness of sexual counselling for sexual problems in patients with cardiovascular disease. There is a clear need for robust, methodologically rigorous, adequately powered RCTs to test the effectiveness of sexual counselling interventions for people with cardiovascular disease and their partners. Output:

We searched the international literature up to March 2015 for studies that compared any intervention designed to address and counsel people with heart disease in relation to sexual problems with usual care. Three randomised controlled trials (clinical trials where people are allocated at random to one of two or more treatments) that included 381 participants in total met our inclusion criteria. The interventions tested in these studies were quite different from each other. All studies included people who had been admitted to hospital with a heart attack. These studies do not provide strong evidence that sexual counselling can improve sexual outcomes for people with heart disease or their partners. One study, which reported the effects of an intensive intervention, involved five hours of sexual counselling provided by a psychotherapist. It reported improved sexual functioning and satisfaction, and reduced length of time taken for people to return to sexual activity following a cardiac event, in people that received the intervention compared to usual care. The other two studies reported no differences between people that received the intervention and usual care on these outcomes (both studies measured rate of return to sexual activity following a cardiac event; one of these two studies measured sexual functioning and satisfaction). There was no evidence that sexual counselling has an effect on quality of life (measured in one study) or marital satisfaction (measured in one study). One study found that patients who received a 15-minute sexual counselling educational video plus written material had higher levels of anxiety than usual care, as well as better knowledge about sex after a heart attack, one month after their cardiac event, but not at any other timepoints. The evidence was of very low quality. We judged the included studies to be at high risk of bias and study results were poorly reported. Bearing this in mind, the results of this review should be interpreted with caution.

CochranePLS1297

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: 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. Output:

All participants in these RCTs received a drug aimed at suppressing the immune response (cyclosporine or tacrolimus). The study by Perkins and coworkers was funded by public and industry sources. The study by Kiehl and coworkers was funded by public sources. The funding source for the study by Bolwell and coworkers was not specified. 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. None of the included studies reported any data related to quality of life. 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. The overall quality of evidence was low.

CochranePLS1298

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: 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. Output:

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.

CochranePLS1299

***TASK*** the task is to simplify the input abstract of a biomedical literature ***INPUT*** the input is the abstract of a biomedical literature ***OUTPUT*** the output is the simplified abstract for the input abstract of a biomedical literature ***DOCUMENTATION*** ***EXAMPLES*** Input: We included seven RCTs (667 women) in this updated review. Most studies were at a low or moderate risk of bias and all compared methotrexate with actinomycin D. Three studies compared weekly intramuscular (IM) methotrexate with bi-weekly pulsed intravenous (IV) actinomycin D (393 women), one study compared five-day IM methotrexate with bi-weekly pulsed IV actinomycin D (75 women), one study compared eight-day IM methotrexate-folinic acid (MTX-FA) with five-day IV actinomycin D (49 women), and one study compared eight-day IM MTX-FA with bi-weekly pulsed IV actinomycin D. One study contributed no data. Moderate-certainty evidence indicates that actinomycin D is probably more likely to lead to primary cure than methotrexate (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.57 to 0.75; six trials, 577 participants; I2 = 26%), and first-line methotrexate treatment is probably more likely to fail than actinomycin D treatment (RR 3.55, 95% CI 1.81 to 6.95; six trials, 577 participants; I2 = 61%; moderate-certainty evidence) Low-certainty evidence suggests that there may be little or no difference between methotrexate and actinomycin D treatment with respect to nausea (four studies, 466 women; RR 0.61, 95% CI 0.29 to 1.26) or any of the other individual side-effects reported, although data for all of these outcomes were insufficient and too inconsistent to be conclusive. Low-certainty evidence suggests that there may be little or no difference in the risk of severe adverse events (SAEs) between the groups overall (five studies, 515 women; RR 0.35, 95% CI 0.08 to 1.66; I² = 60%); however, the direction of effect favours methotrexate and more evidence is needed. Furthermore, evidence from subgroup analyses suggests that actinomycin D may be associated with a greater risk of SAEs than methotrexate (low-certainty evidence). We found no evidence on the effect of these treatments on future fertility. Actinomycin D is probably more likely to achieve a primary cure in women with low-risk GTN, and less likely to result in treatment failure, than a methotrexate regimen. There may be little or no difference between the pulsed actinomycin D regimen and the methotrexate regimen with regard to side-effects. However, actinomycin D may be associated with a greater risk of severe adverse events (SAEs) than a methotrexate regimen. Higher-certainty evidence is still needed on treating low-risk GTN and the four ongoing trials are likely to make a significant contribution to this field. Given the variety of treatment regimens, findings from these trials could facilitate a network meta-analysis in the next version of this review to help women and clinicians determine the best treatment options for low-risk GTN. Output:

This is an updated version of a review that was first published in 2009. Since undertaking this review, we have searched the literature three times (2008, 2012 and 2016), and have identified seven completed randomised controlled trials (RCTs) and four ongoing trials. The completed trials compared three different treatment methotrexate regimens with two different actinomycin D regimens that differed by drug dose and dosing frequency. We assessed these trials as being at low to moderate risk of bias. We extracted and pooled data where possible, grouping the studies according to the treatments compared in the studies. What did we find? Overall, and for each treatment regimen compared, the review evidence shows that actinomycin D is probably more likely to achieve a cure in the first instance than methotrexate, and less likely to fail. Side-effects were reported to be relatively mild with either treatment and the most commonly experienced side-effects among women in the studies were nausea, fatigue and anaemia. However, the evidence on side-effects and serious adverse events is uncertain. Low-certainty evidence suggests that severe adverse events may be more common with actinomycin D, particularly with the five-day regimen. Conclusions Actinomycin D is probably a more effective treatment than methotrexate but the evidence on side-effects and severe adverse effects is uncertain and more evidence is needed. More evidence is also needed on the effects of these treatments on future fertility. Four RCTs comparing methotrexate and actinomycin D regimen are currently underway and these will make an important contribution to this field.