Non-steroidal anti-inflammatory drugs (NSAIDs) for trigger finger.

BACKGROUND: Trigger finger is a common hand condition that occurs when movement of a finger flexor tendon through the first annular (A1) pulley is impaired by degeneration, inflammation, and swelling. This causes pain and restricted movement of the affected finger. Non-surgical treatment options include activity modification, oral and topical non-steroidal anti-inflammatory drugs (NSAIDs), splinting, and local injections with anti-inflammatory drugs. OBJECTIVES: To review the benefits and harms of non-steroidal anti-inflammatory drugs (NSAIDs) versus placebo, glucocorticoids, or different NSAIDs administered by the same route for trigger finger. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, CNKI (China National Knowledge Infrastructure), ProQuest Dissertations and Theses, www.ClinicalTrials.gov, and the WHO trials portal until 30 September 2020. We applied no language or publication status restrictions. SELECTION CRITERIA: We searched for randomised controlled trials (RCTs) and quasi-randomised trials of adult participants with trigger finger that compared NSAIDs administered topically, orally, or by injection versus placebo, glucocorticoid, or different NSAIDs administered by the same route. DATA COLLECTION AND ANALYSIS: Two or more review authors independently screened the reports, extracted data, and assessed risk of bias and GRADE certainty of evidence. The seven major outcomes were resolution of trigger finger symptoms, persistent moderate or severe symptoms, recurrence of symptoms, total active range of finger motion, residual pain, patient satisfaction, and adverse events. Treatment effects were reported as risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs). MAIN RESULTS: Two RCTs conducted in an outpatient hospital setting were included (231 adult participants, mean age 58.6 years, 60% female, 95% to 100% moderate to severe disease). Both studies compared a single injection of a non-selective NSAID (12.5 mg diclofenac or 15.0 mg ketorolac) given at lower than normal doses with a single injection of a glucocorticoid (triamcinolone 20 mg or 5 mg), with maximum follow-up duration of 12 weeks or 24 weeks. In both studies, we detected risk of attrition and performance bias. One study also had risk of selection bias. The effects of treatment were sensitive to assumptions about missing outcomes. All seven outcomes were reported in one study, and five in the other. NSAID injection may offer little to no benefit over glucocorticoid injection, based on low- to very low-certainty evidence from two trials. Evidence was downgraded for bias and imprecision. There may be little to no difference between groups in resolution of symptoms at 12 to 24 weeks (34% with NSAIDs, 41% with glucocorticoids; absolute effect 7% lower, 95% confidence interval (CI) 16% lower to 5% higher; 2 studies, 231 participants; RR 0.83, 95% CI 0.62 to 1.11; low-certainty evidence). The rate of persistent moderate to severe symptoms may be higher at 12 to 24 weeks in the NSAIDs group (28%) compared to the glucocorticoid group (14%) (absolute effect 14% higher, 95% CI 2% to 33% higher; 2 studies, 231 participants; RR 2.03, 95% CI 1.19 to 3.46; low-certainty evidence). We are uncertain whether NSAIDs result in fewer recurrences at 12 to 24 weeks (1%) compared to glucocorticoid (21%) (absolute effect 20% lower, 95% CI 21% to 13% lower; 2 studies, 231 participants; RR 0.07, 95% CI 0.01 to 0.38; very low-certainty evidence). There may be little to no difference between groups in mean total active motion at 24 weeks (235 degrees with NSAIDs, 240 degrees with glucocorticoid) (absolute effect 5% lower, 95% CI 34.54% lower to 24.54% higher; 1 study, 99 participants; MD -5.00, 95% CI -34.54 to 24.54; low-certainty evidence). There may be little to no difference between groups in residual pain at 12 to 24 weeks (20% with NSAIDs, 24% with glucocorticoid) (absolute effect 4% lower, 95% CI 11% lower to 7% higher; 2 studies, 231 participants; RR 0.84, 95% CI 0.54 to 1.31; low-certainty evidence). There may be little to no difference between groups in participant-reported treatment success at 24 weeks (64% with NSAIDs, 68% with glucocorticoid) (absolute effect 4% lower, 95% CI 18% lower to 15% higher; 1 study, 121 participants; RR 0.95, 95% CI 0.74 to 1.23; low-certainty evidence). We are uncertain whether NSAID injection has an effect on adverse events at 12 to 24 weeks (1% with NSAIDs, 1% with glucocorticoid) (absolute effect 0% difference, 95% CI 2% lower to 3% higher; 2 studies, 231 participants; RR 2.00, 95% CI 0.19 to 21.42; very low-certainty evidence). AUTHORS' CONCLUSIONS: For adults with trigger finger, by 24 weeks' follow-up, results from two trials show that compared to glucocorticoid injection, NSAID injection offered little to no benefit in the treatment of trigger finger. Specifically, there was no difference in resolution, symptoms, recurrence, total active motion, residual pain, participant-reported treatment success, or adverse events.

Walking for hypertension.

BACKGROUND: Increased physical activity has been recommended as an important lifestyle modification for the prevention and control of hypertension. Walking is a low-cost form of physical activity and one which most people can do. Studies testing the effect of walking on blood pressure have revealed inconsistent findings. OBJECTIVES: To determine the effect of walking as a physical activity intervention on blood pressure and heart rate. SEARCH METHODS: We searched the following databases up to March 2020: the Cochrane Hypertension Specialised Register, CENTRAL (2020, Issue 2), Ovid MEDLINE, Ovid Embase, CINAHL, PsycINFO, SPORTDiscus, PEDro, the WHO International Clinical Trials Registry Platform, and ClinicalTrials.gov. We also searched the following Chinese databases up to May 2020: Index to Taiwan Periodical Literature System; National Digital Library of Theses and Dissertation in Taiwan; China National Knowledge Infrastructure (CNKI) Journals, Theses & Dissertations; and Wanfang Medical Online. We contacted authors of relevant papers regarding further published and unpublished work. The searches had no language restrictions. SELECTION CRITERIA: Randomised controlled trials of participants, aged 16 years and over, which evaluated the effects of a walking intervention compared to non-intervention control on blood pressure and heart rate were included. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Where data were not available in the published reports, we contacted authors. Pooled results for blood pressure and heart rate were presented as mean differences (MDs) between groups with 95% confidence intervals (CIs). We undertook subgroup analyses for age and sex. We undertook sensitivity analyses to assess the effect of sample size on our findings. MAIN RESULTS: A total of 73 trials met our inclusion criteria. These 73 trials included 5763 participants and were undertaken in 22 countries. Participants were aged from 16 to 84 years and there were approximately 1.5 times as many females as males. The characteristics of walking interventions in the included studies were as follows: the majority of walking interventions was at home/community (n = 50) but supervised (n = 36 out of 47 reported the information of supervision); the average intervention length was 15 weeks, average walking time per week was 153 minutes and the majority of walking intensity was moderate. Many studies were at risk of selection bias and performance bias. Primary outcome We found moderate-certainty evidence suggesting that walking reduces systolic blood pressure (SBP) (MD -4.11 mmHg, 95% CI -5.22 to -3.01; 73 studies, n = 5060). We found moderate-certainty evidence suggesting that walking reduces SBP in participants aged 40 years and under (MD -4.41 mmHg, 95% CI -6.17 to -2.65; 14 studies, n = 491), and low-certainty evidence that walking reduces SBP in participants aged 41 to 60 years (MD -3.79 mmHg, 95% CI -5.64 to -1.94, P < 0.001; 35 studies, n = 1959), and those aged 60 years of over (MD -4.30 mmHg, 95% CI -6.17 to -2.44, 24 studies, n = 2610). We also found low certainty-evidence suggesting that walking reduces SBP in both females (MD -5.65 mmHg, 95% CI -7.89 to -3.41; 22 studies, n = 1149) and males (MD -4.64 mmHg, 95% CI -8.69 to -0.59; 6 studies, n = 203). Secondary outcomes We found low-certainty evidence suggesting that walking reduces diastolic blood pressure (DBP) (MD -1.79 mmHg, 95% CI -2.51 to -1.07; 69 studies, n = 4711) and heart rate (MD -2.76 beats per minute (bpm), 95% CI -4.57 to -0.95; 26 studies, n = 1747). We found moderate-certainty evidence suggesting that walking reduces DBP for participants aged 40 years and under (MD -3.01 mmHg, 95% CI -4.44 to -1.58; 14 studies, n = 491) and low-certainty evidence suggesting that walking reduces DBP for participants aged 41 to 60 years (MD -1.74 mmHg, 95% CI -2.95 to -0.52; 32 studies, n = 1730) and those aged 60 years and over (MD -1.33 mmHg, 95% CI -2.40 to -0.26; 23 studies, n = 2490). We found moderate-certainty evidence that suggests walking reduces DBP for males (MD -2.54 mmHg, 95% CI -4.84 to -0.24; 6 studies, n = 203) and low-certainty evidence that walking reduces DBP for females (MD -2.69 mmHg, 95% CI -4.16 to -1.23; 20 studies, n = 1000). Only 21 included studies reported adverse events. Of these 21 studies, 16 reported no adverse events, the remaining five studies reported eight adverse events, with knee injury being reported five times. AUTHORS' CONCLUSIONS: Moderate-certainty evidence suggests that walking probably reduces SBP. Moderate- or low-certainty evidence suggests that walking may reduce SBP for all ages and both sexes. Low-certainty evidence suggests that walking may reduce DBP and heart rate. Moderate- and low-certainty evidence suggests walking may reduce DBP and heart rate for all ages and both sexes.

Traditional Chinese herbal medicine for vascular dementia.

BACKGROUND: Traditional Chinese herbal medicine (TCHM) is widely used for treating vascular dementia (VaD) in China. Recent studies of a number of TCHMs have demonstrated in vitro biological activity and therapeutic effects in animals, but the published clinical evidence has not been systematically appraised. OBJECTIVES: To evaluate the efficacy and safety of TCHMs listed in either the Chinese Pharmacopoeia (CP) or the Chinese National Essential Drug List (NEDL) that are used to treat VaD. A secondary aim was to identify promising TCHMs for further clinical research. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's Specialised Register (on 14 March 2018) and also several Chinese biomedical databases: the Chinese Biological Medicine Database (January 1979 to May 2015), Wanfang database (January 1998 to May 2015), Chongqing VIP Information Co. Ltd or Weipu (January 1998 to May 2015) and the Chinese National Knowledge Infrastructure (January 1979 to May 2015). SELECTION CRITERIA: We included randomised controlled trials (RCTs) of TCHMs compared to placebo, to Western medicine (WM) or to routine therapy for VaD risk factors. Eligible participants were men and women aged 18 years and above, diagnosed with VaD by any of the following four criteria: (1) Diagnostic and Statistical Manual of Mental Disorders (DSM) versions III, III-R, IV, IV-TR; (2) National Institute of Neurological Disorders and Stroke (NINDS-AIREN); (3) International Classification of Diseases 9 or 10; (4) the Hachinski or the Modified Hachinski Ischaemic Score. We required the use of an imaging technique to differentiate VaD from other dementias. We excluded (1) trials with participants diagnosed with mixed dementia or those that did not use an imaging technique to ascertain VaD; (2) trials of NEDL-listed Gingko biloba or Huperzine A as experimental interventions, to avoid duplication of existing Cochrane Reviews; (3) trials using acupuncture alone as the experimental intervention; (4) trials using another CP- or NEDL-listed TCHM (except for Huperzine A and Gingko which are popular in Western practice) as the control intervention; and (5) trials using purely non-pharmacological interventions as the control intervention unless explicitly described as 'routine therapy for VaD risk factors'. DATA COLLECTION AND ANALYSIS: We assessed the risks of bias using the Cochrane 'Risk of bias' tool and adapted the Outcome Reporting Bias in Trials (ORBIT) classification system for outcome reporting bias. We assessed TCHM effects on five clinically important outcomes: cognition, global performance, safety, activities of daily living and behaviour and summarised the effects using mean differences for continuous outcomes and risk ratios or risk differences for binary outcomes. We stratified the studies into those that estimated the TCHM versus 'no treatment' effect and those that estimated the TCHM versus the WM effect, with further stratification by the specific TCHM tested or by one of the four modes of action. We pooled using a random-effects model. Due to substantial clinical and design heterogeneity, we did not estimate an 'overall TCHM effect'. MAIN RESULTS: We only found studies (47 studies, 3581 participants) for 18 of the 29 eligible TCHMs as defined by our inclusion criteria. All were superiority trials conducted in China between 1997 and 2013, with most employing a two-arm parallel design with sample sizes ranging from 26 to 240 and a median treatment duration of 12 weeks (range: 2 to 24 weeks).We found that reporting and trial methodology were generally poor; in particular, there was a lack of information on randomisation, an absence of blinding of participants and outcome assessors and incomplete reporting of adverse events (AEs). None of the 30 trials published from 2007 onwards adopted the CONSORT recommendations for reporting RCTs of herbal interventions.We found seven TCHMs which each had potentially large benefits in studies estimating the TCHM versus 'no treatment' effect and in studies estimating the TCHM versus the WM effect. Two TCHMs (NaoXinTong and TongXinLuo) were common to both groups. Three of these TCHMs - Nao XinTong, NaoMaiTai and TongXinLuo - had the strongest evidence to justify further research. Two TCHMs (NaoMaiTai and TongXinLuo) had a 5% or more increased risk of AEs compared to the 'no Treatment' control, but the quality of this evidence was poor. AUTHORS' CONCLUSIONS: We found moderate- to very low-quality evidence of benefit and harm of TCHMs for VaD. Methodological inadequacies need to be addressed by better conducted and reported trials. We identified NaoMaiTai, NaoXinTong and TongXinLuo as warranting special research priority.

Omega-3 fatty acids for dialysis vascular access outcomes in patients with chronic kidney disease.

BACKGROUND: Maintaining long-term vascular access patency is necessary for high quality haemodialysis (HD) treatment of patients with the terminal and most serious stage of chronic kidney disease (CKD) - end-stage kidney disease (ESKD). Oral supplementation with omega-3 fatty acids (ω-3FA) may help to prevent blockage of the vascular access by reducing the risk of thrombosis and stenosis. OBJECTIVES: To evaluate the efficacy and safety of ω-3FA supplementation versus placebo or no treatment for maintaining vascular access patency in ESKD patients undergoing HD. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 23 July 2018 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal, and ClinicalTrials.gov. SELECTION CRITERIA: Randomised controlled trials (RCTs) of omega-3 fatty acids versus placebo that assessed the patency of arteriovenous fistula (AVF) or arteriovenous graft (AVG) types of vascular access in ESKD patients. DATA COLLECTION AND ANALYSIS: We assessed the risk of bias of each eligible study using the Cochrane Risk of Bias tool and made separate overall risk of bias judgments for the efficacy and safety outcomes. The certainty of evidence was assessed using the GRADE approach. The primary efficacy outcome was loss of vascular patency and the primary safety outcomes were occurrences of serious adverse events (e.g. death, hospitalisation, cardiovascular events, major bleeding). Secondary outcomes were the occurrence of non-serious adverse events (e.g. minor bleeding, gastrointestinal events and other adverse events). Efficacy effects were reported as risk ratios (RR) and safety effects as risk differences (RD) with 95% confidence intervals (CI). Studies were pooled separately by type of vascular access using a random-effects model. MAIN RESULTS: Five studies (833 participants) were included; one was a very small pilot study of 7 participants. All studies compared oral ω-3FA supplements against placebo. Four studies enrolled participants with arteriovenous grafts (AVGs), and the other had participants with arteriovenous fistulas (AVFs). The risk of bias for both efficacy and safety outcomes was unclear for all studies, due mainly to incomplete reporting for allocation concealment and incompleteness of study follow-up.In AVF patients, ω-3FA supplementation probably makes little or no difference to the 12-month risk of patency loss (1 study, 536 participants: RR 1.01, 95% CI 0.84 to 1.21; moderate certainty evidence), risk of death (1 study, 567 participants: RD 0.00, 95% CI -0.03 to 0.02; moderate certainty evidence) and risk of hospitalisation (1 study, 567 participants: RD 0.00, 95% CI -0.08 to 0.08; low certainty evidence). There was no information on cardiovascular events and major bleeding.In AVG patients, it is very uncertain whether ω-3FA supplementation reduces the risk of patency loss within 6 months (2 studies, 41 participants: RR 0.91, 95% CI 0.36 to 2.28; very low certainty evidence) or 12 months (2 studies, 220 participants: RR 0.59, 95% CI 0.27 to 1.31; very low certainty evidence). ω-3FA supplementation may make little or no difference to the risk of death within 6 to 12 months in AVG patients (4 studies, 261 participants: RD 0.01, 95% CI -0.05 to 0.07; low certainty evidence). It is very uncertain if ω-3FA supplementation increases the risk of hospitalisation (3 studies, 65 participants: RD 0.08, 95% CI -0.11 to 0.28; very low certainty evidence), changes the risk of cardiovascular events (4 studies, 261 participants: RD -0.02, 95% CI -0.11 to 0.07; very low certainty evidence), or increases the risk of major bleeding (3 studies, 65 participants: RD 0.08, 95% CI -0.11 to 0.28; very low certainty evidence) within 6 to 12 months in AVG patients. There may be an increase in the risk of mild gastrointestinal adverse reactions (3 studies, 65 participants: RD 0.25, 95% CI 0.07 to 0.43; low certainty evidence) such as a sensation of bloatedness, gas or a fishy aftertaste. AUTHORS' CONCLUSIONS: In CKD patients with an AVF, there is moderate certainty that ω-3FA supplementation makes little or no difference to preventing patency loss; and in patients with an AVG, it is very uncertain that ω-3FA supplementation prevents patency loss within 12 months.

Automated mandatory bolus versus basal infusion for maintenance of epidural analgesia in labour.

BACKGROUND: Childbirth may cause the most severe pain some women experience in their lifetime. Epidural analgesia is an effective form of pain relief during labour and is considered to be the reference standard. Traditionally epidural analgesia has been delivered as a continuous infusion via a catheter in the epidural space, with or without the ability for the patient to supplement the analgesia received by activating a programmable pump to deliver additional top-up doses, known as patient-controlled epidural analgesia (PCEA). There has been interest in delivering maintenance analgesic medication via bolus dosing (automated mandatory bolus - AMB) instead of the traditional continuous basal infusion (BI); recent randomized controlled trials (RCTs) have shown that the AMB technique leads to improved analgesia and maternal satisfaction. OBJECTIVES: To assess the effects of automated mandatory bolus versus basal infusion for maintaining epidural analgesia in labour. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, the World Health Organization International Clinial Trials Registry Platform (WHO-ICTRP) and ClinicalTrials.gov on 16 January 2018. We screened the reference lists of all eligible trials and reviews. We also contacted authors of included studies in this field in order to identify unpublished research and trials still underway, and we screened the reference lists of the included articles for potentially relevant articles. SELECTION CRITERIA: We included all RCTs that compared the use of bolus dosing AMB with continuous BI for providing pain relief during epidural analgesia for labour in women. DATA COLLECTION AND ANALYSIS: We used the standard methodological procedures expected by Cochrane. Our primary outcomes were: risk of breakthrough pain with the need for anaesthetic intervention; risk of caesarean delivery; risk of instrumental delivery. Secondary outcomes included: duration of labour; local anaesthetic consumption. We used GRADE to assess the certainty of evidence for each outcome. MAIN RESULTS: We included 12 studies with a total of 1121 women. Ten studies enrolled healthy nulliparous women only and two studies enrolled healthy parous women at term as well. All studies excluded women with complicated pregnancies. There were variations in the technique of initiation of epidural analgesia. Seven studies utilized the combined spinal epidural (CSE) technique, and the other five studies only placed an epidural catheter without any intrathecal injection. Seven studies utilized ropivacaine: six with fentanyl and one with sufentanil. Two studies used levobupivacaine: one with sufentanil and one with fentanyl. Three used bupivacaine with or without fentanyl. The overall risk of bias of the studies was low.AMB probably reduces the risk of breakthrough pain compared with BI for maintaining epidural analgesia for labour (from 33% to 20%; risk ratio (RR) 0.60; 95% confidence interval (CI) 0.39 to 0.92, 10 studies, 797 women, moderate-certainty evidence). AMB may make little or no difference to the risk of caesarean delivery compared to BI (15% and 16% respectively; RR 0.92; 95% CI 0.70 to 1.21, 11 studies, 1079 women, low-certainty evidence).AMB may make little or no difference in the risk of instrumental delivery compared to BI (12% and 9% respectively; RR 0.75; 95% CI 0.54 to 1.06, 11 studies, 1079 women, low-certainty evidence). There is probably little or no difference in the mean duration of labour with AMB compared to BI (mean difference (MD) -10.38 min; 95% CI -26.73 to 5.96, 11 studies, 1079 women, moderate-certainty evidence). There is probably a reduction in the hourly consumption of local anaesthetic with AMB compared to BI for maintaining epidural analgesia during labour (MD -1.08 mg/h; 95% CI -1.78 to -0.38, 12 studies, 1121 women, moderate-certainty evidence). Five out of seven studies reported an increase in maternal satisfaction with AMB compared to BI for maintaining epidural analgesia for labour; however, we did not pool these data due to their ordinal nature. Seven studies reported Apgar scores, though there was significant heterogeneity in reporting. None of the studies showed any significant difference between Apgar scores between groups. AUTHORS' CONCLUSIONS: There is predominantly moderate-certainty evidence that AMB is similar to BI for maintaining epidural analgesia for labour for all measured outcomes and may have the benefit of decreasing the risk of breakthrough pain and improving maternal satisfaction while decreasing the amount of local anaesthetic needed.

Estimating Information Processing in a Memory System: The Utility of Meta-analytic Methods for Genetics.

Genetic studies in Drosophila reveal that olfactory memory relies on a brain structure called the mushroom body. The mainstream view is that each of the three lobes of the mushroom body play specialized roles in short-term aversive olfactory memory, but a number of studies have made divergent conclusions based on their varying experimental findings. Like many fields, neurogenetics uses null hypothesis significance testing for data analysis. Critics of significance testing claim that this method promotes discrepancies by using arbitrary thresholds (α) to apply reject/accept dichotomies to continuous data, which is not reflective of the biological reality of quantitative phenotypes. We explored using estimation statistics, an alternative data analysis framework, to examine published fly short-term memory data. Systematic review was used to identify behavioral experiments examining the physiological basis of olfactory memory and meta-analytic approaches were applied to assess the role of lobular specialization. Multivariate meta-regression models revealed that short-term memory lobular specialization is not supported by the data; it identified the cellular extent of a transgenic driver as the major predictor of its effect on short-term memory. These findings demonstrate that effect sizes, meta-analysis, meta-regression, hierarchical models and estimation methods in general can be successfully harnessed to identify knowledge gaps, synthesize divergent results, accommodate heterogeneous experimental design and quantify genetic mechanisms.

Immunotherapy for diabetic amyotrophy.

BACKGROUND: People with diabetes mellitus (DM) sometimes present with acute or subacute, progressive, asymmetrical pain and weakness of the proximal lower limb muscles. The various names for the condition include diabetic amyotrophy, diabetic lumbosacral radiculoplexus neuropathies, diabetic femoral neuropathy or Bruns-Garland syndrome. Some studies suggest that diabetic amyotrophy may be an immune-mediated inflammatory microvasculitis causing ischaemic damage of the nerves. Immunotherapies would therefore be expected to be beneficial. This is the second update of a review first published in 2009. OBJECTIVES: To review the evidence from randomised trials for the efficacy of any form of immunotherapy in the treatment of diabetic amyotrophy. SEARCH METHODS: On 5 September 2016 we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE and Embase. We also contacted authors of relevant publications and other experts to obtain additional references, unpublished trials, and ongoing trials. SELECTION CRITERIA: We intended to include all randomised and quasi-randomised trials of any immunotherapy in participants with the condition fulfilling all the following: diabetes mellitus as defined by internationally recognised criteria; acute or subacute onset of pain and lower motor neuron weakness involving predominantly the proximal muscles of the lower limbs; weakness that is not confined to one nerve or nerve root distribution; and exclusion of other causes of lumbosacral radiculopathies and plexopathy. DATA COLLECTION AND ANALYSIS: Two authors independently examined all references retrieved by the search to select those meeting the inclusion criteria. MAIN RESULTS: We found only one completed placebo-controlled trial (N = 75) using intravenous methylprednisolone in diabetic amyotrophy (Dyck 2006). The results have not been fully published and were not available for analysis. The risk of bias was unclear because there was too little information to make a judgement, but we considered the trial at high risk of selective reporting. The published abstract did not report adverse events. We found no additional trials when the searches were updated in September 2016. AUTHORS' CONCLUSIONS: There is presently no evidence from randomised trials to support a positive or negative effect of any immunotherapy in the treatment in diabetic amyotrophy.

Hyperbaric versus isobaric bupivacaine for spinal anaesthesia for caesarean section.

BACKGROUND: Bupivacaine is an amide local anaesthetic used in hyperbaric and isobaric forms. These are administered intrathecally into the spine to provide regional anaesthesia for caesarean section. Several trials have compared hyperbaric and isobaric bupivacaine but none have conclusively shown the benefit of either. This review was first published in 2013 and updated in 2016. OBJECTIVES: Our objectives were to:1. Determine the effectiveness of hyperbaric bupivacaine compared to isobaric bupivacaine for spinal anaesthesia in women undergoing caesarean section;2. Determine the safety of hyperbaric bupivacaine compared to isobaric bupivacaine for spinal anaesthesia in women undergoing caesarean section. SEARCH METHODS: We originally searched the following databases to January 2011: CENTRAL, MEDLINE and Embase.For this update, we reran our search in the above databases from January 2011 to March 2016; two studies are awaiting a response from authors for assessment and will be dealt with when we next update the review.We imposed no language restriction. SELECTION CRITERIA: We included all randomized controlled trials (RCTs) involving parturients undergoing spinal anaesthesia for elective caesarean section that compared the use of hyperbaric with isobaric bupivacaine. DATA COLLECTION AND ANALYSIS: Two authors independently extracted the data. The data that were extracted included the number of events and the sample sizes in both the intervention and control groups. For continuous outcomes, we extracted mean and standard deviation.We reported odds ratios (ORs) and risk ratios (RRs) for binary outcomes, and mean differences (MDs) for continuous outcomes. MAIN RESULTS: We included three new RCTs in this update, which now comprises 10 studies with a total of 614 participants. We judged most trials as having uncertain risk of bias regarding randomization. Other than this, the overall risk of bias was low. Most included trials had small sample sizes. All of the trials assessed the primary outcome of conversion to general anaesthesia. Ten trials comparing anaesthesia performed with hyperbaric and isobaric bupivacaine failed to show any difference in need for conversion to general anaesthesia (RR 0.33, 95% CI 0.09 to 1.17, 614 participants, very low quality of evidence). Nine trials also failed to show a difference in the need for supplemental analgesics (RR 0.61, 95% CI 0.26 to 1.41, 554 participants, very low quality of evidence). Four trials comparing requirement for ephedrine did not show any difference (RR 0.89, 95% CI 0.57 to 1.38, 256 participants, very low quality of evidence). Seven trials did not provide convincing evidence of difference in nausea and vomiting (RR 0.99, 95% CI 0.57 to 1.72, 433 participants, low quality of evidence). Three trials failed to show a difference in headache (OR 1.82, 95% CI 0.47 to 6.99, 234 participants, low quality of evidence). Two trials showed that the time until sensory block to the thoracic 4th (T4) spinal level was shorter with hyperbaric bupivacaine (MD -1.06 minutes, 95% CI -1.80 to -0.31, 128 participants, moderate quality of evidence). Six trials showed no difference in the amount of ephedrine used (RR 0.23, 95% CI -1.65 to 2.12, 386 participants, moderate quality of evidence). Three trials failed to show any difference in high block (RR 0.88, 95% CI 0.16 to 4.90, 205 participants). AUTHORS' CONCLUSIONS: Data are limited for some of the outcomes. Reporting of the included trials is less than optimal. For these reasons the overall quality of evidence is low or very low for most of the outcomes, based on the GRADE method of assessment. This review found that intrathecal hyperbaric bupivacaine had a more rapid onset of sensory blockade at the 4th thoracic vertebra (T4) level than isobaric bupivacaine. Hower, despite incorporating more data in the analysis, we found little evidence that the need for conversion to general anaesthesia and supplemental analgesia differed between the hyperbaric or isobaric bupivacaine groups. This is mainly due to the rarity of these outcomes, variability in the dose, use of adjuvant drugs and differences in the technique used for regional anaesthesia. There were no differences in the adverse effects studied. Any possible advantage of hyperbaric bupivacaine needs to be confirmed in larger randomized trials. In future research, criteria for conversion to general anaesthesia need to be defined objectively and applied uniformly.

Pitfalls in evidence assessment: the case of chlorhexidine and alcohol in skin antisepsis.

Chlorhexidine has attracted increasing attention for its role in skin antisepsis in recent years. It was tested in several prominent clinical trials and subsequently recommended in important guidelines for blood culture collection, vascular catheter insertion and surgical skin preparation. We noticed and subsequently reported a widespread misinterpretation of evidence surrounding chlorhexidine and its role in skin antisepsis. Multiple clinical trial reports and systematic reviews that had assessed the clinical efficacy of chlorhexidine/alcohol combinations for skin antisepsis had attributed efficacy solely to the chlorhexidine component. This misinterpretation was carried over into the tertiary literature, including evidence-based guidelines. Here we discuss some of the scientific, ethical, patient safety and infection control implications of this misinterpretation, as well as broader implications for evidence-based medicine.

A randomised controlled trial evaluating the impact of targeted vitamin D supplementation on endothelial function in type 2 diabetes mellitus: The DIMENSION trial.

We sought to determine if vitamin D supplementation, to target 25(OH)D concentrations of 30-40 ng/mL, improves endothelial function in Singapore's multi-ethnic type 2 diabetes mellitus population. We randomised 64 type 2 diabetes mellitus patients with hypovitaminosis D to cholecalciferol 4000 International Unit/matching placebo [baseline 25(OH)D < 20 ng/mL] or cholecalciferol 2000 International Unit/matching placebo [baseline 25(OH)D: 20-30 ng/mL] daily for 16 weeks with a down titration at 8 weeks if 25(OH)D > 30 ng/mL. Endothelial function was assessed by peripheral tonometry (reactive hyperaemia index-endothelial peripheral arterial tonometry) and vascular biomarkers: E-selectin, von-Willebrand factor and high-sensitivity C-reactive protein. We compared the change from baseline parameters in the two groups using Student's t-test or Kruskal-Wallis test. A log-normal multivariate regression analysis was used to adjust for relevant baseline variables. The median reactive hyperaemia index in the vitamin D group increased from 0.65 (interquartile range: 0.42) to 0.73 (interquartile range: 0.36), whereas it decreased from 0.73 (interquartile range: 0.65) to 0.65 (interquartile range: 0.38) (p = 0.02) in the placebo group. After adjustment for baseline variables, the change was not statistically significant for reactive hyperaemia index (p = 0.07) and for other vascular biomarkers (p > 0.05). Targeted vitamin D supplementation for 16 weeks resulted in a small but non-significant improvement in endothelial function in a type 2 diabetes mellitus cohort.

Thyroid Autoimmune Antibodies and Major Depressive Disorder in Women.

INTRODUCTION: Anti-thyroid antibodies are associated with extra-thyroid diseases such as Graves' ophthalmopathy and Hashimoto's encephalopathy. Some evidence suggests that anti-thyroid antibodies are also associated with depression. Interleukin (IL)-17 appears to play an important role in autoimmune thyroid disease. This study investigated whether specific thyroid autoantibodies and IL-17 distinguished persons with depression from non-depressed controls. MATERIALS AND METHODS: Forty-seven adult females with non-psychotic, current major depressive disorder and 80 healthy female controls participated in this study. Thyroid peroxidase antibodies, thyroglobulin antibodies, thyroid-stimulating hormone (TSH) receptor antibodies, free T3 and T4, TSH and IL-17 were measured from the serum. Measurements were repeated to assess test-retest reliability. Receiver operating characteristic (ROC) curves were used to estimate discriminatory values of the measurements. Differences between groups and associations between the clinical and biochemical assessments were analysed. RESULTS: Median TSH receptor antibody concentration was significantly higher in the depressed than control group (P <0.001). Area under the ROC curve was 0.80 (95% CI, 0.73 to 0.88). Higher TSH receptor antibody titres were associated with greater depression severity scores (r = 0.33, P <0.05). IL-17 levels were not associated with TSH receptor antibody levels or depression severity scores. Thyroid function and other thyroid autoantibodies were not associated with depression severity. CONCLUSION: TSH receptor antibodies might be a biomarker of immune dysfunction in depression.