GEM/cochrane-simplification huggingface dataset:
Abstract: One cluster-RCT (with 157,259 participants) and four RCTs of individuals (1917 participants) met the inclusion criteria. The cluster-RCT from the former USSR showed that, compared with no vaccine, a live-attenuated vaccine (called STI) protected against clinical anthrax whether given by a needleless device (RR 0.16; 102,737 participants, 154 clusters) or the scarification method (RR 0.25; 104,496 participants, 151 clusters). Confidence intervals were statistically significant in unadjusted calculations, but when a small amount of association within clusters was assumed, the differences were not statistically significant. The four RCTs (of individuals) of inactivated vaccines (anthrax vaccine absorbed and recombinant protective antigen) showed a dose response relationship for the anti-protective antigen IgG antibody titre. Intramuscular administration was associated with fewer injection site reactions than subcutaneous injection, and injection site reaction rates were lower when the dosage interval was longer. One cluster-RCT provides limited evidence that a live-attenuated vaccine is effective in preventing cutaneous anthrax. Vaccines based on anthrax antigens are immunogenic in most vaccinees with few adverse events or reactions. Ongoing randomized controlled trials are investigating the immunogenicity and safety of anthrax vaccines.

Plain-language summary: The authors of this review wanted to evaluate the benefits and harms of vaccines for preventing anthrax. They identified four recent smaller randomized controlled trials of individuals and an older large cluster-randomized controlled trial with over 150,000 participants. The cluster trial provided limited evidence that a vaccine, based on a strain of live anthrax organisms incapable of causing disease, was effective in preventing cutaneous anthrax. More recent types of vaccines tested in the smaller trials, also based on inactivated components of the anthrax bacterium, appear to have few adverse events and to stimulate a good immune response. Several randomized controlled trials testing these newer vaccines are currently in progress. They will provide further information on the immunogenicity and safety of different vaccine regimens to be used for people at risk of anthrax exposure.
Abstract: Our search strategies led to 699 potentially relevant references. Of these, one RCT involving 79 patients was included. We judged the quality of the trial as moderate. The study was reported as a randomised open-label study and published as a full-text article. Even though PFS was statistically significantly improved for patients treated with HD-MTX plus cytarabine (HR 0.54; 95% CI 0.31 to 0.92; P = 0.01), this did not translate to a statistical significant OS benefit (HR 0.65; 95% CI 0.38 to 1.13; P = 0.07). AEs, especially infective complications, hepatotoxicity and haematological toxicities, were assessed more often in patients undergoing HD-MTX therapy combined with cytarabine. However, there were no statistically significant differences in terms of TRM (RR 3.08; 95% CI 0.33 to 28.32; P = 0.35). Owing to the small number of included trials and patients, the findings in this review remain uncertain. In summary, the presently available evidence (one small trial) showed a benefit in terms of PFS, ORR and CRR but no statistically significant difference regarding OS for patients with PCNSL treated with HD-MTX plus cytarabine compared to HD-MTX alone. However, the risk of severe infections and toxicity was significantly higher in patients treated with combined chemotherapy. More RCTs with additional chemotherapy to HD-MTX therapy with higher numbers of patients and longer follow-up periods are needed to confirm the results of this review and determine whether the PFS benefit will translate into an OS advantage. At least the one included study shows that RCTs of moderate quality and with valuable outcomes for this malignant disease are feasible.

Plain-language summary: In this systematic review we summarised and analysed the evidence from randomised controlled trials (RCTs) on efficacy and safety of methotrexate combined with additional chemotherapy in the treatment of adult, immunocompetent PCNSL patients regarding overall survival, progression-free survival, response rate, adverse events, treatment-related mortality and quality of life. We searched several important medical databases such as CENTRAL and MEDLINE and found one RCT with 79 patients that fulfilled our inclusion criteria. As a result, this review shows that patients treated with methotrexate plus cytarabine compared to high-dose methotrexate alone have a statistically significant improvement in progression-free survival and response rate. No statistically significant difference is shown for overall survival. Adverse events, especially infections, hepatotoxicity and haematological toxicities are more common in patients undergoing therapy with methotrexate plus cytarabine, although there are no differences in terms of treatment-related mortality. Owing to the small number of included trials and patients, the findings in this review remain uncertain and more RCTs with enlarged numbers of patients and longer follow-up periods are needed. However, the one analysed study demonstrated that RCTs are feasible on patients with this rare disease and should concentrate on overall survival.
Abstract: Six randomised controlled trials met the inclusion criteria for this review. Four studies compared LED and halogen light sources. Two studies compared LED and compact fluorescent light sources. The duration of phototherapy (six studies, 630 neonates) was comparable in LED and non-LED phototherapy groups (mean difference (hours) -0.43, 95% CI -1.91 to 1.05). The rate of decline of serum total bilirubin (STB) (four studies, 511 neonates) was also similar in the two groups (mean difference (mg/dL/hour) 0.01, 95% CI -0.02 to 0.04). Treatment failure, defined as the need of additional phototherapy or exchange blood transfusion (1 study, 272 neonates), was comparable (RR 1.83, 95% CI 0.47 to 7.17). Side effects of phototherapy such as hypothermia (RR 6.41, 95% CI 0.33 to 122.97), hyperthermia (RR 0.61, 95% CI 0.18 to 2.11) and skin rash (RR 1.83, 95% CI 0.17 to 19.96) were rare and occurred with similar frequency in the two groups. LED light source phototherapy is efficacious in bringing down levels of serum total bilirubin at rates that are similar to phototherapy with conventional (compact fluorescent lamp (CFL) or halogen) light sources. Further studies are warranted for evaluating efficacy of LED phototherapy in neonates with haemolytic jaundice or in the presence of severe hyperbilirubinaemia (STB ≥ 20 mg/dL).

Plain-language summary: In this systematic review, the efficacy of LED phototherapy was compared with conventional (non-LED) phototherapy. LED phototherapy was observed to be efficacious in bringing down the levels of serum total bilirubin, at rates similar to phototherapy with conventional light sources.
Abstract: Twenty studies (1150 women) were included. Women who had caesarean section performed under regional analgesia and had wound infiltration had a decrease in morphine consumption at 24 hours (SMD -1.70mg; 95% confidence interval (CI) -2.75 to -0.94) compared to placebo. In women under general anaesthesia, with caesarean section wound infiltration and peritoneal spraying with local anaesthetic (one study, 100 participants), the need for opioid rescue was reduced (risk ratio (RR) 0.51; 95% CI 0.38 to 0.69). The numerical pain score (0 to10) within the first hour was also reduced (mean difference (MD) -1.46; 95% CI -2.60 to -0.32). Women with regional analgesia who had local anaesthetic and non-steriodal anti-inflammatory cocktail wound infiltration consumed less morphine (one study, 60 participants; MD -7.40 mg; 95% CI -9.58 to -5.22) compared to local anaesthetic control. Women who had regional analgesia with abdominal nerves blocked had decreased opioid consumption (four studies, 175 participants; MD -25.80 mg; 95% CI -50.39 to -5.37). For the outcome of visual analogue scale 0 to 10 over 24 hours, no advantage was demonstrated in the single study of 50 participants who had wound infiltrated with a mixture of local analgesia and narcotics versus local analgesia. Addition of ketamine to the local analgesia in women who had regional analgesia does not confer any advantage. Local analgesia infiltration and abdominal nerve blocks as adjuncts to regional analgesia and general anaesthesia are of benefit in caesarean section by reducing opioid consumption. Nonsteroidal anti-inflammatory drugs as an adjuvant may confer additional pain relief.

Plain-language summary: The authors identified twenty randomised controlled trials of sufficient quality involving 1150 women. These trials were carried out in both developed and developing countries. In general, local anaesthesia wound infiltration was of benefit in women having a caesarean section requiring regional anaesthetics because of a reduction in the use of opioid analgesia. Women undergoing general anaesthesia who had wound infiltration with local anaesthetics and peritoneal spraying required lower amounts of opioids in the first 24 hours post-operation compared to saline control. Those who had a general anaesthetic and the abdominal wall nerves blocked had reduced pain scores within the first 24 hours postoperative. Women who had regional anaesthesia and abdominal nerves blocked also benefited by decrease in opioid requirements. Non-steroidal anti-inflammatory drugs provided additional pain relief but with more side effects of pruritus. The commonly used local anaesthetic agents do have side effects but these are very rare, ranging from allergy to cardiovascular and central nervous system effects. There was no report of side effects in infants following local anaesthetic infiltration but the number of women studied was small. The longer theatre time and cost of the local anaesthetic may be offset by less use of postoperative analgesia. The effect on the development of chronic pelvic pain should be an important area of research.
Abstract: A total of 2061 patients from seven RCTs were included for final analysis, with 1226 patients in the TOR group and 835 patients in the TAM group. The ORR for the TOR group was 25.8% (316/1226) whereas, the ORR for the TAM group was 26.9% (225/835). The pooled risk ratio (RR) suggested that the ORRs were not statistically different between the two groups (RR 1.02, 95% confidence interval (CI) 0.88 to 1.18, P = 0.83). The median TTP was 6.1 months for the TOR group and 5.8 months for the TAM group. The median OS was 27.8 months for the TOR group and 27.6 months for the TAM group. There were no significant differences in TTP and OS between the two therapeutic groups (for TTP: HR 1.08, 95% CI 0.94 to 1.24; for OS: HR 1.02, 95% CI 0.86 to 1.20). The frequencies of most adverse events were also similar in the two groups, while headache seemed to occur less in the TOR group than in the TAM group (RR 0.14, 95% CI 0.03 to 0.74, P = 0.02). There was no significant heterogeneity between studies in most of the above meta-analyses. Sensitivity analysis did not alter the results. TOR and TAM are equally effective and the safety profile of the former is at least not worse than the latter in the first-line treatment of patients with advanced breast cancer. Thus, TOR may serve as a reasonable alternative to TAM when anti-oestrogens are applicable but TAM is not the preferred choice for some reason.

Plain-language summary: Seven eligible studies were identified, all of which provided information on response to treatment (in 2061 patients), five on progression-free survival (in 1436 patients) and four on overall survival (in 1374 patients). The trials were generally old (conducted between late 1980s and early 1990s) and were of modest quality. Based on the data from these trials, 25.8% of the patients in the TOR group responded to the treatment, compared with 26.9% in the TAM group. The cancers of 50% of the patients in the TOR group had progressed after 6.1 months, compared with 5.8 months in the TAM group. Half of the patients in the TOR group survived longer than 27.8 months, compared with 27.6 months in the TAM group. The risk for progression and death in the TOR group was not significantly different from that in the TAM group. The frequencies of most adverse events were also similar in the two groups, except that the number of headaches occurring in the TOR group was only about one-seventh of that in the TAM group. However, considering the results of other large trials, we cannot exclude the possibility that this is purely a play of chance. Due to the lack of data, no conclusions can be made as to the long-term adverse effects achieved with either treatment. The evidence from this review suggests that TOR and TAM are equally effective and the safety profile of the former is at least not worse than the latter in the first-line treatment of patients with advanced breast cancer. Thus, TOR may serve as a reasonable alternative to TAM when anti-oestrogens are applicable but TAM is not the preferred choice for some reason.
Abstract: We found two trials with 132 participants that met our inclusion criteria. One of the included trials was a quasi-randomised trial. Adjunctive corticosteroids reduced the risk of death (typical RR 0.46, 95% confidence interval (CI) 0.24 to 0.88; typical RD -0.19, 95% CI -0.33 to -0.04; NNTB = 6; two studies, 132 participants, very low-quality evidence) but did not have a significant effect on the number of infants with sensorineural deafness at two years (RR 1.80, 95% CI 0.18 to 18.21; RD 0.04, 95% CI -0.12 to 0.21; one study, 38 participants, low-quality evidence). In one trial, dexamethasone reduced the likelihood of hearing loss at four to 10 weeks post discharge (RR 0.41, 95% CI 0.17 to 0.98; RD -0.25, 95% CI -0.48 to -0.01; one study, 59 participants, low-quality evidence). Data reported on the other outcomes of interest were insufficient. Very low-quality data from two randomised controlled trials suggest that some reduction in death and hearing loss may result from use of adjunctive steroids alongside standard antibiotic therapy for treatment of patients with neonatal meningitis. Benefit is not yet seen with regards to reduction in neurological sequelae. Researchers who wish to clarify these findings must conduct more robustly designed trials with greater numbers of participants, evaluating more relevant outcomes and providing adequate follow-up.

Plain-language summary: We identified two studies for inclusion. We found that giving steroids to babies affected with meningitis may reduce the number of children who would die or become deaf from the disease. However, most of this benefit was observed in only one trial. As of now, it appears as though steroids are not helpful with regard to preventing developmental delay. We are not able to make far reaching conclusions at this time, as the evidence that we found is limited and of low quality and could change if more results from larger and better designed studies become available.
Abstract: Nineteen longitudinal studies that followed up a total of over 29,000 baseline nonsmokers met inclusion criteria. The studies measured exposure or receptivity to advertising and promotion in a variety of ways, including having a favourite advertisement or an index of receptivity based on awareness of advertising and ownership of a promotional item. One study measured the number of tobacco advertisements in magazines read by participants. All studies assessed smoking behaviour change in participants who reported not smoking at baseline. In 18 of the 19 studies the nonsmoking adolescents who were more aware of tobacco advertising or receptive to it, were more likely to have experimented with cigarettes or become smokers at follow up. There was variation in the strength of association, and the degree to which potential confounders were controlled for. Longitudinal studies consistently suggest that exposure to tobacco advertising and promotion is associated with the likelihood that adolescents will start to smoke. Based on the strength and specificity of this association, evidence of a dose-response relationship, the consistency of findings across numerous observational studies, temporality of exposure and smoking behaviours observed, as well as the theoretical plausibility regarding the impact of advertising, we conclude that tobacco advertising and promotion increases the likelihood that adolescents will start to smoke.

Plain-language summary: There are no trials of the impact of tobacco advertising and promotional activities on people taking up smoking. However, there are studies following nonsmokers and their exposure to advertising (such as the number of tobacco advertisements in the magazines they read). The review found that in all these studies, nonsmoking adolescents who were more aware of or receptive to tobacco advertising were more likely to become smokers later.
Abstract: Three eligible trials involving 569 patients were identified. Due to methodological limitations in the included studies, there was considerable variation in the results of acute (risk range 38.67% to 96.51%) and chronic pain (risk range 7.83% to 40.47%) across the control groups. Therefore, meta-analysis was not performed but the results of the outcomes in the individual trials were compared. Two trials involving 322 patients reported less chronic pain after preperitoneal repair (relative risk (RR) 0.18, number needed to treat (NNT) 8; RR 0.51, NNT 5), whereas one trial, including 247 patients, described more chronic pain after this repair (RR 1.17, NNT 77). The same trials favoured the preperitoneal technique concerning acute pain (RR 0.17, NNT 3; RR 0.78, NNT 7), whereas in the third trial it was almost omnipresent and thus comparable in both intervention arms (RR 0.997, NNT 333). Early and late hernia recurrence rates were similar across the studies, whereas contrasting results were reported for other early outcomes as infection and hematoma. No late mesh infection occurred in the included trials.  Both techniques are valid as they result in similar low recurrence rates. Evaluation of pain results in the individual trials shows some evidence that preperitoneal repair causes less or comparable acute and chronic pain compared to the Lichtenstein procedure. We emphasize the need for homogeneous high quality randomized trials comparing elective preperitoneal inguinal hernia techniques and Lichtenstein repair in terms of chronic pain.

Plain-language summary: The review authors identified three eligible controlled trials in which 569 patients were randomized to Lichtenstein or preperitoneal mesh repair. Due to methodological limitations in the included trials, the data were not pooled. Comparison of pain results in the individual trials showed that preperitoneal repair causes less chronic pain (relative risk (RR) 0.18, number needed to treat (NNT) 8; RR 0.51, NNT 5) compared to the Lichtenstein procedure in two trials involving 322 patients. One trial, including 247 patients, described more chronic pain after this repair (RR 1.17, NNT 77). The same trials favoured the preperitoneal technique concerning acute pain (RR 0.17, NNT 3; RR 0.78, NNT 7), whereas in the third trial it was almost omnipresent and thus comparable in both intervention arms (RR 0.997, NNT 333). This method also showed similar low recurrence rates after both types of repair. The results for other early complications were not consistent across the included trials. No mesh infections were reported. In conclusion, both techniques are valid causing few recurrences. Analysis of pain results in each trial shows some evidence that preperitoneal repair causes less or comparable acute and chronic pain compared to the Lichtenstein technique. As no robust conclusions concerning chronic pain after elective hernia surgery can be made, we highlight the need for homogeneous trials.
Abstract: Eight trials with 1753 patients were included. One trial with a 2 x 2 design was counted twice in the analysis. The analysis was performed including 11 comparisons based on 1975 patients. The median follow up was six years. The pooled hazard ratio of death was 0.82 (95% confidence interval (CI) 0.71 to 0.95; P = 0.006) corresponding to an absolute survival benefit of 6% at five years from chemotherapy (from 56% to 62%). The pooled hazard ratio of tumour failure or death was 0.76 (95% CI 0.67 to 0.86; P < 0.00001) corresponding to an absolute event-free survival benefit of 10% at five years from chemotherapy (from 42% to 52%). A significant interaction was observed between chemotherapy timings and overall survival (P = 0.005), explaining the heterogeneity observed in the treatment effect (P = 0.03) with the highest benefit from concomitant chemotherapy. Chemotherapy led to a small but significant benefit for overall survival and event-free survival. This benefit was essentially observed when chemotherapy was administered concomitantly with radiotherapy.

Plain-language summary: Eight trials (1753 patients) met the criteria for inclusion in this review. The addition of chemotherapy to standard radiotherapy provides a small but significant benefit in patients with nasopharyngeal cancer, especially when chemotherapy is administered at the same time as radiotherapy. The role of chemotherapy given before or after the radiotherapy is more questionable.