Economic and humanistic impact of medication nonadherence in patients with asthma and chronic obstructive pulmonary disease

Asthma and chronic obstructive pulmonary disease (COPD) significantly impact morbidity and mortality. In spite of the well-known benefits of prophylactic medication use, especially in asthma, the rate of medication nonadherence is more than 50%. In Phase I, this study examined the relationship between refill-based medication nonadherence and healthcare utilization/costs in patients with asthma, COPD, and those with both asthma and COPD from the West Virginia (WV) Public Employees Insurance Agency (PEIA) program. In Phase II, the study measured the relationship between refill-based and self-reported medication nonadherence, health-related quality of life (HRQL), and losses in workplace productivity, all of which were determined via a mailed questionnaire to patients identified from Phase I. Phase I Results: The prevalence of asthma in the study population was similar to national estimates (203/10,000), whereas the prevalence of COPD was higher (598/10,000). Among asthma-only and those with both asthma and COPD, more than half the patients received medications according to NHLBI guidelines. Refill-based medication adherence was highest in patients having both asthma and COPD, as compared to asthma-only or COPD-only enrollees. The number of adverse outcomes such as hospitalizations and ED visits increased with increasing refill-based adherence for the COPD-only patients. Total healthcare costs increased with increasing medication adherence for all three groups. Thus, increasing medication adherence was possibly a reflection of increasing disease severity. Phase II Results: The overall response rate was almost 23% (N = 918), and was highest for the asthma-only group (25%), followed by the \u27both\u27 group (24%), and the COPD-only group (15%). The perception of HRQL among WV PEIA enrollees was similar to those found in other studies. Only 40% of all Phase II respondents reported themselves as high adherent; the prevalence of self-reported adherence being similar in all three sub-groups. The correlations between self-reported and refill-based adherence in the three groups were not clinically significant. Medication adherence was a significant predictor of HRQL for the COPD-only group, with HRQL worsening with increasing adherence. Self-reported health status was a significant predictor of HRQL for each of the three disease groups; and HRQL worsened with deteriorating health status. In all three groups, medication adherence was not significantly associated with losses in workplace productivity dollars

Prevalence of Diagnosed Opioid Abuse and its Economic Burden in the Veterans Health Administration

Objective Evaluate prevalence and risk‐adjusted healthcare costs of diagnosed opioid abuse in the national V eterans H ealth A dministration ( VHA ). Costs were compared between patients with and without diagnosed opioid abuse. Design Medical and pharmacy claims analysis of VHA data (10/01/2006 to 09/30/2010) were retrospectively analyzed. Prevalence was calculated as the percent of patients with diagnosed opioid abuse for the entire VHA membership and those with noncancer pain diagnoses, compared between patients prescribed opioids prior to abuse diagnosis and those not prescribed opioids through the VHA system. Healthcare utilization and costs were estimated using matching techniques and generalized linear models to control for clinical and demographic differences between patients with and without diagnosed opioid abuse. Separate comparisons were made (with diagnosed abuse vs. without) for each cohort: patients with/without opioid prescriptions. Results Five‐year diagnosed opioid abuse was 1.11%. Among patients prescribed opioids, 5‐year abuse prevalence was 3.04%. Pain patients prescribed opioids had the highest abuse rate at 3.26%. Adjusted annual healthcare costs for diagnosed opioid abuse patients were higher than for those without diagnosed abuse, (prescribed opioids overall healthcare costs: $28,882, with diagnosed abuse vs.$13,605 for those without; not prescribed opioids: $25,197 vs.$6350, P ‐value< 0.0001; opioid‐specific healthcare costs for patients prescribed opioids: $8956 vs.$218; patients not prescribed opioids: $8733 vs.$20). Conclusions Diagnosed opioid abuse prevalence is almost 7‐fold higher in the veteran's administration population than in commercial health plans and translates to a significant economic burden. Appropriate interventions should be considered to prevent and reduce opioid abuse.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107356/1/papr12097.pd

Differences in Healthcare Utilization and Associated Costs Between Patients Prescribed vs. Nonprescribed Opioids During an Inpatient or Emergency Department Visit

Objectives Compare healthcare resource utilization ( HCRU ) and costs between patients prescribed opioids ( R x OP ) and those who were not ( N o R x OP ) during an emergency department ( ED ) or inpatient visit. Methods Retrospective cohort analysis was performed ( J anuary 2006 to S eptember 2010). Continuously eligible R x OP patients in ED /inpatient settings ( J anuary 2007 to S eptember 2009) were included if age was ≥ 12 years by initial prescription date (or random date between first ED /inpatient admission and S eptember 30, 2009 [ N oRx OP patients]). Healthcare resource utilization and costs for 12 months after initial prescription were compared. Univariate descriptive analyses were performed for baseline and outcome variables and compared using appropriate tests. Risk adjustment compared HCRU between R x OP and N o R x OP cohorts for the postindex period. Results Of 27,599 eligible patients, R x OP patients ( n  = 18,819) were younger, less likely to be male, more likely to reside in southern U nited S tates and to have Preferred Provider Organization health plans, and had lower comorbidity index scores, compared with N o R x OP patients ( n  = 8,780). R x OP patients were less likely to have nonpain‐related comorbidities and more frequently diagnosed with pain‐related comorbidities. Unmatched and propensity‐matched R x OP patients experienced higher HCRU and costs in all subcategories (total, inpatient, outpatient ED , physician, pharmacy, other outpatient settings). Opioid abuse frequency was low in patients with common diagnoses/procedures within 3 months before initial prescription (0.48%). Average time to abuse was < 1 year (201 days). Conclusion Most patients were prescribed opioids initially during ED /inpatient visits and incurred higher HCRU than those not prescribed opioids. Among those with diagnosed opioid abuse after initiating opioids, time to diagnosis was rapid (range: 14 to 260 days) for patients with common diseases and procedures.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/107375/1/papr12098.pd

Development and Implementation of Integrated Road Traffic Injuries Surveillance – India (IRIS-India): A Protocol

Road traffic accidents stand as one of the leading causes of mortality and morbidity across the globe. The reasons for the high burden of road traffic injuries (RTIs) in developing countries are increasing in the number of motor vehicles, poor enforcement of traffic safety regulations, inadequacy of health infrastructure and poor transport facility. However, the systematic collection of road traffic data is not well developed in many developing countries including India and under-reporting of RTIs and deaths are common. Hence, surveillance of RTIs is recommended to assess the burden, to identify high-risk groups, to establish an association with probable risk factors and to plan interventions to control the RTIs. The broad objective of this study is to establish an electronic-based comprehensive and integrated RTI surveillance system, to assess the burden of RTIs, its risk factors and outcomes across rural and urban settings in India. This study with the support of the Indian Council of Medical Research (ICMR) is progressing in three cities (Chennai, Delhi and Jaipur) and two rural areas (Chittoor and Tehri-Garhwal). At each centre, major sources of data can be categorized under two categories including health facilities and community. In urban areas, one trauma centre, one private hospital and a community of 10000-population are included in the study. In rural areas, a district hospital, a private nursing home and two sub-centres areas of different primary health centres at each site are included for the surveillance. Passive surveillance is done at the trauma centres/district hospitals, while active surveillance is done in private hospitals/nursing homes, sub-centres and communities. Before establishing the surveillance system, situational analysis has been undertaken. Surveillance-related software was developed during the preparatory stage. This electronic surveillance platform allowed to gather data electronically across multiple sites. This internet-enabled surveillance platform has several modules to capture and analyse the data. The present study provides a model of surveillance including both passive and active surveillance to cover maximum number of RTIs. This study further provides the first comprehensive epidemiology of RTIs. The results of these studies will contribute to the setting of research and investment priorities to tackle the burden of RTIs

Development and Implementation of Integrated Road Traffic Injuries Surveillance – India (IRIS-India): A Protocol

Road traffic accidents stand as one of the leading causes of mortality and morbidity across the globe. The reasons for the high burden of road traffic injuries (RTIs) in developing countries are increasing in the number of motor vehicles, poor enforcement of traffic safety regulations, inadequacy of health infrastructure and poor transport facility. However, the systematic collection of road traffic data is not well developed in many developing countries including India and under-reporting of RTIs and deaths are common. Hence, surveillance of RTIs is recommended to assess the burden, to identify high-risk groups, to establish an association with probable risk factors and to plan interventions to control the RTIs. The broad objective of this study is to establish an electronic-based comprehensive and integrated RTI surveillance system, to assess the burden of RTIs, its risk factors and outcomes across rural and urban settings in India. This study with the support of the Indian Council of Medical Research (ICMR) is progressing in three cities (Chennai, Delhi and Jaipur) and two rural areas (Chittoor and Tehri-Garhwal). At each centre, major sources of data can be categorized under two categories including health facilities and community. In urban areas, one trauma centre, one private hospital and a community of 10000-population are included in the study. In rural areas, a district hospital, a private nursing home and two sub-centres areas of different primary health centres at each site are included for the surveillance. Passive surveillance is done at the trauma centres/district hospitals, while active surveillance is done in private hospitals/nursing homes, sub-centres and communities. Before establishing the surveillance system, situational analysis has been undertaken. Surveillance-related software was developed during the preparatory stage. This electronic surveillance platform allowed to gather data electronically across multiple sites. This internet-enabled surveillance platform has several modules to capture and analyse the data. The present study provides a model of surveillance including both passive and active surveillance to cover maximum number of RTIs. This study further provides the first comprehensive epidemiology of RTIs. The results of these studies will contribute to the setting of research and investment priorities to tackle the burden of RTIs

Analysis of the unexplored features of rrs (16S rDNA) of the Genus Clostridium

<p>Abstract</p> <p>Background</p> <p>Bacterial taxonomy and phylogeny based on <it>rrs </it>(16S rDNA) sequencing is being vigorously pursued. In fact, it has been stated that novel biological findings are driven by comparison and integration of massive data sets. In spite of a large reservoir of <it>rrs </it>sequencing data of 1,237,963 entries, this analysis invariably needs supplementation with other genes. The need is to divide the genetic variability within a taxa or genus at their <it>rrs </it>phylogenetic boundaries and to discover those fundamental features, which will enable the bacteria to naturally fall within them. Within the large bacterial community, <it>Clostridium </it>represents a large genus of around 110 species of significant biotechnological and medical importance. Certain <it>Clostridium </it>strains produce some of the deadliest toxins, which cause heavy economic losses. We have targeted this genus because of its high genetic diversity, which does not allow accurate typing with the available molecular methods.</p> <p>Results</p> <p>Seven hundred sixty five <it>rrs </it>sequences (> 1200 nucleotides, nts) belonging to 110 <it>Clostridium </it>species were analyzed. On the basis of 404 <it>rrs </it>sequences belonging to 15 <it>Clostridium </it>species, we have developed species specific: (i) phylogenetic framework, (ii) signatures (30 nts) and (iii) <it>in silico </it>restriction enzyme (14 Type II REs) digestion patterns. These tools allowed: (i) species level identification of 95 <it>Clostridium </it>sp. which are presently classified up to genus level, (ii) identification of 84 novel <it>Clostridium </it>spp. and (iii) potential reduction in the number of <it>Clostridium </it>species represented by small populations.</p> <p>Conclusions</p> <p>This integrated approach is quite sensitive and can be easily extended as a molecular tool for diagnostic and taxonomic identification of any microbe of importance to food industries and health services. Since rapid and correct identification allows quicker diagnosis and consequently treatment as well, it is likely to lead to reduction in economic losses and mortality rates.</p

Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950-2019 : a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2·72 (95% uncertainty interval [UI] 2·66–2·79) in 2000 to 2·31 (2·17–2·46) in 2019. Global annual livebirths increased from 134·5 million (131·5–137·8) in 2000 to a peak of 139·6 million (133·0–146·9) in 2016. Global livebirths then declined to 135·3 million (127·2–144·1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2·1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27·1% (95% UI 26·4–27·8) of global livebirths. Global life expectancy at birth increased from 67·2 years (95% UI 66·8–67·6) in 2000 to 73·5 years (72·8–74·3) in 2019. The total number of deaths increased from 50·7 million (49·5–51·9) in 2000 to 56·5 million (53·7–59·2) in 2019. Under-5 deaths declined from 9·6 million (9·1–10·3) in 2000 to 5·0 million (4·3–6·0) in 2019. Global population increased by 25·7%, from 6·2 billion (6·0–6·3) in 2000 to 7·7 billion (7·5–8·0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58·6 years (56·1–60·8) in 2000 to 63·5 years (60·8–66·1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Erratum: Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning