GEM/cochrane-simplification huggingface dataset:
Abstract: Information was available from 39 Cochrane reviews for 41 different analgesics or analgesic combinations (51 drug/dose/formulations) tested in single oral doses in participants with moderate or severe postoperative pain. This involved around 350 unique studies involving about 35,000 participants. Most studies involved younger participants with pain following removal of molar teeth. For most nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol, and combinations not containing opioids, there were few examples where participants experienced significantly more or fewer adverse events than with placebo. For aspirin 1000 mg and diflunisal 1000 mg, opioids, or fixed-dose combination drugs containing opioids, participants typically experienced significantly more adverse events than with placebo. Studies of combinations of ibuprofen and paracetamol reported significantly fewer adverse events. Serious adverse events were rare, occurring a rate of about 1 in 3200 participants. Most reviews did not report specific adverse events. Despite ongoing problems with the measurement, recording, and reporting of adverse events in clinical trials and in systematic reviews, the large amount of information available for single oral doses of analgesics provides evidence that adverse events rates are generally similar with active drug and placebo in these circumstances, except at higher doses of some drugs, and in combinations including opioids.

Plain-language summary: In this overview, we used information from about 35,000 participants in about 350 studies to look specifically at the adverse events (unwanted effects) experienced with painkillers, and compared the results with those for placebo (dummy pill). Measuring adverse events is complicated because the particular method used to collect information influences how many adverse events are reported. Most people in the studies had wisdom teeth removed, were relatively young and fit, and were likely to take occasional painkillers. Adverse events may be different in people who are less well, older, or who take painkillers for several days or longer. The results we have showed that for most nonsteroidal anti-inflammatory drugs (painkillers like aspirin, ibuprofen, or diclofenac), paracetamol, and combinations of different painkillers that do not contain opioids (drugs like codeine), adverse events happened to the same proportion of people with painkillers and placebo. With aspirin 1000 mg, opioids, or fixed dose combinations containing opioids, people typically experienced significantly more adverse events than with placebo. A combination of ibuprofen and paracetamol resulted in significantly fewer adverse events than placebo. Serious adverse events were rare, occurring a rate of about 1 in 3200 people. The results are not unexpected for single dose studies, which are likely to be different from the situation when analgesics are taken over the medium or longer term.
Abstract: Nineteen trials providing outcome data for 1597 young to middle-aged adults were included. Many trials were at high risk of bias reflecting inadequate methods of randomization, lack of blinding and incomplete assessment of outcome. Pooled data for primary outcomes, reported in a minority of trials, showed no statistically significant differences between the two graft choices for functional assessment (single leg hop test), return to activity, Tegner and Lysholm scores, and subjective measures of outcome. There were also no differences found between the two interventions for re-rupture or International Knee Documentation Committee scores. There were inadequate long-term results, such as to assess the development of osteoarthritis. All tests (instrumental, Lachman, pivot shift) for static stability consistently showed that PT reconstruction resulted in a more statically stable knee compared with HT reconstruction. Conversely, patients experienced more anterior knee problems, especially with kneeling, after PT reconstruction. PT reconstructions resulted in a statistically significant loss of extension range of motion and a trend towards loss of knee extension strength. HT reconstructions demonstrated a trend towards loss of flexion range of motion and a statistically significant loss of knee flexion strength. The clinical importance of the above range of motion losses is unclear. There is insufficient evidence to draw conclusions on differences between the two grafts for long-term functional outcome. While PT reconstructions are more likely to result in statically stable knees, they are also associated with more anterior knee problems.

Plain-language summary: This review included 19 studies reporting the outcomes of ACL reconstruction with patellar tendon versus hamstring tendon grafts in a total of 1597 young to middle-aged adults. Many trials used flawed methods that might have affected their results. The limited data available for functional outcomes including patient-rated assessment did not show whether one graft was better than the other. Similarly, there were no differences found between the two types of graft for re-rupture or in the results of an internationally used knee score. All tests for knee stability favoured patellar tendon grafts. Conversely, people had more anterior knee pain and discomfort with kneeling after patellar tendon reconstruction. After patellar tendon reconstruction, more people had some loss in their ability to straighten out their leg at the knee. In contrast, more people had some loss in their ability to bend their leg at the knee after hamstring tendon reconstruction. It is not clear how important these losses in range of motion of the knee were to the patients themselves. The review concluded that the current evidence was insufficient to recommend which of the two types of graft was better for ACL reconstruction.
Abstract: Only one randomised placebo-controlled, double-blind cross-over study met our selection criteria. In this study, 20 participants with motor tics were enrolled over a three-year recruitment period; 18 (14 of whom had a diagnosis of Tourette’s syndrome) completed the study; in total, 21 focal motor tics were treated. Although we considered most bias domains to be at low risk of bias, the study recruited a small number of participants with relatively mild tics and provided limited data for our key outcomes. The effects of botulinum toxin injections on tic frequency, measured by videotape or rated subjectively, and on premonitory urge, are uncertain (very low-quality evidence). The quality of evidence for adverse events following botulinum toxin was very low. Nine people had muscle weakness following the injection, which could have led to unblinding of treatment group assignment. No data were available to evaluate whether botulinum injections led to immunoresistance to botulinum. We are uncertain about botulinum toxin effects in the treatment of focal motor and phonic tics in select cases, as we assessed the quality of the evidence as very low. Additional randomised controlled studies are needed to demonstrate the benefits and harms of botulinum toxin therapy for the treatment of motor and phonic tics in patients with Tourette’s syndrome.

Plain-language summary: The review authors summarised information from one clinical trial that compared botulinum toxin to a placebo, to treat tics in adults with Tourette’s syndrome. We found one small study. The study was limited by the number of participants (N = 18), who mainly had mild tics. We are very uncertain about the effects of botulinum toxin injections on reducing tic frequency and severity, and measures of overall well-being. Some participants experienced harms, which included weakness, restlessness, and neck discomfort following the injection. We do not know from the study whether participants who received the injection developed resistance to the botulinum injections, which would make them less effective over time. The evidence is current to 25 October 2017.
Abstract: One new included study as well as further participants to a study already included was added to this update involving a further 39 participants. There were a total of three studies included involving 162 participants for this update. For this review two RCTs were included investigating secondary lymphoedema in 60 women after breast cancer surgery and 20 men and women after head and neck cancer surgery. One ongoing trial with preliminary results of 82 participants was also identified studying radiotherapy induced diarrhoea as a secondary outcome. All studies had considerable drawbacks with regards to quality and reporting. One study on secondary lymphoedema reported a decreased number of recurrent erysipela infections in the selenium supplementation group compared to placebo. The second study reported a decreased facial swelling in the selenium group in a two-week period following surgical tumour resection. However, results must be interpreted with caution and cannot be generalised to other populations. The ongoing trial on radiotherapy associated diarrhoea preliminarily reported a lower incidence of diarrhoea in participants receiving selenium supplementation concomitant to pelvic radiation, however, no data were presented. We must await publication of final results to discuss these findings in detail. No RCTs were found studying the effect of selenium supplementation on other therapy-associated toxicities or quality of life/performance status in cancer patients. There is insufficient evidence at present that selenium supplementation alleviates the side effects of tumour specific chemotherapy or radiotherapy treatments or that it improves the after-effects of surgery, or improves quality-of-life in cancer patients or reduces secondary lymphoedema. To date, research findings do not provide a basis for any recommendation in favour or against selenium supplementation in cancer patients. Potential hazards of supplementing a trace mineral should be kept in mind. Since the last version of this review, the one new additional study has not provided information to change the conclusions of the original review.

Plain-language summary: This systematic review looked at studies providing selenium supplements to cancer patients and found no clear evidence that selenium supplements improve side effects of cancer therapy. No adverse effects were reported in the studies, but evidence of overdosing, all be it unintentional and selenium intoxication has occurred in several selenium users. More research is needed to find out which doses of selenium supplements can be reasonably used by cancer patients and whether selenium supplements can affect the side effects of cancer therapy.
Abstract: Seven studies including 494 participants formed the evidence base for this review. Drug treatments assessed in studies in the review included cholinergic agents, alpha-blockers, sedatives and prostaglandin on their own or in combinations. No statistically significant associations were reported between successful treatment or any other outcome and cholinergic agents, alpha-blockers and sedatives as monotherapies. A statistically significant association between intravesically administered prostaglandin and successful voiding was detected, Risk Ratio 3.07 (95% CI 1.22 to 7.72). A statistically significant association was detected between cholinergic agents combined with sedative and an improved likelihood of spontaneous voiding compared with placebo, Risk Ratio 1.39 (95% CI 1.07 to 1.82). Significant heterogeneity was identified between the two studies in this analysis, however. Whilst it may appear that cholinergic agents and intravesically administered prostaglandin offer most promise in the treatment of post-operative urinary retention, the evidence is weak. There is a need for further research into pharmacological alternatives to catheterisation in the treatment of this common surgical complication.

Plain-language summary: This review looked for studies that had considered the effectiveness of drugs used to help patients to empty their bladder after surgery. Few studies were found. There is some evidence that introducing an agent called prostaglandin into the bladder can help patients to regain the ability to empty their bladders. There is weaker evidence that drugs called cholinergics, combined with a sedative, can also help. There is a need for more research in this area.
Abstract: Two Chinese RCTs involving 158 women were included in this review. Although both these trials described adequate methodology they were of limited quality. Neither trial compared CHM with placebo treatment. There was no evidence of a significant difference in rates of symptomatic relief between CHM and gestrinone administered subsequent to laparoscopic surgery (RR 1.04, 95% CI 0.91 to 1.18). There was no significant difference between the CHM and gestrinone groups with regard to the total pregnancy rate (69.6% versus 59.1%; RR 1.18, 95% CI 0.87 to 1.59, one RCT). CHM administered orally and then in conjunction with a herbal enema resulted in a greater proportion of women obtaining symptomatic relief than with danazol (RR 5.06, 95% CI 1.28 to 20.05; RR 5.63, 95% CI 1.47 to 21.54, respectively). Oral plus enema administration of CHM resulted in a greater reduction in average dysmenorrhoea pain scores than did danazol (mean difference (MD) -2.90, 95% CI -4.55 to -1.25).  For lumbosacral pain, rectal discomfort, or vaginal nodules tenderness, there was no significant difference between CHM and danazol. Overall, 100% of women in both studies showed some improvement in their symptoms. Women taking CHM had fewer side effects than those taking either gestrinone or danazol. Post-surgical administration of CHM may have comparable benefits to gestrinone. Oral CHM may have a better overall treatment effect than danazol and it may be more effective in relieving dysmenorrhoea when used in conjunction with a CHM enema. CHM appears to have fewer side effects than either gestrinone or danazol. However, more rigorous research is required to accurately assess the potential role of CHM in treating endometriosis.

Plain-language summary: The two small studies in this review suggest that Chinese herbal medicine (CHM) may be as effective as gestrinone and may be more effective than danazol in relieving endometriosis-related pain, with fewer side effects than experienced with conventional treatment. However, the two trials included in this review were small and of limited quality so these findings must be interpreted cautiously. Better quality randomised controlled trials are needed to investigate a possible role for CHM in the treatment of endometriosis.
Abstract: Twenty-three trials (1459 patients) fulfilled the selection criteria for this review. NSAIDs reduced creatinine clearance by 16 mL/min (95% CI 5 to 28) and potassium output by 38 mmol/day (95% CI 19 to 56) on the first day after surgery compared to placebo. There was no significant difference in serum creatinine on the first day (0 μmol/L, 95% CI -3 to 4) compared to placebo. No significant reduction in urine volume during the early postoperative period was found. There was no significant difference in serum creatinine in the early postoperative period between patients receiving diclofenac, ketorolac, indomethacin, ketoprofen or etodolac. No cases of postoperative renal failure requiring dialysis were described. The trials were not heterogeneous for the primary outcome. NSAIDs caused a clinically unimportant transient reduction in renal function in the early postoperative period in patients with normal preoperative renal function. NSAIDs should not be withheld from adults with normal preoperative renal function because of concerns about postoperative renal impairment.

Plain-language summary: The review of trials found that NSAIDs can cause small, temporary negative effects on the kidneys in adults, but no one in the trials experienced renal failure or serious kidney problems. These results may not apply to children or adults with decreased kidney function
Abstract: We identified five randomised clinical trials with 290 patients. All trials were considered to have high risk of bias. Patients in the experimental group received compound phyllanthus for three months to 12 months. Patients in the antiviral drug group received lamivudine, interferon alpha, thymosin, or thymosin alpha 1. None of the trials reported mortality, hepatitis B-related morbidity, quality of life, or liver histology. Phyllanthus seemed to have a superior effect on clearance of serum HBeAg at the end of treatment in conventional meta-analysis (RR 0.76; 95% CI 0.64 to 0.91, P = 0.002; I2 = 0%), but not when trial sequential analysis was applied. Phyllanthus had no significant effect on clearance of serum HBsAg (RR 1.00; 95% CI 0.93 to 1.08, P = 0.92; I2 = 0%) or HBV DNA (RR 0.83; 95% CI 0.53 to 1.31, P = 0.43; I2 = 70%) when compared with antiviral drugs. Data on HBeAg seroconversion was reported in one trial and no significant difference was found comparing phyllanthus versus lamivudine (RR 0.89; 95% CI 0.71 to 1.11). No data were reported on adverse events in the five trials. There is currently insufficient evidence to support or refute the use of phyllanthus for patients with chronic hepatitis B virus infection. Researchers who are interested in conducting further randomised clinical trials on phyllanthus ought to monitor both beneficial and harmful effects and should primarily test the herb against placebo in addition to antiviral drugs that are known to offer more benefit than harm. Only in this way new interventions can be assessed without compromising personal ethical considerations.

Plain-language summary: The findings of this review are based on five randomised clinical trials with 290 patients. Phyllanthus was tested versus antiviral drugs, including lamivudine, interferon alpha, thymosin, or thymosin alpha 1 for three months to 12 months. The primary findings of this review are that phyllanthus seemed to have a superior effect on clearance of serum HBeAg at the end of treatment in conventional meta-analysis, but not when trial sequential analysis was applied. Phyllanthus had no significant effect on clearance of serum HBsAg, serum HBV DNA, or HBeAg seroconversion when compared with antiviral drugs. No data were identified on mortality or morbidity, adverse events, quality of life, or liver histology. However, the findings in our review are inconclusive due to the small numbers of patients and outcomes, risk of bias, and the study design. We need more randomised trials to confirm or reject the potential effects of phyllanthus. We advocate that phyllanthus is primarily assessed against placebo. This can be done in randomised clinical trials in which all patients receive antiviral drugs that are known to offer more benefit than harm and the patients are then randomised to phyllanthus versus placebo. If the effect of phyllanthus versus placebo is unequivocally demonstrated in such trials, it may be prudent to assess the effects of phyllanthus versus other antiviral drugs superior to placebo in such trials. The quality of trials regarding conduct and report should also be taken into account.
Abstract: Six studies (477 participants) were included in the review. All participants were adult kidney transplant recipients and 70% of participants underwent live-donor kidney transplantation. The overall risk of bias was low for selection bias and unclear for remaining domains. There was no difference in the risk of delayed graft function (3 studies, 298 participants: RR 1.03, 95% CI 0.62 to 1.70) or hyperkalaemia (2 studies, 199 participants: RR 0.48, 95% CI 0.04 to 6.10) for participants who received balanced electrolyte solutions compared to normal saline. Intraoperative balanced electrolyte solutions compared to normal saline were associated with higher blood pH (3 studies, 193 participants: MD 0.07, 95% CI 0.05 to 0.09), higher serum bicarbonate (3 studies, 215 participants: MD 3.02 mEq/L, 95% CI 2.00 to 4.05) and lower serum chloride (3 studies, 215 participants: MD -9.93 mmol/L, 95% CI -19.96 to 0.11). There were four cases of graft loss in the normal saline group and one in the balanced electrolyte solution group, and four cases of acute rejection in the normal saline group compared to two cases in the balanced electrolyte solution group. Balanced electrolyte solutions are associated with less hyperchloraemic metabolic acidosis compared to normal saline, however it remains uncertain whether lower-chloride solutions lead to improved graft outcomes compared to normal saline.

Plain-language summary: We found six studies that included 477 kidney transplant patients. The majority of these patients had a kidney transplant from a living donor. The overall quality of the studies was low to average, and the main problem was the small number of studies and the small size of the studies. There was no information on funding source for most of the studies. Compared to normal saline, giving kidney transplant patients solutions that contain less chloride during their transplant operation resulted in lower blood acid levels but did not affect how the transplant kidney worked after surgery, or the number of patients who had high blood potassium levels. Harmful effects were not reported in many studies. In the group of patients who were given lower-chloride fluids, the transplant failed in one patient and one patient rejected the transplant. In the group of patients who were given normal saline, the transplant failed in four patients, and two patients rejected the transplant. However, this is probably an incomplete picture of harmful effects.
Abstract: Nine studies in dental, orthopedic and gynaecological surgery met the inclusion criteria, testing doses of diflunisal from 125 mg to 1000 mg. For diflunisal 1000 mg, the NNT for at least 50% pain relief over 4 to 6 hours was 2.1 (1.8 to 2.6) (6 studies, 391 participants); the NNT to prevent remedication within 6 hours was 1.9 (1.7 to 2.3), and within 12 hours was 2.2 (1.9 to 2.7) (6 studies, 409 participants). More participants experienced adverse events with diflunisal 100 mg than with placebo, but none were serious or led to withdrawal. For diflunisal 500 mg, the NNT for at least 50% pain relief over 4 to 6 hours was 2.6 (2.1 to 3.3) (6 studies, 357 participants); the NNT to prevent remedication within 6 hours was 2.6 (2.1 to 3.4) (6 studies, 390 participants), and within 12 hours was 2.9 (2.3 to 4.0) (5 studies, 329 participants). Adverse events did not differ significantly from placebo. Diflunisal has an analgesic effect similar to other NSAIDs in single dose, but benefits from providing significant analgesia for about twelve hours. This property may be useful when regular dosing is needed, or when taking several doses of a shorter acting analgesic is impractical.

Plain-language summary: This review assessed evidence from nine randomised, double-blind, placebo-controlled clinical trials, in which there were 906 adults in comparisons of diflunisal (a non-steroidal, anti-inflammatory drug) with placebo for treatment of moderate to severe acute post-operative pain. It is an effective analgesic over the dose range 250 mg to 1000 mg, with a long duration of action. At 1000 mg, the analgesic effect over 4 to 6 hours is as good as the combination of paracetamol 1000 mg and codeine 60 mg in similar studies using the same methods.