GEM/cochrane-simplification huggingface dataset:
Abstract: We included only one small trial (60 participants randomised) which overall was judged to be at low risk of bias. The study examined two doses of menaquinone (vitamin K2) over 3 months in healthy participants aged 40 to 65 years. The primary focus of the trial was to examine the effects of menaquinone (subtype MK7) on different matrix Gla proteins (MGP - vitamin K dependent proteins in the vessel wall) at different doses, but the authors also reported blood pressure and lipid levels. The trial did not report on our primary outcomes (cardiovascular disease clinical events) as it was small, short term and conducted in healthy participants. In terms of cardiovascular disease risk factors, no effects were seen for vitamin K2 on blood pressure or lipid levels, although the trial was small and findings are limited. The trial did not report any of our other secondary outcomes. The very limited results of this review highlight the lack of evidence currently available to determine the effectiveness of vitamin K supplementation for the primary prevention of cardiovascular disease, and demonstrate the need for further high quality trials in this area.

Plain-language summary: We searched scientific databases for randomised controlled trials (clinical trials where people are allocated at random to one of two or more treatments) looking at the effects of vitamin K supplementation in healthy adults or those at high risk of developing CVD. We did not include people who already had CVD (e.g. heart attacks and strokes). The evidence is current to September 2014. Only one small trial met our inclusion criteria. It included 60 participants aged 40 to 65 years. This study looked at the effects of vitamin K2 supplements on CVD risk factors (blood pressure and lipid levels) over three months in healthy participants. No differences in these risk factors were seen between the comparison groups, but this was a small study and the findings are limited. The trial did not look at fatal and non-fatal cardiovascular endpoints as it was small and short term. The evidence is currently extremely limited and further high-quality trials are needed so that the effectiveness of vitamin K supplementation for CVD prevention can be determined. The only trial identified for this review was judged to be at low risk of bias (so there was less chance of arriving at the wrong conclusions because of favouritism by the participants or researchers). However the evidence is limited to one small trial and no firm conclusions can be reached at this time.
Abstract: Ten trials, involving 361 participants, satisfied the inclusion criteria. All the trials were randomised; two had a parallel design while the remainder had a cross-over design. Although some individual studies reported a beneficial effect of pancreatic enzyme over placebo in improving pain, incidence of steatorrhoea and analgesic consumption, the results of the studies could not be pooled for these outcomes. With the use of pancreatic enzymes, we observed a non-significant benefit for weight loss (kg) (SMD 0.06; 95% CI -0.23 to 0.34); a significant reduction in faecal fat (g/day) (SMD -1.03; 95% CI -1.60 to -0.46) and non-significant difference in subjects' Clinical Global Impression of Disease Symptom Scale (SMD -0.63; 95% CI -1.41 to 0.14). We found no significant benefit in reducing faecal fat with any particular schedule of enzyme preparation or type of enzyme. Another small study did not show any significant benefit of timing the administration of enzyme preparations in relation to meals on faecal fat. The role of pancreatic enzymes for abdominal pain, weight loss, steatorrhoea, analgesic use and quality of life in patients with chronic pancreatitis remains equivocal. Good quality, adequately powered studies are much warranted.

Plain-language summary: This practice is based on studies which have shown the benefit of pancreatic enzymes on various outcomes such as abdominal pain, weight loss, analgesic use, fatty stools and quality of life. However, a collective conclusion about the role of pancreatic enzymes in chronic pancreatitis patients needs to be established from these studies. This systematic review aimed to collect all published and unpublished data on this subject in order to evaluate whether pancreatic enzymes have any benefit on various parameters in chronic pancreatitis, to compare different types of enzyme preparations and to evaluate whether different dosage schedules have any influence on the various outcomes. We included 10 studies in the review. These studies had enrolled small numbers of patients. Though individual studies showed benefit of varying degrees on the parameters mentioned above, we could not pool the results of these studies. With the evidence available so far, no definitive conclusion can be drawn for the benefit of pancreatic enzymes in patients with chronic pancreatitis.
Abstract: Thirty two studies were identified, of which four met the inclusion criteria. One of these had been reported in the original Cochrane review. Since then, three other studies have been reported. One large study, comparing atropine, hyoscine hydrobromide and hyoscine butylbromide, showed no difference between the treatment groups. A smaller cross-over study of octreotide and hyoscine hydrobromide also showed no difference whichever treatment was used first. A third study involving 13 participants showed a significant reduction in the sound of noisy breathing when glycopyrronium was given, in comparison to hyoscine hydrobromide, but there was no placebo control. In our original Cochrane review, we concluded that there was no evidence to show that any intervention, be it pharmacological or non-pharmacological, was superior to placebo in the treatment of noisy breathing. This conclusion has not changed. We acknowledge that in the face of heightened emotions when death is imminent, it is difficult for staff not to intervene. It is therefore likely that the current therapeutic options will continue to be used. However, patients need to be closely monitored for lack of therapeutic benefit and adverse effects while relatives need time, explanation and reassurance to relieve their fears and concerns. There remains a need for well-designed multi-centre studies with objective outcome measures which demonstrates the efficacy of intervention against placebo for this condition.

Plain-language summary: The aim of this review is to find out which treatment, if any, is best. Only four of 32 reports identified met the inclusion criteria for this review; none showed a convincing benefit of any single drug over any others. Some treatments may be worth trying but staff should watch carefully for any side effects of the treatment (e.g. agitation or excessively dry mouth). Anxious relatives need explanation, reassurance and discussion about any fears and concerns associated with the terminal phase and 'death rattle'. Research in this difficult area is necessary to understand the cause of the noise, its effect on the patient and those around them and the best ways of managing this condition.
Abstract: 74% of patients had FIGO stage IIIB LACC. Treatment outcome was significantly better for patients receiving the combined treatment (Figures 4 to 6). The pooled data analysis yielded a significantly higher complete response rate (relative risk (RR) 0.56; 95% confidence interval (CI) 0.39 to 0.79; p < 0.001), a significantly reduced local recurrence rate (hazard ratio (HR) 0.48; 95% CI 0.37 to 0.63; p < 0.001) and a significantly better overall survival (OS) following the combined treatment with RHT(HR 0.67; 95% CI 0.45 to 0.99; p = 0.05). No significant difference was observed in treatment related acute (RR 0.99; 95% CI 0.30 to 3.31; p = 0.99) or late grade 3 to 4 toxicity (RR 1.01; CI 95% 0.44 to 2.30; p = 0.96) between both treatments. The limited number of patients available for analysis, methodological flaws and a significant over-representation of patients with FIGO stage IIIB prohibit drawing definite conclusions regarding the impact of adding hyperthermia to standard radiotherapy. However, available data do suggest that the addition of hyperthermia improves local tumour control and overall survival in patients with locally advanced cervix carcinoma without affecting treatment related grade 3 to 4 acute or late toxicity.

Plain-language summary: In several clinical studies it was found that the respons of these tumours to radiotherapy was improved by adding hyperthermia. Hyperthermia is a type of cancer treatment in which body tissue is exposed to high temperatures (i.e. around 42 to 43 degrees Celcius during one hour) to damage and kill cancer cells.. This temperature is in itself able to kill tumour cells under certain conditions and also increases the lethal effect of radiation on tumour cells. can However, the results observed with this treatment were not consistent in subsequent clinical studies. Therefore we analysed the results of all clinical studies published so far comparing the treatment results of radiotherapy alone with the results of combined radiotherapy and hyperthermia in patients with locally advanced cervix carcinoma. The results do suggest a better outcome for patients treated with the combination of radiotherapy with hyperthermia. Thus following treatment a complete disappearance of the tumour was observed more regularly, regrowth of the tumour at the site of origin during follow up was observed less frequently and more patients were still alive at last follow-up. Treatment related side effects were not increased by the addition of hyperthermia to standard radiotherapy. However, the number of patients included in the clinical studies analysed is limited as the majority of patients had stage IIIB disease. The authors therefore conclude that hyperthermia may provide a clinically relevant improvement in treatment outcome for patients with locally advanced cervix carcinoma, in particular patients with stage IIIB disease. Additional clinical data are needed to warrant its use for all patients with locally advanced cervix carcinoma.
Abstract: We included four trials involving 94 participants in this review. There was a significant improvement in activity of daily living (mean difference (MD) 13.20 points on the 'Capacidad funcional' (functional capacity) subscale of the Brazilian-Portuguese version of the SF-36; 95% confidence interval (CI) 8.36 to 18.04; P < 0.00001) and on muscle strength (MD 1.01 Nm/kg; 95% CI 0.19 to 1.83; P = 0.02) but these results should be interpreted with caution because population numbers were small and the results are based on single studies. There was no significant improvement in ability to walk (MD 0.14 m/s; 95% CI -0.32 to 0.606; P = 0.55), postural balance (MD 3.05 points; 95% CI -3.41 to 9.52; P = 0.35) or fitness (MD 3.6 (VO2max; 95% CI -0.53 to 7.73; P = 0.09) after water-based exercises treatment compared to control. Adverse effects were not reported. The evidence from randomised controlled trials so far does not confirm or refute that water-based exercises after stroke might help to reduce disability after stroke. There is a lack of hard evidence for water-based exercises after stroke. Better and larger studies are therefore required.

Plain-language summary: This review of four trials, which included 94 participants, found there is not enough evidence to decide if water-based exercises may reduce disability after stroke. There is a lack of hard evidence for water-based exercises after stroke. More research is therefore needed.
Abstract: Ten randomised trials were included, involving 3944 adults with predominantly SUI, randomised to receive duloxetine or placebo and/ or PFMT. All arms in individual trials were comparable for various baseline characteristics. Treatment duration was between three weeks and 12 weeks. Duloxetine was significantly better than placebo in terms of improving patients' quality of life (weighted mean difference 5.26, 95% confidence interval 3.84 to 6.68. P less than 0.00001) and perception of improvement. Individual studies demonstrated a significant reduction in the Incontinence Episode Frequency (IEF) by approximately 50% during treatment with duloxetine. With regard to objective cure, however, meta-analysis of stress pad test and 24 hour pad weight change failed to demonstrate a benefit for duloxetine over placebo though data were relatively few. Subjective cure favoured duloxetine, albeit with a small effect size (3%). One trial suggested that duloxetine was better than pelvic floor muscle training alone in reducing IEF (P less than 0.05) based on median percentage decrease in IEF per week. Although significant side effects were commonly associated with duloxetine, they were reported as acceptable. The available evidence suggests that duloxetine treatment can significantly improve the quality of life of patients with stress urinary incontinence, but it is unclear whether or not benefits are sustainable. Adverse effects are common but not serious. About one in three participants allocated duloxetine reported adverse effects (most commonly nausea) related to treatment, and about one in eight allocated duloxetine stopped treatment as a consequence.

Plain-language summary: The trials reviewed compared duloxetine against dummy placebo tablets and also pelvic floor muscle training in women with predominantly stress urinary incontinence. Duloxetine reduced the frequency of episodes of incontinence and improved quality of life scores. However, it had little impact on the numbers cured and commonly had side effects, especially nausea. More studies comparing a serotonin and noradrenaline reuptake inhibitor with placebo and surgery are required, especially if conducted independently of pharmaceutical companies.
Abstract: Twenty-five studies met the inclusion criteria, but only 23 studies contributed data to the review. These 23 trials recruited 18,587 women, with 17,842 women included in final analyses. There were no statistically significant differences between women who received calcium supplementation and those who did not in terms of reducing preterm births less than 37 weeks' gestation (risk ratio (RR) 0.86, 95% confidence interval (CI) 0.70 to 1.05; 13 studies, 16,139 women; random-effects model) or less than 34 weeks' gestation (RR 1.04, 95% CI 0.80 to 1.36; four trials, 5669). Most studies were of low risk of bias. We conducted sensitivity analysis for the outcome of preterm birth less than 37 weeks by removing two trials with unclear risk of bias for allocation concealment; the results then favoured treatment with calcium supplementation (RR 0.80, 95% CI 0.65 to 0.99; 11 trials, 15,379 women). There was no significant difference in infant low birthweight between the two treatment groups (RR 0.93, 95% CI 0.81 to 1.07; six trials, 14,162 infants; random-effects model). However, when compared to the control group, women in the calcium supplementation group gave birth to slightly heavier birthweight infants (mean difference 56.40, 95% CI 13.55 to 99.25; 21 trials, 9202 women; random-effects model). Three outcomes were chosen for assessment with the GRADE software: preterm birth less than 37 weeks; preterm birth less than 34 weeks; and low birthweight less than 2500 g. Evidence for these outcomes was assessed as of moderate quality. This review indicates that there are no clear additional benefits to calcium supplementation in prevention of preterm birth or low infant birthweight. While there was a statistically significant difference of 56 g identified in mean infant birthweight, there was significant heterogeneity identified, and the clinical significance of this difference is uncertain.

Plain-language summary: In our review, regular intake of extra calcium tablets during pregnancy did not improve the number of preterm births or other infant outcomes, except for a slight increase in infant birthweight in the group of women who received calcium supplementation. Most studies included in this review were assessed as of low risk of bias, and evidence for specific outcomes was graded as of moderate quality, Taking calcium supplementation did not appear to have any obvious side effects. Our review included 25 randomised controlled studies, but only 23 studies involving 18,587 women contributed outcome data. The majority of the evidence was based on fewer numbers of studies.
Abstract: The search identified 813 references on MEDLINE, 418 on EMBASE, 22 on CINAHL, 666 on PubMed, 291 on PsycINFO and 145 on CENTRAL. When all references were imported into EndNote and duplications were removed, 1348 references remained. Initial screening of titles and abstracts of these references revealed that 42 references were potentially eligible for this review. After reading the full-text versions, we identified no relevant trials comparing hrHPV and cytology testing versus cytology testing alone for detecting residual or recurrent disease during follow-up to LLETZ treatment of adult women with CIN. We found no evidence on the effects of hrHPV and cytology testing on residual or recurrent CIN2 or higher lesions, anxiety and psychosexual morbidity outcomes in women undergoing colposcopy and treatment for CIN. We found no evidence from RCTs to inform decisions about the best surveillance strategy for women following treatment for CIN. A prognostic systematic review is needed to investigate the risk of developing recurrent cervical intraepithelial neoplasia 2+ (CIN2+) in women with a positive hrHPV test after large loop excision of the transformation zone (LLETZ) treatment.

Plain-language summary: We searched for randomised control trials (RCTs) that compared follow-up management strategies following LLETZ treatment for CIN. We checked 1348 titles and abstracts of potentially relevant references, but we identified no randomised controlled trials (RCTs) that met our inclusion criteria. We identified trials of interest, but they were deemed not relevant because of their focus on diagnostic outcomes and examination of how sensitive tests are, rather than on the effects of different follow-up strategies on long-term outcomes. Currently no evidence indicates whether hrHPV post-treatment testing is better or worse in terms of important long-term clinical outcomes. This review highlights the need for good quality trials in this area that do not focus solely on the diagnostic accuracy of testing. We found no evidence from RCTs to inform decisions about the best surveillance strategy following treatment for CIN. A prognostic systematic review is needed to investigate the risks and benefits of different follow-up strategies for women after LLETZ treatment.
Abstract: Ten of 31 studies identified were included (959 patients). Five studies with a low risk of bias examined azithromycin versus placebo and demonstrated consistent improvement in forced expiratory volume in one second over six months (mean difference at six months 3.97% (95% confidence interval 1.74% to 6.19%; n = 549, from four studies)). Patients treated with azithromycin were approximately twice as likely to be free of pulmonary exacerbation at six months, odds ratio 1.96 (95% confidence interval 1.15 to 3.33). With respect to secondary outcomes, there was a significant reduction in need for oral antibiotics and greater weight gain in those taking azithromycin. Adverse events were uncommon and not obviously associated with azithromycin, although a once-weekly high dose regimen was associated with more frequent gastrointestinal adverse events. Treatment with azithromycin was associated with reduced identification of Staphylococcus aureus on respiratory culture, but also a significant increase in macrolide resistance. This review provides evidence of improved respiratory function after six months of azithromycin. Data beyond six months were less clear, although reduction in pulmonary exacerbation was sustained. Treatment appeared safe over a six-month period; however, emergence of macrolide resistance was a concern. A multi-centre trial examining long-term effects of this antibiotic treatment is needed, especially for infants recognised through newborn screening.

Plain-language summary: We have included ten randomised controlled trials with a total of 959 participants in this review. Eight of these trials compared azithromycin (a macrolide antibiotic) to placebo and two compared different doses of azithromycin. Four trials in children and adults (549 participants) showed significant improvements in lung function after treatment with azithromycin compared to placebo at six months; although data from later time points are not so clear. Patients treated with azithromycin were about twice as likely to be free of pulmonary exacerbation; needed fewer oral antibiotics and had fewer instances of Staphylococcus aureus in cultures from their lungs and airways. Adverse events were not common and not obviously associated with azithromycin, although there was an increase in resistance to macrolides. Most studies used a three times a week dosing schedule. Taking a high weekly dose was linked to an increase in mild gastrointestinal adverse events. Further multicentre studies are needed to look at the long-term effects of this antibiotic treatment, especially for infants diagnosed through newborn screening.
Abstract: The updated search in June 2011 did not identify any new trials. One study is included in the review. This study assessed the effect of intraventricular gentamicin in a mixed population of neonates (69%) and older infants (31%) with gram-negative meningitis and ventriculitis. Mortality was statistically significantly higher in the group that received intraventricular gentamicin in addition to intravenous antibiotics compared to the group receiving intravenous antibiotics alone (RR 3.43; 95% CI 1.09 to 10.74; RD 0.30; 95% CI 0.08 to 0.53); NNTH 3; 95% CI 2 to 13). Duration of CSF culture positivity did not differ significantly (MD -1.20 days; 95% CI -2.67 to 0.27). In one trial that enrolled infants with gram-negative meningitis and ventriculitis, the use of intraventricular antibiotics in addition to intravenous antibiotics resulted in a three-fold increased RR for mortality compared to standard treatment with intravenous antibiotics alone. Based on this result, intraventricular antibiotics as tested in this trial should be avoided. Further trials comparing these interventions are not justified in this population.

Plain-language summary: Only one trial was identified. In this trial enrolling infants with gram-negative meningitis and ventriculitis, the use of intraventricular antibiotics in addition to intravenous antibiotics resulted in a three-fold increased risk for mortality compared to standard treatment with intravenous antibiotics alone. Based on this result, intraventricular antibiotics should be avoided. Further trials comparing these interventions are not justified in newborn infants.