The INtegrating DEPrEssioN and Diabetes treatmENT (INDEPENDENT) study: Design and methods to address mental healthcare gaps in India.

INTRODUCTION: Depression and diabetes are highly prevalent worldwide and often co-exist, worsening outcomes for each condition. Barriers to diagnosis and treatment are exacerbated in low and middle-income countries with limited health infrastructure and access to mental health treatment. The INtegrating DEPrEssioN and Diabetes treatmENT (INDEPENDENT) study tests the sustained effectiveness and cost-effectiveness of a multi-component care model for individuals with poorly-controlled diabetes and depression in diabetes clinics in India. MATERIALS AND METHODS: Adults with diabetes, depressive symptoms (Patient Health Questionnaire-9 score≥10), and ≥1 poorly-controlled cardiometabolic indicator (either HbA1c≥8.0%, SBP≥140mmHg, and/or LDL≥130mg/dl) were enrolled and randomized to the intervention or usual care. The intervention combined collaborative care, decision-support, and population health management. The primary outcome is the between-arm difference in the proportion of participants achieving combined depression response (≥50% reduction in Symptom Checklist score from baseline) AND one or more of: ≥0.5% reduction in HbA1c, ≥5mmHg reduction in SBP, or ≥10mg/dl reduction in LDL-c at 24months (12-month intervention; 12-month observational follow-up). Other outcomes include control of individual parameters, patient-centered measures (i.e. treatment satisfaction), and cost-effectiveness. RESULTS: The study trained seven care coordinators. Participant recruitment is complete - 940 adults were screened, with 483 eligible, and 404 randomized (196 to intervention; 208 to usual care). Randomization was balanced across clinic sites. CONCLUSIONS: The INDEPENDENT model aims to increase access to mental health care and improve depression and cardiometabolic disease outcomes among complex patients with diabetes by leveraging the care provided in diabetes clinics in India (clinicaltrials.gov number: NCT02022111).

Liver transplantation for "very early" intrahepatic cholangiocarcinoma: International retrospective study supporting a prospective assessment.

UNLABELLED: The presence of an intrahepatic cholangiocarcinoma (iCCA) in a cirrhotic liver is a contraindication for liver transplantation in most centers worldwide. Recent investigations have shown that "very early" iCCA (single tumors ≤2 cm) may have acceptable results after liver transplantation. This study further evaluates this finding in a larger international multicenter cohort. The study group was composed of those patients who were transplanted for hepatocellular carcinoma or decompensated cirrhosis and found to have an iCCA at explant pathology. Patients were divided into those with "very early" iCCA and those with "advanced" disease (single tumor >2 cm or multifocal disease). Between January 2000 and December 2013, 81 patients were found to have an iCCA at explant; 33 had separate nodules of iCCA and hepatocellular carcinoma, and 48 had only iCCA (study group). Within the study group, 15/48 (31%) constituted the "very early" iCCA group and 33/48 (69%) the "advanced" group. There were no significant differences between groups in preoperative characteristics. At explant, the median size of the largest tumor was larger in the "advanced" group (3.1 [2.5-4.4] versus 1.6 [1.5-1.8]). After a median follow-up of 35 (13.5-76.4) months, the 1-year, 3-year, and 5-year cumulative risks of recurrence were, respectively, 7%, 18%, and 18% in the very early iCCA group versus 30%, 47%, and 61% in the advanced iCCA group, P = 0.01. The 1-year, 3-year, and 5-year actuarial survival rates were, respectively, 93%, 84%, and 65% in the very early iCCA group versus 79%, 50%, and 45% in the advanced iCCA group, P = 0.02. CONCLUSION: Patients with cirrhosis and very early iCCA may become candidates for liver transplantation; a prospective multicenter clinical trial is needed to further confirm these results. (Hepatology 2016;64:1178-1188).

Attenuation of resting energy expenditure following hematopoietic SCT in children.

Children undergoing hematopoietic SCT (HSCT) typically receive parenteral nutrition (PN) due to gastrointestinal toxicities. Accurate determination of resting energy expenditure (REE) may facilitate optimal energy provision and help avoid unintended overfeeding or underfeeding. A multicenter, prospective cohort study of children undergoing allogeneic HSCT was performed, in which REE was measured by indirect calorimetry at baseline and twice weekly until 30 days after transplantation. Change in percent predicted REE over time from admission was analyzed using repeated measures regression analysis. In all, 26 children (14 females) with a mean (s.d.) age of 14.9 (4.2) years who underwent an HLA-matched sibling or unrelated donor transplantation were enrolled. Mean (s.d.) percent predicted REE at baseline was 92.4 (15.2). Baseline REE was highly correlated with lean body mass measured by dual energy X-ray absorptiometry (r=0.78, P<0.0001). REE decreased significantly over time, following a quadratic curve to a nadir of 79% predicted at 14 days post transplantation (P<0.001) and returned to near baseline by day 30. Children undergoing HSCT exhibit a significant reduction in REE in the early weeks after transplantation, a phenomenon that places them at risk for overfeeding. Serial measurements of REE or reductions in energy intake should be considered when PN is the primary mode of nutrition.

Energy requirements derived from total energy expenditure and energy deposition during the first 2 y of life.

BACKGROUND: Current recommendations for energy intake of children are derived from observed intakes. Deriving energy requirements on the basis of energy expenditure and deposition is scientifically more rational than is using the observational approach and is now possible with data on total energy expenditure (TEE), growth, and body composition. OBJECTIVES: The objectives of this study were 1) to define energy requirements during the first 2 y of life on the basis of TEE and energy deposition; 2) to test effects of sex, age, and feeding mode on energy requirements; and 3) to determine physical activity. DESIGN: TEE, sleeping metabolic rate, anthropometry, and body composition were measured in 76 infants. TEE was measured with doubly labeled water, sleeping metabolic rate with respiratory calorimetry, and body composition with a multicomponent model. RESULTS: Total energy requirements were 2.23, 2.59, 2.97, 3. 38, 3.72, and 4.15 MJ/d at 3, 6, 9, 12, 18, and 24 mo, respectively. Energy deposition (in MJ/d) decreased significantly over time (P: = 0.001) and was lower in breast-fed than in formula-fed infants (P: = 0.01). Energy requirements were approximately 80% of current recommendations. Energy requirements differed by age (P: = 0.001), feeding group (P: = 0.03), and sex (P: = 0.03). Adjusted for weight or fat-free mass and fat mass, energy requirements still differed by feeding group but not by age or sex. Temperament and motor development did not affect TEE. CONCLUSION: The TEE and energy-deposition data of these healthy, thriving children provide strong evidence that current recommendations for energy intake in the first 2 y of life should be revised.

Adjustments in energy expenditure and substrate utilization during late pregnancy and lactation.

BACKGROUND: Metabolic adjustments occur during pregnancy and lactation to support fetal growth and milk synthesis; however, the effect of body composition and hormonal milieu on these changes is poorly understood. OBJECTIVE: We hypothesized that energy metabolism changes during pregnancy and lactation to support fetal growth and milk synthesis, and that body composition and hormonal milieu influence these alterations. DESIGN: We measured energy expenditure, body composition, and hormone, metabolite, and catecholamine concentrations in 76 women (40 lactating, 36 nonlactating) at 37 wk gestation and 3 and 6 mo postpartum. Total energy expenditure (TEE), basal metabolic rate (BMR), sleeping metabolic rate (SMR), and minimal SMR (MSMR) were measured with room calorimetry. Fat-free mass (FFM) and fat mass were estimated with a 4-component model. RESULTS: TEE, BMR, SMR, and MSMR were 15-26% higher during pregnancy than postpartum after being adjusted for FFM, fat mass, and energy balance. TEE, SMR, and MSMR were higher in lactating than in nonlactating women. Fasting serum insulin, insulin-like growth factor I, fatty acids, and leptin, and 24-h urinary free norepinephrine, epinephrine, and dopamine correlated positively with TEE, BMR, SMR, and MSMR. In nonlactating women, the respiratory quotient decreased over time, carbohydrate oxidation decreased, and fat oxidation increased. Substrate utilization was not influenced by body composition, fasting serum hormones, or 24-h urinary catecholamines. CONCLUSIONS: These results indicate increased energy expenditure and preferential use of carbohydrates during pregnancy and lactation. Elevated respiratory quotient and carbohydrate utilization during pregnancy continue during lactation, consistent with preferential use of glucose by the fetus and mammary gland.

Ascitic fluid filtration and intravenous infusion versus total-volume paracentesis with infusion of plasma expander in cirrhosis with tense or intractable ascites.

BACKGROUND: Patients with cirrhotic ascites have low serum albumin levels, and paracentesis of ascitic fluid could compromise them further. AIM: We compared the therapeutic efficacy of ascitic fluid filtration and concentrate infusion (AFI) versus total-volume paracentesis (TVP) with colloid infusion in control of tense or intractable cirrhotic ascites. METHODS: Ten patients underwent AFI; their ascitic fluid was filtered repeatedly through hollow-fiber hemodialyzer, and the concentrate reinfused intravenously. In ten patients TVP was done with simultaneous intravenous colloid infusion. Follow-up was done weekly and the study terminated if the patient needed diuretics or developed complications. RESULTS: Pre-study parameters were similar in the two groups. In the AFI and TVP groups, the duration of procedure was median 12 hours and 5.5 hours; fluid removed by paracentesis was 10.2 L and 8.0 L, respectively; and fluid infused intravenously was 0.5 L [with mean (SD) protein content 5.7 (1.3) g/dl] and 1.1 L, respectively. Glomerular filtration rates were lower than normal in the two groups but did not change significantly with the procedure; body weight remained significantly lower up to week 3 and week 2, respectively. The study was terminated at median week 3 (range 1-8) and week 2 (1-4), respectively. Fever was an accompaniment of AFI and one patient developed peritonitis. CONCLUSION: Patients undergoing AFI remained diuretic-free longer; the procedure is cost-effective but needs to be further evaluated to minimize the side-effects.

Hemodynamic response to treadmill exercise in normal volunteers: an assessment by Doppler ultrasonic measurement of ascending aortic blood velocity and acceleration.

Accurate assessment of ascending aortic blood velocity indices and reproducibility of a Doppler ultrasonic system during exercise were determined; the Doppler technique was then used to assess the effects of age, sex, and beta blockade on exercise hemodynamics. Doppler-determined velocity correlated well with an invasive electromagnetic system. Reproducibility of Doppler variables during three exercise tests was high (coefficient of variation less than 10%) and did not deteriorate appreciably with exercise. Peak velocity (PV) and maximum acceleration (MA) were inversely related to age, the relationship being more significant during exercise, whereas the systolic velocity integral showed no such relationship either at rest or during exercise. Doppler variables showed no difference between sexes, except at high levels of exercise. Beta blockade markedly attenuated the exercise response as shown by significant decreases in both MA and PV during exercise. The Doppler velocity data presented in this study provide a reference against which previously documented changes in exercising ischemic patients can be better related.

Ascending aortic blood velocity and acceleration using Doppler ultrasound in the assessment of left ventricular function.

We have used a 2.2 MHz continuous-wave Doppler blood velocity meter (Bach-Simpson BVM 202) to measure ascending aortic blood velocity and acceleration, and have obtained from the velocity signal a noninvasive measure of stroke volume and cardiac output by combining the Doppler technique with M-mode echocardiography. In two separate studies we have systematically altered the loading conditions of the heart with lower body pressure; and the inotropic state of the heart with dobutamine (5 micrograms . kg-1 . min-1), and documented the changes in mean velocity (MV), maximum acceleration (MA), stroke volume (SV), cardiac output (CO) and left ventricular end-diastolic dimension (EDD) (M-mode echocardiography). Application of lower body pressure to subjects in a 30 degrees head-up tilt position caused a systematic increase in preload, as shown by a 9% increase in EDD, which raised SV by a maximum of 33% (p less than or equal to 0.001) and CO by 32% (p less than or equal to 0.01), thus showing a classical Starling response; whilst there was relatively little increase in MA. Conversely, infusion of dobutamine, an inotropic agent, caused a 29.2% increase in MA (p less than or equal to 0.01) with minimal increase in SV. Thus, the ability to measure ascending aortic blood velocity allows noninvasive monitoring of changes in both inotropic state and Starling function, with considerable ease and rapidity.

An assessment of school survey as a method of detection of leprosy cases.

The present study includes the analysis of case-control study and hospital records of leprosy patients. 26 cases of leprosy were detected through examination of 21,412 school children of 5-19 years age, attending 30 and 25 schools in urban and rural area respectively of Surat District. Matched controls of these leprosy cases were selected from their healthy class-mates by employing certain criteria. Home visits paid to these 24 cases and their controls revealed a positive family history in 50% (12/24) of affected students. Case detection rates were 17.9% and 0.0% among the contracts of affected students and their controls respectively. Out of 26 cases, 16 (61.5%) were detected for the first time (undetected cases). However, record analysis revealed that only 32.6% and 39.5% of the detected cases of school going age, were attending schools in rural and urban area respectively. School survey and contact survey of child cases, in spite of certain limitations, can be considered as a useful, cheap and rapid method for detection of leprosy cases in the community.