Objective To examine the association between antihypertensive treatment and specific adverse events. Design Systematic review and meta-analysis. Eligibility criteria Randomised controlled trials of adults receiving antihypertensives compared with placebo or no treatment, more antihypertensive drugs compared with fewer antihypertensive drugs, or higher blood pressure targets compared with lower targets. To avoid small early phase trials, studies were required to have at least 650 patient years of follow-up. Information sources Searches were conducted in Embase, Medline, CENTRAL, and the Science Citation Index databases from inception until 14 April 2020. Main outcome measures The primary outcome was falls during trial follow-up. Secondary outcomes were acute kidney injury, fractures, gout, hyperkalaemia, hypokalaemia, hypotension, and syncope. Additional outcomes related to death and major cardiovascular events were extracted. Risk of bias was assessed using the Cochrane risk of bias tool, and random effects meta-analysis was used to pool rate ratios, odds ratios, and hazard ratios across studies, allowing for between study heterogeneity (τ 2 ). Results Of 15 023 articles screened for inclusion, 58 randomised controlled trials were identified, including 280 638 participants followed up for a median of 3 (interquartile range 2-4) years. Most of the trials (n=40, 69%) had a low risk of bias. Among seven trials reporting data for falls, no evidence was found of an association with antihypertensive treatment (summary risk ratio 1.05, 95% confidence interval 0.89 to 1.24, τ 2 =0.009). Antihypertensives were associated with an increased risk of acute kidney injury (1.18, 95% confidence interval 1.01 to 1.39, τ 2 =0.037, n=15), hyperkalaemia (1.89, 1.56 to 2.30, τ 2 =0.122, n=26), hypotension (1.97, 1.67 to 2.32, τ 2 =0.132, n=35), and syncope (1.28, 1.03 to 1.59, τ 2 =0.050, n=16). The heterogeneity between studies assessing acute kidney injury and hyperkalaemia events was reduced when focusing on drugs that affect the renin angiotensin-aldosterone system. Results were robust to sensitivity analyses focusing on adverse events leading to withdrawal from each trial. Antihypertensive treatment was associated with a reduced risk of all cause mortality, cardiovascular death, and stroke, but not of myocardial infarction. Conclusions This meta-analysis found no evidence to suggest that antihypertensive treatment is associated with falls but found evidence of an association with mild (hyperkalaemia, hypotension) and severe adverse events (acute kidney injury, syncope). These data could be used to inform shared decision making between doctors and patients about initiation and continuation of antihypertensive treatment, especially in patients at high risk of harm because of previous adverse events or poor renal function. Registration PROSPERO CRD42018116860.

Pulmonary rehabilitation (PR) for people with COPD leads to clinically significant improvements in quality of life and exercise capacity [1]. In England and Wales, UK, in 2013-2014, only 15% of eligible patients were referred (51% from primary care), of whom 31% did not attend assessment [2]. We aimed to generate a theory-informed understanding of enablers and barriers to PR referral and uptake from primary care.This mixed-methods study [3] used normalisation process theory (NPT) [4] to understand how PR referral becomes embedded in clinical practice via NPT constructs of coherence (how clinicians understand and value PR), cognitive participation (how PR referral is sustained in practice), collective action (how PR referral is operationalised) and reflexive monitoring (how clinicians judge whether PR referral is worthwhile). Burden of treatment theory (BoT) [5] informed understanding of the patient experience via parallel constructs relating to how patients make sense of their condition and treatment, how they organise self-care work, what taking up PR involves for patients and how patients judge if PR is worthwhile.Online surveys (dichotomous, multiple response, Likert scales and free-text items) were sent to all PR providers in the East of England (EoE), to other PR providers in England and Wales who contributed to the national COPD audit, and to all primary care practices in the EoE. Purposive sampling was used to recruit for semistructured interviews and focus groups, targeting all EoE PR providers and, in EoE areas with higher and lower PR utilisation rates, general practitioners (GPs), practice nurses, commissioners and patients (white British and South Asian) who had accepted a PR offer, declined PR or were not referred. Survey, interview and focus group questions were mapped to NPT constructs. Qualitative data and free-text survey responses were analysed following a framework approach [6] informed by NPT constructs. Qualitative data collection and concurrent analysis continued until saturation was achieved, i.e. deductive codes were adequately represented and no new codes identified [7]. Quantitative data were analysed descriptively. GP and nurse survey responses were compared using Chi-squared analysis. Research questions and interview/focus group guides were reviewed by the patient and participant involvement group.Informed consent was obtained from all participants. The study was approved by Cambridge Central Research Ethics Committee (ref. 17/EE/0136).EoE primary care practices (107 out of 415, 25.8%), EoE PR services (14 out of 20, 70%), and other England and Wales PR services (46 out of 179, 25.7%) completed the surveys. 32 clinicians, six commissioners and 42 COPD patients took part in interviews and focus groups. 28 patients had accepted a PR offer, seven had declined, seven were not referred and seven were of South Asian heritage (table 1).From the survey and qualitative research, we identified enablers and barriers across six domains (figure 1). @ERSpublications Healthcare service and patient ba...

A 71-year-old man with residual poliomyelitis was referred to the orthopaedic surgeons with a neglected left femoral neck fracture of the paralytic limb. He had presented at another hospital with left groin pain and inability to weight bear 4 weeks earlier after a fall from standing height, but had delayed treatment due to his insistence on waiting until he returned to his home country.Successful treatment of residual poliomyelitis fractures requires early union as well as early mobilisation and rehabilitation. This patient presented to the orthopaedic surgeons with a challenging case due to the delay in treatment and the fact that the fracture was basicervical which results in an unstable fracture. Surgical expertise was required to decide on the optimum surgical option and a total hip arthroplasty was performed. The patient made a good recovery following physiotherapy as evidenced clinically and radiologically.

Selective loss of discrete neuronal populations is a prominent feature of many neurodegenerative conditions, but the molecular basis of this is poorly understood. A central role of α-synuclein in the selective neurodegeneration of Parkinson's disease has been speculated, as its level of expression critically determines the propensity of this protein to misfold. To investigate whether the propensity of neuronal cell loss is associated with the level of endogenous α-synuclein expression, non-transgenic rats were given a single intravenous administration of α-synuclein pre-formed fibrils (PFFs) reversibly complexed with the rabies virus glycoprotein peptide (RVG9R). The number of surviving cells in different neuronal populations was systematically quantified using unbiased stereology. Our data demonstrated that a non-selective, transvascular delivery of α-synuclein PFFs led to a time-dependent loss of specific populations of midbrain (but not olfactory) dopaminergic neurons, medullary (but not pontine) cholinergic neurons, and brainstem serotonergic neurons. Contrary to the central role of endogenous α-synuclein expression in determining the seeding and aggregation propensity of pathological α-synuclein, we did not observe an association between the levels of α-synuclein expression in different regions of the rodent brain (although did not ascertain this at the individual cell level) and neurodegenerative propensity. The results from our study highlight the complexity of the neurodegenerative process generated by α-synuclein seeding. Further investigations are therefore required to elucidate the molecular basis of neurodegeneration driven by exogenous pathogenic α-synuclein spread.

How could I apply this information?"Relaxation of the pelvic floor muscle (PFM) is necessary to fully empty the bowel and bladder. Diaphragmatic breathing and relaxation techniques are commonly used to train PFM relaxation in children. The frog jumps in this study were used to fatigue the PFM, thereby inducing relaxation. For children who have difficulty achieving PFM relaxation via diaphragmatic breathing or relaxation techniques, the frog jump intervention may be useful. Alternatively, the frog jumps, followed by child' s pose, may help the child identify the differences between PFM contraction and relaxation. Increasing the child' s awareness of a contracted versus relaxed PFM may help them achieve relaxation more quickly when voiding. Correct toilet posture with pelvis appropriately supported by supporting feet with knees above hips can also assist with PFM relaxation during voiding. "What should I be mindful about when applying this information?"Children who had co-occurring developmental or cognitive diagnoses were excluded from the study. These children often require modifications of interventions due to cognitive, emotional, and mobility impairments and limitations. For example, a child with attention-deficit hyperactive disorder and voiding dysfunction may require additional cues or supports to participate in relaxation techniques. The experimental exercises were designed to achieve relaxation by inducing fatigue of the PFM. It is unclear whether frog hops to fatigue, child' s pose, or the combination of both produced PFM relaxation in subjects. Fatiguing the lower extremities and PFM may result in leakage of bowel and/or bladder prior to arriving to the toilet. In addition, the study only addressed the resting tone of the pelvic floor, rather than the ability of the child to fully void due to the intervention. Finally, norms for PFM relaxation are needed in pediatrics to identify high PFM tone or a contracted state and when the intervention successfully produced low tone or relaxation of PFM.