Management of ß-thalassemia – Consensus and controversies!

The mainstay of treatment of ß-Thalassemia major includes life-long regular packed red cell transfusions and iron chelation. With advances in understanding the molecular biology and its implications in the patients, newer modalities are now being explored to offer a better quality of life to transfusion dependent thalassemic patients. Improved safety of transfusions, newer chelator drugs and combination of chelators have improved outcomes in these patients. Amlodipine along with chelators may be a future option for preventing cardiac iron overload related complications. Drugs which improve HbF levels and thus ameliorate anemia such as hydroxyurea, butyrates azacytidine etc. have also been explored with little relief to transfusion dependent patients. HSCT, which is the only curative treatment available at present, has its own limitations as sibling donors may not be available to many. However, there has been extensive work done on improving outcomes with MUD and Haplo-identical HSCT in the recent times. Gene therapy using lentiviral vectors is also offering great hope to these children. Induced Pluripotent Stem Cells (iPSC) is a promising advance in the treatment of thalassemia. Several newer molecules targeting different pathophysiologic aspects are being explored and have met with good success. These include luspatercept, sotatercept, macrophage inhibition, JAK2 inhibition using ruxolitinib etc. Controversies regarding use of wheat grass and ESAs are relatively less worrisome. But use of thalidomide should be done with great caution. Despite its success reported in anecdotal reports, in the absence of adequate data with larger trials, its role in routine management of thalassemia syndromes remains to be ascertained

Can telemedicine initiative be an effective intervention strategy for improving treatment compliance for pediatric HIV patients: Evidences on costs and improvement in treatment compliance from Maharashtra, India.

BackgroundIndia has recently introduced telemedicine initiatives to enhance access to specialized care at a low cost for the pediatric HIV patients, who face multiple challenges due to growing disease burden and limited preparedness of the health system to address it. There are limited evidences on the cost-effectiveness of these interventions. This study was undertaken in Maharashtra, a province, located in the western region of the country, to inform policy regarding the effectiveness of this programme. The objective was to estimate the unit cost of ART services for pediatric HIV patients and examine the efficiency in the use of resource and treatment compliance resulting from telemedicine initiatives in pediatric HIV compared to usual ART services.MethodsWe selected 6 ART centers (3 from linked centers linked to Pediatric HIV Centre of Excellence (PCoE) and 3 from non-linked centers) randomly from three high, middle and low ART centers, categorized on the basis of case load in each arm. A bottom up costing methodology was adopted to understand the unit cost of services. Loss to follow up and timeliness of the visits were compared between the two arms and were linked to the cost.ResultsThe average cost per-visit was INR 1803 in the linked centers and that for the non-linked centers was INR 3412. There has been 5 percentage point improvement in lost to follow-up in the linked centers compared to non-linked centers against a back-drop of a reduction in per-pediatric patient cost of INR 557. The linkage has resulted in increase in timeliness of the visits in linked centers compared to non-linked centers.Discussion and conclusionThe telemedicine linkage led to an increase in the case load leading to a decrease in cost. The evidence on efficiency in the use of resource and improvement in treatment compliance as suggested by this study could be used to scale up this initiative

Alarming levels of drug-resistant tuberculosis in HIV-infected patients in metropolitan Mumbai, India.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) is a looming threat to tuberculosis control in India. However, no countrywide prevalence data are available. The burden of DR-TB in HIV-co-infected patients is likewise unknown. Undiagnosed and untreated DR-TB among HIV-infected patients is a major cause of mortality and morbidity. We aimed to assess the prevalence of DR-TB (defined as resistance to any anti-TB drug) in patients attending public antiretroviral treatment (ART) centers in greater metropolitan Mumbai, India. METHODS: A cross-sectional survey was conducted among adults and children ART-center attendees. Smear microscopy, culture and drug-susceptibility-testing (DST) against all first and second-line TB-drugs using phenotypic liquid culture (MGIT) were conducted on all presumptive tuberculosis patients. Analyses were performed to determine DR-TB prevalence and resistance patterns separately for new and previously treated, culture-positive TB-cases. RESULTS: Between March 2013 and January 2014, ART-center attendees were screened during 14135 visits, of whom 1724 had presumptive TB. Of 1724 attendees, 72 (4%) were smear-positive and 202 (12%) had a positive culture for Mycobacterium tuberculosis. Overall DR-TB was diagnosed in 68 (34%, 95% CI: 27%-40%) TB-patients. The proportions of DR-TB were 25% (29/114) and 44% (39/88) among new and previously treated cases respectively. The patterns of DR-TB were: 21% mono-resistant, 12% poly-resistant, 38% multidrug-resistant (MDR-TB), 21% pre-extensively-drug-resistant (MDR-TB plus resistance to either a fluoroquinolone or second-line injectable), 6% extensively drug-resistant (XDR-TB) and 2% extremely drug-resistant TB (XDR-TB plus resistance to any group-IV/V drug). Only previous history of TB was significantly associated with the diagnosis of DR-TB in multivariate models. CONCLUSION: The burden of DR-TB among HIV-infected patients attending public ART-centers in Mumbai was alarmingly high, likely representing ongoing transmission in the community and health facilities. These data highlight the need to promptly diagnose drug-resistance among all HIV-infected patients by systematically offering access to first and second-line DST to all patients with 'presumptive TB' rather than 'presumptive DR-TB' and tailor the treatment regimen based on the resistance patterns

Demographic and clinical factors associated with drug-resistant tuberculosis in HIV-infected tuberculosis patients, Mumbai, India.

<p>ART: Antiretroviral treatment, CI; Confidence Intervals ⁺Patients with recorded family income, N = 162* Patients with available information about CD4 count, last visit N = 185** Patients on ART with available information about ART initiation date, N = 126^a aOR; adjusted Odds ratios (calculated by binary logistic regression using multiple imputation for CD4 missing data).</p><p>Demographic and clinical factors associated with drug-resistant tuberculosis in HIV-infected tuberculosis patients, Mumbai, India.</p

Demographic and clinical factors associated with multidrug-resistant tuberculosis in HIV-infected tuberculosis patients, Mumbai, India.

<p>ART: Antiretroviral treatment, CI; Confidence Intervals ⁺Patients with recorded family income, N = 140* Patients with available information about CD4 count, last visit N = 164** Patients on ART with available information about ART initiation date, N = 126^aaOR; adjusted Odds ratios (calculated by binary logistic regression using multiple imputation for CD4 missing data).</p><p>Demographic and clinical factors associated with multidrug-resistant tuberculosis in HIV-infected tuberculosis patients, Mumbai, India.</p

Drug-resistant tuberculosis among HIV-infected patients with presumptive tuberculosis, Mumbai, India.

<p>Drug-resistant tuberculosis among HIV-infected patients with presumptive tuberculosis, Mumbai, India.</p

Demographic and clinical factors associated with culture-positive tuberculosis in HIV-infected patients, Mumbai, India.

<p>ART: Antiretroviral treatment, IQR: Inter-quartile range, CI; Confidence Intervals ⁺Patients with recorded family income, N = 1452* Patients with available information on CD4, last visit, N = 1582** Patients on ART with available information about ART initiation date, N = 1370^a aPR; adjusted Prevalence Ratios (calculated by Poisson regression using multiple imputation for CD4 missing data).</p><p>Demographic and clinical factors associated with culture-positive tuberculosis in HIV-infected patients, Mumbai, India.</p

Resistance profile (first and second-line) for all drug-resistant tuberculosis patients, Mumbai, India.

<p>H-isoniazid, R-rifampicin, E-ethambutol, Eto-ethionamide, Km-kanamycin, Cm-capreomycin, Ofx-ofloxacin, Mfx-Moxifloxacin, Lin- Linezolid, PAS- para-aminosalicylic acid.</p><p>Resistance profile (first and second-line) for all drug-resistant tuberculosis patients, Mumbai, India.</p

Demographic and clinical characteristics of HIV-infected patients with presumptive TB, Mumbai, India.

<p>ART: Antiretroviral treatment* Patients on ART with available information about ART initiation date, N = 1370.</p><p>Demographic and clinical characteristics of HIV-infected patients with presumptive TB, Mumbai, India.</p