Single case research results as clinical outcomes

BACKGROUND People with severe-to-profound intellectual disability and sensory-motor impairment tend to be passive and detached from their immediate context. OBJECTIVE This study assessed a new technology system using a webcam to detect participants’ responses (ie, hand contact with objects) and to trigger computer delivery of preferred environmental stimulation, such as music, contingent on (immediately after) the occurrence of those responses. METHODS In total, 8 adults with severe to profound intellectual disability and extensive motor and visual impairments participated in the study. Each participant was exposed to an ABACB design. The technology system did not provide stimulation during the A (baseline) phases, provided stimulation contingent on the responses during the B (intervention) phases, and provided stimulation throughout the sessions during the C (control) phase. Sessions lasted 5 minutes. RESULTS During the first baseline phase, the participants’ mean frequency of responses per session was between about 3 and 6.5. During the first intervention phase, it increased to between about 10 and 18. It showed a clear decline during the second baseline phase, remained low during the control phase, and increased again during the second intervention phase. During this phase, it ranged from about 13 to 19.5. CONCLUSIONS The new technology system might be a useful tool to help people with intellectual and sensory-motor disabilities increase object contact and stimulation control.

BackgroundNutrition support is a common means for patients with gastric cancer, especially for those undergoing elective surgery. Recently, enteral immunonutrition (EIN) was increasingly found to be more effective than enteral nutrition (EN) in enhancing the host immunity and eventually improving the prognosis of gastric cancer patients undergoing gastrectomy. However, the results reported were not consistent. This meta-analysis aimed to assess the impact of EIN for patients with GC on biochemical, immune indices and clinical outcomes.MethodsFour electronical databases (Medline, EMBASE, Scopus and Cochrane library) were used to search articles in peer-reviewed, English-language journals. Mean difference (MD), Relative risk (RR), or standard mean difference (SMD) with 95% confidence interval (CI) were calculated. Heterogeneity was assessed by Cochrane Q and I2 statistic combined with corresponding P-value. The analysis was carried out with RevMan 5.3.ResultsSeven studies involving 583 patients were eligible for the pooled analysis. EIN, when beyond a 7-day time-frame post-operatively (D ≥ 7), increased level of CD4+ (SMD = 0.99; 95% CI, 0.65–1.33; P < 0.00001), CD4+/ CD8+ (SMD = 0.34; 95% CI, 0.02–0.67; P = 0.04), the IgM (SMD = 1.15; 95% CI, 0.11–2.20; P = 0.03), the IgG (SMD = 0.98; 95% CI, 0.55–1.42; P < 0.0001), the lymphocyte (SMD = 0.69; 95% CI, 0.32–1.06; P = 0.0003), and the proalbumin (SMD = 0.73; 95% CI, 0.33–1.14; P = 0.0004). However, those increased effects were not obvious within a 7-day time-frame post-operatively (D < 7). The levels of CD8+ and other serum proteins except proalbumin were not improved both on D ≥ 7 and D < 7. Clinical outcomes such as systemic inflammatory response syndrone (SIRS) (MD, - 0.89 days; 95% CI, - 1.40 to - 0.39; P = 0.005), and postoperative complications (RR, 0.29; 95% CI, 0.14–0.60; P = 0.001) were significantly reduced in EIN group. Pulmonary infection and length of hospitalization (LHS) were not improved no matter what time after surgery.ConclusionsEIN was found to improve the cellular immunity, modulate inflammatory reaction and reduce postoperative complication for GC patients undergoing radical gastrointestinal surgery. Exclusion of grey literature and non-English language studies was the key limitation in this study.

Cupping therapy, a form of traditional Chinese medicine, has recently gained popularity as a therapeutic modality among sports medicine clinicians. While the use of cupping therapy to decrease musculoskeletal pain is supported by recent research findings, evaluations on the use of cupping therapy to influence range of motion (ROM) are limited. The purpose of the study was to identify if cupping therapy applied passively for 10 minutes increases flexibility compared to sham treatment or control conditions. Twenty-five participants with hamstring ROM less than 80° and no previous cupping therapy experience completed the study. Participants reported to the laboratory on three occasions for one of three randomly assigned treatment conditions (cupping, sham, or control) for 10 minutes while prone. Hamstring flexibility was evaluated three times (pre-treatment, post-treatment, and 10-minutes post-treatment) via ROM measured during an active straight leg raise. Participants returned on two other occasions to receive the remaining treatment conditions. A 3 (treatment condition) × 3 (time) repeated measures analysis of variance was utilized for statistical analysis. There was no interaction between condition and time (p = 0.78). Within-subjects effects for time (p = 0.76) was not significant. Post hoc pairwise comparison of treatment conditions found no differences between control and cupping (p = 0.36), cupping and sham (p = 0.35), or control and sham (p=0.98) conditions. Cupping therapy applied statically for 10 minutes does not increase hamstring flexibility compared to a sham treatment or control condition.

Preterm and low birth weight infants are born with low stores in zinc, which is a vital trace element for growth, cell differentiation and immune function. Preterm infants are at risk of zinc deficiency during the postnatal period of rapid growth. Systematic reviews in the older paediatric population have previously shown that zinc supplementation potentially improves growth and positively influences the course of infectious diseases. In paediatric reviews, the effect of zinc supplementation was most pronounced in those with low nutritional status, which is why the intervention could also benefit preterm infants typically born with low zinc stores and decreased immunity. To determine whether enteral zinc supplementation, compared with placebo or no supplementation, affects important outcomes in preterm infants, including death, neurodevelopment, common morbidities and growth. Our searches are up-to-date to 20 February 2020. For the first search, we used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2017, Issue 8), MEDLINE via PubMed (1966 to 29 September 2017), Embase (1980 to 29 September 2017), and CINAHL (1982 to 29 September 2017). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-RCTs. We ran an updated search from 1 January 2017 to 20 February 2020 in the following databases: CENTRAL via CRS Web, MEDLINE via Ovid, and CINAHL via EBSCOhost. We included RCTs and quasi-RCTs that compared enteral zinc supplementation versus placebo or no supplementation in preterm infants (gestational age < 37 weeks), and low birth weight babies (birth weight < 2500 grams), at any time during their hospital admission after birth. We included zinc supplementation in any formulation, regimen, or dose administered via the enteral route. We excluded infants who underwent gastrointestinal (GI) surgery during their initial hospital stay, or had a GI malformation or another condition accompanied by abnormal losses of GI juices, which contain high levels of zinc (including, but not limited to, stomas, fistulas, and malabsorptive diarrhoea). We used the standard methods of Cochrane Neonatal. Two review authors separately screened abstracts, evaluated trial quality and extracted data. We synthesised effect estimates using risk ratios (RR), risk differences (RD), and standardised mean differences (SMD). Our primary outcomes of interest were all-cause mortality and neurodevelopmental disability. We used the GRADE approach to assess the certainty of evidence. We included five trials with a total of 482 preterm infants; there was one ongoing trial. The five included trials were generally small, but of good methodological quality. Enteral zinc supplementation compared to no zinc supplementation Enteral zinc supplementation started in hospitalised preterm infants may decrease all-cause mortality (between start of intervention and end of follow-up period) (RR 0.55, 95% CI 0.31 to 0.97; 3 studies, 345 infants; low-certainty evidence). No data were available on long-term neurodevelopmental outcomes at 18 to 24 months of (post-term) age. Enteral zinc supplementation may have little or no effect on common morbidities such as bronchopulmonary dysplasia (RR 0.66, 95% CI 0.31 to 1.40, 1 study, 193 infants; low-certainty evidence), retinopathy of prematurity (RR 0.14, 95% CI 0.01 to 2.70, 1 study, 193 infants; low-certainty evidence), bacterial sepsis (RR 1.11, 95% CI 0.60 to 2.04, 2 studies, 293 infants; moderate-certainty evidence), or necrotising enterocolitis (RR 0.08, 95% CI 0.00 to 1.33, 1 study, 193 infants; low-certainty evidence). The intervention probably improves weight gain (SMD 0.46, 95% CI 0.28 to 0.64; 5 studies, 481 infants; moderate-certainty evidence); and may slightly improve linear growth (SMD 0.75, 95% CI 0.36 to 1.14, 3 studies, 289 infants; low-certainty evidence), but may have little or no effect on head growth (SMD 0.21, 95% CI -0.02 to 0.44, 3 studies, 289 infants; moderate-certainty evidence). Enteral supplementation of zinc in preterm infants compared to no supplementation or placebo may moderately decrease mortality and probably improve short-term weight gain and linear growth, but may have little or no effect on common morbidities of prematurity. There are no data to assess the effect of zinc supplementation on long-term neurodevelopment.

Role of Antimuscarinics Combined With Alpha-blockers in the Management of Urinary Storage Symptoms in Patients With Benign Prostatic Hyperplasia: An Updated Systematic Review and Meta-analysis.

Small numbers of studies and participants in each comparison limited our confidence in the evidence. Sclerosing agents were more effective than placebo for resolution or improvement of telangiectasias but also caused more adverse events (moderate-certainty evidence), and may result in more pain (low-certainty evidence). There was no evidence of a benefit in resolution or improvement for any sclerosant compared to another or to laser. There may be more resolution or improvement of telangiectasias in the combined laser and polidocanol group compared to polidocanol alone (low-certainty evidence). There may be differences between treatments in adverse events and pain. Compared to other sclerosing agents polidocanol probably causes less pain; STS resulted in more hyperpigmentation, matting and probably pain; foam may cause more matting (low-certainty evidence); laser treatment may result in less hyperpigmentation (moderate-certainty evidence). Further well-designed studies are required to provide evidence for other available treatments and important outcomes (such as recurrence, time to resolution and delayed adverse events); and to improve our confidence in the identified comparisons.

General anaesthesia combined with epidural analgesia may have a beneficial effect on clinical outcomes. However, use of epidural analgesia for cardiac surgery is controversial due to a theoretical increased risk of epidural haematoma associated with systemic heparinization. This review was published in 2013, and it was updated in 2019. To determine the impact of perioperative epidural analgesia in adults undergoing cardiac surgery, with or without cardiopulmonary bypass, on perioperative mortality and cardiac, pulmonary, or neurological morbidity. We searched CENTRAL, MEDLINE, and Embase in November 2018, and two trial registers up to February 2019, together with references and relevant conference abstracts. We included all randomized controlled trials (RCTs) including adults undergoing any type of cardiac surgery under general anaesthesia and comparing epidural analgesia versus another modality of postoperative pain treatment. The primary outcome was mortality. We used standard methodological procedures as expected by Cochrane. We included 69 trials with 4860 participants: 2404 given epidural analgesia and 2456 receiving comparators (systemic analgesia, peripheral nerve block, intrapleural analgesia, or wound infiltration). The mean (or median) age of participants varied between 43.5 years and 74.6 years. Surgeries performed were coronary artery bypass grafting or valvular procedures and surgeries for congenital heart disease. We judged that no trials were at low risk of bias for all domains, and that all trials were at unclear/high risk of bias for blinding of participants and personnel taking care of study participants.Epidural analgesia versus systemic analgesiaTrials show there may be no difference in mortality at 0 to 30 days (risk difference (RD) 0.00, 95% confidence interval (CI) -0.01 to 0.01; 38 trials with 3418 participants; low-quality evidence), and there may be a reduction in myocardial infarction at 0 to 30 days (RD -0.01, 95% CI -0.02 to 0.00; 26 trials with 2713 participants; low-quality evidence). Epidural analgesia may reduce the risk of 0 to 30 days respiratory depression (RD -0.03, 95% CI -0.05 to -0.01; 21 trials with 1736 participants; low-quality evidence). There is probably little or no difference in risk of pneumonia at 0 to 30 days (RD -0.03, 95% CI -0.07 to 0.01; 10 trials with 1107 participants; moderate-quality evidence), and epidural analgesia probably reduces the risk of atrial fibrillation or atrial flutter at 0 to 2 weeks (RD -0.06, 95% CI -0.10 to -0.01; 18 trials with 2431 participants; moderate-quality evidence). There may be no difference in cerebrovascular accidents at 0 to 30 days (RD -0.00, 95% CI -0.01 to 0.01; 18 trials with 2232 participants; very low-quality evidence), and none of the included trials reported any epidural haematoma events at 0 to 30 days (53 trials with 3982 participants; low-quality evidence). Epidural analgesia probably reduces the duration of tracheal intubation by the equivalent of 2.4 hours (standardized mean difference (SMD) -0.78, 95% CI -1.01 to -0.55; 40 trials with 3353 participants; moderate-quality evidence). Epidural analgesia reduces pain at rest and on movement up to 72 hours after surgery. At six to eight hours, researchers noted a reduction in pain, equivalent to a reduction of 1 point on a 0 to 10 pain scale (SMD -1.35, 95% CI -1.98 to -0.72; 10 trials with 502 participants; moderate-quality evidence). Epidural analgesia may increase risk of hypotension (RD 0.21, 95% CI 0.09 to 0.33; 17 trials with 870 participants; low-quality evidence) but may make little or no difference in the need for infusion of inotropics or vasopressors (RD 0.00, 95% CI -0.06 to 0.07; 23 trials with 1821 participants; low-quality evidence).Epidural analgesia versus other comparatorsFewer studies compared epidural analgesia versus peripheral nerve blocks (four studies), intrapleural analgesia (one study), and wound infiltration (one study). Investigators provided no data for pulmonary complications, atrial fibrillation or flutter, or for any of the comparisons. When reported, other outcomes for these comparisons (mortality, myocardial infarction, neurological complications, duration of tracheal intubation, pain, and haemodynamic support) were uncertain due to the small numbers of trials and participants. Compared with systemic analgesia, epidural analgesia may reduce the risk of myocardial infarction, respiratory depression, and atrial fibrillation/atrial flutter, as well as the duration of tracheal intubation and pain, in adults undergoing cardiac surgery. There may be little or no difference in mortality, pneumonia, and epidural haematoma, and effects on cerebrovascular accident are uncertain. Evidence is insufficient to show the effects of epidural analgesia compared with peripheral nerve blocks, intrapleural analgesia, or wound infiltration.

BackgroundA recent systematic review and meta-analysis of RCTs of early vs late tracheostomy in mechanically ventilated patients suggest that early tracheostomy reduces the duration of ICU stay and mechanical ventilation, but does not reduce short-term mortality or ventilator-associated pneumonia (VAP). Meta-analysis of randomised trials is typically performed using a frequentist approach, and although reporting confidence intervals, interpretation is usually based on statistical significance. To provide a robust basis for clinical decision-making, we completed the search used from the previous review and analysed the data using Bayesian methods to estimate posterior probabilities of the effect of early tracheostomy on clinical outcomes. MethodsThe search was completed for RCTS comparing early vs late tracheostomy in the databases PubMed, EMBASE, and Cochrane library in June 2022. Effect estimates and 95% confidence intervals were calculated for the outcomes short-term mortality, VAP, duration of ICU stay, and mechanical ventilation. A Bayesian meta-analysis was performed with uninformative priors. Risk ratios (RRs) and standardised mean differences (SMDs) with 95% credible intervals were reported alongside posterior probabilities for any benefit (RR<1; SMD<0), a small benefit (number needed to treat, 200; SMD<–0.5), or modest benefit (number needed to treat, 100; SMD<–1). ResultsNineteen RCTs with 3508 patients were included. Comparing patients with early vs late tracheostomy, the posterior probabilities for any benefit, small benefit, and modest benefit, respectively, were: 99%, 99%, and 99% for short-term mortality; 94%, 78%, and 51% for VAP; 97%, 43%, and 1% for duration of mechanical ventilation; and 97%, 75%, and 27% and for length of ICU stay. ConclusionsBayesian meta-analysis suggests a high probability that early tracheostomy compared with delayed tracheostomy has at least some benefit across all clinical outcomes considered.

Substance use disorders (SUDs) are highly prevalent and associated with a substantial public health burden. Although evidence-based interventions exist for treating SUDs, many individuals remain symptomatic despite treatment, and relapse is common.Mindfulness-based interventions (MBIs) have been examined for the treatment of SUDs, but available evidence is mixed. To determine the effects of MBIs for SUDs in terms of substance use outcomes, craving and adverse events compared to standard care, further psychotherapeutic, psychosocial or pharmacological interventions, or instructions, waiting list and no treatment. We searched the following databases up to April 2021: Cochrane Drugs and Alcohol Specialised Register, CENTRAL, PubMed, Embase, Web of Science, CINAHL and PsycINFO. We searched two trial registries and checked the reference lists of included studies for relevant randomized controlled trials (RCTs). RCTs testing a MBI versus no treatment or another treatment in individuals with SUDs. SUDs included alcohol and/or drug use disorders but excluded tobacco use disorders. MBIs were defined as interventions including training in mindfulness meditation with repeated meditation practice. Studies in which SUDs were formally diagnosed as well as those merely demonstrating elevated SUD risk were eligible. We used standard methodological procedures expected by Cochrane. Forty RCTs met our inclusion criteria, with 35 RCTs involving 2825 participants eligible for meta-analysis. All studies were at high risk of performance bias and most were at high risk of detection bias. Mindfulness-based interventions (MBIs) versus no treatment Twenty-four RCTs included a comparison between MBI and no treatment. The evidence was uncertain about the effects of MBIs relative to no treatment on all primary outcomes: continuous abstinence rate (post: risk ratio (RR) = 0.96, 95% CI 0.44 to 2.14, 1 RCT, 112 participants; follow-up: RR = 1.04, 95% CI 0.54 to 2.01, 1 RCT, 112 participants); percentage of days with substance use (post-treatment: standardized mean difference (SMD) = 0.05, 95% CI -0.37 to 0.47, 4 RCTs, 248 participants; follow-up: SMD = 0.21, 95% CI -0.12 to 0.54, 3 RCTs, 167 participants); and consumed amount (post-treatment: SMD = 0.10, 95% CI -0.31 to 0.52, 3 RCTs, 221 participants; follow-up: SMD = 0.33, 95% CI 0.00 to 0.66, 2 RCTs, 142 participants). Evidence was uncertain for craving intensity and serious adverse events. Analysis of treatment acceptability indicated MBIs result in little to no increase in study attrition relative to no treatment (RR = 1.04, 95% CI 0.77 to 1.40, 21 RCTs, 1087 participants). Certainty of evidence for all other outcomes was very low due to imprecision, risk of bias, and/or inconsistency. Data were unavailable to evaluate adverse events. Mindfulness-based interventions (MBIs) versus other treatments (standard of care, cognitive behavioral therapy, psychoeducation, support group, physical exercise, medication) Nineteen RCTs included a comparison between MBI and another treatment. The evidence was very uncertain about the effects of MBIs relative to other treatments on continuous abstinence rate at post-treatment (RR = 0.80, 95% CI 0.45 to 1.44, 1 RCT, 286 participants) and follow-up (RR = 0.57, 95% CI 0.28 to 1.16, 1 RCT, 286 participants), and on consumed amount at post-treatment (SMD = -0.42, 95% CI -1.23 to 0.39, 1 RCT, 25 participants) due to imprecision and risk of bias. The evidence suggests that MBIs reduce percentage of days with substance use slightly relative to other treatments at post-treatment (SMD = -0.21, 95% CI -0.45 to 0.03, 5 RCTs, 523 participants) and follow-up (SMD = -0.39, 95% CI -0.96 to 0.17, 3 RCTs, 409 participants). The evidence was very uncertain about the effects of MBIs relative to other treatments on craving intensity due to imprecision and inconsistency. Analysis of treatment acceptability indicated MBIs result in little to no increase in attrition relative to other treatments (RR = 1.06, 95% CI 0.89 to 1.26, 14 RCTs, 1531 participants). Data were unavailable to evaluate adverse events. In comparison with no treatment, the evidence is uncertain regarding the impact of MBIs on SUD-related outcomes. MBIs result in little to no higher attrition than no treatment. In comparison with other treatments, MBIs may slightly reduce days with substance use at post-treatment and follow-up (4 to 10 months). The evidence is uncertain regarding the impact of MBIs relative to other treatments on abstinence, consumed substance amount, or craving. MBIs result in little to no higher attrition than other treatments. Few studies reported adverse events.

Venoactive drugs (VADs) are considered an important component of the medical (conservative) treatment of chronic venous disorders (CVDs). However, the efficacy of certain VADs on one or more individual leg symptoms may have not been extensively studied to justify a high level or grade of recommendation in guidelines on CVD. The aim of the present systematic review and meta-analysis was to study the effectiveness of VADs containing Ruscus across the spectrum of defined venous symptoms. On November 14 2016, a literature search of the databases MEDLINE and Scopus was performed, supplemented by hand searching, to identify randomized double-blind placebo-controlled trials on Ruscus extracts in patients with CVD. The main outcome measures were the effects of Ruscus on individual symptoms and leg edema, which were expressed as risk ratio (RR) or standardized mean difference (SMD) with 95% confidence interval (CI). Trial quality of evidence was graded using the GRADE system. We identified 10 trials, mostly with low risk of bias, on 719 patients. On qualitative analysis, Ruscus significantly improved seven defined leg symptoms, including pain, heaviness, fatigue, feeling of swelling, cramps, itching and paresthesia compared to placebo. On quantitative analysis, Ruscus compared with placebo, assessed as a categorical variable, reduced leg pain (RR=0.35, P=0.01, number needed to treat [NNT] 5, with no heterogeneity), heaviness (RR=0.26, P<0.00001, NNT=2.4, with a small amount of heterogeneity), feeling of swelling (RR=0.53, P<0.0001, NNT=4, with considerable heterogeneity, minimized after sensitivity analysis), paresthesia (RR=0.27, P<0.0001, NNT=1.8), global symptoms (RR=0.54, P<0.00001, NNT=4.3) and the total number of venous symptoms (RR 0.41, P=0.002). Similarly, Ruscus compared to placebo, assessed as a continuous variable reduced pain (SMD=-0.80, 95% CI: -1.21 to -0.39), heaviness (SMD=-1.23, 95% CI: -1.60 to -0.86), fatigue (SMD -1.16, 95% CI: -1.71 to -0.61), feeling of swelling (SMD=-2.27, 95% CI: -3.83 to -0.70), and paresthesia (SMD=-0.86, 95% CI: -1.51 to -0.21). Regarding objective assessments of leg edema, the use of Ruscus compared with placebo reduced ankle circumference (SMD=-0.74, 95% CI: -1.01 to -0.47) and leg or foot volume (SMD=-0.61, 95% CI: -0.91 to -0.31). The existing evidence, where sufficient, was mostly of high quality. Based on high quality evidence, Ruscus extracts are highly effective in reducing symptoms and edema of patients with CVD.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited disorder causing kidney disease. Current clinical management of ADPKD focuses primarily on symptom control and reducing associated complications, particularly hypertension. In recent years, improved understanding of molecular and cellular mechanisms involved in kidney cyst growth and disease progression has resulted in new pharmaceutical agents to target disease pathogenesis to prevent progressive disease. We aimed to evaluate the effects of interventions for preventing ADPKD progression on kidney function, kidney endpoints, kidney structure, patient-centred endpoints (such as cardiovascular events, sudden death, all-cause mortality, hospitalisations, BP control, quality of life, and kidney pain), as well as the general and specific adverse effects related to their use. We searched the Cochrane Renal Group's Specialised Register to 6 June 2015 using relevant search terms. Randomised controlled trials (RCTs) comparing any interventions for preventing the progression of ADPKD with other interventions or placebo were considered for inclusion without language restriction. Two authors independently assessed study risks of bias and extracted data. We summarised treatment effects on clinical outcomes, kidney function and structure and adverse events using random effects meta-analysis. We assessed heterogeneity in estimated treatment effects using the Cochran Q test and I(2) statistic. Summary treatment estimates were calculated as a mean difference (MD) or standardised mean difference (SMD) for continuous outcomes and a risk ratio (RR) for dichotomous outcomes together with their 95% confidence intervals. We included 30 studies (2039 participants) that investigated 11 pharmacological interventions (angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), calcium channel blockers, beta blockers, vasopressin receptor 2 (V2R) antagonists, mammalian target of rapamycin (mTOR) inhibitors, somatostatin analogues, antiplatelet agents, eicosapentaenoic acids, statins and vitamin D compounds) in this review.ACEi significantly reduced diastolic blood pressure (9 studies, 278 participants: MD -4.96 mm Hg, 95% CI -8.88 to -1.04), but had uncertain effects on kidney volumes (MD -42.50 mL, 95% CI -115.68 to 30.67), GFR (MD -3.41 mL/min/1.73 m(2), 95% CI -15.83 to 9.01), and SCr (MD -0.02 mg/dL, 95% CI -0.14 to 0.09), in data largely restricted to children. ACEi did not show different effects on GFR (MD -8.19 mL/min/1.73 m(2), 95% CI -29.46 to 13.07) and albuminuria (SMD -0.19, 95% CI -1.77 to 1.39) when compared with beta-blockers, or SCr (MD 0.00 mg/dL, 95% CI -0.09 to 0.10) when compared with ARBs.Data for effects of V2R antagonists on kidney function and volumes compared to placebo were limited to narrative information within a single study while these agents increased thirst (1444 participants: RR 2.70, 95% CI 2.24 to 3.24) and dry mouth (1455 participants: RR 1.33, 95% CI 1.01 to 1.76).Compared with no treatment, mTOR inhibitors had uncertain effects on kidney function (2 studies, 115 participants: MD 4.45 mL/min/1.73 m(2), 95% CI -3.20 to 12.11) and kidney volume (MD -0.08 L, 95% CI -0.75 to 0.59) but in three studies (560 participants) caused angioedema (RR 13.39, 95% CI 2.56 to 70.00), oral ulceration (RR 6.77, 95% CI 4.42 to 10.38), infections (RR 1.14, 95% CI 1.04 to 1.25) and diarrhoea (RR 1.70, 95% CI 1.26 to 2.29).Somatostatin analogues (6 studies, 138 participants) slightly improved SCr (MD -0.43 mg/dL, 95% CI -0.86 to -0.01) and total kidney volume (MD -0.62 L, 95% CI -1.22 to -0.01) but had no definite effects on GFR (MD 9.50 mL/min, 95% CI -4.45 to 23.44) and caused diarrhoea (RR 3.72, 95% CI 1.43 to 9.68).Data for calcium channel blockers, eicosapentaenoic acids, statins, vitamin D compounds and antiplatelet agents were sparse and inconclusive.Random sequence generation was adequate in eight studies, and in almost half of the studies, blinding was not present or not specified. Most studies did not adequately report outcomes, which adversely affected our ability to assess this bias. The overall drop-out rate was over 10% in nine studies, and few were conducted using intention-to-treat analyses. Although several interventions are available for patients with ADPKD, at present there is little or no evidence that treatment improves patient outcomes in this population and is associated with frequent adverse effects. Additional large randomised studies focused on patient-centred outcomes are needed.

Enhanced recovery after surgery is increasingly applied in older adults undergoing colorectal surgery. This systematic review and meta-analysis evaluated the impact of enhanced recovery protocols on clinical outcomes including hospital-acquired geriatric syndromes in older adults undergoing colorectal surgery. This review was conducted according to PRISMA guidelines. Ovid MEDLINE, Embase, PsycINFO, Scopus, Cochrane Central Register of Controlled Trials, CINAHL, and trial registry databases were searched (January 1980 to April 2020). Two researchers independently screened all articles for eligibility. Randomized controlled trials evaluating enhanced recovery protocols in older adults undergoing colorectal surgery were included. The enhanced recovery protocol was utilized. Primary outcomes of interest were functional decline and delirium. Other outcomes studied were length of stay, complications, readmission, mortality, gut function, mobilization, pain, reoperation, quality of life, and psychological status. Seven randomized trials (n = 1277 participants) were included. In terms of hospital-acquired geriatric syndromes, functional decline was reported in 1 study with benefits reported in enhanced recovery after surgery participants, and meta-analyses showed reduced incidence of delirium (risk ratio, 0.45; 95% CI, 0.21-0.98). Meta-analyses also showed reduction in urinary tract infections (risk ratio, 0.53; 95% CI, 0.31-0.90), time to first flatus (standardized mean differences, -1.00; 95% CI, -1.98 to -0.02), time to first stool (standardized mean differences, -0.59; 95% CI, -0.76 to -0.42), time to mobilize postoperatively (standardized mean differences, -0.92; 95% CI, -1.27 to -0.58), time to achieve pain control (standardized mean differences, -0.59; 95% CI, -0.90 to -0.28), and hospital stay (mean differences, -2.20; 95% CI, -3.46 to -0.94). The small number of randomized trials in older adults is a limitation of this study. Enhanced recovery protocols in older adults undergoing colorectal surgery appear to reduce the incidence of delirium and functional decline, 2 important hospital-acquired geriatric syndromes, as well as to improve other clinical outcomes. Future research should measure these geriatric syndromes and focus on high-risk older adults including those with frailty.

Hyponatremia, defined as a nonartifactual serum sodium level <135 mmol/L, is the most common fluid and electrolyte abnormality in clinical practice. Traditional managements (fluid restriction, hypertonic saline and loop diuretics, etc.) are difficult to maintain or ineffective. Recently, vasopressin receptor antagonists (VRAs) have shown promise for the treatment of hyponatremia.We aimed to conduct a meta-analysis to evaluate the efficacy and safety of VRAs in patients with euvolemic or hypervolemic hyponatremia. We searched Pubmed, Cochrane Library, Web of Science and Springer, etc. (latest search on June 4, 2015) for English publications with randomized controlled trials. Two authors independently screened the citations and extracted data. We calculated pooled relative risk (RR), risk difference (RD), weighted mean difference (WMD) or standard mean difference (SMD), and 95% confidence intervals (CIs) by using random and fixed effect models.We collected data from 18 trials involving 1806 patients. Both random and fixed effect meta-analyses showed that VRAs significantly increased the net change of serum sodium concentration (WMDrandom = 4.89 mEq/L, 95%CIs = 4.35–5.43 and WMDfixed = 4.70 mEq/L, 95%CIs = 4.45–4.95), response rate (RRrandom = 2.77, 95%CIs = 2.29–3.36 and RRfixed = 2.95, 95%CIs = 2.56–3.41), and 24-hour urine output (SMDrandom = 0.82, 95%CIs = 0.65–1.00 and SMDfixed = 0.79, 95%CIs = 0.66–0.93) compared to placebo. Furthermore, VRAs significantly decreased body weight (WMDrandom = −0.87 kg, 95%CIs = −1.24 to −0.49 and WMDfixed = −0.91 kg, 95%CIs = −1.22 to −0.59). In terms of safety, rates of drug-related adverse events (AEs), rapid sodium level correction, constipation, dry mouth, thirst, and phlebitis in the VRA-treated group were greater than those in control group. However, there was no difference in the total number of AEs, discontinuations due to AEs, serious AEs, death, headache, hypotension, nausea, anemia, hypernatremia, urinary tract infection, renal failure, pyrexia, upper gastrointestinal bleeding, diarrhea, vomiting, peripheral edema, and dizziness between the 2 groups. Random effect meta-analyses showed that post treatment urine osmolality, supine systolic blood pressure, and diastolic blood pressure were lowered (WMDrandom = −233.07 mOsmol/kg, 95%CIs = −298.20–147.94; WMDrandom = −6.11 mmHg, 95%CIs = −9.810 to −2.41; WMDrandom = −2.59 mmHg, 95%CIs = −4.06 to −1.11, respectively), but serum osmolality was increased (WMDrandom = 9.29 mOsmol/kg, 95%CIs = 5.56–13.03). There was no significant change from baseline in serum potassium concentration between the 2 groups (WMDfixed = 0.00 mmHg, 95%CIs = −0.07–0.06).VRAs are relatively effective and safe for the treatment of hypervolemic and euvolemic hyponatremia.

Moderate- to low-quality evidence suggests that mobile bearing prostheses may have similar effects on knee pain, clinical and functional scores, health-related quality of life, revision surgery, mortality, reoperation rate and other serious adverse events compared with fixed bearing prostheses in posterior cruciate retaining TKA. Therefore we cannot draw firm conclusions. Most (98.5%) participants had OA, so the findings primarily reflect results reported in participants with OA. Future studies should report in greater detail outcomes such as those presented in this systematic review, with sufficient follow-up time to allow gathering of high-quality evidence and to inform clinical practice. Large registry-based studies may have added value, but they are subject to treatment-by-indication bias. Therefore, this systematic review of RCTs can be viewed as the best available evidence.

BackgroundThe net health benefit of using antipsychotics in children and adolescents with ASD is unclear. This review was performed to provide the evidence necessary to inform the Italian national guidelines for the management of ASD.MethodsWe performed a systematic review of randomized controlled trials (RCTs) comparing antipsychotics versus placebo for the treatment of ASD in children and adolescents. For efficacy, acceptability and safety we considered outcomes evaluated by the guideline panel critical and important for decision-making. Continuous outcomes were analyzed by using standardized mean difference (SMD), and dichotomous outcomes by calculating the risk ratio (RR), with their 95% confidence interval (95% CI). Data were analyzed using a random effects model. We used the Cochrane tool to assess risk of bias of included studies. Certainty in the evidence of effects was assessed according to the GRADE approach.ResultsWe included 21 RCTs with 1,309 participants, comparing antipsychotics to placebo. Antipsychotics were found effective on “restricted and repetitive interests and behaviors” (SMD − 0.21, 95% CI − 0.35 to − 0.07, moderate certainty), “hyperactivity, inattention, oppositional, disruptive behavior” (SMD − 0.67, 95% CI − 0.92 to − 0.42, moderate certainty), “social communication, social interaction” (SMD − 0.38, 95% CI − 0.59 to − 0.16, moderate certainty), “emotional dysregulation/irritability” (SMD − 0.71, 95% CI − 0.98 to − 0.43, low certainty), “global functioning, global improvement” (SMD − 0.64, 95% CI − 0.96 to − 0.33, low certainty), “obsessions, compulsions” (SMD − 0.30, 95% CI − 0.55 to − 0.06, moderate certainty). Antipsychotics were not effective on “self-harm” (SMD − 0.14, 95% CI − 0.58 to 0.30, very low certainty), “anxiety” (SMD − 0.38, 95% CI − 0.82 to 0.07, very low certainty). Antipsychotics were more acceptable in terms of dropout due to any cause (RR 0.61, 95% CI 0.48 to 0.78, moderate certainty), but were less safe in terms of patients experiencing adverse events (RR 1.19, 95% CI 1.07 to 1.32, moderate certainty), and serious adverse events (RR 1.07, 95% CI 0.48 to 2.43, low certainty).ConclusionsOur systematic review and meta-analysis found antipsychotics for children and adolescents with ASD more efficacious than placebo in reducing stereotypies, hyperactivity, irritability and obsessions, compulsions, and in increasing social communication and global functioning. Antipsychotics were also found to be more acceptable, but less safe than placebo.