Validation study of bullous pemphigoid and pemphigus vulgaris recording in routinely collected electronic primary healthcare records in England.

OBJECTIVES The validity of bullous pemphigoid and pemphigus vulgaris recording in routinely collected healthcare data in the UK is unknown. We assessed the positive predictive value (PPV) for bullous pemphigoid and pemphigus vulgaris primary care Read codes in the Clinical Practice Research Datalink (CPRD) using linked inpatient data (Hospital Episode Statistics (HES)) as the diagnostic benchmark. SETTING:Adult participants with bullous pemphigoid or pemphigus vulgaris registered with HES-linked general practices in England between January 1998 and December 2017. Code-based algorithms were used to identify patients from the CPRD and extract their benchmark blistering disease diagnosis from HES. PRIMARY OUTCOME MEASURE The PPVs of Read codes for bullous pemphigoid and pemphigus vulgaris. RESULTS:Of 2468 incident cases of bullous pemphigoid and 431 of pemphigus vulgaris, 797 (32.3%) and 85 (19.7%) patients, respectively, had a hospitalisation record for a blistering disease. The PPV for bullous pemphigoid Read codes was 93.2% (95% CI 91.3% to 94.8%). Of the bullous pemphigoid cases, 3.0% had an HES diagnosis of pemphigus vulgaris and 3.8% of another blistering disease. The PPV for pemphigus vulgaris Read codes was 58.5% (95% CI 48.0% to 68.9%). Of the pemphigus vulgaris cases, 24.7% had an HES diagnosis of bullous pemphigoid and 16.5% of another blistering disease. CONCLUSIONS:The CPRD can be used to study bullous pemphigoid, but recording of pemphigus vulgaris needs to improve in primary care

Efficacy and potential determinants of exercise therapy in knee and hip osteoarthritis: a systematic review and meta-analysis

Background. Exercise is an effective treatment for osteoarthritis. However, the effect may vary from one patient (or study) to another.Objective. To evaluate the efficacy of exercise and its potential determinants for pain, function, performance, and quality of life (QoL) in knee and hip osteoarthritis (OA).Methods. We searched 9 electronic databases (AMED, CENTRAL, CINAHL, EMBASE, MEDLINE Ovid, PEDro, PubMed, SPORTDiscus and Google Scholar) for reports of randomised controlled trials (RCTs) comparing exercise-only interventions with usual care. The search was performed from inception up to December 2017 with no language restriction. The effect size (ES), with its 95% confidence interval (CI), was calculated on the basis of between-group standardised mean differences. The primary endpoint was at or nearest to 8 weeks. Other outcome time points were grouped into intervals, from less than 1 month to ≥18 months, for time-dependent effects analysis. Potential determinants were explored by subgroup analyses. Level of significance was set at p≤0.10.Results. Data from 77 RCTs (6472 participants) confirmed statistically significant exercise benefits for pain (ES 0.56, 95% CI 0.44–0.68), function (0.50, 0.38–0.63), performance (0.46, 0.35–0.57), and QoL (0.21, 0.11–0.31) at or nearest to 8 weeks. Across all outcomes, the effects appeared to peak around 2 months and then gradually decreased and became no better than usual care after 9 months. Better pain relief was reported by trials investigating participants who were younger (mean age less than 60 years), had knee OA, and were not awaiting joint replacement surgery.Conclusions. Exercise significantly reduces pain and improves function, performance and QoL in people with knee and hip OA as compared with usual care at 8 weeks. The effects are maximal around 2 months and thereafter slowly diminish, being no better than usual care at 9 to 18 months. Participants with younger age, knee OA and not awaiting joint replacement may benefit more from exercise therapy. These potential determinants, identified by study-level analyses, may have implied ecological bias and need to be confirmed with individual patient data

Long-term oral prednisolone exposure in primary care for bullous pemphigoid: population-based study

Background Oral prednisolone is the mainstay treatment for bullous pemphigoid, an autoimmune blistering skin disorder affecting older people. Treatment with moderate-to-high doses is often initiated in secondary care, but then continued in primary care. Aim To describe long-term oral prednisolone prescribing in UK primary care for adults with bullous pemphigoid from 1998 to 2017. Design and setting A prospective cohort study using routinely collected data from the Clinical Practice Research Datalink, a primary care database containing the healthcare records for over 17 million people in the UK. Method Oral prednisolone exposure was characterised in terms of the proportion of individuals with incident bullous pemphigoid prescribed oral prednisolone following their diagnosis, and the duration and dose of prednisolone. Results In total, 2312 (69.6%) of 3322 people with bullous pemphigoid were prescribed oral prednisolone in primary care. The median duration of exposure was 10.6 months (interquartile range [IQR] 3.4-24.0). Of prednisolone users, 71.5% were continuously exposed for >3 months, 39.7% for >1 year, 14.7% for >3 years, 5.0% for >5 years, and 1.7% for >10 years. The median cumulative dose was 2974 mg (IQR 1059-6456). Maximum daily doses were ≥10 mg/day in 74.4% of prednisolone users, ≥20 mg/day in 40.7%, ≥30 mg/day in 18.2%, ≥40 mg/day in 6.6%, ≥50 mg/day in 3.8%, and ≥60 mg/day in 1.9%. Conclusion A high proportion of people with incident bullous pemphigoid are treated with oral prednisolone in UK primary care. Action is required by primary and second care services to encourage use of steroid-sparing alternatives and, where switching is not possible, ensure prophylactic treatments and proactive monitoring of potential side effects are in place

The association between prescription drugs and vaccines commonly prescribed to older people and bullous pemphigoid: a UK population-based study

IntroductionBullous pemphigoid (BP) is a serious skin disease that results in large painful blisters developing over the body and occurs most commonly in older people (over 70 years). Despite several comorbidities such as stroke and a threefold increase in mortality, BP remains under-researched. The cause of BP is unclear. The auto-immune process may be triggered by medicines such as diuretics, but current evidence mainly comprises case-reports and small hospital-based studies. Electronic healthcare records from the Clinical Practice Research Datalink (CPRD) provide an opportunity to conduct a large population-based study, representative of people with BP in the UK, to assess exposure to prescribed medicines. Early identification of BP and prompt withdrawal of suspect medicines may lead to BP remission and improve long-term patient outcomes, including quality of life. We aim to determine whether medicines/vaccines, prescribed for common conditions in older people, are associated with BP in the UK population. The objectives are:i.To determine the adjusted odds ratio of developing BP per therapeutic group and class, and for multiple exposure (i.e. the use of more than one therapeutic group of medicine/vaccine during the observation period), for medicines/vaccines commonly prescribed to older people in the UK.ii.To identify which of the above are less associated with risk of BP, giving clinicians/prescribers alternative treatment options.iii.To identify additional medicines associated with BP using machine learning.iv.To identify associations between combinations of medicines prescribed to BP patients using machine learning.v.To describe patient characteristics of those at risk of BP, following medicine use, using machine learning.MethodsA UK population-based nested case-control study using the CPRD to determine associations between identified medicines/vaccines and BP. BP cases will be matched to up to 4 controls (age, sex, GP practice) using incidence density sampling. Exposure: medicines/vaccines commonly prescribed for older people; antibacterial, medicine for the cardiovascular system, stroke, diabetes, dementia, and influenza vaccination in the year leading up to diagnosis. Outcome measures: the odds of BP per therapeutic group, per class, and individual medicine; (reference=no exposure). Analysis: multivariable conditional logistic regression adjusted for a priori confounders. Confounding by indication will be considered and different exposure criteria assessed. We will undertake exploratory association rule mining to identify individual and combinations of medicines prescribed prior to BP. We will conduct unsupervised machine learning cluster analysis to identify groups of patients with demographic and clinical characteristics and their associations with prescribed medicines linked to BP.DiscussionThis study will (i) provide greater awareness of the risk of drug-associated BP amongst specialist and non-specialist healthcare professionals and therefore may facilitate earlier diagnosis of BP; (ii) support withdrawal of suspect medicines and switching to alternatives, where available, to achieve earlier remission of BP

Effect of vitamin D supplementation on pain and physical function in patients with knee osteoarthritis (OA): An OA Trial Bank protocol for a systematic review and individual patient data (IPD) meta-analysis

Introduction Observational data suggest that vitamin D deficiency is associated with the onset and progression of knee osteoarthritis (OA). However, randomised controlled trials (RCTs) to date investigating the efficacy of vitamin D supplementation in knee OA have reported conflicting results. Further research is needed to clarify the effects of vitamin D on patient-reported outcomes and determine whether there are patient subgroups who may benefit from the supplementation. The aim of this individual patient data (IPD) meta-analysis is to identify patient-level predictors of treatment response to vitamin D supplementation on pain and physical function. Methods and analysis A systematic literature search will be conducted for RCTs of vitamin D supplementation on knee OA. Authors of original RCTs will be contacted to obtain the IPD. The primary outcomes will include long-term (≥12 months) pain and physical function. Secondary outcomes will include medium-term (≥6 months and <12 months) and short-term (<6 months) pain and physical function, as well as patient global assessment, quality of life and adverse events. Potential treatment effect modifiers to be examined in the subgroup analyses include age, gender, body mass index, baseline knee pain severity and physical function, baseline vitamin D level, radiographic stage, presence of bone marrow lesions on MRI, presence of clinical signs of local inflammation and concomitant depressive symptoms. Both one-step and two-step modelling methods will be used to determine the possible modifiable effect of each subgroup of interest. Ethics and dissemination Research ethical or governance approval is exempt for this study as no new data are being collected. This study will be the first IPD meta-analysis to clarify the effect of vitamin D supplementation on clinical symptoms in different subgroups of patients with knee OA. The findings will be disseminated through peer-review publications and conference presentations. PROSPERO registration number CRD42018107740

Outcomes of Patients Presenting with Mild Acute Respiratory Distress Syndrome Insights from the LUNG SAFE Study

BACKGROUND: Patients with initial mild acute respiratory distress syndrome are often underrecognized and mistakenly considered to have low disease severity and favorable outcomes. They represent a relatively poorly characterized population that was only classified as having acute respiratory distress syndrome in the most recent definition. Our primary objective was to describe the natural course and the factors associated with worsening and mortality in this population. METHODS: This study analyzed patients from the international prospective Large Observational Study to Understand the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) who had initial mild acute respiratory distress syndrome in the first day of inclusion. This study defined three groups based on the evolution of severity in the first week: "worsening" if moderate or severe acute respiratory distress syndrome criteria were met, "persisting" if mild acute respiratory distress syndrome criteria were the most severe category, and "improving" if patients did not fulfill acute respiratory distress syndrome criteria any more from day 2. RESULTS: Among 580 patients with initial mild acute respiratory distress syndrome, 18% (103 of 580) continuously improved, 36% (210 of 580) had persisting mild acute respiratory distress syndrome, and 46% (267 of 580) worsened in the first week after acute respiratory distress syndrome onset. Global in-hospital mortality was 30% (172 of 576; specifically 10% [10 of 101], 30% [63 of 210], and 37% [99 of 265] for patients with improving, persisting, and worsening acute respiratory distress syndrome, respectively), and the median (interquartile range) duration of mechanical ventilation was 7 (4, 14) days (specifically 3 [2, 5], 7 [4, 14], and 11 [6, 18] days for patients with improving, persisting, and worsening acute respiratory distress syndrome, respectively). Admissions for trauma or pneumonia, higher nonpulmonary sequential organ failure assessment score, lower partial pressure of alveolar oxygen/fraction of inspired oxygen, and higher peak inspiratory pressure were independently associated with worsening. CONCLUSIONS: Most patients with initial mild acute respiratory distress syndrome continue to fulfill acute respiratory distress syndrome criteria in the first week, and nearly half worsen in severity. Their mortality is high, particularly in patients with worsening acute respiratory distress syndrome, emphasizing the need for close attention to this patient population.status: publishe

Mechanical ventilation in patients with cardiogenic pulmonary edema: a sub-analysis of the LUNG SAFE study

Abstract Background Patients with acute respiratory failure caused by cardiogenic pulmonary edema (CPE) may require mechanical ventilation that can cause further lung damage. Our aim was to determine the impact of ventilatory settings on CPE mortality. Methods Patients from the LUNG SAFE cohort, a multicenter prospective cohort study of patients undergoing mechanical ventilation, were studied. Relationships between ventilatory parameters and outcomes (ICU discharge/hospital mortality) were assessed using latent mixture analysis and a marginal structural model. Results From 4499 patients, 391 meeting CPE criteria (median age 70 [interquartile range 59–78], 40% female) were included. ICU and hospital mortality were 34% and 40%, respectively. ICU survivors were younger (67 [57–77] vs 74 [64–80] years, p &lt; 0.001) and had lower driving (12 [8–16] vs 15 [11–17] cmH2O, p &lt; 0.001), plateau (20 [15–23] vs 22 [19–26] cmH2O, p &lt; 0.001) and peak (21 [17–27] vs 26 [20–32] cmH2O, p &lt; 0.001) pressures. Latent mixture analysis of patients receiving invasive mechanical ventilation on ICU day 1 revealed a subgroup ventilated with high pressures with lower probability of being discharged alive from the ICU (hazard ratio [HR] 0.79 [95% confidence interval 0.60–1.05], p = 0.103) and increased hospital mortality (HR 1.65 [1.16–2.36], p = 0.005). In a marginal structural model, driving pressures in the first week (HR 1.12 [1.06–1.18], p &lt; 0.001) and tidal volume after day 7 (HR 0.69 [0.52–0.93], p = 0.015) were related to survival. Conclusions Higher airway pressures in invasively ventilated patients with CPE are related to mortality. These patients may be exposed to an increased risk of ventilator-induced lung injury. Trial registration Clinicaltrials.gov NCT02010073 </jats:sec