Patient and caregiver perspectives of select non-communicable diseases in India: A scoping review.

BACKGROUND AND OBJECTIVES: Patient-reported measures of encounters in healthcare settings and consideration of their preferences could provide valuable inputs to improve healthcare quality. Although there are increasing reports of user experiences regarding health care in India in recent times, there is a lack of evidence from Indian healthcare settings on the care provided for patients with chronic diseases. METHODS: We selected diabetes mellitus and cancer as representatives of two common conditions requiring different care pathways. We conducted a scoping review of studies reporting experiences or preferences of patients/caregivers for these conditions, in PubMed, Global Index Medicus and grey literature, from the year 2000 onwards. Both published and emergent themes were derived from the data and summarised as a narrative synthesis. RESULTS: Of 95 included studies (49 diabetes, 46 cancer), 73% (65) were exclusively quantitative surveys, 79% included only patients (75), and 59.5% (44) were conducted in government centres. Studies were concentrated in a few states in India, with the underrepresentation of vulnerable population groups and representative studies. There was a lack of standardised tools and comprehensive approaches for assessing experiences and preferences of patients and caregivers, concerning diabetes and cancers in India. The commonest type of care assessed was therapeutic (74), with 14 cancer studies on diagnosis and nine on palliative care. Repeated visits to crowded centres, drug refill issues, unavailability of specific services in government facilities, and expensive private care characterised diabetes care, while cancer care involved delayed diagnosis and treatment, communication, and pain management issues. CONCLUSIONS: There is a need for robust approaches and standardised tools to measure responsiveness of the healthcare system to patient needs, across geographical and population subgroups in India. Health system reforms are needed to improve access to high-quality care for treatment and palliation of cancer and management of chronic diseases such as diabetes.

Association of dietary patterns and health outcomes by spatial regression analysis of nationally representative survey data from India.

Background: Our aim was to study the regional differences in dietary patterns in India and their association with population-level nutrition-related health indicators such as the prevalence of anemia, overweight, undernutrition, and hyperglycemia. Objectives: To identify and characterize the dietary patterns from publicly available nationally representative survey data on food consumption conducted by the National Sample Survey Office (NSSO) to study the regional differences in dietary patterns. Methods: Dietary patterns were identified by factor analysis of per capita food consumption data from the household consumer expenditure survey (2011). Mean factor scores of dietary patterns were calculated for each district separately for urban and rural regions. Ecological association of factor scores with the district-level percentage prevalence of health indicators from the National Family Health Survey-4 (2015-2016) data was done by the Spatial Durbin Model of spatial regression analysis. Results: Factor analyses revealed four dietary patterns which were similar in terms of the food items that characterized the factors for both rural and urban regions. Direct effects of dietary patterns by spatial regression analyses were observed with several health outcomes after adjusting for differences in socioeconomic development. Prevalence of anemia was positively associated with "Milk and wheat-rich diet" among men in the rural regions but negatively associated with other dietary patterns. Prevalence of overweight and high blood glucose was positively associated with "Rice and meat-rich diet" and "Coconut and seafood rich diet" in the rural regions. "Refined oil and tur dal-rich diet" was positively associated with the prevalence of overweight and hypertension in urban regions and negatively associated with underweight and anemia in men in rural and urban regions. Conclusions: Spatial regression analyses revealed several important associations between dietary patterns and health outcomes, mostly in rural regions and some in urban regions. These results suggest the role of the major food items consumed in different regions and their impact on health outcomes in India and may have implications in tailoring dietary modifications accordingly.

Rituximab biosimilar for the treatment of diffuse large B-cell lymphoma: a phase 3 randomized study in India.

PURPOSE: Very few studies have demonstrated the rituximab biosimilarity in terms of efficacy, safety, pharmacokinetics, pharmacodynamics, and immunogenicity in patients with diffuse large B-cell lymphoma (DLBCL) in India. Therefore, we compared the efficacy, safety, pharmacokinetic, pharmacodynamic, and immunogenicity of our biosimilar rituximab with the reference rituximab (Ristova, Roche products [India] Pvt. Ltd) in patients with DLBCL in India. METHODS: A phase 3, randomized, assessor-blind, parallel-group, two-arm study was conducted across 28 sites in India. A total of 153 newly diagnosed DLBCL patients were randomized to receive either biosimilar rituximab or reference rituximab. The study drugs were administered at a dose of 375 mg/m2 by intravenous infusion every 3 weeks for six cycles. The primary end point was objective response rate (ORR) at the end of Cycle 6. Secondary end points included: pharmacokinetic, pharmacodynamics, immunogenicity, and safety assessment. RESULTS: The ORR at the end of Cycle 6 was 82.14% in the biosimilar rituximab and 85.71% in the reference rituximab group. The risk difference (90% CIs) was - 3.57 (- 14.80, 7.66). It met the non-inferiority margin of - 20%. The pharmacokinetic and pharmacodynamic parameters were comparable between the two treatment groups. The incidence rate of immunogenicity was very low and similar in both the treatment groups. The safety profile of both the treatments was comparable with no major difference in terms of nature, frequency and severity of TEAEs. CONCLUSION: The study demonstrated the biosimilarity between the biosimilar rituximab and the reference rituximab. Our biosimilar rituximab could add to the cost-effective treatment alternatives for patients with DLBCL in India.

Short-duration podcasts as a supplementary learning tool: perceptions of medical students and impact on assessment performance.

BACKGROUND: Use of podcasts has several advantages in medical education. Podcasts can be of different types based on their length: short (1-5 min), moderate (6-15 min) and long (>15 min) duration. Short-duration podcasts are unique since they can deliver high-yield information in a short time. The perceptions of medical students towards short-duration podcasts are not well understood and this study aimed to analyze the same. An exploratory analysis of students' podcast usage and performance in summative assessments was also undertaken. METHODS: First-year medical students (N = 94) participated in the study. Eight audiovisual podcasts, each ≤3 min duration (3-MinuTe Lessons; 3MTLs) were developed for two topics in biochemistry. The podcasts were made available for students after didactic lectures on the topics. Feedback was collected from students about their perceptions to 3MTLs using a self-reported questionnaire. The scores of students in summative assessments were compared based on their usage of 3MTLs. RESULTS: Feedback revealed that 3MTLs were well received by students as a useful and convenient supplementary tool. Students used 3MTLs for topic review, to get an overview, as well as for quick revision and felt that 3MTLs were helpful in improving their understanding of the topic, clarify concepts and focus on important points and in turn, in preparation for assessments. A significant proportion (49%) felt that 3-min duration was optimal while, an equal proportion suggested an increase in the duration to 5 min with more information. The overall mean scores in assessments were not different between students based on 3MTLs usage. The pairwise comparisons revealed better scores amongst students who used 3MTLs for both topics. CONCLUSION: Overall, short-duration podcasts were perceived by students as useful supplementary learning tools that aided them for revision and in preparation for assessments.

Association between apolipoprotein E genotype and cancer susceptibility: a meta-analysis.

BACKGROUND: Apolipoprotein E (ApoE), a protein primarily involved in lipoprotein metabolism, occurs in three isoforms (E2, E3 and E4). Studies evaluating the association between APOE genotype and incidence of malignancies have given inconclusive results. OBJECTIVE: The objective of the present study was to analyze the association between APOE genotype and incidence of cancer by a meta-analysis. METHODS: We conducted a literature search in the electronic databases for studies with information on APOE genotype in malignancies. Sixteen studies (14 case-control and 2 cohort; 77,970 controls and 12,010 cases) were included for the present meta-analysis. Pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated assuming a random-effect model for all the genotypes and alleles. Subgroup analyses based on study design, ethnicity of populations, site of cancer and source of controls were performed as a post hoc measure. Appropriate tests to detect heterogeneity, publication bias and sensitivity were done at all stages. The review protocol is registered with the PROSPERO database vide registration number CRD42013006496. RESULTS: The pooled effect measure for the comparisons did not reveal an association in primary analyses. In the subgroup analyses, we observed a negative association between APOE4+ genotypes and overall risk of cancer in the cohort study subgroup (pooled OR 0.86; 95 % CI 0.82-0.91; p < 0.00001; I (2) = 0 %). Sensitivity analyses did not alter the overall pooled effect measure, and there were no evidences to suggest a publication bias. CONCLUSION: Overall, the present meta-analysis did not show any association between APOE alleles and genotypes with incidence of cancer in general.

Acute coronary syndrome in a patient with Eisenmenger's syndrome.

Eisenmenger's syndrome is a complex multisystem disease which occurs as a consequence of large left to right shunt affecting the pulmonary vasculature causing suprasystemic pulmonary artery pressures and subsequent right to left shunt. Usually Eisenmenger's syndrome is characterised by coronary artery dilation but coronary artery disease and occurrence of acute coronary syndrome is a rare association seldom described in literature. We present the case of a 33-year-old man who presented with an anterior wall ST elevation mycocardial infarction and was thrombolysed. The occurrence of acute coronary event in a case of Eisenmenger's syndrome is a rare event and needs to be discussed and kept in mind by physicians and cardiologists who deal with such cases so that a high index of suspicion may be developed and emergent management may be possible.

Antibodies that cross-neutralize the tier-2 pseudoviruses are produced in antiretroviral-naïve HIV-1-infected children from northern India.

In this cross-sectional study, we evaluated the efficiency of the plasma of 38 antiretroviral-naïve HIV-1-infected children from northern India against a standard panel of pseudoviruses (3 clade C and 3 clade B) by TZM-bl assay. Neutralization potential was observed to a variable extent, with a potency ranging up to reciprocal ID(50) titers of 1967. Cross-neutralization was observed in 28.9 % (11/38) of the children. There was a significant positive correlation between viremia and neutralization efficiency against two of the viruses studied (Du172 r = 0.49; p = 0.007 and RHPA r = 0.47; p = 0.01), suggesting that persistent antigenic stimulation is necessary for the generation of broadly neutralizing antibody responses in these children. Further mapping of the epitope specificities of the neutralization determinants in the polyclonal plasma would provide important information for immunogen design.

Binding antibody responses to the immunogenic regions of viral envelope in HIV-1-infected Indian children.

Limited information exists on the antibody responses elicited against the viral envelope in HIV-1-infected children. In this cross-sectional study, we assessed the antibody responses against three different immunogenic regions of HIV-1 envelope, namely V3 region of gp120, membrane proximal external region (MPER), and immunodominant loop (IDL) of gp41 in HIV-1-infected children from north India. We recruited 75 HIV-1-infected (40 antiretroviral naive and 35 treated) children, with age ranging from 1.5 to 16 y. Antibodies to V3 and the IDL region were found in a majority of the infected children, whereas antibodies to MPER were found in approximately one-third of the children studied. Higher antibody titers to the immunogenic regions corresponded to the symptomatic stages of HIV-1 infection in both naive and antiretroviral therapy (ART)-treated children. High titers of anti-V3C and anti-IDL antibodies were observed in a subset of antiretroviral-naive patients with suppressed viremia (<47 RNA copies/mL), suggesting that antibodies to these immunogenic regions are present regardless of their viremic status. Further, the antibody titers were significantly lower in the plasma of treated patients compared to naive patients, regardless of whether they were virologically suppressed or not. This is the first report on the antibody responses elicited in HIV-1-infected children in India. The study may help to understand the humoral antibody responses directed against viral envelope in HIV-1-infected children.

Efficient neutralization of primary isolates by the plasma from HIV-1 infected Indian children.

We tested the plasma of 51 HIV-1-infected children (23 naïve and 28 ART treated) for neutralization against five primary isolates (PIs) generated from adult Indian HIV-1-infected patients. The plasma exhibited neutralization potential with significantly higher neutralizing antibody titers in ART-treated children than naïve children against three out of five PIs (p<0.0001). Further, in treated children, neutralizing antibody titers were higher in those children with suppressed viremia (<1000 RNA copies/mL) than non-suppressors against two of the three PIs. We report here for the first time the neutralization potential of the plasma of HIV-1-infected Indian children.

Relative reactivity of HIV-1 polyclonal plasma antibodies directed to V3 and MPER regions suggests immunodominance of V3 over MPER and dependence of high anti-V3 antibody titers on virus persistence.

Antibodies to two crucial regions, the third variable loop (V3) of gp120 and the membrane-proximal external region (MPER) of gp41 are important for HIV-1 neutralization. We here evaluated the relative binding of polyclonal plasma antibodies from 99 HIV-1-infected individuals from India to the consensus-C V3 and MPER peptides and observed immunodominance of V3 over MPER (p < 0.0001). We further examined the V3- and MPER-specific antibody correlates with clinical parameters. Our results revealed that anti-V3 antibody titers are significantly lower in patients on ART compared to drug-naive individuals (p < 0.0001), most likely due to a decrease in plasma viral load, irrespective of their CD4 counts and total IgG. No such association was observed for MPER, with a similar trend in four follow-up patients. These findings strongly suggest that high titers of V3-specific antibodies are dependent on persistence of virus in circulation, while antibodies to MPER are probably not.

The neuroleptic malignant syndrome: an Indian experience.

A study was performed to investigate the clinical presentation and outcome of the neuroleptic malignant syndrome (NMS) in a large teaching psychiatric hospital in India. Thirteen cases were identified after a thorough search of intensive care unit (ICU) records during the 4-year period between 1990 and 1993. Information collected from these cases was then compared against data from a representative control group of 252 inpatients who received neuroleptics, drawn randomly from each of the 4 years of the study. Statistical comparisons were made using Student's t test, the chi-square test, and Fisher's exact test. The incidence of NMS was 1.41 per 1,000 cases treated with neuroleptics (95% confidence interval, 0.71 to 2.14 per 1,000) and the mortality from NMS was 38%. Patients who developed NMS had a significantly higher incidence of coexisting physical or neurological illness and received a higher mean neuroleptic dose. Neuroleptic loading rates were not different in the NMS and control samples. Fluphenazine decanoate was implicated as a causative factor of NMS in a significantly higher proportion of these patients. The group with a fatal outcome was significantly older and received a higher neuroleptic dose than the control group, but not compared with the group that recovered.

Sequences flanking the core DNA-binding domain of bovine papillomavirus type 1 E2 contribute to DNA-binding function.

We have compared a series of molecular constructs that contain the minimal DNA-binding and dimerization domain of bovine papillomavirus type 1 (BPV-1) E2 alone or this binding domain plus the adjacent 16 or 40 amino acids to test the role of the flanking sequences in E2 function. The presence of these sequences resulted in an up to eightfold increase in the affinity of E2 for its target DNA and stabilized the protein against denaturation both in the absence of DNA and in the form of DNA-protein complexes. In addition, an aspartic acid-to-tyrosine mutation within the flanking region blocked DNA binding and function. These data demonstrate that sequences flanking the core domain contribute to E2 function and are, in fact, an integral part of the DNA-binding domain of BPV-1 E2.

The BPV-1 E2 DNA-contact helix cysteine is required for transcriptional activation but not replication in mammalian cells.

The papillomavirus E2 protein contains an amino-terminal region thought necessary and sufficient to support transcriptional activation and a carboxy-terminal region shown to direct sequence-specific DNA binding and dimerization. A cysteine residue in the center of the E2 DNA recognition helix is highly conserved among papillomavirus E2 proteins. Mutations of this cysteine in bovine papillomavirus type 1 E2 to serine and glycine resulted in proteins which failed to activate E2-dependent promoters in mammalian cells. These E2 mutants were DNA-binding competent, dimeric, and nuclear. When fused to the VP16 transactivation domain, C-terminal regions of E2 containing the mutations at 340 supported transcriptional activation, indicating that the heterologous trans-activation domain did not require cysteine in the DNA-binding helix as did the full-length E2 transactivating protein. Although cysteine-340 was required for transcriptional activation it was not required for DNA replication in vivo. Together, these results suggest that the E2 DNA-binding domain may directly contribute to functions of transcriptional activation previously thought limited to the N-terminal domain.

The tryptophan bridge is a critical feature of the papillomavirus E2 DNA binding domain.

The papillomavirus E2 protein is a DNA binding protein that regulates viral transcription and replication. E2 binds DNA as a dimer. Recent crystallographic data for E2 complexed to DNA revealed that novel peptide structures in E2 mediated dimerization and DNA binding. To identify important features of these motifs we have used limited proteolysis and urea denaturation as biochemical probes for structure, applying these techniques to E2 alone, E2 bound to DNA, cross-linked products, and mutants that were targeted at Trp360, a contact point along the dimer interface. DNA binding stabilized E2 structure, shifting the point at which it denatures from 5 to 7.6 M urea. In contrast, Trp360 mutant proteins, while dimeric, were more sensitive to denaturation by urea when bound to DNA. The most striking results came from uv cross-linking studies in which Trp360 was targeted as the site of cross-linking. Ultraviolet cross-linking dramatically increased the resistance of E2 to proteolysis regardless of the protease tested and with no deleterious effect on the affinity of E2 for DNA. Cross-linking through Cys356 with bismaleimidohexane did not promote stabilization. The ability to stabilize or destabilize E2 by Trp360-targeted modifications demonstrates the importance of the Trp360-Trp360 interaction, which may represent a general feature of the beta-barrel motif.