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.

Relationship between reduced folate carrier gene polymorphism and non-syndromic cleft lip and palate in Indian population

Objective: Folate metabolism involves absorption, transport, modifications and interconversions of folates. The reduced folate carrier does not participate directly in folate metabolism but plays a major role in intracellular transport of metabolically active 5-methyltetrahydrofolate and maintains the intracellular concentrations of folate. The purpose of this study was to identify the prevalence of reduced folate carrier 1 (RFC1) A80G polymorphism and to further delineate its association with non-syndromic cleft lip and palate (NSCLP) in a south Indian population.

Methods: In the present case-control study, we studied RFC1 gene A80G polymorphism to evaluate its impact on NSCLP risk in south Indian population. Blood samples of 142 cases with NSCLP and 141 controls were collected and genotyped using PCR-RFLP.

Results: The genotype distribution in the control group followed Hardy–Weinberg equilibrium (p?=?0.633). The G allele frequency of cases was 64.8% (184/284) and was significantly lower than that found in the control group 56.4% (160/282). The genotype distributions between NSCLP cases and controls was not significantly different (p?=?0.131). The allelic model significantly increased the risk of NSCLP (G versus A; OR?=?1.40; 95% CI: 1.00–1.97; p?=?0.050). In subgroup analysis, the A80G variant showed significant association for the CLP group in dominant and allelic models.

Conclusions: Altogether, our findings support the hypothesis that RFC1 A80G variant may contribute to NSCLP susceptibility in a south Indian population.     

Myocardial tissue remodeling after orthotopic heart transplantation: a pilot cardiac magnetic resonance study

After orthotopic heart transplantation (OHT), the allograft undergoes characteristic alterations in myocardial structure, including hypertrophy, increased ventricular stiffness, ischemia, and inflammation, all of which may decrease overall graft survival. Methods to quantify these phenotypes may clarify the pathophysiology of progressive graft dysfunction post-OHT. We performed cardiac magnetic resonance (CMR) with T1 mapping in 26 OHT recipients (mean age 47?±?7 years, 30?% female, median follow-up post-OHT 6 months) and 30 age-matched healthy volunteers (mean age 50.5?±?15 years; LVEF 63.5?±?7?%). OHT recipients had a normal left ventricular ejection fraction (LVEF 65.3?±?11?%) with higher LV mass relative to age-matched healthy volunteers (114?±?27 vs. 85.8?±?18 g; p?<?0.001). There was no late gadolinium enhancement in either group. Both myocardial extracellular volume fraction (ECV) and intracellular lifetime of water (τ_ic), a measure of cardiomyocyte hypertrophy, were higher in patients post-OHT (ECV: 0.39?±?0.06 vs. 0.28?±?0.03, p?<?0.0001; τ_ic: 0.12?±?0.08 vs. 0.08?±?0.03, p?<?0.001). ECV was associated with LV mass (r?=?0.74, p?<?0.001). In follow-up, OHT recipients with normal biopsies by pathology (ISHLT grade 0R) in the first year post-OHT exhibited a lower ECV relative to patients with any rejection ≥2R (0.35?±?0.02 for 0R vs. 0.45?±?0, p?<?0.001). Higher ECV but not LVEF was significantly associated with a reduced rejection-free survival. After OHT, markers of tissue remodeling by CMR (ECV and τ_ic) are elevated and associated with myocardial hypertrophy. Interstitial myocardial remodeling (by ECV) is associated with cellular rejection. Further research on the impact of graft preservation and early immunosuppression on tissue-level remodeling of the allograft is necessary to delineate the clinical implications of these findings.     

Keratoglobus: An experience at a tertiary eye care center in India

Context:

This study was carried out as a part of an internal audit and is the largest series of patients having keratoglobus, published in the literature. Poor visual acuity of the patients indicates the blinding nature of the disease.

Aims:

We report our experience with patients having keratoglobus at a tertiary eye care center in India.

Settings and Design:

Retrospective study.

Materials and Methods:

We analyzed adults and pediatric patients (<16 years) with keratoglobus, seen during 2008–2012. The age, gender, consanguinity, presenting ocular signs, ocular and systemic associations, visual acuity, corneal topography, and surgeries were documented.

Results:

Forty-eight patients (mean age 22 ± 15 years, 31 males) having keratoglobus were analyzed. 21 patients (42 eyes) were <16 years. Twelve eyes (16 events) had positive history of trauma. The presenting clinical signs were corneal scars/scars of tear repair (15 eyes), hydrops, healed and acute (14 eyes) and corneal or globe rupture (9 eyes). Best-corrected visual acuity was >20/40 in 6/42 (14.3%) pediatric eyes and 15/53 (28.30%) adults. Visual acuity ranging from counting of fingers to no light perception was noted in 20/53 (37.74%) adults and 21/42 (50%) pediatric patients; 13/20 (65%) with blue sclera and 8/22 eyes (36.37%) without blue sclera. Vernal keratoconjunctivitis was present in one pediatric patient. Choroidal osteoma, retinitis pigmentosa, and retinal detachment were present in adults. Surgeries performed were corneal tear repair (5 eyes), tissue adhesive application (2 eyes), descematopexy (4 eyes) and penetrating keratoplasty (PK - 8 eyes: Three had post-PK glaucoma, graft failure-one eye, 4 patients wore scleral lens - prosthetic replacement of the ocular surface ecosystem).

Conclusions:

About 50% of pediatric eyes (65% having blue sclera) had no functional vision. Trivial trauma was responsible for corneal rupture indicating need for protective glasses. About 50% patients had post-PK glaucoma though grafts were clear.     

Rabeprazole improves health-related quality of life in patients with erosive gastroesophageal reflux disease

The purpose of this study was to assess the effect of rabeprazole 20 mg once a day on patient-reported health-related quality of life in routine clinical practice. Patients with erosive gastroesophageal reflux disease participating in an open-label, 8-week study completed the SF-36 Health Survey before and after treatment with rabeprazole. For all SF-36 scales, there was a statistically significant (p 0.007) improvement in mean scores from baseline to week 8. Improvements in each of the subscales, except for physical functioning, general health, and mental health, were at least 5% in magnitude, a level considered clinically meaningful. Furthermore, while baseline scores were significantly poorer than general United States population scores, follow-up scores for four of the subscales (role limitations due to physical problems, social functioning, role limitations due to emotional problems, and mental health) were comparable to general population scores. In conclusion, rabeprazole significantly improved health-related quality of life in erosive gastroesophageal reflux disease patients and restored social functioning and emotional well-being to levels comparable to those observed in the United States general population.     

Crystal structure of Taq DNA polymerase in complex with an inhibitory Fab: The Fab is directed against an intermediate in the helix-coil dynamics of the enzyme

We report the crystal structure of Thermus aquaticus DNA polymerase I in complex with an inhibitory Fab, TP7, directed against the native enzyme. Some of the residues present in a helical conformation in the native enzyme have adopted a γ turn conformation in the complex. Taken together, structural information that describes alteration of helical structure and solution studies that demonstrate the ability of TP7 to inhibit 100% of the polymerase activity of the enzyme suggest that the change in conformation is probably caused by trapping of an intermediate in the helix-coil dynamics of this helix by the Fab. Antibodies directed against modified helices in proteins have long been anticipated. The present structure provides direct crystallographic evidence. The Fab binds within the DNA binding cleft of the polymerase domain, interacting with several residues that are used by the enzyme in binding the primer:template complex. This result unequivocally corroborates inferences drawn from binding experiments and modeling calculations that the inhibitory activity of this Fab is directly attributable to its interference with DNA binding by the polymerase domain of the enzyme. The combination of interactions made by the Fab residues in both the polymerase and the vestigial editing nuclease domain of the enzyme reveal the structural basis of its preference for binding to DNA polymerases of the Thermus species. The orientation of the structure-specific nuclease domain with respect to the polymerase domain is significantly different from that seen in other structures of this polymerase. This reorientation does not appear to be antibody-induced and implies remarkably high relative mobility between these two domains.     

Norfloxacin and cisapride combination decreases the incidence of spontaneous bacterial peritonitis in cirrhotic ascites

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a serious complication of cirrhosis with ascites, having high recurrence despite antibiotic prophylaxis. Small bowel dysmotility and bacterial overgrowth have been documented to be related to SBP. The purpose of the present paper was (i) to study whether addition of a prokinetic agent to norfloxacin ameliorates the development of SBP in high-risk patients; and (ii) to identify risk factors for SBP development. METHODS: A prospective, single blinded, randomized controlled trial was conducted in high-risk cirrhotic patients with ascites who had either recovered from an episode of SBP or who had low ascitic fluid protein. Norfloxacin 400 mg once daily (group I) or norfloxacin 400 mg once daily with cisapride 20 mg twice a day (group II) was given and occurrence of side-effects of therapy and mortality were recorded. RESULTS: Of the 94 patients, 48 (51%) were in group I, and 46 (49%) in group II. The actuarial probability of developing SBP at 12 month in group I was 56.8% and in group II, 21.7% (P = 0.026). Treatment failure was observed in five patients (10%) in group I and none in group II (P = 0.003). The actuarial probability of death at 18 months was 20.6% in group I and 6.2% in group II (P = 0.1). Low serum albumin, low ascitic fluid protein and alcoholic cirrhosis were related to development of SBP (P < 0.05). Additionally, low serum albumin (2.8 g/dL), gastrointestinal bleeding, alcoholic cirrhosis and low ascitic fluid protein were significantly associated with multiple occurrences of SBP. CONCLUSIONS: Prophylaxis with norfloxacin and cisapride significantly reduces the incidence of SBP in high-risk cirrhosis patients; low serum albumin, low ascitic fluid protein and alcoholic cirrhosis predispose to the development of SBP in high-risk cirrhosis patients; and low ascitic fluid protein should also be considered as a risk factor for the development of SBP requiring prophylaxis.