How effective are leukotriene inhibitors for asthma in children?

Evidence on the use of leukotriene inhibitors in children is insufficient to permit conclusions regarding efficacy. Given the proven efficacy of inhaled corticosteroids in asthma management, leukotriene inhibitors should not replace inhaled corticosteroids for maintenance of asthma in children (strength of recommendation: B). Current guidelines that list leukotriene inhibitors as a potential addition or alternative to corticosteroid therapy in children with asthma appear to be based on scant studies and extrapolation from adult research

Evidence for CO2-rich fluids in rocks from the type charnockite area near Pallavaram, Tamil Nadu

Fluid inclusion and mineral chemistry data was presented for samples from the type charnockite area near Pallavaram (Tamil Nadu, India). The results indicate the presence of a dense CO2 fluid phase, but the data cannot distinguish between influx of this fluid from elsewhere or localized migration of CO2-rich fluids associated with dehydration melting

Diabetes Pharmacotherapies and Bladder Cancer: A Medicare Epidemiologic Study

Objective: Patients with type II diabetes have an increased risk of bladder cancer and are commonly treated with thiazolidinediones and angiotensin receptor blockers (ARBs), which have been linked to cancer risk. We explored the relationship between use of one or both of these medication types and incident bladder cancer among diabetic patients (diabetics) enrolled in Medicare. Research Design and Methods: We constructed both a prevalent and incident retrospective cohort of pharmacologically treated prevalent diabetics enrolled in a Medicare fee-for-service plan using inpatient, outpatient (2003–2011) and prescription (2006–2011) administrative data. The association of incident bladder cancer with exposure to pioglitazone, rosiglitazone and ARBs was studied using muitivariable Cox’s hazard models with time-dependent covariates in each of the two cohorts. Results: We identified 1,161,443 prevalent and 320,090 incident pharmacologically treated diabetics, among whom 4433 and 1159, respectively, developed incident bladder cancers. In the prevalent cohort mean age was 75.1 years, mean follow-up time was 38.0 months, 20.2% filled a prescription for pioglitazone during follow-up, 10.4% received rosiglitazone, 31.6% received an ARB and 8.0% received combined therapy with pioglitazone + ARB. We found a positive association between bladder cancer and duration of pioglitazone use in the prevalent cohort (P for trend = 0.008), with ≥24 months of pioglitazone exposure corresponding to a 16% (95% confidence interval 0–35%) increase in the incidence of bladder cancer compared to no use. There was a positive association between bladder cancer and rosiglitazone use for \u3c24 months in the prevalent cohort, but no association with ARB use. There were no significant associations in the incident cohort. Conclusions: We found that the incidence of bladder cancer increased with duration of pioglitazone use in a prevalent cohort of diabetics aged 65+ years residing in the USA, but not an incident cohort

Association of Receiving Multiple, Concurrent Fracture-Associated Drugs With Hip Fracture Risk

Importance: Many prescription drugs increase fracture risk, which raises concern for patients receiving 2 or more such drugs concurrently. Logic suggests that risk will increase with each additional drug, but the risk of taking multiple fracture-associated drugs (FADs) is unknown. Objective: To estimate hip fracture risk associated with concurrent exposure to multiple FADs. Design, Setting, and Participants: This cohort study used a 20% random sample of Medicare fee-for-service administrative data for age-eligible Medicare beneficiaries from 2004 to 2014. Sex-stratified Cox regression models estimated hip fracture risk associated with current receipt of 1, 2, or 3 or more of 21 FADs and, separately, risk associated with each FAD and 2-way FAD combination vs no FADs. Models included sociodemographic characteristics, comorbidities, and use of non-FAD medications. Analyses began in November 2018 and were completed April 2019. Exposure: Receipt of prescription FADs. Main Outcomes and Measures: Hip fracture hospitalization. Results: A total of 11.3 million person-years were observed, reflecting 2,646,255 individuals (mean [SD] age, 77.2 [7.3] years, 1,615,613 [61.1%] women, 2,136,585 [80.7%] white, and 219 579 [8.3%] black). Overall, 2,827,284 person-years (25.1%) involved receipt of 1 FAD; 1,322,296 (11.7%), 2 FADs; and 954,506 (8.5%), 3 or more FADs. In fully adjusted, sex-stratified models, an increase in hip fracture risk among women was associated with the receipt of 1, 2, or 3 or more FADs (1 FAD: hazard ratio [HR], 2.04; 95% CI, 1.99-2.11; P\u3c.001; 2 FADs: HR, 2.86; 95% CI, 2.77-2.95; P\u3c.001; ≥3 FADs: HR, 4.50; 95% CI, 4.36-4.65; P\u3c.001). Relative risks for men were slightly higher (1 FAD: HR, 2.23; 95% CI, 2.11-2.36; P\u3c.001; 2 FADs: HR, 3.40; 95% CI, 3.20-3.61; P\u3c.001; ≥3 FADs: HR, 5.18; 95% CI, 4.87-5.52; P\u3c.001). Among women, 2 individual FADs were associated with HRs greater than 3.00; 80 pairs of FADs exceeded this threshold. Common, risky pairs among women included sedative hypnotics plus opioids (HR, 4.90; 95% CI, 3.98-6.02; P\u3c.001), serotonin reuptake inhibitors plus benzodiazepines (HR, 4.50; 95% CI, 3.76-5.38; P\u3c.001), and proton pump inhibitors plus opioids (HR, 4.00; 95% CI, 3.56-4.49; P\u3c.001). Receipt of 1, 2, or 3 or more non-FADs was associated with a small, significant reduction in fracture risk compared with receipt of no non-FADs among women (1 non-FAD: HR, 0.93; 95% CI, 0.90-0.96; P\u3c.001; 2 non-FADs: HR, 0.84; 95% CI, 0.81-0.87; P\u3c.001; ≥3 non-FADs: HR, 0.74; 95% CI, 0.72-0.77; P\u3c.001). Conclusions and Relevance: Among older adults, FADs are commonly used and commonly combined. In this cohort study, the addition of a second and third FAD was associated with a steep increase in fracture risk. Many risky pairs of FADs included potentially avoidable drugs (eg, sedatives and opioids). If confirmed, these findings suggest that fracture risk could be reduced through tighter adherence to long-established prescribing guidelines and recommendations

Cost-effectiveness of a model consultation to support self-management in patients with osteoarthritis

Objectives: The aim of this study was to estimate the cost-effectiveness of a model OA consultation for OA to support self-management compared with usual care. Methods: An incremental cost-utility analysis using patient responses to the three-level EuroQoL-5D (EQ-5D) questionnaire was undertaken from a UK National Health Service perspective alongside a two-arm cluster-randomized controlled trial. Uncertainty was explored through the use of cost-effectiveness acceptability curves. Results: Differences in health outcomes between the model OA consultation and usual care arms were not statistically significant. On average, visits to the orthopaedic surgeon were lower in the model OA consultation arm by -0.28 (95% CI: -0.55, -0.06). The cost-utility analysis indicated that the model OA consultation was associated with a non-significant incremental cost of £-13.11 (95% CI: -81.09 to 54.85) and an incremental quality adjusted life year (QALY) of -0.003 (95% CI: -0.03 to 0.02), with a 44% chance of being cost-effective at a threshold of £20 000 per QALY gained. The percentage of participants who took time off and the associated productivity cost were lower in the model OA consultation arm. Conclusion: Implementing National Institute for Health and Care Excellence guidelines using a model OA consultation in primary care does not appear to lead to increased costs, but health outcomes remain very similar to usual care. Even though the intervention seems to reduce the demand for orthopaedic surgery, overall it is unlikely to be cost-effective

Impact of socioeconomic deprivation on rate and cause of death in severe mental illness

Background: Socioeconomic status has important associations with disease-specific mortality in the general population. Although individuals with Severe Mental Illnesses (SMI) experience significant premature mortality, the relationship between socioeconomic status and mortality in this group remains under investigated.<p></p> Aims: To assess the impact of socioeconomic status on rate and cause of death in individuals with SMI (schizophrenia and bipolar disorder) relative to the local (Glasgow) and wider (Scottish) populations.<p></p> Methods: Cause and age of death during 2006-2010 inclusive for individuals with schizophrenia or bipolar disorder registered on the Glasgow Psychosis Clinical Information System (PsyCIS) were obtained by linkage to the Scottish General Register Office (GRO). Rate and cause of death by socioeconomic status, measured by Scottish Index of Multiple Deprivation (SIMD), were compared to the Glasgow and Scottish populations.<p></p> Results: Death rates were higher in people with SMI across all socioeconomic quintiles compared to the Glasgow and Scottish populations, and persisted when suicide was excluded. Differences were largest in the most deprived quintile (794.6 per 10,000 population vs. 274.7 and 252.4 for Glasgow and Scotland respectively). Cause of death varied by socioeconomic status. For those living in the most deprived quintile, higher drug-related deaths occurred in those with SMI compared to local Glasgow and wider Scottish population rates (12.3% vs. 5.9%, p = <0.001 and 5.1% p = 0.002 respectively). A lower proportion of deaths due to cancer in those with SMI living in the most deprived quintile were also observed, relative to the local Glasgow and wider Scottish populations (12.3% vs. 25.1% p = 0.013 and 26.3% p = <0.001). The proportion of suicides was significantly higher in those with SMI living in the more affluent quintiles relative to Glasgow and Scotland (54.6% vs. 5.8%, p = <0.001 and 5.5%, p = <0.001). Discussion and conclusions: Excess mortality in those with SMI occurred across all socioeconomic quintiles compared to the Glasgow and Scottish populations but was most marked in the most deprived quintiles when suicide was excluded as a cause of death. Further work assessing the impact of socioeconomic status on specific causes of premature mortality in SMI is needed

Recovery of Salivary Function: Contralateral Parotid-sparing Intensity-modulated Radiotherapy versus Bilateral Superficial Lobe Parotid-sparing Intensity-modulated Radiotherapy.

Aims To establish whether there is a difference in recovery of salivary function with bilateral superficial lobe parotid-sparing intensity-modulated radiotherapy (BSLPS-IMRT) versus contralateral parotid-sparing IMRT (CLPS-IMRT) in patients with locally advanced head and neck squamous cell cancers.Materials and methods A dosimetric analysis was carried out on data from two studies in which patients received BSLPS-IMRT (PARSPORT II) or CLPS-IMRT (PARSPORT). Acute (National Cancer Institute, Common Terminology Criteria for adverse events - NCI CTCAEv3.0) and late (Late Effects of Normal Tissue- subjective, objective, management analytical - LENTSOMA and Radiation Therapy Oncology Group) xerostomia scores were dichotomised: recovery (grade 0-1) versus no recovery (≥grade 2). Incidence of recovery of salivary function was compared between the two techniques and dose-response relationships were determined by fitting dose-response curves to the data using non-linear logistic regression analysis.Results Seventy-one patients received BSLPS-IMRT and 35 received CLPS-IMRT. Patients received 65 Gy in 30 fractions to the primary site and involved nodal levels and 54 Gy in 30 fractions to elective nodal levels. There were significant differences in mean doses to contralateral parotid gland (29.4 Gy versus 24.9 Gy, P < 0.005) and superficial lobes (26.8 Gy versus 30.5 Gy, P = 0.02) for BSLPS and CLPS-IMRT, respectively. Lower risk of long-term ≥grade 2 subjective xerostomia (LENTSOMA) was reported with BSLPS-IMRT (odds ratio 0.50; 95% confidence interval 0.29-0.86; P = 0.012). The percentage of patients who reported recovery of parotid saliva flow at 1 year was higher with BSLPS-IMRT compared with CLPS-IMRT techniques (67.1% versus 52.8%), but the difference was not statistically significant (P = 0.12). For the whole parotid gland, the tolerance doses, D50, were 25.6 Gy (95% confidence interval 20.6-30.5), k = 2.7 (0.9-4.5) (CLPS-IMRT) and 28.9 Gy (26.1-31.9), k = 2.4 (1.4-3.4) (BSLPS-IMRT). For the superficial lobe, D50 were similar: BSLPS-IMRT 23.5 Gy (19.3-27.6), k = 1.9 (0.5-3.8); CLPS-IMRT 24.0 Gy (17.7-30.1), k = 2.1 (0.1-4.1).Conclusion BSLPS-IMRT reduces the risk of developing high-grade subjective xerostomia compared with CLPS-IMRT. The D50 of the superficial lobe may be a more reliable predictor of recovery of parotid function than the whole gland mean dose

Place of death in patients with lung cancer: a retrospective cohort study from 2004-2013

Introduction: Many patients with cancer die in an acute hospital bed, which has been frequently identified as the least preferred location, with psychological and financial implications. This study looks at place and cause of death in patients with lung cancer and identifies which factors are associated with dying in an acute hospital bed versus at home. Methods and Findings: We used the National Lung Cancer Audit linked to Hospital Episode Statistics and Office for National Statistics data to determine cause and place of death in those with lung cancer; both overall and by cancer Network. We used multivariate logistic regression to compare features of those who died in an acute hospital versus those who died at home. Results: Of 143627 patients identified 40% (57678) died in an acute hospital, 29% (41957) died at home and 17% (24108) died in a hospice. Individual factors associated with death in an acute hospital bed compared to home were male sex, increasing age, poor performance status, social deprivation and diagnosis via an emergency route. There was marked variation between cancer Networks in place of death. The proportion of patients dying in an acute hospital ranged from 28% to 48%, with variation most notable in provision of hospice care (9% versus 33%). Cause of death in the majority was lung cancer (86%), with other malignancies, chronic obstructive pulmonary disease (COPD) and ischaemic heart disease (IHD) comprising 9% collectively. Conclusions: A substantial proportion of patients with lung cancer die in acute hospital beds and this is more likely with increasing age, male sex, social deprivation and in those with poor performance status. There is marked variation between Networks, suggesting a need to improve end-of-life planning in those at greatest risk, and to review the allocation of resources to provide more hospice beds, enhanced community support and ensure equal access