Pharmacogenomics-assisted schizophrenia management: A hybrid type 2 effectiveness-implementation study protocol to compare the clinical utility, cost-effectiveness, and barriers.

OBJECTIVES: The response to antipsychotic therapy is highly variable. Pharmacogenomic (PGx) factors play a major role in deciding the effectiveness and safety of antipsychotic drugs. A hybrid type 2 effectiveness-implementation research will be conducted to evaluate the clinical utility (safety and efficacy), cost-effectiveness, and facilitators and barriers in implementing PGx-assisted management compared to standard of care in patients with schizophrenia attending a tertiary care hospital in eastern India. METHODS: In part 1, a randomized controlled trial will be conducted. Adult patients with schizophrenia will be randomized (2: 1) to receive PGx-assisted treatment (drug and regimen selection depending on the results of single-nucleotide polymorphisms in genes DRD2, HTR1A, HTR2C, ABCB1, CYP2D6, CYP3A5, and CYP1A2) or the standard of care. Serum drug levels will be measured. The patients will be followed up for 12 weeks. The primary endpoint is the difference in the Udvalg for Kliniske Undersøgelser Side-Effect Rating Scale score between the two arms. In part 2, the cost-effectiveness of PGx-assisted treatment will be evaluated. In part 3, the facilitators and barriers to implementing PGx-assisted treatment for schizophrenia will be explored using a qualitative design. EXPECTED OUTCOME: The study findings will help in understanding whether PGx-assisted management has a clinical utility, whether it is cost-effective, and what are the facilitators and barriers to implementing it in the management of schizophrenia. TRIAL REGISTRATION: The study has been registered with the Clinical Trials Registry-India (CTRI/2023/08/056210).

Facilitators and barriers to the uptake of COVID-19 vaccine precaution dose among adult population: qualitative analysis across six different states of India.

Introduction: India launched the COVID-19 vaccination drive on 16th January 2021 by vaccinating the adult population above 18 years of age. This was followed by the introduction of an additional precaution dose. As on 18th October 2022, 1,02,66,96,808 (1.02 Billion) first dose and 94, 95, 39,516 (949 Million) second doses of COVID-19 vaccine were administered. However, when compared to the uptake of the primary doses, the precaution dose uptake lagged behind with only 21,75, 12,721 (217 million) doses administered. Even though, the uptake of the primary doses remained optimal, irrespective of different interventions by the Government of India, the uptake of the precaution dose remained poor. In this context, the Ministry of Health & Family Welfare wanted to understand the facilitators and Barriers for precaution dose uptake among adults so that future immunization campaigns could address these issues. Methods: An exploratory qualitative study was conducted to assess the facilitators and barriers for COVID-19 precaution dose uptake at community level across 6 different states in India. From each of the states, two districts with the highest and lowest rates of COVID-19 vaccine precaution dose uptake were selected. In each of these districts, 2 block Primary Healthcare Centres (PHCs), one with high and one with low uptake were identified. Within these block PHCs, a PHC field area with high and low precaution dose uptakes was identified. From the identified sites a minimum of four IDIs, four FGDs were conducted among the community members. KIIs of the State Immunization Officers, District Immunisation Officers, PHC Medical Officers, healthcare workers like Accredited Social Health Activist/Auxiliary Nurse Midwife were also conducted. The data was audio recorded and it was transcribed, translated and analysed using framework approach. Results: It was observed that rise in COVID-19 cases prompted the community to take the precaution dose, this along with the cost of hospitalization and the number of productive days being lost as a result of being infected resulted in vaccine uptake. The fear of non-availability of COVID-19 vaccines latter on also prompted people for vaccine uptake. While the barriers were, poor accessibility to vaccination centers, long hours of travel, poor road connectivity and lack of transportation facilities. However, the most prominent barriers observed across all study sites was that a sense of pandemic fatigue and complacency had developed both among the providers as well as the beneficiaries. Other barriers include differences in vaccination schedules and longer duration between the primary doses of some vaccines. Media was identified to be both a barrier and facilitator for Covid-19 Precaution dose uptake. Even though media played an important role in disseminating information in the beginning of the campaign, it was soon followed by the circulation of both misinformation and disinformation. Discussion: The study identified that dissemination of accurate information and community involvement at each stage of planning and implementation are crucial for the success of any campaign. Efforts should be constantly made to address and re-invent strategies that will be most suitable for the needs of the community. Therefore, in order to ensure successful vaccination campaigns, it is crucial that along with political will it is also important to have a decentralized approach with inter-sectoral coordination with different stakeholders such as healthcare workers, community members and the different departments such as the local self-governments, education department, law & order department etc. These lessons learnt from COVID-19 vaccination campaigns must not be forgotten and must be applied in future vaccination campaigns and while framing public health policies.

Tubercular longitudinally extensive transverse myelitis (LETM): An enigma for primary care physicians.

Albeit, all forms of tuberculosis (TB) are endemic in India, spinal intramedullary TB and tubercular longitudinally extensive transverse myelitis (LETM) is deemed extremely rare. With recent advances in the field of neurology, autoimmune astrocytopathy (neuromyelitis optica spectrum disorders, NMOSD), myelin-oligodendrocyte glycoprotein associated encephalomyelitis (MOG-EM), metabolic myelopathy, connective tissue diseases and viral infections have gained considerable focus in the list of differentials of LETM whereas tubercular association is often forgotten. This report presents a rare case of acute transverse myelopathy which unveiled previously undiagnosed pulmonary tuberculosis in an adult rural Indian male. The patient responded well to anti-tubercular therapy and corticosteroids. Exact pathogenesis of LETM in TB remains elusive. Association of TB with MOG-EM has been one of the recent hot-cakes. However, an ill-defined immune-inflammatory response to the infectious agent is the likely cause of tubercular LETM. Hence, the primary care physicians who are the first medical contacts of acute LETM cases and in most cases due to diagnostic dilemma there is an unavoidable delay in accurate diagnosis and initiation of therapy. Primary care doctors should nurture a high index of suspicion to diagnose this potentially lifetime-debilitating yet absolutely treatable clinical condition i.e. tubercular LETM.

Perceived morbidity, healthcare-seeking behavior and their determinants in a poor-resource setting: observation from India.

BACKGROUND: To control the double burden of communicable and non-communicable diseases (NCDs), in the developing world, understanding the patterns of morbidity and healthcare-seeking is critical. The objective of this cross-sectional study was to determine the distribution, predictors and inter-relationship of perceived morbidity and related healthcare-seeking behavior in a poor-resource setting. METHODS: Between October 2013 and July 2014, 43999 consenting subjects were recruited from 10107 households in Malda district of West Bengal state in India, through multistage random sampling, using probability proportional-to-size. Information on socio-demographics, behaviors, recent ailments, perceived severity and healthcare-seeking were analyzed in SAS-9.3.2. RESULTS: Recent illnesses were reported by 55.91% (n=24,600) participants. Among diagnosed ailments (n=23,626), 50.92% (n=12,031) were NCDs. Respiratory (17.28%, n=7605)), gastrointestinal (13.48%, n=5929) and musculoskeletal (6.25%, n=2749) problems were predominant. Non-qualified practitioners treated 53.16% (n=13,074) episodes. Older children/adolescents [adjusted odds ratio for private healthcare providers (AORPri)=0.76, 95% confidence interval=0.71-0.83) and for Govt. healthcare provider (AORGovt)=0.80(0.68-0.95)], females [AORGovt=0.80(0.73-0.88)], Muslims [AORPri=0.85(0.69-0.76) and AORGovt=0.92(0.87-0.96)], backward castes [AORGovt=0.93(0.91-0.96)] and rural residents [AORPri=0.82(0.75-0.89) and AORGovt=0.72(0.64-0.81)] had lower odds of visiting qualified practitioners. Apparently less severe NCDs [acid-peptic disorders: AORPri=0.41(0.37-0.46) & AORGovt=0.41(0.37-0.46), osteoarthritis: AORPri=0.72(0.59-0.68) & AORGovt=0.58(0.43-0.78)], gastrointestinal [AORPri=0.28(0.24-0.33) & AORGovt=0.69(0.58-0.81)], respiratory [AORPri=0.35(0.32-0.39) & AORGovt=0.46(0.41-0.52)] and skin infections [AORPri=0.65(0.55-0.77)] were also less often treated by qualified practitioners. Better education [AORPri=1.91(1.65-2.22) for ≥graduation], sanitation [AORPri=1.58(1.42-1.75)] and access to safe water [AORPri=1.33(1.05-1.67)] were associated with healthcare-seeking from qualified private practitioners. Longstanding NCDs [chronic obstructive pulmonary diseases: AORPri=1.80(1.46-2.23), hypertension: AORPri=1.94(1.60-2.36), diabetes: AORPri=4.94(3.55-6.87)] and serious infections [typhoid: AORPri=2.86(2.04-4.03)] were also more commonly treated by qualified private practitioners. Potential limitations included temporal ambiguity, reverse causation, generalizability issues and misclassification. CONCLUSION: In this poor-resource setting with high morbidity, ailments and their perceived severity were important predictors for healthcare-seeking. Interventions to improve awareness and healthcare-seeking among under-privileged and vulnerable population with efforts to improve the knowledge and practice of non-qualified practitioners probably required urgently.