Cost-effectiveness Analysis of Subcutaneous Infliximab for Inflammatory Bowel Diseases in Sequential Biologic Treatment.

BACKGROUND: Inflammatory bowel disease (IBD) guidelines recommend tumor necrosis factor-α inhibitors (TNFis) for patients who have not responded to conventional therapy, and vedolizumab in case of inadequate response to conventional therapy and/or TNFis. Recent studies have shown that vedolizumab may also be effective in the earlier treatment lines. Therefore, we conducted cost-effectiveness analyses to determine the optimal treatment sequence in patients with IBD. METHODS: A Markov model with a 10-year time horizon compared the cost-effectiveness of different biologic treatment sequences in patients with moderate to severe ulcerative colitis (UC) and Crohn's disease (CD) from the UK and French perspectives. Subcutaneous formulations of infliximab, vedolizumab, and adalimumab were evaluated. Comparative effectiveness was based on a network meta-analysis of clinical trials and real-world evidence. Costs included pharmacotherapy, surgery, adverse events, and disease management. RESULTS: The results indicated that treatment sequences starting with infliximab were less costly and more effective than those starting with vedolizumab for patients with UC in the United Kingdom and France, and patients with just CD in France. For patients with CD in the United Kingdom, treatment sequences starting with infliximab resulted in better health outcomes with incremental cost-effectiveness ratios (ICERs) near the threshold. CONCLUSIONS: Based on the ICERs, treatment sequences starting with infliximab are the dominant option for patients with UC in the United Kingdom, and patients with UC and CD in France. In UK patients with CD, ICERs were near the assumed "willingness to pay" threshold. These results reinforce the UK's National Institute for Health and Care Excellence recommendations for using infliximab prior to using vedolizumab in biologics-naïve patients.

A Markov model compared the cost-effectiveness of biologic treatment sequences in patients with moderate to severe inflammatory bowel diseases from a European perspective. The results indicated that treatment sequences starting with infliximab are the dominant option than those starting with vedolizumab.

A 65-Year-Old Woman With Dyspnea After Atrial Fibrillation Ablation.

CASE PRESENTATION: A 65-year-old woman with a history of chronic persistent atrial fibrillation, tobacco use, and COPD was admitted to the hospital 2 months after catheter ablation for persistent atrial fibrillation and dyspnea. Her dyspnea was present at rest and worsened by exertion with limitation to ambulating less than two blocks. She also endorsed a 1-month history of cough with minimally productive whitish sputum with frequent nocturnal exacerbations and orthopnea. She denied any fevers, chest pain, or hemoptysis.

Burden of non-communicable diseases from infectious causes in 2017: a modelling study.

BACKGROUND: Non-communicable diseases (NCDs) cause a large burden of disease globally. Some infectious diseases cause an increased risk of developing specific NCDs. Although the NCD burden from some infectious causes has been quantified, in this study, we aimed to more comprehensively quantify the global burden of NCDs from infectious causes. METHODS: In this modelling study, we identified NCDs with established infectious risk factors and infectious diseases with long-term non-communicable sequelae, and did narrative reviews between April 11, 2018, and June 10, 2020, to obtain relative risks (RRs) or population attributable fractions (PAFs) from studies quantifying the contribution of infectious causes to NCDs. To determine infection-attributable burden for the year 2017, we applied estimates of PAFs to estimates of disease burden from the Global Burden of Disease Study (GBD) 2017 for pairs of infectious causes and NCDs, or used estimates of attributable burden directly from GBD 2017. Morbidity and mortality burden from these conditions was summarised with age-standardised rates of disability-adjusted life-years (DALYs), for geographical regions as defined by the GBD. Estimates of NCD burden attributable to infectious causes were compared with attributable burden for the groups of risk factors with the highest PAFs from GBD 2017. FINDINGS: Globally, we quantified 130 million DALYs from NCDs attributable to infection, comprising 8·4% of all NCD DALYs. The infection-NCD pairs with the largest burden were gastric cancer due to H pylori (14·6 million DALYs), cirrhosis and other chronic liver diseases due to hepatitis B virus (12·2 million) and hepatitis C virus (10·4 million), liver cancer due to hepatitis B virus (9·4 million), rheumatic heart disease due to streptococcal infection (9·4 million), and cervical cancer due to HPV (8·0 million). Age-standardised rates of infection-attributable NCD burden were highest in Oceania (3564 DALYs per 100 000 of the population) and central sub-Saharan Africa (2988 DALYs per 100 000) followed by the other sub-Saharan African regions, and lowest in Australia and New Zealand (803 DALYs per 100 000) followed by other high-income regions. In sub-Saharan Africa, the proportion of crude NCD burden attributable to infectious causes was 11·7%, which was higher than the proportion of burden attributable to each of several common risk factors of NCDs (tobacco, alcohol use, high systolic blood pressure, dietary risks, high fasting plasma glucose, air pollution, and high LDL cholesterol). In other broad regions, infectious causes ranked between fifth and eighth in terms of crude attributable proportions among the nine risks compared. The age-standardised attributable proportion for infectious risks remained highest in sub-Saharan Africa of the broad regions, but age-standardisation caused infectious risks to fall below dietary risks, high systolic blood pressure, and fasting plasma glucose in ranked attributable proportions within the region. INTERPRETATION: Infectious conditions cause substantial NCD burden with clear regional variation, and estimates of this burden are likely to increase as evidence that can be used for quantification expands. To comprehensively avert NCD burden, particularly in low-income and middle-income countries, the availability, coverage, and quality of cost-effective interventions for key infectious conditions need to be strengthened. Efforts to promote universal health coverage must address infectious risks leading to NCDs, particularly in populations with high rates of these infectious conditions, to reduce existing regional disparities in rates of NCD burden. FUNDING: Leona M and Harry B Helmsley Charitable Trust.

Cognitive tests for the detection of mild cognitive impairment (MCI), the prodromal stage of dementia: Meta-analysis of diagnostic accuracy studies.

INTRODUCTION: Mild cognitive impairment (MCI) is regarded as a prodrome to dementia. Various cognitive tests can help with diagnosis; meta-analysis of diagnostic accuracy studies would assist clinicians in choosing optimal tests. METHODS: We searched online databases for "mild cognitive impairment" and "diagnosis" or "screening" from 01/01/1999 to 01/07/2017. Articles assessing the diagnostic accuracy of a cognitive test compared with standard diagnostic criteria were extracted. Risk of bias was assessed. Bivariate random-effects meta-analysis was used to evaluate sensitivity and specificity. RESULTS: Eight cognitive tests (ACE-R, CERAD, CDT-Sunderland, IQCODE, Memory Alteration Test, MMSE, MoCA, and Qmci) were considered for meta-analysis. ACE-R, CERAD, MoCA, and Qmci were found to have similar diagnostic accuracy, while the MMSE had lower sensitivity. Memory Alteration Test had the highest sensitivity and equivalent specificity to the other tests. DISCUSSION: Multiple cognitive tests have comparable diagnostic accuracy. The Memory Alteration Test is short and has the highest sensitivity. New cognitive tests for MCI diagnosis should not be compared with the MMSE.

Changes in health in England, with analysis by English regions and areas of deprivation, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

BACKGROUND: In the Global Burden of Disease Study 2013 (GBD 2013), knowledge about health and its determinants has been integrated into a comparable framework to inform health policy. Outputs of this analysis are relevant to current policy questions in England and elsewhere, particularly on health inequalities. We use GBD 2013 data on mortality and causes of death, and disease and injury incidence and prevalence to analyse the burden of disease and injury in England as a whole, in English regions, and within each English region by deprivation quintile. We also assess disease and injury burden in England attributable to potentially preventable risk factors. England and the English regions are compared with the remaining constituent countries of the UK and with comparable countries in the European Union (EU) and beyond. METHODS: We extracted data from the GBD 2013 to compare mortality, causes of death, years of life lost (YLLs), years lived with a disability (YLDs), and disability-adjusted life-years (DALYs) in England, the UK, and 18 other countries (the first 15 EU members [apart from the UK] and Australia, Canada, Norway, and the USA [EU15+]). We extended elements of the analysis to English regions, and subregional areas defined by deprivation quintile (deprivation areas). We used data split by the nine English regions (corresponding to the European boundaries of the Nomenclature for Territorial Statistics level 1 [NUTS 1] regions), and by quintile groups within each English region according to deprivation, thereby making 45 regional deprivation areas. Deprivation quintiles were defined by area of residence ranked at national level by Index of Multiple Deprivation score, 2010. Burden due to various risk factors is described for England using new GBD methodology to estimate independent and overlapping attributable risk for five tiers of behavioural, metabolic, and environmental risk factors. We present results for 306 causes and 2337 sequelae, and 79 risks or risk clusters. FINDINGS: Between 1990 and 2013, life expectancy from birth in England increased by 5·4 years (95% uncertainty interval 5·0-5·8) from 75·9 years (75·9-76·0) to 81·3 years (80·9-81·7); gains were greater for men than for women. Rates of age-standardised YLLs reduced by 41·1% (38·3-43·6), whereas DALYs were reduced by 23·8% (20·9-27·1), and YLDs by 1·4% (0·1-2·8). For these measures, England ranked better than the UK and the EU15+ means. Between 1990 and 2013, the range in life expectancy among 45 regional deprivation areas remained 8·2 years for men and decreased from 7·2 years in 1990 to 6·9 years in 2013 for women. In 2013, the leading cause of YLLs was ischaemic heart disease, and the leading cause of DALYs was low back and neck pain. Known risk factors accounted for 39·6% (37·7-41·7) of DALYs; leading behavioural risk factors were suboptimal diet (10·8% [9·1-12·7]) and tobacco (10·7% [9·4-12·0]). INTERPRETATION: Health in England is improving although substantial opportunities exist for further reductions in the burden of preventable disease. The gap in mortality rates between men and women has reduced, but marked health inequalities between the least deprived and most deprived areas remain. Declines in mortality have not been matched by similar declines in morbidity, resulting in people living longer with diseases. Health policies must therefore address the causes of ill health as well as those of premature mortality. Systematic action locally and nationally is needed to reduce risk exposures, support healthy behaviours, alleviate the severity of chronic disabling disorders, and mitigate the effects of socioeconomic deprivation. FUNDING: Bill & Melinda Gates Foundation and Public Health England.

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013.

BACKGROUND: The Global Burden of Disease, Injuries, and Risk Factor study 2013 (GBD 2013) is the first of a series of annual updates of the GBD. Risk factor quantification, particularly of modifiable risk factors, can help to identify emerging threats to population health and opportunities for prevention. The GBD 2013 provides a timely opportunity to update the comparative risk assessment with new data for exposure, relative risks, and evidence on the appropriate counterfactual risk distribution. METHODS: Attributable deaths, years of life lost, years lived with disability, and disability-adjusted life-years (DALYs) have been estimated for 79 risks or clusters of risks using the GBD 2010 methods. Risk-outcome pairs meeting explicit evidence criteria were assessed for 188 countries for the period 1990-2013 by age and sex using three inputs: risk exposure, relative risks, and the theoretical minimum risk exposure level (TMREL). Risks are organised into a hierarchy with blocks of behavioural, environmental and occupational, and metabolic risks at the first level of the hierarchy. The next level in the hierarchy includes nine clusters of related risks and two individual risks, with more detail provided at levels 3 and 4 of the hierarchy. Compared with GBD 2010, six new risk factors have been added: handwashing practices, occupational exposure to trichloroethylene, childhood wasting, childhood stunting, unsafe sex, and low glomerular filtration rate. For most risks, data for exposure were synthesised with a Bayesian meta-regression method, DisMod-MR 2.0, or spatial-temporal Gaussian process regression. Relative risks were based on meta-regressions of published cohort and intervention studies. Attributable burden for clusters of risks and all risks combined took into account evidence on the mediation of some risks such as high body-mass index (BMI) through other risks such as high systolic blood pressure and high cholesterol. FINDINGS: All risks combined account for 57·2% (95% uncertainty interval [UI] 55·8-58·5) of deaths and 41·6% (40·1-43·0) of DALYs. Risks quantified account for 87·9% (86·5-89·3) of cardiovascular disease DALYs, ranging to a low of 0% for neonatal disorders and neglected tropical diseases and malaria. In terms of global DALYs in 2013, six risks or clusters of risks each caused more than 5% of DALYs: dietary risks accounting for 11·3 million deaths and 241·4 million DALYs, high systolic blood pressure for 10·4 million deaths and 208·1 million DALYs, child and maternal malnutrition for 1·7 million deaths and 176·9 million DALYs, tobacco smoke for 6·1 million deaths and 143·5 million DALYs, air pollution for 5·5 million deaths and 141·5 million DALYs, and high BMI for 4·4 million deaths and 134·0 million DALYs. Risk factor patterns vary across regions and countries and with time. In sub-Saharan Africa, the leading risk factors are child and maternal malnutrition, unsafe sex, and unsafe water, sanitation, and handwashing. In women, in nearly all countries in the Americas, north Africa, and the Middle East, and in many other high-income countries, high BMI is the leading risk factor, with high systolic blood pressure as the leading risk in most of Central and Eastern Europe and south and east Asia. For men, high systolic blood pressure or tobacco use are the leading risks in nearly all high-income countries, in north Africa and the Middle East, Europe, and Asia. For men and women, unsafe sex is the leading risk in a corridor from Kenya to South Africa. INTERPRETATION: Behavioural, environmental and occupational, and metabolic risks can explain half of global mortality and more than one-third of global DALYs providing many opportunities for prevention. Of the larger risks, the attributable burden of high BMI has increased in the past 23 years. In view of the prominence of behavioural risk factors, behavioural and social science research on interventions for these risks should be strengthened. Many prevention and primary care policy options are available now to act on key risks. FUNDING: Bill & Melinda Gates Foundation.

A multidisciplinary total hip arthroplasty protocol with accelerated postoperative rehabilitation: does the patient benefit?

Since its debut over 10 years ago, minimally invasive total hip arthroplasty (THA) has often been associated with accelerated postoperative rehabilitation when compared with THA performed with a traditional surgical approach. The objective of this study was to investigate the effect of accelerated postoperative rehabilitation and early mobilization on length of stay and hospital readmissions in patients undergoing THA at one institution. We retrospectively reviewed a consecutive series of 590 patients who underwent THA between January 31, 2011 and April 30, 2011. Six arthroplasty surgeons using varying surgical techniques participated. One hundred ninety patients received accelerated rehabilitation and were mobilized on the day of surgery. The remaining 400 patients were mobilized on postoperative day one (POD1). Length of stay for the accelerated rehabilitation group was 2.06 days and 3.38 days for the standard group. One patient was readmitted to the hospital within 30 days (.52%) in the accelerated group compared to 19 re-hospitalizations (4.72%) in the POD1 group. Ninety-six percent of the accelerated group were discharged home versus 62% in POD1 group. Our results support the use of an accelerated rehabilitation protocol at one institution following total hip replacement surgery.

Schizophrenia and increased risks of cardiovascular disease.

OBJECTIVE: The aim of the study is to review the absolute and relative impacts of the major causes for premature mortality among patients with schizophrenia. DATA SOURCES: We reviewed published articles on causes of mortality in the general population as well as among patients with schizophrenia. STUDY SELECTION: We selected articles which published total and cause-specific mortality rates. DATA EXTRACTION: We reviewed the causes of mortality and their risk factors. DATA SYNTHESIS: The average life expectancy of the general population is 76 years (72 years in men, 80 years in women), whereas the corresponding figure is 61 years (57 years in men, 65 years in women) among patients with schizophrenia. Thus, patients with schizophrenia have approximately a 20% reduced life expectancy compared with the general population. Although patients with schizophrenia are 10 to 20 times more likely than the general population to commit suicide, more than two thirds of patients with schizophrenia, compared with approximately one-half in the general population, die of coronary heart disease (CHD). The chief risk factors for this excess risk of death are cigarette smoking, obesity leading to dyslipidemia, insulin resistance and diabetes, and hypertension. CONCLUSIONS: The chief cause of excess premature mortality among patients with schizophrenia is CHD, caused mainly by their adverse risk factor profile. Because patients with schizophrenia have less access to medical care, consume less medical care, and are less compliant with their regimens, the choice of antipsychotic drug regimens that do not further adversely affect their risk factor for CHD is a major clinical and public health challenge among patients with schizophrenia.

Metabolic issues and cardiovascular disease in patients with psychiatric disorders.

Individuals with psychiatric disorders tend to have excessive morbidity. They typically have high rates of respiratory illnesses, infectious diseases, substance abuse (including smoking), obesity, diabetes mellitus, and cardiovascular disease (CVD). Persons with schizophrenia and affective disorders also have a high prevalence of risk factors for CVD, such as diabetes and obesity, which are on the order of 1.5 to 2.0 times higher than in the general population; this translates into increased mortality rates due to CVD. The use of certain psychotropics results in metabolic sequelae, such as obesity, dyslipidemia, glucose dysregulation, and the metabolic syndrome. These sequelae exacerbate the already elevated risk of CVD and diabetes in this group of people. Therefore, the use of psychotropic agents that result in, for example, excessive weight gain not only add another complication for physicians managing a patient with schizophrenia but also may have serious prognostic and cost implications with respect to treatment-related diabetes and coronary disease incidence. The recent American Diabetes Association (ADA) Consensus Panel concluded that some agents are associated with greater diabetes risk than others. The current review describes the prevalence of the metabolic syndrome in people with affective disorders and schizophrenic populations, its prognostic relevance, and its exacerbation among patients treated with particular psychotropic agents, including certain atypical antipsychotics, selective serotonin reuptake inhibitors, and mood stabilizers. The costs associated with the treatment of the metabolic syndrome, diabetes, and coronary heart disease in populations with schizophrenia are also described.

Recruitment of murine neutrophils in vivo through endogenous sialidase activity.

Upon activation with various noncytokine stimuli, polymorphonuclear leukocytes (PMNs) mobilize intracellular sialidase to the plasma membrane, where the sialidase releases sialic acid from the cell surface. This desialylation enhances PMN adherence, spreading, deformability, and motility, functions critical to diapedesis. We now have examined the role of sialidase activity in PMN adhesion to and migration across the endothelium in vivo. A polyclonal antibody prepared against Clostridium perfringens neuraminidase 1) detected surface expression of sialidase on human PMNs stimulated with IL-8 in vitro and on murine PMNs stimulated in vivo, but not on that of unstimulated cells, 2) recognized proteins in human PMN lysates and granule preparations that were not detected by preimmune antibody, 3) inhibited bacterial neuraminidase and human PMN sialidase activities in vitro, and 4) inhibited both pulmonary leukostasis in mice systemically infused with cobra venom factor and intrapulmonary transendothelial migration of PMNs into the bronchoalveolar compartment of mice intranasally challenged with interleukin-8. We conclude that the chemokine interleukin-8, like other PMN agonists, induces the translocation of sialidase to the PMN surface and that surface expression of this sialidase is a prerequisite to PMN recruitment in vivo. The ability of antibodies raised against a prokaryotic neuraminidase to recognize eukaryotic sialidase extends the concept of the neuraminidase superfamily to mammalian enzymes. Inhibition of mobilized endogenous sialidase may provide a novel strategy for limiting the inflammatory response.