Cost effectiveness of decentralised care model for managing MDR-TB in India

Background

In India, multidrug-resistant tuberculosis (MDR-TB) patients are usually treated in hospitals. Decentralised care model, however, has been suggested as a possible alternative by the World Health Organization (WHO). In the “End TB Strategy”, the WHO highlights, as one of the key targets for 2035, that ‘no TB-affected families should face catastrophic hardship due to the tuberculosis’. Removal of financial barriers to health-care access and mitigation of catastrophic expenditures are therefore considered vital to achieve the universal health coverage (UHC) goal. Since forgoing healthcare due to the financial constraints is a known fact in India, decentralised care as an intervention choice (as against hospital-based care) might enhance equity provided it is an affordable choice. Thus, an economic evaluation was conducted, from the perspective of the national health system in India, to assess the cost-effectiveness of decentralised care compared to centralised care for MDR-TB.

Postoperative Atrial Fibrillation or Flutter Following Transcatheter or Surgical Aortic Valve Replacement: PARTNER 3 Trial

ObjectivesThe aim of this study was to assess the incidence and prognostic impact of early and late postoperative atrial fibrillation or flutter (POAF) in patients with severe aortic stenosis (AS) treated with transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR).BackgroundThere is an ongoing controversy regarding the incidence, recurrence rate, and prognostic impact of early (in-hospital) POAF and late (postdischarge) POAF in patients with AS undergoing TAVR or SAVR.MethodsIn the PARTNER (Placement of Aortic Transcatheter Valve) 3 trial, patients with severe AS at low surgical risk were randomized to TAVR or SAVR. Analyses were performed in the as-treated population excluding patients with preexistent atrial fibrillation or flutter.ResultsAmong 781 patients included in the analysis, early POAF occurred in 152 (19.5%) (18 of 415 [4.3%] and 134 of 366 [36.6%] following TAVR and SAVR, respectively). Following discharge, 58 new or recurrent late POAF events occurred within 1 year following the index procedure in 55 of 781 patients (7.0%). Early POAF was not an independent predictor of late POAF following discharge (odds ratio: 1.04; 95% CI: 0.52-2.08; P = 0.90). Following adjustment, early POAF was not an independent predictor of the composite outcome of death, stroke, or rehospitalization (hazard ratio: 1.10; 95% CI: 0.64-1.92; P = 0.72), whereas late POAF was associated with an increased adjusted risk for the composite outcome (hazard ratio: 8.90; 95% CI: 5.02-15.74; P < 0.0001), irrespective of treatment modality.ConclusionsIn the PARTNER 3 trial, early POAF was more frequent following SAVR compared with TAVR. Late POAF, but not early POAF, was significantly associated with worse outcomes at 2 years, irrespective of treatment modality.     

Prenatal diagnosis of thyroid hormone resistance

A 29-yr-old woman with pituitary resistance to thyroid hormones (PRTH) was found to harbor a novel point mutation (T337A) on exon 9 of the thyroid hormone receptor beta (TRbeta) gene. She presented with symptoms and signs of hyperthyroidism and was successfully treated with 3,5,3'-triiodothyroacetic acid (TRIAC) until the onset of pregnancy. This therapy was then discontinued in order to prevent TRIAC, a compound that crosses the placental barrier, from exerting adverse effects on normal fetal development. However, as the patient showed a recurrence of thyrotoxic features after TRIAC withdrawal, we sought to verify, by means of genetic analysis and hormone measurements, whether the fetus was also affected by RTH, in order to rapidly reinstitute TRIAC therapy, which could potentially be beneficial to both the mother and fetus. At 17 weeks gestation, fetal DNA was extracted from chorionic villi and was used as a template for PCR and restriction analysis together with direct sequencing of the TRbeta gene. The results indicated that the fetus was also heterozygous for the T337A mutation. Accordingly, TRIAC treatment at a dose of 2.1 mg/day was restarted at 20 weeks gestation. The mother rapidly became euthyroid, and the fetus grew normally up to 24 weeks gestation. At 29 weeks gestation mild growth retardation and fetal goiter were observed, prompting cordocentesis. Circulating fetal TSH was very high (287 mU/L) with a markedly reduced TSH bioactivity (B/I: 1.1 +/- 0.4 vs 12.7 +/- 1.2), while fetal FT4 concentrations were normal (8.7 pmol/L; normal values in age-matched fetuses: 5-22 pmol/L). Fetal FT3 levels were raised (7.1 pmol/L; normal values in age-matched fetuses: <4 pmol/L), as a consequence of 100% cross-reactivity of TRIAC in the FT3 assay method. To reduce the extremely high circulating TSH levels and fetal goiter, the dose of TRIAC was increased to 3.5 mg/day. To monitor the possible intrauterine hypothyroidism, another cordocentesis was performed at 33 weeks gestation, showing that TSH levels were reduced by 50% (from 287 to 144 mU/L). Furthermore, a simultaneous ultrasound examination revealed a clear reduction in fetal goiter. After this latter cordocentesis, acute complications occured, prompting delivery by cesarean section. The female neonate was critically ill, with multiple-organ failure and respiratory distress syndrome. In addition, a small goiter and biochemical features ofhypothyroidism were noted transiently and probably related to the prematurity of the infant. At present, the baby is clinically euthyroid, without goiter, and only exhibits biochemical features of RTH. In summary, although further fetal studies in cases of RTH are necessary to determine whether elevated TSH levels with a markedly reduced bioactivity are a common finding, our data suggest transient biochemical hypothyroidism in RTH during fetal development. Furthermore, we advocate prenatal diagnosis of RTH and adequate treatment of the disease in case of maternal hyperthyroidism, to avoid fetal thyrotrope hyperplasia, reduce fetal goiter, and maintain maternal euthyroidism during pregnancy.     

Characteristics of atherosclerotic plaque distribution in coronary artery bifurcations: an intravascular ultrasound analysis

OBJECTIVE: Vessel bifurcations are prone to atherosclerotic plaque accumulation. Using volumetric intravascular ultrasound analysis, we investigated atheroma distribution at human coronary bifurcations in vivo. METHODS: We analyzed plaque distribution in 49 left anterior descending coronary artery-diagonal and 20 left circumflex coronary artery-obtuse marginal bifurcations with <50% angiographic stenosis. Cross-sections were analyzed at 1 mm intervals in segments 5 mm proximal and distal from the bifurcation. Planimetry of the lumen and external elastic membrane (EEM) was performed and plaque thickness measured at four different points relative to the branch: 0 degrees, 90 degrees, 180 degrees and 270 degrees. EEM, lumen and plaque volume and percentage plaque burden (plaque volume/EEM volume) were calculated in the proximal and distal segments. The side-branch take-off angle was analyzed in the cross-sectional images. RESULTS: Volumetric analysis showed that EEM, lumen and plaque were larger (P<0.001) in proximal segments than distal segments, whereas percent plaque burden was similar in these segments. Plaque accumulated on the opposite wall to the flow divider. Plaque distribution tended to be more eccentric in distal segments (P=0.05) compared to proximal segments. In 26 of 69 lesions, an asymmetric side-branch take-off was found and was associated with asymmetric plaque distribution compared to those lesions that had a symmetric side-branch take-off (P<0.01). CONCLUSION: We found characteristic patterns of plaque distribution at coronary bifurcations. Proximal segments demonstrated larger plaque volume than distal segments, despite similar percentages of plaque burden. Plaque volume accumulated opposite to the flow divider, especially in distal segments. The side-branch take-off angle in the cross-sectional plane influenced the plaque distribution in bifurcation lesions.     

The mouse Pax21Neu mutation is identical to a human PAX2 mutation in a family with renal-coloboma syndrome and results in developmental defects of the brain, ear, eye, and kidney

We describe a new mouse frameshift mutation (Pax2^1Neu) with a 1-bp insertion in the Pax2 gene. This mutation is identical to a previously described mutation in a human family with renal-coloboma syndrome [Sanyanusin, P., McNoe, L. A., Sullivan, M. J., Weaver, R. G. & Eccles, M. R. (1995) Hum. Mol. Genet. 4, 2183–2184]. Heterozygous mutant mice exhibit defects in the kidney, the optic nerve, and retinal layer of the eye, and in homozygous mutant embryos, development of the optic nerve, metanephric kidney, and ventral regions of the inner ear is severely affected. In addition, we observe a deletion of the cerebellum and the posterior mesencephalon in homozygous mutant embryos demonstrating that, in contrast to mutations in Pax5, which is also expressed early in the mid-hindbrain region, loss of Pax2 gene function alone results in the early loss of the mid-hindbrain region. The mid-hindbrain phenotype is similar to Wnt1 and En1 mutant phenotypes, suggesting the conservation of gene regulatory networks between vertebrates and Drosophila.     

Galanin abolishes the inhibitory effect of cholinergic blockade on growth hormone-releasing hormone-induced secretion of growth hormone in man

In five healthy normal male volunteers, pretreatment with the cholinergic muscarinic antagonist pirenzepine (30 mg i.v.) almost abolished the growth hormone (GH) response to a maximal dose (120 micrograms i.v.) of growth hormone-releasing hormone (GHRH) (GH response at 40 min 5.6 + 1.3 mU/l with GHRH and pirenzepine vs 40.8 +/- 5.3 mU/l with GHRH alone, P less than 0.02). Concomitant i.v. infusion of galanin (40 pmol/kg/min) with pirenzepine not only restored but significantly potentiated the GH response to GHRH (GH at 40 min 72.2 +/- 10.5 mU/l, P less than 0.001 vs GHRH and pirenzepine, P less than 0.02 vs GHRH alone). Previous studies have proposed that cholinergic pathways control GH release via somatostatin and this study suggests that galanin may act by modulating hypothalamic somatostatinergic tone either directly or, possibly, by facilitating cholinergic neurotransmission.     

Estimating the effectiveness of a hospital’s interventions in India: impact of the choice of disability weights

ObjectiveTo calculate the effect of using two different sets of disability weights for estimates of disability-adjusted life-years (DALYs) averted by interventions delivered in one hospital in India.MethodsDALYs averted by surgical and non-surgical interventions were estimated for 3445 patients who were admitted to a 106-bed private hospital in a semi-urban area of northern India in 2012–2013. Disability weights were taken from global burden of disease (GBD) studies. We used the GBD 1990 disability weights and then repeated all of our calculations using the corresponding GBD 2010 weights. DALYs averted were estimated for surgical and non-surgical interventions using disability weight, risk of death and/or disability, and effectiveness of treatment.FindingsThe disability weights assigned in the GBD 1990 study to the sequelae of conditions such as cataract, cancer and injuries were substantially different to those assigned in the GBD 2010 study. These differences in weights led to large differences in estimates of DALYs averted. For all surgical interventions delivered to this patient cohort, 11 517 DALYs were averted if we used the GDB 1990 weights and 9401 DALYs were averted if we used the GDB 2010 disability weights. For non-surgical interventions 5168 DALYs were averted using the GDB 1990 disability weights and 5537 DALYS were averted using the GDB 2010 disability weights.ConclusionEstimates of the effectiveness of hospital interventions depend upon the disability weighting used. Researchers and resource allocators need to be very cautious when comparing results from studies that have used different sets of disability weights.