Synthesis of 2,2-dimethyl-chroman-based stereochemically flexible and constrained anti-breast cancer agents.

Receptors are proteinous macromolecules which remain in the apo form under normal/unliganded conditions. As the ligand approaches, there are specific stereo-chemical changes in the apo form of the receptor as per the stereochemistry of a ligand. Accordingly, a series of substituted dimethyl-chroman-based stereochemically flexible and constrained Tamoxifen analogs were synthesized as anti-breast cancer agents. The synthesized compounds 19a-e, 20a-e, 21, and 22a-e, showed significant antiproliferative activity against estrogen receptor-positive (ER+, MCF-7) and negative (ER-, MDA MB-231) cells within IC50 value 8.5-25.0 µM. Amongst all, four potential molecules viz 19b, 19e, 22a, and 22c, were evaluated for their effect on the cell division cycle and apoptosis of ER+ and ER- cancer cells (MCF-7 & MDA MB-231cells), which showed that these compounds possessed antiproliferative activity through triggering apoptosis. In-silico docking experiments elucidated the possible affinity of compounds with estrogen receptors-α and -ß.

Subthreshold laser compared to oral spironolactone for the treatment of chronic central serous chorioretinopathy: a retrospective study.

PURPOSE: To compare functional and morphological outcomes of Subthreshold Laser (STL) and Oral Spironolactone (SPR) in treating chronic central serous chorioretinopathy (CSCR). METHODS: This is a retrospective observational study. Treatment-naïve patients with chronic CSCR treated with STL or SPR were included, and data was reviewed at baseline, 1, 3, 6 and 12-month follow-up. Main outcome measures were changes in Central Macular Thickness (CMT) and Subretinal Fluid (SRF) height, and complete resolutions of SRF. Sub-analysis based on retinal pigmented epithelium (RPE) status at baseline was performed. RESULTS: 47 and 47 patients received STL and SPR, respectively. At all timepoints, both treatments significantly improved CMT and SRF (p < 0.05). No significant changes in best corrected visual acuity (BCVA) were recorded and no significant differences between treatment groups were present at each corresponding follow-up. Complete resolution of SRF was achieved in 29% and 36% of patients treated with STL or SPR, respectively, at 12-months follow up. Eyes treated with STL and intact RPE showed significant SRF decrease at 6 months and significantly better BCVA at 1, 3 and 6 months compared to eyes with disrupted RPE layer (p < 0.05). In both treatment groups, intact RPE was associated with a higher rate of complete SRF resolutions, with 43% vs 13% in the STL group and 50% vs 26% in the SPR group. CONCLUSION: STL and SPR are effective treatments for chronic CSCR. Greater resolution of subretinal fluid was observed in eyes with intact RPE, hence both treatments should be initiated in the earlier stages of the disease.

High-Flow Humidified Oxygen as an Early Intervention in Children With Acute Severe Asthma: Protocol for a Feasibility Randomized Controlled Trial.

BACKGROUND: Acute severe asthma (ASA) is a leading cause of hospital attendance in children. Standard first-line therapy consists of high-dose inhaled bronchodilators plus oral corticosteroids. Treatment for children who fail to respond to first-line therapy is problematic: the use of intravenous agents is inconsistent, and side effects are frequent. High-flow humidified oxygen (HiFlo) is widely used in respiratory conditions and is increasingly being used in ASA, but with little evidence for its effectiveness. A well-designed, adequately powered randomized controlled trial (RCT) of HiFlo therapy in ASA is urgently needed, and feasibility data are required to plan such an RCT. In this study, we describe the protocol for a feasibility study designed to fill this knowledge gap. OBJECTIVE: This study aims to establish whether a full RCT of early HiFlo therapy in children with ASA can be conducted successfully and safely, to establish whether recruitment using deferred consent is practicable, and to define appropriate outcome measures and sample sizes for a definitive RCT. The underlying hypothesis is that early HiFlo therapy in ASA will reduce the need for more invasive treatments, allow faster recovery and discharge from hospital, and in both these ways reduce distress to children and their families. METHODS: We conducted a feasibility RCT with deferred consent to assess the use of early HiFlo therapy in children aged 2 to 11 years with acute severe wheeze not responding to burst therapy (ie, high-dose inhaled salbutamol with or without ipratropium). Children with a Preschool Respiratory Assessment Measure score ≥5 after burst therapy were randomized to commence HiFlo therapy or follow standard care. The candidate primary outcomes assessed were treatment failure requiring escalation and time to meet hospital discharge criteria. Patient and parent experiences were also assessed using questionnaires and telephone interviews. RESULTS: The trial was opened to recruitment in February 2020 but was paused for 15 months owing to the COVID-19 pandemic. The trial was reopened at the lead site in July 2021 and opened at the other 3 sites from August to December 2022. Recruitment was completed in June 2023. CONCLUSIONS: This feasibility RCT of early HiFlo therapy in children with ASA recruited to the target despite major disturbances owing to the COVID-19 pandemic. The data are currently being analyzed and will be published separately. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number Registry ISRCTN78297040; https://www.isrctn.com/ISRCTN78297040. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54081.

Impact of Lung Function on Asthma Exacerbation Rates in Children Treated with Dupilumab: The VOYAGE Study.

Background: Severe, uncontrolled asthma and asthma exacerbations in children are associated with abnormal lung function and airway development, and increased risk of chronic obstructive lung disease in adulthood. The rationale for this post hoc analysis was to explore the relationship between changes in asthma exacerbation rates and lung function in children treated with dupilumab. Methods: This post hoc analysis included children aged 6 to 11 years with uncontrolled, moderate-to-severe type 2 asthma (blood eosinophils ≥150 cells/µL or fractional exhaled nitric oxide ≥20 ppb) who received dupilumab or placebo in the phase 3 LIBERTY ASTHMA VOYAGE study (NCT02948959). Endpoints were the proportion of patients achieving clinically meaningful improvements (≥5% or ≥10%) in pre-bronchodilator percent-predicted forced expiratory volume in 1 second (ppFEV1) by Week 12, annualized severe asthma exacerbation rates from Week 12-52, and mean change from baseline in ppFEV1 to Week 12. Results: At Week 12 of VOYAGE, 141/236 (60%) of children treated with dupilumab and 57/114 (50%) of children receiving placebo showed improvements of ≥5% in ppFEV1; 106/236 (45%) children receiving dupilumab and 36/114 (32%) receiving placebo achieved improvements in ppFEV1 ≥10%. During the Week 12-52 treatment period, dupilumab vs placebo significantly reduced severe exacerbation rates in all subgroups by 52-60% (all P<0.05). Dupilumab treatment resulted in rapid and sustained improvements in ppFEV1 (Week 12 least squares mean difference [95% CI] vs placebo: 3.54 [0.30, 6.78] percentage points; P=0.03) in children who achieved improvements of ≥5%. Conclusion: Dupilumab vs placebo significantly improved pre-bronchodilator ppFEV1, with a higher proportion of patients achieving a clinically meaningful response at Week 12. Dupilumab also significantly reduced severe exacerbation rates, independent of pre-bronchodilator ppFEV1 response at Week 12. Trial Registration: NCT02948959.

Phase 3 efficacy and safety trial of proposed liraglutide biosimilar for reduction of glycosylated hemoglobin (HbA1c) in patients with Type 2 diabetes mellitus.

Liraglutide is indicated for glycaemic control in adults with Type 2 diabetes mellitus (T2DM) as an adjunct to diet and exercise. A proposed biosimilar of liraglutide (Levim Liraglutide) was investigated for efficacy & safety in a phase 3 study against the originator reference liraglutide (Victoza®) manufactured by Novo Nordisk A/S, Denmark. Patients aged 18-65 years of age with glycosylated hemoglobin (HbA1c) between 7 and 10 %, among other criteria, were included in the study. Patients were randomized 1:1 to receive daily doses of either Levim liraglutide or reference liraglutide for 24 weeks. The least square mean (standard error, SE) for the primary efficacy endpoint of reduction in HbA1c% at Week 24 was -1.09 (0.15)% for Levim liraglutide group and -1.04 (0.14)% for reference liraglutide. The upper bound of the confidence interval for treatment difference was less than the non-inferiority margin of 0.4 % at one-sided alpha of 0.025 (P-value = 0.0003). The secondary endpoints for proportion of patients achieving reduction in HbA1c, glycaemic level and weight, changes in cardiovascular parameters and the overall safety profiles of the study drugs were comparable. Levim liraglutide demonstrated non-inferior efficacy and similar safety to reference liraglutide and may be an option in treatment of T2DM (CTRI.nic.in, no. CTRI/2022/02/040261).

Combat ocular trauma in counterinsurgency operations.

PURPOSE: To identify the pattern, distribution, and causes of ocular injuries among the security personnel participating in counterinsurgency operations (CIOps). METHODS: This was a multicentric, retrospective review of chart records of patients reporting to three hospitals located in the geographic region affected by CIOps. The hospital registry was examined for all patients diagnosed with any type of ocular trauma between January 1, 2016, and December 31, 2019. A standardized proforma was filled out using the case records, and entries were validated. RESULTS: A total of 131 ocular injuries fulfilled the criteria of the study. The mean age of the patients was 32.46 ± 10.2 years. All the patients were males. The causes of the injuries were explosive blasts in 60 eyes (45.80%), gunshot wounds in 15 eyes (11.42%), stone pelting in 16 eyes (12.21%), training-related causes in 26 eyes (29.84%), vehicular accidents in 13 eyes (9.92%), and battery blast in one eye (0.76%). Among the type of injuries, open globe injuries included 66 eyes (50.38%), closed globe injuries included 35 eyes (26.72%), isolated lid lacerations included 14 eyes (10.68%), and isolated chemical injury was seen in two eyes (1.52%). Optic nerve head avulsion was seen in two eyes (1.52%). CONCLUSION: The study revealed a considerable number of ocular injuries related to combat, with explosive bursts being the leading cause. The incidence of ocular injuries was found to be highest in zone 1. This study emphasizes the importance of the need for soldiers deployed in active CIOps regions to wear protective eyewear, such as ballistic goggles or military combat eye protection, to reduce the risk of ocular injuries.

Effect of health promotion interventions on small portion size consumption behavior among college students.

Background: Large food portion size is contributing toward overweight and obesity rates and has been found directly proportional to increase in portion size. Objectives: The study was done to see the effect of health promotion intervention on small portion size consumption behavior using multitheory model (MTM). Materials and Methods: A quasi-experimental study was conducted among students of age groups 18 - 21 years in two different colleges from North India between 2019 to 2020. About 150 participants in the intervention group as well as control group were selected and health promotion intervention in the form of motivational group counseling, one-to-one counseling, Power Point presentations, lectures, and messages were given to participants in intervention group. Difference in difference of proportions for meal consumption behavior and the difference in the difference of means for body mass index, waist-hip ratio and for constructs of MTM for portion size consumption behavior were calculated. Paired t-test was used to test the significance between the continuous variables. Results: There was a significant reduction (46% vs. 11%, P < 0.001) in proportion of participants consuming large portion-sized meals in the intervention group as compared to the control group. The mean change in constructs (participatory dialogues,behavioral confidence, change in physical environment, emotional transformation and practice for change) for portion size consumption behavior of participants in the intervention and control groups at base line and end line was found statistically significant. Conclusion: MTM is a useful tool for health promotion and health education to predict the initiation and sustenance of health behavior change.

Is Hypoglycemia Secondary to Metastatic Retroperitoneal Sarcoma - A Therapeutic Challenge? Case Report and Review of Literature.

Most soft tissue sarcomas afflict the extremities; however, the retro peritoneum can also be affected rarely. Retroperitoneal sarcomas are relatively asymptomatic. Although tumor-induced hypoglycemia is rare in tumors other than insulinomas, extrapancreatic tumors are a subset that displays this phenomenon. The occurrence of hypo-insulinemic hypoglycemia with low GH and IGF-1 should prompt consideration of the secretion of a hypoglycemic substance impeding the secretion of insulin and GH, such as IGF-2 or one of its related substances. The present case report is of a 38-year-old male with retroperitoneal round cell sarcoma with liver metastasis with severe symptomatic hypoglycemia who was managed with multipronged symptomatic therapy and oncological management after which he had shown significant improvement in hypoglycemic episodes and symptom profile. A literature review revealed our case report to be the first reported case of a young male (preponderance in the older population) with hypoglycemia associated with retroperitoneal sarcoma which presented with liver metastasis and the only one treated with Gemcitabine /Docetaxel. The presence of these features might point toward a poorer prognosis in a disease with an already dismal course. All these points towards the need for further research regarding intensified oncological treatment after evidence-based prognostication of high-risk groups and modalities for the management of symptomatic hypoglycemia such as Somatostatin analogs and glucagon which aid in symptom control.

Growth of Medicare Advantage After Plan Payment Reductions.

Importance: Various policy proposals would reduce federal payments to Medicare Advantage (MA) plans. However, it is unclear whether payment reductions would compromise beneficiary access to the MA program. Objective: To quantify the association between MA payment reductions under the Affordable Care Act (ACA) and MA enrollment growth. Design, Setting, and Participants: This retrospective cohort study examined the MA market before and after the ACA, which mandated cuts to MA benchmark payment rates. Using 2008 to 2019 county-level enrollment and payment data, a difference-in-differences analysis was conducted comparing MA enrollment changes between counties with larger vs smaller benchmark reductions, before vs after the ACA. Main Outcomes and Measures: The primary outcome was the MA enrollment rate, defined as the proportion of a county's Medicare beneficiaries enrolled in MA. A secondary analysis examined MA plan payments per member per month. Results: Among 3138 counties with 37 639 county-year observations, ACA-induced benchmark cuts were sizeable and varied, ranging from 0% to 42.9% (mean [SD], 5.9% [6.6%]). Counties with benchmark cuts above the 75th percentile had population-weighted average benchmark cuts of 14.9% compared with 4.4% in other counties. In the 8 years following the ACA, there was no differential change in MA enrollment between counties with larger vs smaller benchmark cuts (difference-in-differences estimate, 0.02 [95% CI, -1.18 to 1.21] percentage points; P = .98). Plan payments differentially fell in counties with larger benchmark cuts by $78.35 (95% CI, $62.21-$94.48) per member per month (P < .001). Conclusion and Relevance: This cohort study found no evidence that the MA benchmark and ensuing payment cuts imposed by the ACA were associated with reduced MA enrollment, compromising access to MA. This evidence can inform ongoing policy debates regarding the growth of MA, concerns about excess payments to MA plans, and proposed Medicare reforms, including further reductions in MA payments.

Synthesis of 6-alkoxy and 6-hydroxy-alkyl amine derivatives of braylin as vasorelaxing agents.

Braylin (10b) is a 8,8-dimethyl chromenocoumarin present in the plants of the family Rutaceae and Meliaceae and possesses vasorelaxing and anti-inflammatory activities. In this study, six 6-alkoxy (10b, 15-19), and twelve 6-hydroxy-alkyl amine (20a-20l) derivatives of braylin (11 and 12) were synthesized to delineate its structural requirement for vasorelaxing activity. The synthesized compounds were evaluated for vasorelaxation response in preconstricted intact rat Main Mesenteric Artery (MMA). The compounds showed l-type VDCC channel blockade depended and endothelium-independent vasorelaxation within the range of Emax < 50.00-96.70 % at 30 µM. Amongst all, 6-alkoxy derivatives were more active than 6-hydroxy-alkyl amine derivatives. The structural refinements about braylin showed that deletion of its methoxy group or homologation beyond ethoxy group presented deleterious effect on vasorelaxation response of braylin. Interestingly, substituting the ethoxy group in 10b presented the best activity and selectivity towards l-type VDCC channel blockade, a specific target cardiovascular function.

Definitions of non-response and response to biological therapy for severe asthma: a systematic review.

Background: Biologics have proven efficacy for patients with severe asthma but there is lack of consensus on defining response. We systematically reviewed and appraised methodologically developed, defined and evaluated definitions of non-response and response to biologics for severe asthma. Methods: We searched four bibliographic databases from inception to 15 March 2021. Two reviewers screened references, extracted data, and assessed methodological quality of development, measurement properties of outcome measures and definitions of response based on COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). A modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach and narrative synthesis were undertaken. Results: 13 studies reported three composite outcome measures, three asthma symptoms measures, one asthma control measure and one quality of life measure. Only four measures were developed with patient input; none were composite measures. Studies utilised 17 definitions of response: 10 out of 17 (58.8%) were based on minimal clinically important difference (MCID) or minimal important difference (MID) and 16 out of 17 (94.1%) had high-quality evidence. Results were limited by poor methodology for the development process and incomplete reporting of psychometric properties. Most measures rated "very low" to "low" for quality of measurement properties and none met all quality standards. Conclusions: This is the first review to synthesise evidence about definitions of response to biologics for severe asthma. While high-quality definitions are available, most are MCIDs or MIDs, which may be insufficient to justify continuation of biologics in terms of cost-effectiveness. There remains an unmet need for universally accepted, patient-centred, composite definitions to aid clinical decision making and comparability of responses to biologics.

Synthesis of amide derivatives of 3-aryl-3H-benzopyrans as osteogenic agent concomitant with anticancer activity.

The present study reports a series of 3-aryl-3H-benzopyran-based amide derivatives as osteogenic agents concomitant with anticancer activity. Six target compounds viz 22e, 22f, 23i, and 24b-d showed good osteogenic activity at 1 pM and 100 pM concentrations. One of the potential molecules, 24b, effectively induced ALP activity and mRNA expression of osteogenic marker genes at 1 pM and bone mineralization at 100 pM concentrations. These molecules also presented significant growth inhibition of osteosarcoma (MG63) and estrogen-dependent and -independent (MCF-7 and MDA-MB-231) breast cancer cells. The most active compound, 24b, inhibited the growth of all the cancer cells within the IC50 10.45-12.66 µM. The mechanistic studies about 24b showed that 24b induced apoptosis via activation of the Caspase-3 enzyme and inhibited cancer cell migration. In silico molecular docking performed for 24b revealed its interaction with estrogen receptor-ß (ER-ß) preferentially.

The effect of performance pay incentives on market frictions: evidence from medicare.

Medicare has increased the use of performance pay incentives for hospitals, with the goal of increasing care coordination across providers, reducing market frictions, and ultimately to improve quality of care. This paper provides new empirical evidence by using novel operations and claims data from a large, independent home health care firm with the Hospital Readmissions Reduction Program (HRRP) penalty on hospitals providing identifying variation. We find that the penalty incentive to reduce re-hospitalizations passed through from hospitals to the firm for at least some types of patients, since it provided more care inputs for heart disease patients discharged from hospitals at greater penalty risk and that contributed more patients to the firm. This evidence suggests that HRRP helped increase coordination between hospitals and home health firms without formal integration. Greater home health effort does not appear to have led to lower patient readmissions.

Racial bias in recruitment to clinical trials on paediatric asthma.

Asthma is now the commonest chronic disease of childhood, but not all children with asthma receive equivalent standards of medical care which influences their clinical outcomes. In this paper we sought to determine the proportion of participants in registered clinical trials relating to paediatric or adolescent asthma over the last decade that were from white and non-white backgrounds. We searched the ClinicalTrials.gov database for all completed interventional studies between the dates 1st January 2011 and 1st January 2021 that were on the topic of 'asthma', and included participants below 18 years of age. Of the 500 studies returned, 208 had results available on the ClinicalTrials.gov website. In total, of the 112,327 patients studied, almost 69 % (77,333) of the patients were described as White or Caucasian, and fewer than 13 % (14,189) were described as Black, African, or African-American. Overall, approximately 30 % of study participants - some 34,207 children - were from non-white backgrounds. To redress this imbalance, researchers designing clinical trials must ensure that their study populations are as representative of the target population for the intervention as possible.

Physical activity and liver disease affect the fat-free mass in adolescents with cystic fibrosis.

Cystic fibrosis (CF) is predominantly a lung disease but is also characterised by impaired skeletal muscularity and a reduction in fat-free mass. We aimed to test the hypothesis that clinical and anthropometric parameters would determine fat-free mass impairment in adolescents with CF. We measured the fat-free mass index (FFMI) using bioelectrical impedance, the lung function using spirometry, the number of shuttles as a measure of exercise tolerance and the reported physical activity in children and young people with CF in a tertiary centre at King's College Hospital, London, UK. CF-related liver disease was diagnosed by abnormal liver enzymes and/or ultrasonography. We studied 28 children and young people (11 male) with a median (interquartile range (IQR)) age of 15 (13-17) years. They had a median (IQR) FFMI of 13.5 (11.6-15.1) kg/m2. The FFMI significantly correlated with age (rho = 0.568, p = 0.002), number of shuttles (rho = 0.691, p < 0.001) and reported hours of activity per day (rho = 0.426, p = 0.024). The median (IQR) FFMI was significantly higher in male [15.1 (13.1-18.6) kg/m2] compared to female participants [12.7 (11.6-14.1) kg/m2, p = 0.008]. The median (IQR) FFMI was significantly lower in the 10 (36%) participants with liver disease [11.9 (11.5-13.4) kg/m2] compared to the FFMI in the remaining 18 participants without liver disease [14.4 (12.5-15.9) kg/m2, p = 0.027]. CONCLUSION: Fat-free mass increases with increasing age and growth in adolescents with CF. Physical activity exerts a beneficial effect on fat-free mass, and CF-related liver disease negatively affects fat-free mass in adolescents with CF. WHAT IS KNOWN: • Health behaviours in adolescence influence lifelong health in cystic fibrosis (CF). • A normal body mass index in CF might fail to reveal a low fat-free mass (FFM), and quality of life in CF is strongly associated with a reduced FFM. WHAT IS NEW: • FFM increases with increasing age and growth in adolescents with CF. • Physical activity exerts a beneficial effect, and liver disease negatively affects FFM in adolescents with CF.

Is the Corpus Ready for Machine Translation? A Case Study with Python to Pseudo-Code Corpus.

The availability of data is the driving force behind most of the state-of-the-art techniques for machine translation tasks. Understandably, this availability of data motivates researchers to propose new techniques and claim about the superiority of their techniques over the existing ones by using suitable evaluation measures. However, the performance of underlying learning algorithms can be greatly influenced by the correctness and the consistency of the corpus. We present our investigations for the relevance of a publicly available python to pseudo-code parallel corpus for automated documentation task, and the studies performed using this corpus. We found that the corpus had many visible issues like overlapping of instances, inconsistency in translation styles, incompleteness, and misspelled words. We show that these discrepancies can significantly influence the performance of the learning algorithms to the extent that they could have caused previous studies to draw incorrect conclusions. We performed our experimental study using statistical machine translation and neural machine translation models. We have recorded a significant difference ( ∼  10% on BLEU score) in the models' performance after removing the issues from the corpus.

Development of Core Outcome Measures sets for paediatric and adult Severe Asthma (COMSA).

BACKGROUND: Effectiveness studies with biological therapies for asthma lack standardised outcome measures. The COMSA (Core Outcome Measures sets for paediatric and adult Severe Asthma) Working Group sought to develop Core Outcome Measures (COM) sets to facilitate better synthesis of data and appraisal of biologics in paediatric and adult asthma clinical studies. METHODS: COMSA utilised a multi-stakeholder consensus process among patients with severe asthma, adult and paediatric clinicians, pharmaceutical representatives, and health regulators from across Europe. Evidence included a systematic review of development, validity and reliability of selected outcome measures plus a narrative review and a pan-European survey to better understand patients' and carers' views about outcome measures. It was discussed using a modified GRADE (Grading of Recommendations Assessment, Development and Evaluation) Evidence to Decision framework. Anonymous voting was conducted using predefined consensus criteria. RESULTS: Both adult and paediatric COM sets include forced expiratory volume in 1 s (FEV1) as z-scores, annual frequency of severe exacerbations and maintenance oral corticosteroid use. Additionally, the paediatric COM set includes the Paediatric Asthma Quality of Life Questionnaire and Asthma Control Test or Childhood Asthma Control Test, while the adult COM set includes the Severe Asthma Questionnaire and Asthma Control Questionnaire-6 (symptoms and rescue medication use reported separately). CONCLUSIONS: This patient-centred collaboration has produced two COM sets for paediatric and adult severe asthma. It is expected that they will inform the methodology of future clinical trials, enhance comparability of efficacy and effectiveness of biological therapies, and help assess their socioeconomic value. COMSA will inform definitions of non-response and response to biological therapy for severe asthma.

Elevated end-of-life spending: A new measure of potentially wasteful health care spending at the end of life.

OBJECTIVE: To construct a new measure of end-of-life (EoL) spending-the elevated EoL spending-and examine its associations with measures of quality of care and patient and physician preferences in comparison with the commonly used total Medicare EoL spending measures. DATA SOURCES AND STUDY SETTING: Medicare claims data for a 20% random sample of Medicare fee-for-service (FFS) patients, from the health care quality data for 2015-2016, from the Hospital Compare and the Medicare Geographic Variation public use file, and survey data about patient and physician preferences. STUDY DESIGN: We constructed the elevated EoL spending measure as the differential monthly spending between decedents and survivors with the same one-year mortality risk, where the risk was predicted using machine learning models. We then examined the associations of the hospital referral region (HRR)-level elevated EoL spending with various health care quality measures and with the survey-elicited patient and provider preferences. We also examined analogous associations for monthly total EoL spending on decedents. DATA EXTRACTION METHODS: Medicare FFS patients who were continuously enrolled in Medicare Parts A & B in 2015 and were alive as of January 1, 2016. PRINCIPAL FINDINGS: We found a large variation in the elevated EoL spending across HRRs in the United States. There was no evidence of an association between HRR-level elevated EoL spending and established health care quality measures, including those specific to EoL care, whereas total EoL spending was positively associated with certain quality of care measures. We also found no evidence that elevated EoL spending was associated with patient preferences for EoL care. However, elevated EoL spending was positively and significantly associated with physician preferences for treatment intensity. CONCLUSIONS: Our findings suggested that elevated EoL spending captures different resource use from conventional measures of EoL spending and may be more valuable in identifying potentially wasteful spending.

Fifteen-minute consultation: A structured approach to children with parapneumonic effusion and empyema thoracis.

Parapneumonic effusion is defined as the accumulation of pleural fluid associated with lung infection/pneumonia. Parapneumonic effusions can be uncomplicated or complicated. They are caused by the spread of infection and inflammation to the pleural space, and can develop into empyema thoracis-frank pus in the pleural space. Chest radiograph and thoracic ultrasound are the key imaging modalities for the diagnosis of parapneumonic effusion. Management aims are reducing inflammation and bacteria in the pleural cavity, and enabling full lung expansion. Broad-spectrum intravenous antibiotics, with the addition of chest tube drainage and fibrinolytic therapy for larger collections, are the mainstays of management. This article provides a clear, evidence-based and structured approach to the assessment and management of parapneumonic effusion/empyema thoracis in children and young people.

Is employment group insurance financing of expensive gene therapies threatened in the United States?

Despite the potential of gene therapy to transform the lives of patients with rare genetic diseases, serious concern has been raised about the financing of the high up-front costs for such treatments and about the ability of the employer-sponsored insurance system in the United States, particularly in small firms, to pay for discoveries of this type. In this paper, we provide a conceptual framework and empirical evidence to support the proposition that, at present, private group insurance financing of cost-effective gene therapies is not only feasible and competitively necessary in the labor market for employers, regardless of group size, but also that, currently, the number of US workers in small firms who might be stressed by very high-priced claims is a tiny fraction of the group market for genetic treatments. The current system of employer-paid self-insurance supplemented by stop-loss coverage should be able to facilitate the use of new cost-effective gene therapies. Other alternative methods of financing that have been proposed may not be urgently needed. There are, however, some concerns about the long-term resilience of this system if stop-loss premiums continue to have high growth.