Morbidity compression or expansion? A temporal analysis of the age at onset of non-communicable diseases in India

While there is evidence of morbidity compression in many countries, temporal patterns of non-communicable diseases (NCDs) in developing countries, such as India, are less clear. Age at onset of disease offers insights to understanding epidemiologic trends and is a key input for public health programs. Changes in age at onset and duration of major NCDs were estimated for 2004 (n = 38,044) and 2018 (n = 43,239) using health surveys from the India National Sample Survey (NSS). Survival regression models were used to compare trends by sociodemographic characteristics. Comparing 2004 to 2018, there were reductions in age at onset and increases in duration for overall and cause-specific NCDs. Median age at onset decreased for NCDs overall (57 to 53 years) and for diabetes, hypertension, heart disease, asthma, mental diseases, eye disease, and bone disease in the range of 2–7 years and increased for cancer, neurological disorders, some genitourinary disorders, and injuries/accidents in the range of 2–14 years. Hazards of NCDs were higher among females for cancers (HR 1.51, 95% CI 1.19–1.90) and neurological disorders (HR 1.18, 95% CI 1.06–1.32) but lower for heart diseases (HR 0.88, 95% CI 0.79–0.97) and injuries/accidents (HR 0.87, 95% CI 0.77–0.99). Hazards were greater among those with lower educational attainment at younger ages and higher educational attainment later in life. Unlike many countries, chronic disease morbidity may be expanding in India for many chronic diseases, indicating excess strain on the health system. Public health programs should focus on early diagnosis and prevention of NCDs.

     

Clinical variability of Fanconi anemia (type C) results from expression of an amino terminal truncated Fanconi anemia complementation group C polypeptide with partial activity

Fanconi anemia (FA) is an autosomal recessive disease characterized by congenital anomalies, aplastic anemia, and cancer susceptibility. Mutations within the FA complementation group C (FAC) gene account for approximately 14% of diagnosed FA cases. Two mutations, one in exon 1 (delG322) and one in exon 4 (IVS4 + 4 A to T), account for 90% of known FAC mutations. The delG322 mutation results in a mild FA phenotype, while the IVS4 + 4 A to T mutation results in severe FA phenotype. To determine the molecular basis for this clinical variability, we analyzed patient-derived cell lines for the expression of characteristic mutant FAC polypeptides. All cell lines with the delG322 mutation expressed a 50-kD FAC polypeptides, FRP-50 (FAC-related protein), shown to be an amino terminal truncated isoform of FAC reinitiated at methionine 55. All cell lines with the IVS4 + 4 A to T mutation lacked FRP-50. Overexpression of a cDNA encoding FRP-50 in an FA(C) cell line resulted in partial correction of mitomycin C sensitivity. In conclusion, expression of an amino terminal truncated FAC protein accounts, at least in part, for the clinical heterogeneity among FA(C) patients.     

Pilot Trial of a Comprehensive Summer Psychosocial Treatment for High-Functioning Young Children with ASD

This study examined the feasibility and preliminary outcomes of a comprehensive summer psychosocial treatment (summerMAX^yc) for high-functioning young children, ages 4–6 years, with ASD (HFASD). The 5-week treatment, conducted 5 days per week, 6 h per day, included skills instruction and therapeutic activities targeting social/social-communication skills, facial-emotion recognition, and interest expansion. A behavioral system was implemented to increase skills acquisition and maintenance and reduce ASD symptoms and problem behaviors. Feasibility was supported in high levels of treatment fidelity and child, parent, and staff clinician satisfaction. Significant post-treatment improvements were found for 9 of 10 outcome measures including parent and staff clinician ratings of targeted social/social-communication skills, ASD symptoms, and broader adaptive social and communication skills, and staff clinician ratings of daily living skills. Results suggested that summerMAX^yc was feasible and may yield positive outcomes for 4–6 year olds with HFASD.     

The interplay between metabolic alterations,diastolic strain rate and exercise capacity in mild heart failure with preserved ejection fraction: a cardiovascular magnetic resonance study

Background

Heart failure (HF) is characterized by altered myocardial substrate metabolism which can lead to myocardial triglyceride accumulation (steatosis) and lipotoxicity. However its role in mild HF with preserved ejection fraction (HFpEF) is uncertain. We measured myocardial triglyceride content (MTG) in HFpEF and assessed its relationships with diastolic function and exercise capacity.

Methods

Twenty seven HFpEF (clinical features of HF, left ventricular EF >50%, evidence of mild diastolic dysfunction and evidence of exercise limitation as assessed by cardiopulmonary exercise test) and 14 controls underwent ¹H-cardiovascular magnetic resonance spectroscopy (¹H-CMRS) to measure MTG (lipid/water, %), ³¹P-CMRS to measure myocardial energetics (phosphocreatine-to-adenosine triphosphate - PCr/ATP) and feature-tracking cardiovascular magnetic resonance (CMR) imaging for diastolic strain rate.

Results

When compared to controls, HFpEF had 2.3 fold higher in MTG (1.45?±?0.25% vs. 0.64?±?0.16%, p?=?0.009) and reduced PCr/ATP (1.60?±?0.09 vs. 2.00?±?0.10, p?=?0.005). HFpEF had significantly reduced diastolic strain rate and maximal oxygen consumption (VO₂ max), which both correlated significantly with elevated MTG and reduced PCr/ATP. On multivariate analyses, MTG was independently associated with diastolic strain rate while diastolic strain rate was independently associated with VO₂ max.

Conclusions

Myocardial steatosis is pronounced in mild HFpEF, and is independently associated with impaired diastolic strain rate which is itself related to exercise capacity. Steatosis may adversely affect exercise capacity by indirect effect occurring via impairment in diastolic function. As such, myocardial triglyceride may become a potential therapeutic target to treat the increasing number of patients with HFpEF.

     

System for Rapid Assessment of Pneumonia and Influenza-Related Mortality—Ohio, 2009–2010

Rapid mortality surveillance is critical for state emergency preparedness. To enhance timeliness during the 2009–2010 influenza A H1N1 pandemic, the Ohio Department of Health activated a drop-down menu within Ohio’s Electronic Death Registration System for reporting of pneumonia- or influenza-related deaths approximately 5 days postmortem. We used International Classification of Diseases—Tenth Revision (ICD-10) codes, available 2–3 months postmortem as the standard, and assessed their agreement with drop-down-menu codes for pneumonia- or influenza-related deaths. Among 56 660 Ohio deaths during September 2009–March 2010, agreement was 97.9% for pneumonia (κ = 0.85) and 99.9% for influenza (κ = 0.79). Sensitivity was 80.2% for pneumonia and 73.9% for influenza. Drop-down menu coding enhanced timeliness while maintaining high agreement with ICD-10 codes.     

Diagnostic strategies and outcomes on three New Zealand deer farms with severe outbreaks of bovine tuberculosis

SETTING: Three commercial deer herds, each containing more than 500 deer, experienced outbreaks of tuberculosis (TB) ranging from a 6% prevalence to disease levels >50%. Intensive diagnostic testing was carried out over short time intervals after the initial diagnosis of TB. OBJECTIVE: To eradicate M. bovis infection from herds of farmed red deer (Cervus elaphus) in New Zealand, which had significant outbreaks of tuberculosis (>5%), using complementary diagnostic tests and elective slaughter of all test positive animals. DESIGN: Whole herd mid cervical skin tests (MCT) were used as the primary test and a comparative cervical test (CCT) as an ancillary test. In an attempt to enhance TB eradication, ancillary blood tests comprising; lymphocyte transformation tests (LT) and enzyme-linked immunosorbent assays (ELISA) were used in parallel with MCT, or as serial tests, to complement skin testing. RESULTS: One deer herd (N), which had an acute outbreak (6%) of TB in adult stock, responded quickly to testing and the disease was eradicated within 12 months. A second more chronically infected herd (B), with low prevalence (2%) of TB initially in pregnant hinds which were retained over the breeding cycle, developed widespread uncontrollable spread of infection, that could not be contained by exhaustive testing. The final herd (S), which had an acute outbreak of TB at a prevalence >90% in young fawns, responded well to testing and became TB-free within 1 year. CONCLUSIONS: TB can be eradicated from infected farmed deer herds, using currently available TB tests, irrespective of disease prevalence. The caveat is that disease must be diagnosed early in the acute phase of infection. Undiagnosed infection over winter in breeding hinds in one herd produced a refractory infection in adult males and females and uncontrollable spread to newborn fawns. Disease could not be eradicated using comprehensive diagnostic schedules. A widespread but controllable outbreak of acute TB in another herd, appeared to have caused sufficient selective pressure on adult stock that genetically resistant adults were selected within a very short time frame (<1 year).