Digital technology for delivering and monitoring exercise programs for people with cystic fibrosis.

BACKGROUND: Although exercise is recommended as part of the cystic fibrosis (CF) therapeutic routine, adherence to exercise is still limited. Digital health technologies can provide easy-to-access health information and may help improve healthcare and outcomes in individuals with long-term conditions. However, its effects for delivering and monitoring exercise programs in CF have not yet been synthesized. OBJECTIVES: To evaluate the benefits and harms of digital health technologies for delivering and monitoring exercise programs, increasing adherence to exercise regimens, and improving key clinical outcomes in people with CF. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 21 November 2022. SELECTION CRITERIA: We included randomized controlled trials (RCTs) or quasi-RCTs of digital health technologies for delivering or monitoring exercise programs in CF. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. physical activity, 2. self-management behavior, and 3. pulmonary exacerbations. Our secondary outcomes were 4. usability of technologies, 5. quality of life, 6. lung function, 7. muscle strength, 8. exercise capacity, 9. physiologic parameters, and 10. ADVERSE EVENTS: We used GRADE to assess certainty of evidence. MAIN RESULTS: We identified four parallel RCTs (three single-center and one multicenter with 231 participants aged six years or older). The RCTs evaluated different modes of digital health technologies with distinct purposes, combined with diverse interventions. We identified important methodologic concerns in the RCTs, including insufficient information on the randomization process, blinding of outcome assessors, balance of non-protocol interventions across groups, and whether the analyses performed corrected for bias due to missing outcome data. Non-reporting of results may also be a concern, especially because some planned outcome results were reported incompletely. Furthermore, each trial had a small number of participants, resulting in imprecise effects. These limitations on the risk of bias, and on the precision of effect estimates resulted in overall low- to very low-certainty evidence. We undertook four comparisons and present the findings for our primary outcomes below. There is no information on the effectiveness of other modes of digital health technologies for monitoring physical activity or delivering exercise programs in people with CF, on adverse events related to the use of digital health technologies either for delivering or monitoring exercise programs in CF, and on their long-term effects (more than one year). Digital health technologies for monitoring physical activity Wearable fitness tracker plus personalized exercise prescription compared to personalized exercise prescription alone One trial (40 adults with CF) evaluated this outcome, but did not report data for any of our primary outcomes. Wearable fitness tracker plus text message for personalized feedback and goal setting compared to wearable fitness tracker alone The evidence is very uncertain about the effects of a wearable fitness tracker plus text message for personalized feedback and goal setting, compared to wearable technology alone on physical activity measured by step count at six-month follow-up (mean difference [MD] 675.00 steps, 95% confidence interval [CI] -2406.37 to 3756.37; 1 trial, 32 participants). The same study measured pulmonary exacerbation rates and reported finding no difference between groups. Web-based application to record, monitor, and set goals on physical activity plus usual care compared to usual care alone Using a web-based application to record, monitor, and set goals on physical activity plus usual care may result in little to no difference on time spent in moderate-to-vigorous physical activity measured via accelerometry compared to usual care alone at six-month follow-up (MD -4 minutes/day, 95% CI -37 to 29; 1 trial, 63 participants). Low certainty-evidence from the same trial suggests that the intervention may result in little to no difference on pulmonary exacerbations during 12 months of follow-up (median 1 respiratory hospitalization, interquartile range [IQR] 0 to 3) versus control (median 1 respiratory hospitalization, IQR 0 to 2; P = 0.6). Digital health technologies for delivering exercise programs Web-based versus face-to-face exercise delivery The evidence is very uncertain about the effects of web-based compared to face-to-face exercise delivery on adherence to physical activity as assessed by the number of participants who completed all exercise sessions after three months of intervention (risk ratio 0.92, 95% CI 0.69 to 1.23; 1 trial, 51 participants). AUTHORS' CONCLUSIONS: The evidence is very uncertain about the effects of an exercise program plus the use of a wearable fitness tracker integrated with a social media platform compared with exercise prescription alone and on the effects of receiving a wearable fitness tracker plus text message for personalized feedback and goal setting, compared to a wearable fitness tracker alone. Low-certainty evidence suggests that using a web-based application to record, monitor, and set goals on physical activity plus usual care may result in little to no difference in time spent in moderate-to-vigorous physical activity, total time spent in activity, pulmonary exacerbations, quality of life, lung function, and exercise capacity compared to usual care alone. Regarding the use of digital health technologies for delivering exercise programs in CF, the evidence is very uncertain about the effects of using a wearable fitness tracker plus personalized exercise prescription compared to personalized exercise prescription alone. Further high-quality RCTs, with blinded outcome assessors, reporting the effects of digital health technologies on clinically important outcome measures, such as physical activity participation and intensity, self-management behavior, and the occurrence of pulmonary exacerbations in the long term are needed. The results of six ongoing RCTs identified through our searches may help clarify the effects of different modes of digital health technologies for delivering and monitoring exercise programs in people with CF.

Sodium-glucose cotransporter-2 inhibitors for type 2 diabetes mellitus in adults: An overview of 46 systematic reviews.

AIMS: To summarize the evidence from systematic reviews (SRs) of randomized controlled trials (RCTs) evaluating the efficacy and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors versus placebo or active comparators for type 2 diabetes mellitus. MATERIALS AND METHODS: We searched six databases between 2014 and 2021. We assessed the quality of evidence using Assessment of Multiple Systematic Reviews (AMSTAR 2) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) and summarized the main outcome results according to their evidence of benefit (PROSPERO ID: CRD42019132431). RESULTS: We included 46 SRs, comprising 175 RCTs and 136 096 participants. The results showed "clear evidence of benefit" in relation to: myocardial infarction (odds ratio [OR]/hazard ratio [HR] 0.85 to 0.91); cardiovascular mortality (OR/HR 0.67 to 0.86); heart failure (OR/HR 0.64 to 0.69); albuminuria progression and composite renal outcome (relative risk [RR]/HR 0.55 to 0.63); glycated haemoglobin (HbA1c) versus placebo (mean difference [MD] -0.49% to -0.77% [5.4 to 8.4 mmol/mol]); and weight versus placebo (MD -1.09 kg to -2.99 kg). "Possible benefit" was observed in relation to major adverse cardiovascular events (OR/HR 0.80 to 0.89), all-cause mortality and nonalcoholic fatty liver disease. SGLT2 inhibitors showed "clear evidence of no effect or equivalence" in relation to stroke and fractures. "Clear evidence of harm" was observed in relation to genital infections (RR/OR 2.06 to 5.25) and ketoacidosis (HR/OR 1.36 to 2.20). Regarding amputation risk and urinary tract infections, we found "no conclusions possible due to lack of evidence". CONCLUSIONS: Our results showed that SGLT2 inhibitors have beneficial effects in relation to renal and cardiovascular outcomes (except for stroke), HbA1c and weight. Further studies are needed to assess urinary infections and amputation risk.

WITHDRAWN: Treatments for adults with prominent lower front teeth.

BACKGROUND: Prominent lower front teeth may be associated with a large or prognathic lower jaw (mandible) or a small or retrusive upper jaw (maxilla). Edward Angle, who may be considered the father of modern orthodontics, classified the malocclusion in this situation as Class III. The individual is described as having a negative or reverse overjet as the lower front teeth are more prominent than the upper front teeth. OBJECTIVES: The purpose of this systematic review was to evaluate different treatments of Angle Class III malocclusion in adults. SEARCH METHODS: The following databases were searched: Cochrane Oral Health Group Trials Register (to 22 March 2012); CENTRAL (The Cochrane Library 2012, Issue 1); MEDLINE via OVID (1950 to 22 March 2012); EMBASE via OVID (1980 to 22 March 2012); LILACs (1982 to 22 March 2012); BBO (1986 to 22 March 2012); and SciELO (1997 to 22 March 2012). SELECTION CRITERIA: All randomized or quasi-randomized controlled trials of treatments for adults with an Angle Class III malocclusion were included. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed the eligibility of the identified reports. Two review authors independently extracted data and assessed the risk of bias in the included studies. The mean differences with 95% confidence intervals were calculated for continuous data. MAIN RESULTS: Two randomized controlled trials were included in this review. There are different types of surgery for this type of malocclusion but only trials of mandible reduction surgery were identified. One trial compared intraoral vertical ramus osteotomy (IVRO) with sagittal split ramus osteotomy (SSRO) and the other trial compared vertical ramus osteotomy (VRO) with and without osteosynthesis. Neither trial found any difference between the two treatments. The trials did not provide adequate data for assessing effectiveness of the techniques described. AUTHORS' CONCLUSIONS: There is insufficient evidence from the two included trials, to conclude that one procedure is better or worse than another. The included trials compared different interventions and were at high risk of bias and therefore no implications for practice can be given. Further high quality randomized controlled trials with long term follow-up are required.

Metoclopramide for post-pyloric placement of naso-enteral feeding tubes.

BACKGROUND: Enteral nutrition by feeding tube is a common and efficient method of providing nutritional support to prevent malnutrition in hospitalised patients who have adequate gastrointestinal function but who are unable to eat. Gastric feeding may be associated with higher rates of food aspiration and pneumonia than post-pyloric naso-enteral tubes. Thus, enteral feeding tubes are placed directly into the small intestine rather than the stomach, and the use of metoclopramide, a prokinetic agent, has been recommended to achieve post-pyloric placement, but its efficacy is controversial. Moreover, metoclopramide may include adverse reactions, which with high doses or prolonged use may be serious and irreversible. OBJECTIVES: To determine the effect of intravenous metoclopramide on post-pyloric placement of the naso-enteral tube in adults. SEARCH METHODS: Trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 10) which includes the CUGPD group's specialised register of trials, MEDLINE (1996 to 21 October 2014), EMBASE (1988 to 21 October 2014), LILACS (2005 to 21 October 2014)   We did not confine our search to English language publications. Searches in all databases were updated originally in January 2005, then in November 2008 and again in October 2014. No new studies were found in 2008 or in 2014. SELECTION CRITERIA: We selected randomised controlled trials of adults needing enteral nutrition, who received intravenous or intramuscular metoclopramide to aid placement of transpyloric naso-enteral feeding tubes, compared to placebo or no intervention. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by The Cochrane Collaboration. All analyses were performed according to the intention-to-treat method. We present risk ratios (RR) with 95% confidence intervals (CI). MAIN RESULTS: Four studies, with a total of 204 participants were included and analysed. The trials compared metoclopramide with placebo (two trials) or with no intervention (two trials). Metoclopramide was investigated at doses of 10 mg (two trials) and 20 mg (two trials). There was no statistically significant difference between metoclopramide versus placebo or no intervention administered to promote tube placement (RR 0.82, 95% CI 0.61 to 1.10). Metoclopramide at doses of 10 mg (RR 0.82, 95% CI 0.60 to 1.11) and 20 mg (RR 0.62, 95% CI 0.15 to 2.62) were equally ineffective in facilitating post-pyloric intubation when compared with placebo or no intervention. AUTHORS' CONCLUSIONS: In this review, we found only four studies that fitted our inclusion criteria. These were small, underpowered studies, in which metoclopramide was given at doses of 10 mg and 20 mg. Our analysis showed that metoclopramide did not assist post-pyloric placement of naso-enteral feeding tubes.Ideally randomised clinical trials should be performed that have a significant sample size, administering metoclopramide against control, however, given the lack of efficacy revealed by this review it is unlikely that further studies will be performed.

Early versus late tracheostomy for critically ill patients.

BACKGROUND: Long-term mechanical ventilation is the most common situation for which tracheostomy is indicated for patients in intensive care units (ICUs). 'Early' and 'late' tracheostomies are two categories of the timing of tracheostomy. Evidence on the advantages attributed to early versus late tracheostomy is somewhat conflicting but includes shorter hospital stays and lower mortality rates. OBJECTIVES: To evaluate the effectiveness and safety of early (≤ 10 days after tracheal intubation) versus late tracheostomy (> 10 days after tracheal intubation) in critically ill adults predicted to be on prolonged mechanical ventilation with different clinical conditions. SEARCH METHODS: This is an update of a review last published in 2012 (Issue 3, The Cochrane Library) with previous searches run in December 2010. In this version, we searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2013, Issue 8); MEDLINE (via PubMed) (1966 to August 2013); EMBASE (via Ovid) (1974 to August 2013); LILACS (1986 to August 2013); PEDro (Physiotherapy Evidence Database) at www.pedro.fhs.usyd.edu.au (1999 to August 2013) and CINAHL (1982 to August 2013). We reran the search in October 2014 and will deal with any studies of interest when we update the review. SELECTION CRITERIA: We included all randomized and quasi-randomized controlled trials (RCTs or QRCTs) comparing early tracheostomy (two to 10 days after intubation) against late tracheostomy (> 10 days after intubation) for critically ill adult patients expected to be on prolonged mechanical ventilation. DATA COLLECTION AND ANALYSIS: Two review authors extracted data and conducted a quality assessment. Meta-analyses with random-effects models were conducted for mortality, time spent on mechanical ventilation and time spent in the ICU. MAIN RESULTS: We included eight RCTs (N = 1977 participants). At the longest follow-up time available in these studies, evidence of moderate quality from seven RCTs (n = 1903) showed lower mortality rates in the early as compared with the late tracheostomy group (risk ratio (RR) 0.83, 95% confidence interval (CI) 0.70 to 0.98; P value 0.03; number needed to treat for an additional beneficial outcome (NNTB) ≅ 11). Divergent results were reported on the time spent on mechanical ventilation and no differences were noted for pneumonia, but the probability of discharge from the ICU was higher at day 28 in the early tracheostomy group (RR 1.29, 95% CI 1.08 to 1.55; P value 0.006; NNTB ≅ 8). AUTHORS' CONCLUSIONS: The whole findings of this systematic review are no more than suggestive of the superiority of early over late tracheostomy because no information of high quality is available for specific subgroups with particular characteristics.

Beta-blockers for preventing stroke recurrence.

BACKGROUND: Stroke affects 15 million people per year worldwide. Despite recent developments in acute stroke treatment, prevention remains very important. Stroke has a high rate of recurrence; therefore secondary prevention is also important. Many clinical approaches to control risk factors have been proposed. One of these approaches is the prescription of beta-blockers that have effects beyond the reduction of blood pressure, which can reduce the recurrence of stroke. OBJECTIVES: To evaluate the efficacy of beta-blockers for preventing stroke recurrence and for reducing death and major vascular events in people with a previous stroke or transient ischaemic attack (TIA), and to determine their safety, particularly with regard to the development of diabetes mellitus. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (May 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews (CDSR) (The Cochrane Library 2014, Issue 5), the Database of Abstracts of Reviews of Effects (DARE) (May 2014), MEDLINE (1966 to May 2014), EMBASE (1980 to May 2014), and Latin American and Caribbean Health Sciences Literature (LILACS) (1982 to May 2014). We also searched ongoing trials registers and reference lists. SELECTION CRITERIA: Randomised controlled trials (RCTs) that included participants with previous stroke or TIA due to arterial thrombosis or embolism. The intervention was any beta-blocker versus control, or beta-blocker plus other treatment versus other treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the trials identified, appraised quality, and extracted data. MAIN RESULTS: We included two RCTs involving 2193 participants in the review. Both studies randomised participants to either beta-blocker (atenolol 5 mg) or placebo and were of a high methodological quality. We noted no statistical differences among the groups in risks of fatal and non-fatal stroke (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.76 to 1.18). For other outcomes analysed (major vascular events, death from all causes, death from cardiovascular causes) , we observed no significant differences between the groups. There were minor blood pressure reductions in the intervention group. Neither of the included studies reported the occurrence of diabetes among their outcomes or assessed quality of life. Adverse events were significantly more frequent in participants taking atenolol than in those given placebo, and were the most common reason given for discontinuing treatment (RR 1.85, 95% CI 1.45 to 2.35). AUTHORS' CONCLUSIONS: To date, no available evidence supports the routine use of beta-blockers for secondary prevention after stroke or TIA. More studies with larger samples are needed.

Halofuginone for non-hospitalized adult patients with COVID-19 a multicenter, randomized placebo-controlled phase 2 trial. The HALOS trial.

BACKGROUND: Halofuginone (PJS-539) is an oral prolyl-tRNA synthetase inhibitor that has a potent in vitro activity against SARS-CoV-2 virus. The safety and efficacy of halofuginone in Covid-19 patients has not been studied. METHODS: We conducted a phase II, randomized, double-blind, placebo-controlled, dose ranging, safety and tolerability trial of halofuginone in symptomatic (≤ 7 days), mostly vaccinated, non-hospitalized adults with mild to moderate Covid-19. Patients were randomized in a 1:1:1 ratio to receive halofuginone 0.5mg, 1mg or placebo orally once daily for 10 days. The primary outcome was the decay rate of the SARS-CoV-2 viral load logarithmic curve within 10 days after randomization. RESULTS: From September 25, 2021, to February 3, 2022, 153 patients were randomized. The mean decay rate in SARS-CoV-2 viral load log10 within 10 days was -3.75 (95% CI, -4.11; -3.19) in the placebo group, -3.83 (95% CI, -4.40; -2.27) in the halofuginone 0.5mg group and -4.13 (95% CI, -4.69; -3.57) in the halofuginone 1mg group, with no statistically significant difference in between placebo vs. halofuginone 0.5mg (mean difference -0.08; 95% CI -0.82 to 0.66, p = 0.96) and between placebo vs. halofuginone 1mg (mean difference -0.38; 95% CI, -1.11; 0.36, p = 0.41). There was no difference on bleeding episodes or serious adverse events at 28 days. CONCLUSIONS: Among non-hospitalized adults with mild to moderate Covid-19 halofuginone treatment was safe and well tolerated but did not decrease SARS-CoV-2 viral load decay rate within 10 days.

Interventions for treating traumatised permanent front teeth: luxated (dislodged) teeth.

BACKGROUND: Dental trauma is common especially in children and young adults. One group of dento-alveolar injuries is classified as luxation. This group includes a subgroup of severe injuries where the tooth is displaced from its original position. These injuries are classified further by the direction in which the tooth has been displaced, namely: intrusion, extrusion and lateral luxation. OBJECTIVES: To evaluate the effects of a range of interventions for treating displaced luxated permanent front teeth. SEARCH METHODS: Search strategies were developed for MEDLINE via OVID and revised appropriately for the following databases: Cochrane Oral Health Group's Trials Register (to 20 August 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 8), MEDLINE via OVID (1966 to August 2012), EMBASE via Elsevier (1974 to August 2012), and LILACS via BIREME (1982 to August 2012). Dissertations, Theses and Abstracts were searched as were reference lists from articles. There were no language restrictions. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials of treatment interventions for displaced luxated permanent front teeth. Included trials had to have a minimum follow-up period of 12 months. DATA COLLECTION AND ANALYSIS: Two review authors independently and in duplicate assessed the eligibility of all reports identified in the searches. Authors were contacted for additional information where required. MAIN RESULTS: No randomised or quasi-randomised controlled trials were found. AUTHORS' CONCLUSIONS: We found no randomised or quasi-randomised trials of interventions to treat displaced luxated permanent front teeth. Current clinical guidelines are based on available information from case series studies and expert opinions. Randomised controlled trials in this area of dental trauma are required to robustly identify the benefits of different treatment strategies.

Depot versus daily administration of gonadotrophin-releasing hormone agonist protocols for pituitary down regulation in assisted reproduction cycles.

BACKGROUND: Gonadotrophin-releasing hormone agonist (GnRHa) is commonly used to switch off (down regulate) the pituitary gland and thus suppress ovarian activity in women undergoing in vitro fertilisation (IVF). Other fertility drugs (gonadotrophins) are then used to stimulate ovulation in a controlled manner. Among the various types of pituitary down regulation protocols in use, the long protocol achieves the best clinical pregnancy rate. The long protocol requires GnRHa administration until suppression of ovarian activity occurs, within approximately 14 days. GnRHa can be used either as daily low-dose injections or through a single injection containing higher doses of the drug (depot). It is unclear which of these two forms of administration is best, and whether single depot administration may require higher doses of gonadotrophins. OBJECTIVES: To compare the effectiveness and safety of a single depot dose of GHRHa versus daily GnRHa doses in women undergoing IVF. SEARCH METHODS: We searched the following databases: Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched July 2012), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7), MEDLINE (1966 to July 2012), EMBASE (1980 to July 2012) and LILACS (1982 to July 2012). We also screened the reference lists of articles. SELECTION CRITERIA: We included RCTs comparing depot and daily administration of GnRHa for long protocols in IVF treatment cycles in couples with any cause of infertility, using various methods of ovarian stimulation. The primary review outcomes were live birth or ongoing pregnancy, clinical pregnancy and ovarian hyperstimulation syndrome (OHSS). Other outcomes included number of oocytes retrieved, miscarriage, multiple pregnancy, number of gonadotrophin (FSH) units used for ovarian stimulation, duration of gonadotrophin treatment, cost and patient convenience. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies, extracted data and assessed study quality. For dichotomous outcomes, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) per woman randomised. Where appropriate, we pooled studies. MAIN RESULTS: Sixteen studies were eligible for inclusion (n = 1811 participants), 12 (n = 1366 participants) of which were suitable for meta-analysis. No significant heterogeneity was detected.There were no significant differences between depot GnRHa and daily GnRHa in live birth/ongoing pregnancy rates (OR 0.95, 95% CI 0.70 to 1.31, seven studies, 873 women), but substantial differences could not be ruled out. Thus for a woman with a 24% chance of achieving a live birth or ongoing pregnancy using daily GnRHa injections, the corresponding chance using GnRHa depot would be between 18% and 29%.There was no significant difference between the groups in clinical pregnancy rate (OR 0.96, 95% CI 0.75 to 1.23, 11 studies, 1259 women). For a woman with a 30% chance of achieving clinical pregnancy using daily GnRHa injections, the corresponding chance using GnRHa depot would be between 25% and 35%.There was no significant difference between the groups in the rate of severe OHSS (OR 0.84, 95% CI 0.29 to 2.42, five studies, 570 women), but substantial differences could not be ruled out. For a woman with a 3% chance of severe OHSS using daily GnRHa injections, the corresponding risk using GnRHa depot would be between 1% and 6%.Compared to women using daily GnRHa, those on depot administration required significantly more gonadotrophin units for ovarian stimulation (standardised mean difference (SMD) 0.26, 95% CI 0.08 to 0.43, 11 studies, 1143 women) and a significantly longer duration of gonadotrophin use (mean difference (MD) 0.65, 95% CI 0.46 to 0.84, 10 studies, 1033 women).Study quality was unclear due to poor reporting. Only four studies reported live births as an outcome and only five described adequate methods for concealment of allocation. AUTHORS' CONCLUSIONS: We found no evidence of a significant difference between depot and daily GnRHa use for pituitary down regulation in IVF cycles using the long protocol, but substantial differences could not be ruled out. Since depot GnRHa requires more gonadotrophins and a longer duration of use, it may increase the overall costs of IVF treatment.

Beta-blockers for preventing stroke recurrence.

BACKGROUND: Stroke affects 15 million people per year worldwide. Despite recent developments in acute stroke treatment, prevention remains very important. Stroke has a high rate of recurrence; therefore secondary prevention is also important. Many clinical approaches to control risk factors have been proposed. One of these approaches is the prescription of beta-blockers that have effects beyond the reduction of blood pressure, which can reduce the recurrence of stroke. OBJECTIVES: To evaluate the efficacy of beta-blockers for preventing stroke recurrence and for reducing death and major vascular events in people with a previous stroke or transient ischaemic attack (TIA), and to determine their safety, particularly with regard to the development of diabetes mellitus. SEARCH METHODS: We searched the Cochrane Stroke Group Trials Register (December 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews (CDSR) (The Cochrane Library 2011, Issue 12), the Database of Abstracts of Reviews of Effects (DARE) (December 2011), MEDLINE (1966 to December 2011), EMBASE (1980 to December 2011), and Latin American and Caribbean Health Sciences Literature (LILACS) (1982 to December 2011). We also searched ongoing trials registers and reference lists. SELECTION CRITERIA: Randomised controlled trials (RCTs) that included participants with previous stroke or TIA due to arterial thrombosis or embolism.The intervention was any beta-blocker versus control, or beta-blocker plus other treatment versus other treatment. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the trials identified, appraised quality, and extracted data. MAIN RESULTS: We included two RCTs involving 2193 participants in the review. Both studies randomised participants to either beta-blocker (atenolol 5 mg) or placebo. No statistical differences were noted among the groups in risks of fatal and non-fatal stroke (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.75 to 1.17). For all other outcomes analysed (death from all causes, cardiac death, non-fatal myocardial infarction, major vascular events), we observed no significant differences between the groups. AUTHORS' CONCLUSIONS: To date, no available evidence supports the routine use of beta-blockers for secondary prevention after stroke or TIA. More studies with larger samples are needed.

Economic burden of respiratory syncytial and parainfluenza viruses in children of upper-middle-income countries: a systematic review.

OBJECTIVE: To identify and assess the current evidence available about the costs of managing hospitalized pediatric patients diagnosed with Respiratory Syncytial Virus (RSV) and Parainfluenza Virus Type 3 (PIV3) in upper-middle-income countries. METHODS: The authors conducted a systematic review across seven key databases from database inception to July 2022. Costs extracted were converted into 2022 International Dollars using the Purchasing Power Parity-adjusted. PROSPERO identifier: CRD42020225757. RESULTS: No eligible study for PIV3 was recovered. For RSV, cost analysis and COI studies were performed for populations in Colombia, China, Malaysia, and Mexico. Comparing the total economic impact, the lowest cost per patient at the pediatric ward was observed in Malaysia ($ 347.60), while the highest was in Colombia ($ 709.66). On the other hand, at pediatric ICU, the lowest cost was observed in China ($ 1068.26), while the highest was in Mexico ($ 3815.56). Although there is no consensus on the major cost driver, all included studies described that the medications (treatment) consumed over 30% of the total cost. A high rate of inappropriate prescription drugs was observed. CONCLUSION: The present study highlighted how RSV infection represents a substantial economic burden to health care systems and to society. The findings of the included studies suggest a possible association between baseline risk status and expenditures. Moreover, it was observed that an important amount of the cost is destinated to treatments that have no evidence or support in most clinical practice guidelines.

Early versus late tracheostomy for critically ill patients.

BACKGROUND: Long-term mechanical ventilation is the most common situation where tracheostomy is indicated for patients in intensive care units (ICU). 'Early' and 'late' tracheostomies are two categories of the timing of tracheostomy. The evidence on the advantages attributed to early over late tracheostomy is somewhat conflicting but includes shorter hospital stays and lower mortality rates. OBJECTIVES: To evaluate the effectiveness and safety of early (≤ 10 days after intubation) versus late tracheostomy (> 10 days after intubation) in critically ill adult patients predicted to be on prolonged mechanical ventilation and with different clinical conditions. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 12); MEDLINE (via PubMed) (1966 to December 2010); EMBASE (via Ovid) (from 1974 to December 2010); LILACS (1986 to December 2010); PEDro (Physiotherapy Evidence Database) at www.pedro.fhs.usyd.edu.au (1999 to December 2010) and CINAHL (1982 to December 2010). SELECTION CRITERIA: We included all randomized or quasi-randomized controlled trials which compared early tracheostomy (two to10 days after intubation) against late tracheostomy (> 10 days after intubation) for critically ill adult patients expected to be on prolonged mechanical ventilation. There was no language restriction. DATA COLLECTION AND ANALYSIS: Two authors extracted data and conducted a quality assessment. Meta-analyses using the random-effects model were conducted for mortality and pneumonia. MAIN RESULTS: We included four studies, with a high risk of bias, in which a total of 673 patients were randomized to either early or late tracheostomy. We could not pool data in a meta-analysis because of clinical, methodological and statistical heterogeneity between the included studies. There is no strong evidence for real differences between early and late tracheostomy in the primary outcome of mortality. In one study a statistically significant result favouring early tracheostomy was observed in the outcome measuring time spent on ventilatory support (mean difference (MD) -9.80 days, 95% CI -11.48 to -8.12, P < 0.001). AUTHORS' CONCLUSIONS: Updated evidence is of low quality, and potential differences between early and late tracheostomy need to be better investigated by means of randomized controlled trials. At present there is no specific information about any subgroup or individual characteristics potentially associated with better outcomes with either early or late tracheostomy.

Treatments for adults with prominent lower front teeth.

BACKGROUND: Prominent lower front teeth may be associated with a large or prognathic lower jaw (mandible) or a small or retrusive upper jaw (maxilla). Edward Angle, who may be considered the father of modern orthodontics, classified the malocclusion in this situation as Class III. The individual is described as having a negative or reverse overjet as the lower front teeth are more prominent than the upper front teeth. OBJECTIVES: The purpose of this systematic review was to evaluate different treatments of Angle Class III malocclusion in adults. SEARCH METHODS: The following databases were searched: Cochrane Oral Health Group Trials Register (to 22 March 2012); CENTRAL (The Cochrane Library 2012, Issue 1); MEDLINE via OVID (1950 to 22 March 2012); EMBASE via OVID (1980 to 22 March 2012); LILACs (1982 to 22 March 2012); BBO (1986 to 22 March 2012); and SciELO (1997 to 22 March 2012). SELECTION CRITERIA: All randomized or quasi-randomized controlled trials of treatments for adults with an Angle Class III malocclusion were included. DATA COLLECTION AND ANALYSIS: Three review authors independently assessed the eligibility of the identified reports. Two review authors independently extracted data and assessed the risk of bias in the included studies. The mean differences with 95% confidence intervals were calculated for continuous data. MAIN RESULTS: Two randomized controlled trials were included in this review. There are different types of surgery for this type of malocclusion but only trials of mandible reduction surgery were identified. One trial compared intraoral vertical ramus osteotomy (IVRO) with sagittal split ramus osteotomy (SSRO) and the other trial compared vertical ramus osteotomy (VRO) with and without osteosynthesis. Neither trial found any difference between the two treatments. The trials did not provide adequate data for assessing effectiveness of the techniques described. AUTHORS' CONCLUSIONS: There is insufficient evidence from the two included trials, to conclude that one procedure is better or worse than another. The included trials compared different interventions and were at high risk of bias and therefore no implications for practice can be given. Further high quality randomized controlled trials with long term follow-up are required.

Indications for accurate and appropriate use of personal protective equipment for healthcare professionals. A systematic review.

BACKGROUND: The speed of the spread of coronavirus disease 2019 (COVID-19) has put enormous pressure on hospitals and other healthcare facilities. This, together with blockages in several countries, has hindered the availability and accessibility of the necessary personal protective equipment (PPE). OBJECTIVE: To identify, systematically evaluate and summarize the available scientific evidence on the efficacy, safety, safe use and reuse of PPE for healthcare professionals, for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DESIGN AND SETTING: Systematic review of studies analyzing products for disinfecting and enabling reuse of PPE for coronavirus within the evidence-based health program of a federal university in São Paulo (SP), Brazil. METHODS: A systematic search of the relevant literature was conducted in the PubMed, EMBASE, Cochrane Library, CINAHL, SCOPUS, Web of Science and LILACS databases, for articles published up to November 30, 2020. RESULTS: Ten studies were selected. These analyzed the use of N95, surgical and cotton masks, face shields, flexible enclosures with plastic covers or polycarbonate intubation boxes and plastic curtains; and also PPE disinfection using several substances. CONCLUSION: Combined use of a face shield with a N95 mask proved to be superior to other associations for protecting healthcare workers. Some products are useful for disinfecting PPE, such as 70% ethanol, 0.1% sodium hypochlorite and a mixture of quaternary ammonium and H2O2, and hydrogen peroxide. Ultraviolet light and dry heat at 70 °C can be used to decontaminate N95 masks. REGISTRATION NUMBER: DOI: 10.17605/OSF.IO/4V5FD at the OPENSCIENCE Framework.

Hospitalization costs of coronaviruses diseases in upper-middle-income countries: A systematic review.

BACKGROUND: COVID-19, SARS and MERS are diseases that present an important health burden worldwide. This situation demands resource allocation to the healthcare system, affecting especially middle- and low-income countries. Thus, identifying the main cost drivers is relevant to optimize patient care and resource allocation. OBJECTIVE: To systematically identify and summarize the current status of knowledge on direct medical hospitalization costs of SARS, MERS, or COVID-19 in Upper-Middle-Income Countries. METHODS: We conducted a systematic review across seven key databases (PubMed, EMBASE, BVS Portal, CINAHL, CRD library, MedRxiv and Research Square) from database inception to February 2021. Costs extracted were converted into 2021 International Dollars using the Purchasing Power Parity-adjusted. The assessment of quality was based on the protocol by the BMJ and CHEERS. PROSPERO 2020: CRD42020225757. RESULTS: No eligible study about SARS or MERS was recovered. For COVID-19, five studies presented cost analysis performed in Brazil, China, Iran, and Turkey. Regarding total direct medical costs, the lowest cost per patient at ward was observed in Turkey ($900.08), while the highest in Brazil ($5,093.38). At ICU, the lowest was in Turkey ($2,984.78), while the highest was in China ($52,432.87). Service care was the most expressive (58% to 88%) cost driver of COVID-19 patients at ward. At ICU, there was no consensus between service care (54% to 87%) and treatment (72% to 81%) as key burdens of total cost. CONCLUSION: Our findings elucidate the importance of COVID-19 on health-economic outcomes. The marked heterogeneity among studies leaded to substantially different results and made challenging the comparison of data to estimate pooled results for single countries or regions. Further studies concerning cost estimates from standardized analysis may provide clearer data for a more substantial analysis. This may help care providers and policy makers to organize care for patients in the most efficient way.

The relationship between the authentic leadership of nurses and structural empowerment: a systematic review.

OBJECTIVE: To verify the relationship between authentic leadership of nurses and structural empowerment. METHOD: This is a systematic review carried out at the Virtual Health Library on the Journal Portal of the Coordination for the Improvement of Higher Education Personnel, Online System for the Search and Analysis of Medical Literature, Scientific Electronic Library Online and Science Direct/Embase, and consulted until April 2019. Studies with nurses, evidencing the relationship between authentic leadership and structural empowerment, published between 2012 and 2018 in Brazilian Portuguese, English or Spanish were included. RESULTS: Five studies were included, with variables other than structural empowerment: job satisfaction, burnout, bulling, mental health, performance, social capital, working environment, nurse retention, and quality of care. Authentic leadership showed a positive relationship with structural empowerment, improving engagement and job satisfaction, reducing burnout and increasing quality of care. CONCLUSION: Health institutions, in addition to Canada, where researchers on this topic are located, can invest in authentic leadership to improve structural empowerment by providing greater commitment from nurses, increased job satisfaction and quality of care provided.

5-FU for genital warts in non-immunocompromised individuals.

BACKGROUND: Genital warts are common and usually are harmless but can be painful and psychologically burdensome. Several local treatments can be used, including topical 5-Fluorouracil (5-FU). OBJECTIVES: To determine the effectiveness and safety of 5-FU topical treatment for genital warts in nonimmunocompromised individuals. SEARCH STRATEGY: Databases searched were Cochrane Central Register of Controlled Trials (The Cochrane Library 2009 Issue 3), MEDLINE (1966 to August 2009), EMBASE (until August 2009), LILACS (1982 to August 2009). The search had no language or publication restrictions. SELECTION CRITERIA: The review included randomised controlled trials (RCTs) among women, men, or both sexes, aged 18 years and older, comparing: 5-FU versus placebo or no treatment; 5-FU in any dose versus other isolated treatment, topical or systemic; 5-FU in any dose associated with other treatment versus placebo; 5-FU in any dose associated with other treatment versus other isolated treatment, topical or systemic; 5-FU in any dose associated with other treatment versus other associated treatment, topical or systemic. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data from the original publications. MAIN RESULTS: Six trials involving 988 patients (645 women and 343 men) and reporting eight comparisons were found. Two studies reported withdrawals and dropouts, but none mentioned analysis by intention to treat (ITT). 5-FU presented better results for cure than placebo or no treatment (relative risk (RR) 0.39, 95% confidence interval (CI) 0.23 to 0.67), meta-cresol-sulfonic acid (MCSA) (RR 2.11, 95% CI 0.83 to 5.37), Podophylin 2%, 4% or 25% (RR 1.26, 95% CI 0.86 to 1.82). There were no statistical differences for treatment failure for 5-FU versus CO2 Laser (RR 0.69, 95% CI 0.43 to 1.11) versus 5-FU + INFalpha-2a (low dose) (RR 1.02, 95% CI 0.87 to 1.119). Worse results were found for 5-FU versus 5-FU + INFalpha-2a (high dose) (RR 10.78, 95% CI 1.50 to 77.36), and 5-FU + CO2 Laser INFalpha-2a (high dose) (RR 7.97, 95% CI 2.87 to 22.13). AUTHORS' CONCLUSIONS: The reviewed trials were highly variable in methods and quality, and the evidence provided by these studies was weak. Cure rates with several treatments were variable, and although 5-FU presents therapeutic results that are inferior to those seen with 5-FU + Inf alpha-2a (high dose) and 5-FU + CO2 Laser + Inf alpha-2a (high dose), the treatment should not be abandoned. Topical treatment with 5-FU has a therapeutic effect; however, the benefits and risks have not been determined clearly and further studies are needed.

Pharmacological treatment for Kleine-Levin Syndrome.

BACKGROUND: Kleine-Levin Syndrome (KLS) is a rare disorder which mainly affects adolescent men. It is characterized by recurrent episodes of hypersomnia, usually accompanied by hyperphagia, cognitive and mood disturbances, abnormal behavior such as hypersexuality, and signs of dysautonomia.In 1990 the diagnostic criteria for Kleine-Levin Syndrome were modified in the International Classification of Sleep Disorders, where it was defined as a syndrome composed of recurring episodes of undue sleepiness lasting some days, which may or may not be associated with hyperphagia and abnormal behavior.The etiology of Kleine-Levin Syndrome remains unknown and several treatment strategies have been used. Some medications have been reported to provide some benefit for the treatment of Kleine-Levin Syndrome patients, but because of the rarity of the condition no long-term follow-up therapies have yet been described. OBJECTIVES: This review aimed to evaluate:1. whether pharmacological treatment for Kleine-Levin Syndrome is effective and safe; and 2. which drug or category of drugs is effective and safe. SEARCH STRATEGY: We obtained relevant trials from the following sources: the Cochrane Epilepsy Group Specialized Register (1 December 2007); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2007); MEDLINE (1966 to December 2007); EMBASE (1980 to December 2007); LILACS (1982 to December 2007); reference lists of sleep medicine textbooks; review articles and reference lists of articles identified by the search strategies. SELECTION CRITERIA: All randomized controlled trials (RCTs) and quasi-randomized controlled trials looking at pharmacological interventions for Kleine-Levin Syndrome. We included both parallel group and cross-over studies. DATA COLLECTION AND ANALYSIS: Two review authors (MO and CC) extracted the data reported in the original articles. MAIN RESULTS: No studies met the inclusion criteria for this systematic review. AUTHORS' CONCLUSIONS: Therapeutic trials of pharmacological treatment for Kleine-Levin Syndrome, with a double-blind, placebo-controlled design are needed.

What do Cochrane systematic reviews say about telemedicine for healthcare?

BACKGROUND: Telemedicine has emerged as a tool for overcoming the challenges of healthcare systems and is likely to become increasingly viable, since information and communication technologies have become more sophisticated and user-friendly. OBJECTIVE: We aimed to identify all Cochrane systematic reviews (CSRs) on telemedicine within healthcare and to summarize the current evidence regarding its use. DESIGN AND SETTING: Review of CSRs, developed at the Discipline of Emergency and Evidence-Based Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo. METHODS: We searched for studies that compared use of telemedicine with conventional treatment or management of diseases within healthcare. Diagnostic telemedicine studies or studies using automatic text, voice-text or even self-managed care were excluded. The main characteristics and the certainty of evidence were synthetized and critically discussed by all authors. RESULTS: We included 10 CSRs that investigated a broad range of diseases. There is still insufficient evidence to determine what types of telemedicine interventions are effective, for which patients and in which settings, and whether such interventions can be used as a replacement for the standard treatment. Harm relating to telemedicine technologies needs to be better investigated and addressed. CONCLUSION: Telemedicine might be an excellent way to facilitate access to treatment, monitoring and dissemination of important clinical knowledge. However, given the recognition of systematic reviews as the best evidence resource available for decision-making, further randomized controlled trials with stricter methods are necessary to reduce the uncertainties in evidence-based use of telemedicine.