Modeling the impact of bedaquiline treatment strategies on the multidrug-resistant tuberculosis burden in India.

SETTING: Bedaquiline (BDQ) has been approved in India for the treatment of multidrug-resistant tuberculosis (MDR-TB), but is currently recommended for MDR-TB patients who have failed initial treatment with standard regimens. While some have argued that such deferred BDQ use allows a second line of defense with a potent drug, this strategy may not be optimal. OBJECTIVE: To compare several distinct scenarios of BDQ access and use, and their potential impact on the MDR-TB disease burden and the associated net economic benefit in India. METHOD: We used a state-transition model to carry out this evaluation. The scenarios differed in the timing and breadth of BDQ access. RESULTS: The simulations showed that a strategy reliant on reserving the use of BDQ for those who have failed other MDR-TB regimens is likely to result in worse treatment outcomes for patients and in inferior public health outcomes for communities, leading to reduced net monetary benefit. CONCLUSION: Our study suggests that deferring patient access to new drugs such as BDQ until front-line regimens have failed, in order to 'save' these drugs for later use, could be detrimental to patients and to public health, and could reduce the economic benefit of treating MDR-TB.

Impact of cardiovascular risk factors and disease on length of stay and mortality in patients with acute coronary syndromes.

BACKGROUND: Traditional risk factors for cardiovascular disease (CVD) have been thoroughly investigated. We aimed to investigate the impact of comorbid cardiovascular risk factors and diseases on length of stay (LOS) and mortality in patients presenting with acute coronary syndromes (ACS). METHODS: We examined prevalence of CVD, LOS and mortality from 25,287 consecutive admissions for ACS from seven hospitals across North West England between 2000 and 2013 using the ACALM (Algorithm for Comorbidities, Associations, Length of stay and Mortality) protocol using ICD-10 and OPCS-4 coding systems. RESULTS: Mean LOS was 7.0days and there were 9653 (38.2%) deaths in the ACS cohort over the 13-year period. Hypertension and hyperlipidaemia were associated with decreased LOS (6.95 and 4.8days respectively, P<0.001) and mortality (36.8% and 19.4% respectively, P<0.001), as was angina pectoris (5.4days and 33.5%, P<0.001). Type 2 diabetes was associated with increased LOS and mortality (7.8days, P<0.05; 44.4%, P<0.001), whereas type 1 diabetes was associated with increased mortality only (7.0days, P=0.42; 41.3%, P<0.001). Other concomitant CVD was associated with an increased LOS and mortality: peripheral vascular disease (8.6days, P<0.05; 53%, P<0.001), atrial fibrillation (10.9days, P<0.001; 63.5%, P<0.001), cerebrovascular disease (15.9days, P<0.001; 76%, P<0.001), heart failure (11days, P<0.001; 69.9%, P<0.001), and ischaemic heart disease (6.7days, P<0.001; 38.7%, P<0.05). CONCLUSION: CVD risk factors have a significant and varied impact on LOS and mortality in patients with ACS and it may be inappropriate to group them when assessing in-hospital risk. These factors should be used to identify patients at an increased risk of prolonged admissions and death post-ACS, and services should be directed accordingly.

Risk factors for mortality in Down syndrome.

BACKGROUND: Down syndrome is a genetic condition that contributes to a significantly shorter life expectancy compared with the general population. We investigated the most common comorbidities in a population of acute hospital patients with Down syndrome and further explored what the most common risk factors for mortality are within this population. METHOD: From our database of one million patients admitted to National Health Service (NHS) Trusts in northern England, we identified 558 people who had Down syndrome. We compared this group with an age- and gender-matched control group of 5580 people. RESULTS: The most prevalent comorbid diseases within the Down's population were hypothyroidism (22.9%) and epilepsy (20.3%). However, the conditions that had the highest relative risks (RRs) in the Down's population were septal defects and dementia. Respiratory failure, dementia and pneumonia were the most significantly related comorbidities to mortality in the Down syndrome population. In the control population, respiratory failure, dementia and renal failure were the most significant disease contributors. When these contributors were analysed using multivariate analysis, heart failure, respiratory failure, pneumonia and epilepsy were the identified risk factors for in-hospital mortality in the Down syndrome population. Respiratory failure was the sole risk factor for mortality in the Down syndrome population [RR = 9.791 (1.6-59.9) P ≤ 0.05], when compared with the risk factors for mortality in the control population. CONCLUSIONS: There is significant medical morbidity in Down syndrome. This morbidity contributes to the lower life expectancy. Respiratory failure is a risk factor for mortality in Down syndrome. We need to thoroughly investigate people with Down syndrome to ensure any treatable illnesses are well managed.

Assessment of tuberculosis burden in China using a dynamic disease simulation model.

SETTING: Although a preventable and treatable disease, tuberculosis (TB) is among the top 10 causes of death worldwide. A consequence of inadequately treated drug-susceptible TB (DS-TB) is multidrug-resistant TB (MDR-TB). OBJECTIVES: To improve our understanding of the primary drivers of incidence and prevalence of DS- and MDR-TB in China. METHODS: The Tuberculosis Disease Transmission Model (TBDTM) uses historical and current disease epidemiology and transmission trends and treatment effectiveness, and accounts for annual changes to these to estimate future DS-TB and MDR-TB burden. RESULTS: The model shows that in China, by 2050, incidence, prevalence and mortality of DS-TB will decrease by 32%, 50% and 41%, respectively, whereas MDR-TB will increase by respectively 60%, 48% and 35%. Reduction in DS-TB is a result of high treatment and cure rates leading to a decrease in the prevalence of latent tuberculous infection (LTBI), while the increase in MDR-TB is attributed to inappropriate treatment, leading to high transmission of infection and increased LTBI prevalence. CONCLUSIONS: These results demonstrate a reduction in DS-TB in China over the next 40 years, while MDR-TB will increase. Improvements in the diagnosis and treatment of MDR-TB are needed to counter this threat. The TBDTM tool has potential value in public health practice by demonstrating the impact of interventions and estimating their cost-effectiveness.

Alzheimer's disease and co-morbidity: increased prevalence and possible risk factors of excess mortality in a naturalistic 7-year follow-up.

BACKGROUND: Subjects with late-onset Alzheimer's disease (AD) have to be sufficiently healthy to live long enough to experience and to be diagnosed with dementia in later life. In contrast, neurodegeneration and cognitive deficits in AD may increase the frequency of co-morbid disorders and their possible influence on mortality. Consequently, we investigated whether the pattern of co-morbidity and its relevance for later death differed between hospitalized AD and age-matched controls subjects. METHODS: Co-morbid diseases with a prevalence of more than 1% at hospital admission were compared between 634 hospitalized AD and 72,244 control subjects aged above 70 years admitted to the University of Birmingham NHS Trust between 1 January 2000 to 31 December 2007. Risk factors, i.e. co-morbid diseases that were predictors of mortality within the 7-year follow-up, were identified and compared. RESULTS: Subjects with AD suffer more eating disorders, infections, brain diseases and neck of femur fractures than other hospitalized elderly patients. In contrast, some cardiovascular diseases and diabetes mellitus were less prevalent in AD subjects in comparison with hospitalized controls. Diseases that might have contributed to later mortality in AD were pneumonia, ischemic heart disease and gastroenteritis, but there were no significant differences in their impact on mortality compared to other hospitalized elderly subjects with the same co-morbidities in multivariate logistic regression analyses. CONCLUSION: Patients with AD have a different pattern of co-morbidity, but die from the same diseases as other hospitalized patients. Infections including pneumonia and diseases that may occur secondary to neurodegeneration and cognitive decline may need special attention in patients with AD who may not be able to identify or report the early symptoms. Preventive measures may be helpful to reduce the high risk and fatal consequences of undetected disease in AD.

Type-2 diabetes mellitus in schizophrenia: increased prevalence and major risk factor of excess mortality in a naturalistic 7-year follow-up.

OBJECTIVE: Physical co-morbidity including type 2 diabetes mellitus is more prevalent in patients with schizophrenia compared to the general population. However, there is little consistent evidence that co-morbidity with diabetes mellitus and/or other diseases leads to excess mortality in schizophrenia. Thus, we investigated whether co-morbidity with diabetes and other somatic diseases is increased in schizophrenics, and if these are equally or more relevant predictors of mortality in schizophrenia than in age- and gender-matched hospitalised controls. METHODS: During 2000-2007, 679 patients with schizophrenia were admitted to University Hospital Birmingham NHS Trust. Co-morbidities were compared with 88,778 age- and gender group-matched hospital controls. Predictors of mortality were identified using forward Cox regression models. RESULTS: The prevalence of type 2 diabetes mellitus was increased in schizophrenia compared to hospitalised controls (11.3% versus 6.3%). The initial prevalence of type 2 diabetes mellitus was significantly higher in the 100 later deceased schizophrenic patients (24.0%) than in those 579 surviving over 7 years (9.2%). Predictors of mortality in schizophrenia were found to be age (relative risk [RR] = 1.1/year), type 2 diabetes mellitus (RR = 2.2), pneumonia (RR = 2.7), heart failure (RR = 2.9) and chronic renal failure (RR = 3.2). The impact of diabetes mellitus on mortality was significantly higher in schizophrenia than in hospital controls (RR = 2.2 versus RR = 1.1). In agreement, deceased schizophrenics had significantly suffered more diabetes mellitus than deceased controls (24.0 versus 10.5%). The relative risks of mortality for other disorders and their prevalence in later deceased subjects did not significantly differ between schizophrenia and controls. CONCLUSION: Schizophrenics have more and additionally suffer more from diabetes: co-morbidity with diabetes mellitus is increased in schizophrenia in comparison with hospital controls; type 2 diabetes mellitus causes significant excess mortality in schizophrenia. Thus, monitoring for and prevention of type 2 diabetes mellitus is of utmost relevance in hospitalised patients with schizophrenia.

Apolipoprotein E allele 4 is not a sufficient or a necessary predictor of the development of Mild Cognitive Impairment.

The presence of Mild Cognitive Impairment (MCI) and of an apolipoprotein E (apoE) varepsilon4 allele both predict the development of Alzheimer's disease. However, the extent to which this allele also predicts the development of MCI is unclear even though MCI is an early transitional stage in the development of Alzheimer's disease. The present study investigates the prevalence of the apoE varepsilon4 allele in incipient MCI. Participants were recruited from the population-based Leipzig Longitudinal Study of the Aged (LEILA75+). All subjects who were initially cognitively healthy, i.e. did not meet MCI criteria described by Petersen [Petersen RC. Mild cognitive impairment. J Intern Med 2004; 256(3): 183-94], and whose apoE status could be determined were followed-up. After 4.5 years, 15.5% of the cognitively healthy target population had developed MCI. The frequencies of the apoE varepsilon4 genotype did not differ between individuals with incipient MCI (12.9%) and individuals who remained cognitively healthy during the study (18.4%, p>0.5). Consequently, the apoE varepsilon4 genotype is not a necessary or sufficient risk factor for MCI. Further studies need to investigate the influence of the whole range of genetic and environmental risk factors on the course of Alzheimer's disease including the initial development of MCI and the later conversion to Alzheimer's disease.

Secular trends in the cardiovascular risk profile and mortality of stroke admissions in an inner city, multiethnic population in the United Kingdom (1997-2005).

Our objective was to study ethnic differences in the cardiovascular risk profile and mortality of stroke admissions to an inner city teaching hospital serving a multiethnic population in Birmingham, UK, over a 9-year period (1997-2005). Hospital case notes and registry data of 3083 patients admitted with a first onset stroke were reviewed. Secular trends in the prevalence of risk factors (hypertension, diabetes, hyperlipidaemia, atrial fibrillation and myocardial infarction), hospital admission rates and 30-day mortality among Afro-Caribbean, European Caucasian and South Asian ethnic groups were analysed. Between 1997 and 2005, there were 3083 first onset strokes, of whom 47.6% (1595) were men, 9.3% Afro-Caribbean, 57.8% European Caucasian and 15.1% South Asian. There was a significant trend towards a reduction in non-haemorrhagic stroke admissions over the study period (P<0.001), with no ethnic variation (P=0.07). Increases in hypertension and hyperlipidaemia were observed (P<0.001), whereas myocardial infarction showed a decline (P<0.001). Compared to other ethnic groups, South Asian patients were younger on admission (P<0.001), had more hyperlipidaemia (P<0.05) and poorer survival at 30 days (P=002). We conclude that cardiovascular risk profiles among patients admitted with non-haemorrhagic stroke have changed over the last decade. In particular, hyperlipidaemia has increased, especially among South Asians. The reduced decline in stroke admissions and 30-day survival of stroke in South Asians in recent years warrants further investigation and highlights the importance of a targeted health-care approach in the migrant ethnic minorities.

Increased 5-year mortality in the migrant South Asian stroke patients with diabetes mellitus in the United Kingdom: the West Birmingham Stroke Project.

BACKGROUND: Stroke is a major cause of premature mortality in Britain, but its burden is markedly greater amongst South Asians. Because of the paucity of data in this area, we investigated the magnitude and impact of risk from cardiovascular comorbidities on survival amongst South Asian stroke patients. METHODS: We reviewed hospital case records of consecutive first in life time ischaemic stroke patients [self reported ethnicity and International Classification of Disease (ICD) 10th revision, codes 430-438] admitted to an inner city hospital in the UK between 1997 and 2001. In-hospital mortality data and CVD risk factors were analysed. Five-year mortality data was obtained from the National Health Tracing Services. RESULTS: Of 1474 ischaemic stroke patients, 242 (16%) were South Asian of whom, 143 (59.1%) were male. The prevalence of hypertension was 70.2%, followed by diabetes 56.2%, hyperlipidaemia 7% and myocardial infarction 10.3%. At 5 years follow-up, 40.5% had died. Cumulative event-free survival at 5 years was significantly poorer in patients with diabetes (log-rank test, p=0.009). On Cox regression analysis, incorporating age, gender and other CVD risk factors, diabetes mellitus was an independent predictor of mortality odds ratio=1.65 (1.02-2.6, p=0.039). Hypertension and dyslipidaemia did not discriminate survival amongst South Asian patients. CONCLUSION: Stroke mortality in South Asians is associated with presence of diabetes mellitus. This highlights the significance of early and intensive CVD risk modification strategies in ethnic minorities particularly in patients with diabetes. Further research is warranted in South Asians to examine the underlying basis and related pathophysiological abnormalities.