Adverse Events In People Research Articles

Prophylactic antibiotics for adults with chronic obstructive pulmonary disease: a network meta-analysis.

Prophylactic antibiotics for adults with chronic obstructive pulmonary disease: a network meta-analysis.

Real-World Safety of CFTR Modulators in the Treatment of Cystic Fibrosis: A Systematic Review.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapies target the underlying cause of cystic fibrosis (CF), and are generally well-tolerated; however, real-world studies indicate the frequency of discontinuation and adverse events (AEs) may be higher than what was observed in clinical trials. The objectives of this systematic review were to summarize real-world AEs reported for market-available CFTR modulators (i.e., ivacaftor (IVA), lumacaftor/ivacaftor (LUM/IVA), tezacaftor/ivacaftor (TEZ/IVA), and elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA)), and to identify ways in which the pharmacist on CF healthcare teams may contribute to mitigating and managing these AEs. The MEDLINE, EMBASE, CINAHL, and Web of Science Core Collection online databases were searched from 2012 to 1 Aug 2020. Full manuscripts or conference abstracts of observational studies, case series, and case reports were eligible for inclusion. The included full manuscripts and conference abstracts comprised of 54 observational studies, 5 case series, and 9 case reports. The types of AEs reported generally aligned with what have been observed in clinical trials. LUM/IVA was associated with a higher frequency of respiratory-related AE and discontinuation in real-world studies. A signal for mental health and neurocognitive AEs was identified with all 4 CFTR modulators. A systematic approach to monitoring for AEs in people with CF on CFTR modulators in the real-world setting is necessary to help better understand potential AEs, as well as patient characteristics that may be associated with higher risk of certain AEs. Pharmacists play a key role in the safe initiation and monitoring of people with CF on CFTR modulator therapies.

Transcranial direct current stimulation (tDCS) for improving activities of daily living, and physical and cognitive functioning, in people after stroke.

Transcranial direct current stimulation (tDCS) for improving activities of daily living, and physical and cognitive functioning, in people after stroke.

The effect of statin therapy on disease-related outcomes in idiopathic pulmonary fibrosis: A systematic review and meta-analysis

BackgroundIdiopathic pulmonary fibrosis is a progressive disease and antifibrotic therapies do not reverse existing fibrosis. There has been emerging evidence of potential role for statins in idiopathic pulmonary fibrosis. The aim of this review is to synthesise the evidence on the efficacy of statins in idiopathic pulmonary fibrosis, focusing on associations with all-cause mortality, disease-specific mortality and change in pulmonary function. MethodsMedline and Embase were reviewed to identify relevant publications. Studies were selected if they examined disease-related outcomes including mortality, pulmonary function and adverse events in people with idiopathic pulmonary fibrosis receiving statin therapy. ResultsFive studies with a total of 3407 people with IPF were selected and analysed. The overall risk of bias of five included studies was moderate to serious. In the fixed effect meta-analysis, statin use was associated with a reduction in mortality (RR 0.8; 95% CI 0.72–0.99). However, in the random effects model, there was no longer any significant association between statin use and all-cause mortality (RR 0.87; 95% CI 0.68–1.12). There was no statistically significant association between statin use and decline in FVC % predicted. ConclusionThere is currently insufficient evidence to conclude the effect of statin therapy on disease-related outcomes in idiopathic pulmonary fibrosis. Considering the limitations of available literature, we would recommend a prospective cohort study with capture of dosage and preparation of statin, statin adherence and use of concurrent antifibrotic treatment. PROSPERO registration numberCRD42019122745.

Non-nutritive sweeteners for diabetes mellitus.

Products sweetened with non-nutritive sweeteners (NNS) are widely available. Many people with type 1 or type 2 diabetes use NNS as a replacement for nutritive sweeteners to control their carbohydrate and energy intake. Health outcomes associated with NNS use in diabetes are unknown. To assess the effects of non-nutritive sweeteners in people with diabetes mellitus. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Scopus, the WHO ICTRP, and ClinicalTrials.gov. The date of the last search of all databases (except for Scopus) was May 2019. We last searched Scopus in January 2019. We did not apply any language restrictions. We included randomised controlled trials (RCTs) with a duration of four weeks or more comparing any type of NNS with usual diet, no intervention, placebo, water, a different NNS, or a nutritive sweetener in individuals with type 1 or type 2 diabetes. Trials with concomitant behaviour-changing interventions, such as diet, exercise, or both, were eligible for inclusion, given that the concomitant interventions were the same in the intervention and comparator groups. Two review authors independently screened abstracts, full texts, and records retrieved from trials registries, assessed the certainty of the evidence, and extracted data. We used a random-effects model to perform meta-analysis, and calculated effect estimates as risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs). We assessed risk of bias using the Cochrane 'Risk of bias' tool and the certainty of evidence using the GRADE approach. We included nine RCTs that randomised a total of 979 people with type 1 or type 2 diabetes. The intervention duration ranged from 4 to 10 months. We judged none of these trials as at low risk of bias for all 'Risk of bias' domains; most of the included trials did not report the method of randomisation. Three trials compared the effects of a dietary supplement containing NNS with sugar: glycosylated haemoglobin A1c (HbA1c) was 0.4% higher in the NNS group (95% CI -0.5 to 1.2; P = 0.44; 3 trials; 72 participants; very low-certainty evidence). The MD in weight change was -0.1 kg (95% CI -2.7 to 2.6; P = 0.96; 3 trials; 72 participants; very low-certainty evidence). None of the trials with sugar as comparator reported on adverse events. Five trials compared NNS with placebo. The MD for HbA1c was 0%, 95% CI -0.1 to 0.1; P = 0.99; 4 trials; 360 participants; very low-certainty evidence. The 95% prediction interval ranged between -0.3% and 0.3%. The comparison of NNS versus placebo showed a MD in body weight of -0.2 kg, 95% CI -1 to 0.6; P = 0.64; 2 trials; 184 participants; very low-certainty evidence. Three trials reported the numbers of participants experiencing at least one non-serious adverse event: 36/113 participants (31.9%) in the NNS group versus 42/118 participants (35.6%) in the placebo group (RR 0.78, 95% CI 0.39 to 1.56; P = 0.48; 3 trials; 231 participants; very low-certainty evidence). One trial compared NNS with a nutritive low-calorie sweetener (tagatose). HbA1c was 0.3% higher in the NNS group (95% CI 0.1 to 0.4; P = 0.01; 1 trial; 354 participants; very low-certainty evidence). This trial did not report body weight data and adverse events. The included trials did not report data on health-related quality of life, diabetes complications, all-cause mortality, or socioeconomic effects. There is inconclusive evidence of very low certainty regarding the effects of NNS consumption compared with either sugar, placebo, or nutritive low-calorie sweetener consumption on clinically relevant benefit or harm for HbA1c, body weight, and adverse events in people with type 1 or type 2 diabetes. Data on health-related quality of life, diabetes complications, all-cause mortality, and socioeconomic effects are lacking.

Naloxone dosing in the era of ultra-potent opioid overdoses: a systematic review.

Evaluate the relationship between naloxone dose (initial and cumulative) and opioid toxicity reversal and adverse events in undifferentiated and presumed fentanyl/ultra-potent opioid overdoses. We searched Embase, MEDLINE, Cochrane Central Register of Controlled Trials, DARE, CINAHL, Science Citation Index, reference lists, toxicology websites, and conference proceedings (1972 to 2018). We included interventional, observational, and case studies/series reporting on naloxone dose and opioid toxicity reversal or adverse events in people >12 years old. A total of 174 studies (110 case reports/series, 57 observational, 7 interventional) with 26,660 subjects (median age 35 years; 74% male). Heterogeneity precluded meta-analysis. Where reported, we abstracted naloxone dose and proportion of patients with toxicity reversal. Among patients with presumed exposure to fentanyl/ultra-potent opioids, 56.9% (617/1,085) responded to an initial naloxone dose ≤0.4 mg compared with 80.2% (170/212) of heroin users, and 30.4% (7/23) responded to an initial naloxone dose >0.4 mg compared with 59.1% (1,434/2,428) of heroin users. Among patients who responded, median cumulative naloxone doses were higher for presumed fentanyl/ultra-potent opioids than heroin overdoses in North America, both before 2015 (fentanyl/ultra-potent opioids: 1.8 mg [interquartile interval {IQI}, 1.0, 4.0]; heroin: 0.8 mg [IQI, 0.4, 0.8]) and after 2015 (fentanyl/ultra-potent opioids: 3.4 mg [IQI, 3.0, 4.1]); heroin: 2 mg [IQI, 1.4, 2.0]). Where adverse events were reported, 11% (490/4,414) of subjects experienced withdrawal. Variable reporting, heterogeneity and poor-quality studies limit conclusions. Practitioners have used higher initial doses, and in some cases higher cumulative naloxone doses to reverse toxicity due to presumed fentanyl/ultra-potent opioid exposure compared with other opioids. High-quality comparative naloxone dosing studies assessing effectiveness and safety are needed.

Motor neuroprosthesis for promoting recovery of function after stroke.

Motor neuroprosthesis for promoting recovery of function after stroke.

Factors associated to modification of first-line antiretroviral therapy due to adverse events in people living with HIV/AIDS

Antiretroviral therapy (ART) has modified the outcome of patients with HIV infection, providing virological control and reducing mortality. However, there are several reasons as to why patients may discontinue their antiretroviral therapy, with adverse events being one of the main reasons reported in the literature. This is a case-control nested in a cohort of people living with HIV/AIDS, conducted to identify the incidence of ART modification due to adverse events and the associated factors, in two referral services in Recife, Brazil, between 2011 and 2014. Of the modifications occurred in the first year of ART, 25.7% were driven by adverse events. The median time elapsed between initiating ART and the first modification due to adverse events was 70.5 days (95% CI: 26-161 days). The main adverse events were dermatological, neuropsychiatric and gastrointestinal. Dermatological events were the earliest to appear after initiating ART. Efavirenz was the most prescribed and most modified drug during the study period. The group of participants who used zidovudine, lamivudine, and efavirenz had a 2-fold greater chance (adjusted OR: 2.16 95% CI: 1.28-3.65) of switching ART due to adverse events when compared to the group that used tenofovir with lamivudine and efavirenz.

Long-term effectiveness and safety of varenicline and nicotine replacement therapy in people with neurodevelopmental disorders: A prospective cohort study

This study aimed to determine the effectiveness and safety of varenicline versus NRT for smoking cessation in people with neurodevelopmental disorders, compared to those without, at up to four years after exposure. We analysed electronic medical records from the Clinical Practice Research Datalink using three different statistical approaches: multivariable logistic regression, propensity score matching (PSM), and instrumental variable analysis. Exposure was prescription of varenicline versus NRT and the primary outcome was smoking cessation at 2-years. We included 235,314 people aged 18 and above with eligible smoking cessation prescriptions in the effectiveness analysis. Smokers with neurodevelopmental disorders were 48% less likely (95% confidence interval: 42%, 54%) to be prescribed varenicline than NRT, compared to smokers without neurodevelopmental disorders. At 2-year follow-up, smokers with neurodevelopmental disorders prescribed varenicline were 38% more likely to quit smoking (95% confidence interval: 6%, 78%). Similar results were obtained using PSM and instrumental variable analyses. There was little evidence showing that varenicline increased the likelihood of mental health related adverse events in people with neurodevelopmental disorders. Varenicline is less likely to be prescribed to people with neurodevelopmental disorders despite results suggesting it is more effective than NRT and little evidence of increased likelihood of mental health related adverse events.

Maternal Parenting Stress Following Paternal or Close Family Incarceration: Bayesian Model-Based Profiling Using the HILDA Longitudinal Survey

Objectives To: (1) examine the existence and extent of heterogeneity in efects of paternal incarceration (PI) or close family incarceration (CFI) on maternal parenting stress; (2) identify key variables related to the efect of PI and CFI on maternal parenting stress. Methods Using data from HILDA, an Australian longitudinal survey, we investigate changes in maternal parenting stress for mothers who experienced either PI or CFI. There were 15 demographic and stress-related explanatory variables. Using Bayesian profle regression, we examine the average changes in maternal parenting stress after incarceration compared to the mother’s average level of parenting stress in prior waves, simultaneously with model-based clustering to characterise the profles of mothers having a diferent degree of change. Results Three profles of mothers were identifed: (1) A small decrease in parental stress levels (n=112); (2) No measurable average change in parental stress levels (n=46); (3) A small increase in parental stress levels (n=117). Only for the second cluster did the 95% posterior credible intervals for the means include zero as a plausible value. The estimated means for clusters 1 (decrease) and 3 (increase) did not overlap and are clearly separated. Conclusions Neither PI nor CFI helped profle mothers. Thus, research should examine wider family incarceration efects on children and caregivers. Prior adversity, wellbeing and family demographics contributed to the cluster profles. Parenting stress is heterogeneous and improved methods are needed to disentangle the efects of incarceration from other contextual, recent and cumulative adverse events in people’s lives.

Exercise training undertaken by people within 12 months of lung resection for non-small cell lung cancer.

Decreased exercise capacity and health-related quality of life (HRQoL) are common in people following lung resection for non-small cell lung cancer (NSCLC). Exercise training has been demonstrated to confer gains in exercise capacity and HRQoL for people with a range of chronic conditions, including chronic obstructive pulmonary disease and heart failure, as well as in people with prostate and breast cancer. A programme of exercise training may also confer gains in these outcomes for people following lung resection for NSCLC. This systematic review updates our 2013 systematic review. The primary aim of this review was to determine the effects of exercise training on exercise capacity and adverse events in people following lung resection (with or without chemotherapy) for NSCLC. The secondary aims were to determine the effects of exercise training on other outcomes such as HRQoL, force-generating capacity of peripheral muscles, pressure-generating capacity of the respiratory muscles, dyspnoea and fatigue, feelings of anxiety and depression, lung function, and mortality. We searched for additional randomised controlled trials (RCTs) in the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2019, Issue 2 of 12), MEDLINE (via PubMed) (2013 to February 2019), Embase (via Ovid) (2013 to February 2019), SciELO (The Scientific Electronic Library Online) (2013 to February 2019), and PEDro (Physiotherapy Evidence Database) (2013 to February 2019). We included RCTs in which participants with NSCLC who underwent lung resection were allocated to receive either exercise training, which included aerobic exercise, resistance exercise, or a combination of both, or no exercise training. Two review authors screened the studies and identified those eligible for inclusion. We used either postintervention values (with their respective standard deviation (SD)) or mean changes (with their respective SD) in the meta-analyses that reported results as mean difference (MD). In meta-analyses that reported results as standardised mean difference (SMD), we placed studies that reported postintervention values and those that reported mean changes in separate subgroups. We assessed the certainty of evidence for each outcome by downgrading or upgrading the evidence according to GRADE criteria. Along with the three RCTs included in the original version of this review (2013), we identified an additional five RCTs in this update, resulting in a total of eight RCTs involving 450 participants (180 (40%) females). The risk of selection bias in the included studies was low and the risk of performance bias high. Six studies explored the effects of combined aerobic and resistance training; one explored the effects of combined aerobic and inspiratory muscle training; and one explored the effects of combined aerobic, resistance, inspiratory muscle training and balance training. On completion of the intervention period, compared to the control group, exercise capacity expressed as the peak rate of oxygen uptake (VO2peak) and six-minute walk distance (6MWD) was greater in the intervention group (VO2peak: MD 2.97 mL/kg/min, 95% confidence interval (CI) 1.93 to 4.02 mL/kg/min, 4 studies, 135 participants, moderate-certainty evidence; 6MWD: MD 57 m, 95% CI 34 to 80 m, 5 studies, 182 participants, high-certainty evidence). One adverse event (hip fracture) related to the intervention was reported in one of the included studies. The intervention group also achieved greater improvements in the physical component of general HRQoL (MD 5.0 points, 95% CI 2.3 to 7.7 points, 4 studies, 208 participants, low-certainty evidence); improved force-generating capacity of the quadriceps muscle (SMD 0.75, 95% CI 0.4 to 1.1, 4 studies, 133 participants, moderate-certainty evidence); and less dyspnoea (SMD -0.43, 95% CI -0.81 to -0.05, 3 studies, 110 participants, very low-certainty evidence). We observed uncertain effects on the mental component of general HRQoL, disease-specific HRQoL, handgrip force, fatigue, and lung function. There were insufficient data to comment on the effect of exercise training on maximal inspiratory and expiratory pressures and feelings of anxiety and depression. Mortality was not reported in the included studies. Exercise training increased exercise capacity and quadriceps muscle force of people following lung resection for NSCLC. Our findings also suggest improvements on the physical component score of general HRQoL and decreased dyspnoea. This systematic review emphasises the importance of exercise training as part of the postoperative management of people with NSCLC.

Adverse events in people taking macrolide antibiotics versus placebo for any indication.

Adverse events in people taking macrolide antibiotics versus placebo for any indication.

Blood concentration, efficacy, and adverse events of phenobarbital: A prospective study in rural China

ObjectiveThis study evaluated the relationship between blood concentration of phenobarbital (PB) and its efficacy as well as adverse events in people with epilepsy in rural China. MethodsPeople with epilepsy being treated with PB monotherapy were recruited and followed up for averagely 2.5 years. Data of clinical characteristics were collected using a standardized questionnaire by face-to-face interviews both at baseline and follow-up. Plasma concentration of PB was detected by the high-performance liquid chromatography. ResultsData on treatment response and PB blood concentration was obtained from 225 subjects. Among them, 119 (52.9%) were recognized as effective cases and 106 (47.1%) as ineffective cases. In the effective group, the blood concentration of 95% subjects ranged from 1.22 μg/ml to 41.36 μg/ml with a median at 13.18 μg/ml (IQR = 8.32–20.19 μg/ml). The PB concentration of 95% of the subjects in the ineffective group ranged from 2.73 μg/ml to 70.16 μg/ml with a median at 19.80 μg/ml (IQR = 11.30–30.40 μg/ml), which was significantly higher than that of the effective group (p < 0.001). Multivariate logistic regression analysis showed that PB concentration ≥26.38 μg/ml was related to a 4.5-fold (95% confidence interval [CI], 1.85–11.08) higher risk of inefficacy. A receiver operation characteristic curve was performed to determine the cutoff value of concentration for PB efficacy at 19.02 μg/ml. SignificanceBlood concentration may be an important indicator for clinical decision making when PB monotherapy cannot achieve a good efficacy and more attention should be paid on it in clinical practice especially in resource-poor settings.

Prophylactic antibiotics for adults with chronic obstructive pulmonary disease: a network meta-analysis

Prophylactic antibiotics for adults with chronic obstructive pulmonary disease: a network meta-analysis

Exercise training for bronchiectasis

Exercise training for bronchiectasis

Neuromuscular electrostimulation for adults with chronic obstructive pulmonary disease.

In people with chronic obstructive pulmonary disease (COPD), the use of neuromuscular electrostimulation (NMES) either alone, or together with conventional exercise training, might improve the condition of the peripheral muscles, increase exercise capacity and functional performance, reduce symptoms and improve health-related quality of life (HRQoL). To determine the effects of NMES, applied in isolation or concurrently with conventional exercise training to one or more peripheral muscles, on peripheral muscle force and endurance, muscle size, exercise capacity, functional performance, symptoms, HRQoL and adverse events in people with COPD. We searched the Cochrane Airways Group Specialised Register, the Physiotherapy Evidence Database, clinical trial registries and conference abstracts on 14 March 2018. Randomised controlled trials that recruited adults with COPD if they had compared outcomes between a group that received NMES and a group that received usual care or compared outcomes between a group that received NMES plus conventional exercise training and a group that participated in conventional exercise training alone. Two review authors independently extracted data and assessed risk of bias using the Cochrane 'Risk of bias' tool. We expressed continuous data as either the standardised mean difference (SMD) or mean difference (MD) with the corresponding 95% confidence interval (CI). We assessed the quality of evidence using the GRADE approach. Nineteen studies met the inclusion criteria of which 16 contributed data on 267 participants with COPD (mean age 56 to 76 years and 67% were men). Of these 16 studies, seven explored the effect of NMES versus usual care and nine explored the effect of NMES plus conventional exercise training versus conventional exercise training alone. Six studies utilised sham stimulation in the control group. When applied in isolation, NMES produced an increase in peripheral muscle force (SMD 0.34, 95% CI 0.02 to 0.65; low-quality evidence) and quadriceps endurance (SMD 1.36, 95% CI 0.59 to 2.12; low-quality evidence) but the effect on thigh muscle size was unclear (MD 0.25, 95% CI -0.11 to 0.61; low-quality evidence). There were increases in six-minute walk distance (6MWD) (MD 39.26 m, 95% CI 16.31 to 62.22; low-quality evidence) and time to symptom limitation exercising at a submaximal intensity (MD 3.62 minutes, 95% CI 2.33 to 4.91). There was a reduction in the severity of leg fatigue on completion of an exercise test (MD -1.12 units, 95% CI -1.81 to -0.43). The increase in peak rate of oxygen uptake (VO2peak) was of borderline significance (MD 0.10 L/minute, 95% CI 0.00 to 0.19).For NMES with conventional exercise training, there was an uncertain effect on peripheral muscle force (SMD 0.47, 95% CI -0.10 to 1.04; very low-quality evidence) and there were insufficient studies to undertake a meta-analysis on the effect on quadriceps endurance or thigh muscle size. However, there was an increase in 6MWD in favour of NMES combined with conventional exercise training (MD 25.87 m, 95% CI 1.06 to 50.69; very low-quality evidence). In people admitted to either in an intensive care unit or a respiratory high dependency centre, NMES combined with conventional exercise reduced the time taken for participants to first sit out of bed by 4.98 days (95% CI -8.55 to -1.41; very low-quality evidence), although the statistical heterogeneity for this analysis was high (I2 = 60%). For both types of studies (i.e. NMES versus usual care and NMES with conventional exercise training versus conventional exercise training alone), there was no risk difference for mortality or minor adverse events in participants who received NMES. NMES, when applied in isolation, increased quadriceps force and endurance, 6MWD and time to symptom limitation exercising at a submaximal intensity, and reduced the severity of leg fatigue on completion of exercise testing. It may increase VO2peak, but the true effect on this outcome measure could be trivial. However, the quality of evidence was low or very low due to risk of bias within the studies, imprecision of the estimates, small number of studies and inconsistency between the studies. Although there were no additional gains in quadriceps force with NMES plus conventional exercise training, there was evidence of an increase in 6MWD. Further, in people who were the most debilitated, the addition of NMES may have accelerated the achievement of a functional milestone, that is, the first time someone sits out of bed.

Fludrocortisone for orthostatic hypotension

Background Orthostatic hypotension is an excessive fall in blood pressure (BP) while standing and is the result of a decrease in cardiac output or defective or inadequate vasoconstrictor mechanisms. Fludrocortisone is a mineralocorticoid that increases blood volume and blood pressure. Fludrocortisone is considered the first- or second-line pharmacological therapy for orthostatic hypotension alongside mechanical and positional measures such as increasing fluid and salt intake and venous compression methods. However, there has been no Cochrane Review of the benefits and harms of this drug for this condition. Objectives To identify and evaluate the benefits and harms of fludrocortisone for orthostatic hypotension. Search methods We searched the following databases on 11 November 2019: Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase and CINAHL. We also searched trials registries. Selection criteria We included all studies evaluating the benefits and harms of fludrocortisone compared to placebo, another drug for orthostatic hypotension, or studies without comparators, including randomized controlled trials (RCTs), quasi-RCTs and observational studies. We included studies in people with orthostatic hypotension due to a chronic peripheral neuropathy, a central autonomic neuropathy, or autonomic failure from other causes, but not medication-induced orthostatic hypotension or orthostatic hypotension from acute volume depletion or blood loss. Data collection and analysis We used Cochrane methodological procedures for most of the review. We developed and used a tool to prioritize observational studies that offered the best available evidence where there are gaps in the evidence from RCTs. We assessed the certainty of evidence for fludrocortisone versus placebo using GRADE. Main results We included 13 studies of 513 participants, including three cross-over RCTs and 10 observational studies (three cohort studies, six case series and one case-control study). The included RCTs were small (total of 28 participants in RCTs), short term (two to three weeks), only examined fludrocortisone for orthostatic hypotension in people with two conditions (diabetes and Parkinson disease), and had variable risk of bias (two had unclear risk of bias and one had low risk of bias). Heterogeneity in participant populations, comparators and outcome assessment methods prevented meta-analyses of the RCTs. We found very low-certainty evidence about the effects of fludrocortisone versus placebo on drop in BP in people with diabetes (-26 mmHg versus -39 mmHg systolic; -7 mmHg versus -11 mmHg diastolic; 1 cross-over study, 6 participants). For people with Parkinson disease, we found very-low certainty evidence about the effects of fludrocortisone on drop in BP compared to pyridostigmine (-14 mmHg versus -22.1 mmHg diastolic; P = 0.036; 1 cross-over study, 9 participants) and domperidone (no change after treatment in either group; 1 cross-over study, 13 participants). For orthostatic symptoms, we found very low-certainty evidence for fludrocortisone versus placebo in people with diabetes (4 out of 5 analyzed participants had improvements in orthostatic symptoms, 1 cross-over study, 6 participants), for fludrocortisone versus pyridostigmine in people with Parkinson disease (orthostatic symptoms unchanged; 1 cross-over study, 9 participants) or fludrocortisone versus domperidone (improvement to 6 for both interventions on the Composite Autonomic Symptom Scale-Orthostatic Domain (COMPASS-OD); 1 cross-over study, 13 participants). Evidence on adverse events was also very low-certainty in both populations, but indicated side effects were minimal. Observational studies filled some gaps in evidence by examining the effects in larger groups of participants, with more diverse conditions, over longer periods of time. One cohort study (341 people studied retrospectively) found fludrocortisone may not be harmful in the long term for familial dysautonomia. However, it is unclear if this translates to long-term improvements in BP drop or a meaningful improvement in orthostatic symptoms. Authors' conclusions The evidence is very uncertain about the effects of fludrocortisone on blood pressure, orthostatic symptoms or adverse events in people with orthostatic hypotension and diabetes or Parkinson disease. There is a lack of information on long-term treatment and treatment of orthostatic hypotension in other disease states. There is a need for standardized reporting of outcomes and for standardization of measurements of blood pressure in orthostatic hypotension.

Celecoxib for rheumatoid arthritis.

Celecoxib for rheumatoid arthritis.

Topiramate for essential tremor.

Essential tremor (ET) is one of the most common movement disorders. The management is primarily based on pharmacological agents and in clinical practice propranolol and primidone are considered the first-line therapy. However, these treatments can be ineffective in 25% to 55% of people and are frequently associated with serious adverse events (AEs). For these reasons, it is worthwhile evaluating other treatments for ET. Topiramate has been suggested as a potentially useful agent for the treatment of ET but there is uncertainty about its efficacy and safety. To assess the efficacy and safety of topiramate in the treatment of ET. We carried out a systematic search without language restrictions to identify all relevant trials in the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (January 1966 to January 2017), Embase (January 1988 to January 2017), National Institute for Health and Care Excellence (1999 to January 2017), ClinicalTrials.gov (1997 to January 2017) and World Health Organization International Clinical Trials Registry Platform (ICTRP; 2004 to January 2017). We searched BIOSIS Citation Index (2000 to January 2017) for conference proceedings. We handsearched grey literature and the reference lists of identified studies and reviews. We included allrandomised controlled trials (RCTs) of topiramate versus placebo/open control or any other treatments. We included studies in which the diagnosis of ET was made according to accepted and validated diagnostic criteria. We excluded studies conducted in people presenting with secondary forms of tremor or reporting only neurophysiological parameters to assess outcomes. Two review authors independently collected and extracted data using a data collection form. We assessed the risk of bias and the quality of evidence. We used a fixed-effect meta-analysis for data synthesis. This review included three trials comparing topiramate to placebo (309 participants). They were all at high overall risk of bias. The quality of evidence ranged from very low to low. Compared to placebo, participants treated with topiramate showed a significant improvement in functional disability and an increased risk of withdrawal (risk ratio (RR) 1.78, 95% confidence interval (CI) 1.23 to 2.60). There were more AEs for topiramate-treated participants, particularly paraesthesia, weight loss, appetite decrease and memory difficulty. This systematic review highlighted the presence of limited data and very low to low quality evidence to support the apparent efficacy and the occurrence of treatment-limiting AEs in people with ET treated with topiramate. Further research to assess topiramate efficacy and safety on ET is needed.

Effect of 3 years of biannual mass drug administration with albendazole on lymphatic filariasis and soil-transmitted helminth infections: a community-based study in Republic of the Congo

The standard treatment strategy of mass drug administration with ivermectin plus albendazole for lymphatic filariasis cannot be applied in central Africa, because of the risk of serious adverse events in people with high Loa loa microfilaraemia. Thus, alternative strategies are needed. We investigated one such alternative strategy for mass drug administration for elimination of lymphatic filariasis and soil-transmitted helminth infections in Republic of the Congo. In 2012, we started a 3 year community trial of biannual mass administration of albendazole in a village in Republic of the Congo. All volunteering inhabitants aged 2 years or older were offered albendazole (400 mg) every 6 months. Infection with Wuchereria bancrofti was diagnosed with a rapid card immunochromatographic test for antigenaemia. People with antigenaemia were tested for microfilaraemia by night blood smears. Individuals were also tested for soil-transmitted helminth infections (ie, hookworm, Ascaris lumbricoides, Trichuris trichiura) with the Kato-Katz method. Assessment surveys were done at 12, 24, and 36 months. The main outcome measure was change in infection rates from baseline to year 3. Therapeutic coverage was more than 80% in all six rounds of mass administration of albendazole. Between 2012 and 2015, W bancrofti antigenaemia and microfilaraemia rates in the community fell significantly, from 17·3% (95% CI 14·7-20·0) to 4·7% (3·3-6·6; p<0·0001) and from 5·3% (3·9-7·1) to 0·3% (0·1-1·2; p<0·0001), respectively. The geometric mean microfilaria count in microfilaraemic people fell from 199·4 (120·4-330·5) per mL in 2012 to 39·1 (95% CIs not computed) per mL in 2015 (p=0·0095). Hookworm infection was undetectable after 1 year. Between 2012 and 2015, the number of A lumbricoides eggs expelled per g of faeces fell from 9844·6 (8209·0-11 480·0) to 724·4 (340·7-1114·2; p<0·0001), and of T trichiura eggs from 1107·4 (878·5-1336·3) to 366·0 (255·7-476·2; p<0·0001). Our findings strongly support WHO's provisional strategy of biannual mass administration of albendazole to eliminate lymphatic filariasis in areas where loiasis is co-endemic and ivermectin cannot be safely mass administered. Bill & Melinda Gates Foundation.