Defining clinical subtypes of adult asthma using electronic health records : analysis of a large UK primary care database with external validation

Acknowledgments EMFH was supported by a Medical Research Council PhD Studentship (eHERC/Farr). This work is carried out with the support of the Asthma UK Centre for Applied Research [AUKAC-2012-01] and Health Data Research UK which receives its funding from HDR UK Ltd (HDR-5012) funded by the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation and the Wellcome Trust. The funders had no role in the study and the decision to submit this work to be considered for publication. This Project is based in part/wholly on Data from the Optimum Patient Care Research Database (opcrd.co.uk) obtained under licence from Optimum Patient Care Limited and its execution is approved by recognised experts affiliated to the Respiratory Effectiveness Group. However, the interpretation and conclusion contained in this report are those of the author/s alone. This study makes use of anonymised data held in the Secure Anonymised Information Linkage (SAIL) Databank. We would like to acknowledge all the data providers who make anonymised data available for research. SAIL is not responsible for the interpretation of these data.Peer reviewedPublisher PD

Acute kidney injury in acute-on-chronic liver failure: where does hepatorenal syndrome fit?

Renal dysfunction occurs in 25% to 50% of patients with cirrhosis admitted to the hospital with an acute episode of hepatic decompensation and may be due to underlying chronic kidney disease, an acute deterioration, or both. An acute deterioration in renal function in cirrhotic patients is now collectively referred to as acute kidney injury (AKI), which has been subclassified into different grades of severity that identify prognostic groups. Acute-on-chronic liver failure is characterized by acute hepatic and/or extrahepatic organ failure driven by a dysregulated immune response and systemic inflammatory response. AKI is also one of the defining features of ACLF and a major component in grading the severity of acute-on-chronic liver failure. As such, the pattern of AKI now observed in patients admitted to the hospital with acutely decompensated liver disease is likely to be one of inflammatory kidney injury including acute tubular injury (referred in this review as non-hepatorenal syndrome [HRS]-AKI) rather than HRS. As the management and supportive treatment of non-HRS-AKI potentially differ from those of HRS, then from the nephrology perspective, it is important to distinguish between non-HRS-AKI and HRS-AKI when reviewing patients with acute-on-chronic liver failure and AKI, so that appropriate and early management can be instituted

High prevalence of vitamin D deficiency among women of child-bearing age in Lahore Pakistan, associating with lack of sun exposure and illiteracy

BACKGROUND: Vitamin D status is a key determinant of maternal and neonatal health. Deficiency has been reported to be common in Pakistani women, but information regarding environmental and genetic determinants of vitamin D status is lacking in this population. METHODS: We conducted a cross-sectional study among three groups of healthy women living in Lahore, Pakistan: university students, students or employees of Medrasas or Islamic Institutes, and employees working in office, hospital or domestic settings. Multivariate analysis was performed to identify environmental and genetic determinants of vitamin D status: polymorphisms in genes encoding the vitamin D receptor, vitamin D 25-hydroxylase enzyme CYP2R1 and vitamin D binding protein [DBP] were investigated. We also conducted analyses to identify determinants of body ache and bone pain in this population, and to determine the sensitivity and specificity of testing for hypocalcaemia and raised serum alkaline phosphatase to screen for vitamin D deficiency. RESULTS: Of 215 participants, 156 (73 %) were vitamin D deficient (serum 25[OH]D <50 nmol/L). Risk of vitamin D deficiency was independently associated with illiteracy (adjusted OR 4.0, 95 % CI 1.03–15.52, P = 0.04), <30 min sun exposure per day (adjusted OR 2.13, 95 % CI 1.08–4.19, P = 0.02), sampling in January to March (adjusted OR 2.38, 95 % CI 1.20–4.70), P = 0.01) and lack of regular intake of multivitamins (adjusted OR 2.61, 95 % CI 1.32–5.16, p = 0.005). Participants with the GG genotype of the rs4588 polymorphism in the gene encoding vitamin D binding protein tended to have lower 25(OH)D concentrations than those with GT/TT genotypes (95 % CI for difference 22.7 to −0.13 nmol/L, P = 0.053). Vitamin D deficiency was independently associated with increased risk of body ache or bone pain (adjusted OR 4.43, 95 % CI 2.07 to 9.49, P = 0.001). Hypocalcaemia (serum calcium concentration ≤9.5 mg/dL) and raised alkaline phosphatase concentration (≥280 IU/L) had low sensitivity and very low specificity for identification of vitamin D deficiency. CONCLUSION: Vitamin D deficiency is common among healthy women of child-bearing age in Lahore, Pakistan: illiteracy, decreased sun exposure and lack of multivitamin intake are risk factors

Whole home exercise intervention for depression in older care home residents (the OPERA study) : a process evaluation

Background: The ‘Older People’s Exercise intervention in Residential and nursing Accommodation’ (OPERA) cluster randomised trial evaluated the impact of training for care home staff together with twice-weekly, physiotherapist-led exercise classes on depressive symptoms in care home residents, but found no effect. We report a process evaluation exploring potential explanations for the lack of effect. Methods: The OPERA trial included over 1,000 residents in 78 care homes in the UK. We used a mixed methods approach including quantitative data collected from all homes. In eight case study homes, we carried out repeated periods of observation and interviews with residents, care staff and managers. At the end of the intervention, we held focus groups with OPERA research staff. We reported our first findings before the trial outcome was known. Results: Homes showed large variations in activity at baseline and throughout the trial. Overall attendance rate at the group exercise sessions was low (50%). We considered two issues that might explain the negative outcome: whether the intervention changed the culture of the homes, and whether the residents engaged with the intervention. We found low levels of staff training, few home champions for the intervention and a culture that prioritised protecting residents from harm over encouraging activity. The trial team delivered 3,191 exercise groups but only 36% of participants attended at least 1 group per week and depressed residents attended significantly fewer groups than those who were not depressed. Residents were very frail and therefore most groups only included seated exercises. Conclusions: The intervention did not change the culture of the homes and, in the case study homes, activity levels did not change outside the exercise groups. Residents did not engage in the exercise groups at a sufficient level, and this was particularly true for those with depressive symptoms at baseline. The physical and mental frailty of care home residents may make it impossible to deliver a sufficiently intense exercise intervention to impact on depressive symptoms

Determinants of mortality in patients with cirrhosis and uncontrolled variceal bleeding

BACKGROUND AND AIM: Failure to control oesophago-gastric variceal bleeding (OGVB) and acute-on-chronic liver failure (ACLF) are both important prognostic factors in liver cirrhosis. The aims of this study were to determine whether ACLF and its severity define the risk of death in OGVB and whether insertion of rescue transjugular intrahepatic stent-shunt (TIPSS) improves the survival of patients with failure to control OGVB and ACLF. METHODS: From a prospectively maintained ICU registry, data of 174 consecutive eligible patients with failure to control OGVB between 2005 and 2015, were included. Rescue TIPSS was defined as technically successful TIPSS within 72-hours of presentation with failure to control OGVB. Cox proportional hazards regression analyses were applied to explore the impact of ACLF and TIPSS on survival in failure-to-control OGVB. RESULTS: ACLF patients (n=119) were significantly older, had organ failures and higher white cell count compared with patients with acute decompensation (AD, n=55). Mortality at 42-days and 1-year was significantly higher in ACLF (47.9% and 61.3%) as compared to AD patients (9.1% and 12.7%, p<0.001), whereas there was no difference in the number of endoscopies and transfusion requirements between these groups. TIPSS was inserted in 78 patients [AD: 21 (38.2%); ACLF: 57 (47.8%), p=0.41]. In ACLF, rescue TIPSS insertion was an independent favorable prognostic factor for 42-day mortality. In contrast, rescue TIPSS did not impact on the outcome of AD patients. CONCLUSIONS: This study shows for the first time that in patients with failure to control OGVB, the presence and severity of ACLF determines the risk of 42-day and 1-year mortality. Rescue TIPSS is associated with improved survival of ACLF patients

Vitamin D Levels in Asymptomatic Adults-A Population Survey in Karachi, Pakistan

Background: It is well established that low levels of 25(OH) Vitamin D (/dL) are a common finding world over, affecting over a billion of the global population. Our primary objective was to determine the prevalence of vitamin D deficiency and insufficiency in the asymptomatic adult population of Karachi, Pakistan and the demographic, nutritional and co-morbidity characteristics associated with serum vitamin D levels. Methods: A cross-sectional population survey was conducted at two spaced out densely populated areas of the city. Serum levels of 25OH vitamin D were measured and GFR as renal function was assessed by using 4 variable MDRD formula. Results: Our sample of 300 had a median age of 48(interquartile range 38-55) years. The median level of serum vitamin D was 18.8 (IQ range 12.65-24.62) ng/dL. A total of 253 (84.3%) respondents had low levels (/dL) of 25OH vitamin D. Serum PTH and vitamin D were negatively correlated (r = -0.176, p = 0.001). The median PTH in the vitamin D sufficiency group was 38.4 (IQ range28.0-48.8)pg/mL compared with 44.4 (IQ range 34.3-56.8) pg/mL in the deficiency group (p = 0.011).The median serum calcium level in the sample was 9.46(IQ range 9.18-9.68) ng/dL. Low serum levels of vitamin D were not associated with hypertension (p = 0.771) or with an elevated spot blood pressure (p = 0.164).In our sample 75(26%) respondents had an eGFR corresponding to stage 2 and stage 3 CKD. There was no significant correlation between levels of vitamin D and eGFR (r = -0.127, p-value = 0.277). Respondents using daily vitamin D supplements had higher 25 OH vitamin D levels (p-value = 0.021). Conclusion: We observed a high proportion of the asymptomatic adult population having low levels of vitamin D and subclinical deterioration of eGFR. The specific cause(s) for this observed high prevalence of low 25OH vitamin D levels are not clear and need to be investigated further upon

Long-term safety and outcome of a temporary self-expanding metallic stent for achalasia: a prospective study with a 13-year single-center experience

To prospectively evaluate the long-term clinical safety and efficacy of a newly designed self-expanding metallic stent (SEMS) in the treatment of patients with achalasia. Seventy-five patients with achalasia were treated with a temporary SEMS with a 30-mm diameter. The SEMSs were placed under fluoroscopic guidance and removed by gastroscopy 4–5 days after stent placement. Follow-up data focused on dysphagia score, technique and clinical success, clinical remissions and failures, and complications and was performed at 6 months, 1 year, and within 3 to 5 years, 5 to 8 years, 8 to 10 years, and >10 years postoperatively. Stent placement was technically successful in all patients. Complications included stent migration (n = 4, 5.33%), chest pain (n = 28, 38.7%), reflux (n = 15, 20%), and bleeding (n = 9, 12%). No perforation or 30-day mortality occurred. Clinical success was achieved in all patients 1 month after stent removal. The overall remission rates at 6 months, 1, 1–3, 3–5, 5–8, 8–10, and >10 year follow-up periods were 100%, 96%, 93.9%, 90.9%, 100%, 100%, and 83.3%, respectively. Stent treatment failed in six patients, and the overall remission rate in our series was 92%. The median and mean primary patencies were 2.8 ± 0.28 years (95% CI: 2.25–3.35) and 4.28 ± 0.40 years (95% CI: 3.51–5.05), respectively. The use of temporary SEMSs with 30-mm diameter proved to be a safe and effective approach for managing achalasia with a long-term satisfactory clinical remission rate

A Novel Structural Assessment Technique to Prevent Damaged FRP-Wrapped Concrete Bridge Piers from Collapse

Repairing deteriorated concrete bridge piers using externally wrapped fiber reinforced polymer (FRP) composites have been proven as an effective approach. This technique has also been applied to low-rise building structures. Failures in FRP-wrapped concrete structures may occur by flexural failures of critical sections or by debonding of FRP plate from the concrete substrate. Debonding in the FRP/adhesive/concrete interface region may cause a significant decrease in member capacity leading to a premature failure of the system. In this chapter, a novel structural assessment technique aiming at inspecting the near-surface FRP debonding and concrete cracking of damaged FRP-wrapped concrete bridge piers to prevent the structures from collapse is presented. In the first part of this chapter, failure mechanisms of FRP-wrapped concrete systems are briefly discussed. The second part of this chapter introduces a novel structural assessment technique in which far-field airborne radar is applied. In this development, emphasis is placed on inspection of debonding in glass FRP (GFRP)-wrapped concrete cylinders, while the technique is also applicable to beams and slabs with bonded GFRP composites. Physical radar measurements on laboratory specimens with structural damages were conducted and used for validating the technique. Processed experimental measurements have shown promising results for the future application of the technique. Finally, research findings and issues are summarized.National Science Foundation (U.S.) (Grant CMS-0324607)Lincoln Laborator