Sociocultural Framework for Psychiatric Case Formulation.

ABSTRACT: A Cultural Formulation Interview (CFI) field trial in India, widely reported racist violence in the United States, and casteist and religious communal conflicts in India highlighted inattention to structural issues affecting mental health problems in the Outline for Cultural Formulation (OCF) and the CFI in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). Consequently, we revised the OCF as a sociocultural formulation (SCF) to better consider structures of society and culture. We studied and compared clinicians' ratings of SCF case formulations from a constructed assessment instrument (SCF Interview [SCFI]) and the CFI. Socio-cultural formulations from SCFI interviews were rated higher for details of societal structural impact, and overall interrater agreement was better. CFI interviews were rated higher for clinical rapport. Revision of the CFI should enhance consideration of structural issues and incorporate them in SCFs that better integrate assessment process and case formulation content. The need to acknowledge structural sources of mental health problems is clear, and our study indicates how a sociocultural framework may be used for that.

Quest for Biomarkers of Positive Health: A Review.

The positive health of a person can be defined as the ability to live long in good health, possibly with no activity limitation. No method is yet available for its objective assessment in individuals, and we propose a framework in this communication that can operationalize this concept. Instead of distal factors, such as diet and lifestyle because these are subjective and difficult to measure, we concentrate on the objectively measurable biomarkers such as immunity level, endorphins, and handgrip strength. The focus is on the major parameters that may protect from diseases and infirmity and can be assessed by noninvasive methods. A combination of such parameters may signify positive health. This may be a novel way to measure positive health at the individual level. In this communication, we briefly review the literature and identify a few major biomarkers that provide a protective shield and could determine the status of positive health at the individual level. This exercise demonstrates that the assessment of the positive health of a person is feasible. A scale based on these and other relevant parameters can be developed later that could quantitatively measure the exact level of positive health. As the exact combination of the parameters that protects from ailments is not fully known yet, a framework such as this may help in identifying the data gaps that require attention in this context. The proposed framework may initiate a discussion on indicators of positive health and characterize the parameters for intervention that could increase a healthy life.

Co-administration of AYUSH 64 as an adjunct to standard of care in mild and moderate COVID-19: A randomized, controlled, multicentric clinical trial.

OBJECTIVE: Evaluate the efficacy of AYUSH 64, a standard polyherbal Ayurvedic drug in COVID-19. METHODS: During the first pandemic wave, 140 consenting and eligible hospitalized adult participants with mild-moderate symptomatic disease (specific standard RT-PCR assay positive) were selected as per a convenience sample, and randomized (1:1 ratio) to an open-label (assessor blind) two-arm multicentric drug trial; standard of care (SOC as per Indian guidelines) versus AYUSH 64 combined with SOC (AYUSH plus). Participants were assessed daily and discharged once clinical recovery (CR, primary efficacy) was achieved which was based on a predetermined set of criteria (resolution of symptoms, normal peripheral oximetry, and negative specific RT-PCR assay). Each participant was followed using an indigenous software program(mobile phone) and completed a 12-week study period. The dose of AYUSH 64 was 2 tablets oral, 500 mg each, bid for 12 weeks (AYUSH plus only). Significant P was <0.05 (two-sided). On randomization, the groups were found well matched. RESULTS: The mean interval time from randomization to CR was significantly superior in the AYUSH plus group [mean 6.45 days versus 8.26 days, 95% Confidence Interval of the difference -3.02 to -0.59 (P = 0.003, Student's 't test] as per-protocol analysis (134 participants); significant (P = 0.002) on an intention to treat analysis. 70% of the participants in AYUSH plus recovered during the first week (P = 0.046, Chi-square) and showed a significantly better change in physical health, fatigue, and quality of life measures. 48 adverse events, mostly mild and gut related, were reported by each group. There were 20 patient withdrawals (8 in AYUSH plus) but none due to an AE. There were no deaths. Daily assessment (hospitalization) and supervised drug intake ensured robust efficacy data. The open-label design was a concern (study outcome). CONCLUSIONS: AYUSH 64 in combination with SOC hastened recovery, reduced hospitalization, and improved health in COVID-19. It was considered safe and well-tolerated. Further clinical validation (Phase III) is required. TRIAL REGISTRATION: CTRI/2020/06/025557.

Corrigendum: Randomized, Double Blind, Placebo Controlled, Clinical Trial to Study Ashwagandha Administration in Participants Vaccinated Against COVID-19 on Safety, Immunogenicity, and Protection With COVID-19 Vaccine-A Study Protocol.

[This corrects the article DOI: 10.3389/fmed.2022.761655.].

Randomized, Double Blind, Placebo Controlled, Clinical Trial to Study Ashwagandha Administration in Participants Vaccinated Against COVID-19 on Safety, Immunogenicity, and Protection With COVID-19 Vaccine-A Study Protocol.

INTRODUCTION: Vaccines have emerged as the most effective tool in the fight against COVID-19. Governments all over the world have rolled out the COVID-19 vaccine program for their populations. Oxford-AstraZeneca COVID-19 vaccine (COVISHIELD™) is widely used in India. A large number of Indian people have been consuming various traditional medicines in the hope of better protection against COVID-19 infection. Several studies have reported immunological benefits of Withania somnifera (Ashwagandha) and its potential as a vaccine adjuvant. We propose to study the safety, immunogenicity and clinical protection offered by a 6-month regimen of Ashwagandha in participants who volunteer to be vaccinated against COVID-19 (COVISHIELDTM) in the ongoing national program of vaccination. METHODS AND ANALYSIS: We designed a prospective, randomized, double-blind, parallel-group, placebo-controlled, two-arm, exploratory study on healthy volunteers receiving the COVISHIELDTM vaccine. The administration of Ashwagandha will begin within 7 days of the first or second dose of COVISHIELDTM. Primary outcome measure is immunogenicity as measured by SARS-CoV-2 spike (S1) and RBD-specific IgG antibody titres. Secondary outcome measures are safety, protective immune response and quality of life measures. All adverse events will be monitored at each time throughout the study. Participants will be tracked on a daily basis with a user-friendly mobile phone application. Following power calculation 600 participants will be recruited per arm to demonstrate superiority by a margin of 7% with 80% power. Study duration is 28 weeks with interim analysis at the end of 12 weeks. ETHICS AND DISSEMINATION: Ethics approval was obtained through the Central and Institutional Ethics Committees. Participant recruitment commenced in December 2021. Results will be presented in conferences and published in preprints followed by peer-reviewed medical journals. CLINICAL TRIAL REGISTRATION: [www.ClinicalTrials.gov], identifier [CTRI/2021/06/034496].

Feasibility, acceptability and clinical utility of the Cultural Formulation Interview: mixed-methods results from the DSM-5 international field trial.

BackgroundThere is a need for clinical tools to identify cultural issues in diagnostic assessment.AimsTo assess the feasibility, acceptability and clinical utility of the DSM-5 Cultural Formulation Interview (CFI) in routine clinical practice.MethodMixed-methods evaluation of field trial data from six countries. The CFI was administered to diagnostically diverse psychiatric out-patients during a diagnostic interview. In post-evaluation sessions, patients and clinicians completed debriefing qualitative interviews and Likert-scale questionnaires. The duration of CFI administration and the full diagnostic session were monitored.ResultsMixed-methods data from 318 patients and 75 clinicians found the CFI feasible, acceptable and useful. Clinician feasibility ratings were significantly lower than patient ratings and other clinician-assessed outcomes. After administering one CFI, however, clinician feasibility ratings improved significantly and subsequent interviews required less time.ConclusionsThe CFI was included in DSM-5 as a feasible, acceptable and useful cultural assessment tool.

Epidemiological evaluation quality of life in patients suffering from early rheumatoid arthritis: a pragmatic, prospective, randomized, blind allocation controlled of a modular program group intervention.

OBJECTIVES: Epidemiology has taken on new roles in the management of health care services. In this study, we developed a non-pharmacological self-management modular program group intervention and evaluated its efficacy as an adjunct therapy in patients suffering from early rheumatoid arthritis (RA). METHODS: Patients were randomized to either participate in a non-equivalent intervention group along with the standard of care or only receive standard-of-care treatment at a community rheumatology center. The outcomes measured were a pain visual analog scale (VAS), patient general health (GH) on a VAS, and the Short Form 36 Health Survey version 2 scale measuring quality of life. These parameters were evaluated in the first week to obtain baseline values, and at 20, 32, 48, and 60 weeks to evaluate the efficacy of the intervention group. RESULTS: The patients were randomized, with 100 patients in the intervention group and 106 in the control group. The intervention and control groups were similar with regard to the percentage of women (86% vs. 89.6%), tobacco usage (25% vs. 19.8%), mean age (42.6±13.2 years vs. 46.6±10.9 years), and disease duration (15.3±6.7 months vs. 14.5±6.6 months). The mean outcomes were significantly different between the two groups, and post-hoc pairwise analysis demonstrated significant deterioration in the control group in contrast to improvement in the intervention group at the second, third, fourth, and fifth evaluations. Improvements were often seen as early as the 12-week and 24-week follow-up visits. CONCLUSIONS: Epidemiology contributes to the evaluation of how well specific therapies or other health interventions prevent or control health problems. The modular program group intervention implemented in this study appears to be a suitable and feasible method to facilitate much more comprehensive management of early RA in socioeconomically challenged communities.

Clinical value of the cultural formulation interview in Pune, India.

CONTEXT: Development of the cultural formulation interview (CFI) in DSM-5 required validation for cross-cultural and global use. AIMS: To assess the overall value (OV) of CFI in the domains of feasibility, acceptability, and utility from the vantage points of clinician-interviewers, patients and accompanying relatives. SETTINGS AND DESIGN: We conducted cross-sectional semi-structured debriefing interviews in a psychiatric outpatient clinic of a general hospital. MATERIALS AND METHODS: We debriefed 36 patients, 12 relatives and eight interviewing clinicians following the audio-recorded CFI. We transformed their Likert scale responses into ordinal values - positive for agreement and negative for disagreement (range +2 to -2). STATISTICAL ANALYSIS: We compared mean ratings of patients, relatives and clinician-interviewers using nonparametric tests. Clinician-wise grouping of patients enabled assessment of clinician effects, inasmuch as patients were randomly interviewed by eight clinicians. We assessed the influence of the presence of relatives, clinical diagnosis and interview characteristics by comparing means. Patient and clinician background characteristics were also compared. RESULTS: Patients, relatives and clinicians rated the CFI positively with few differences among them. Patients with serious mental disorders gave lower ratings. Rating of OV was lower for patients and clinicians when relatives were present. Clinician effects were minimal. Clinicians experienced with culturally diverse patients rated the CFI more positively. Narratives clarified the rationale for ratings. CONCLUSIONS: Though developed for the American DSM-5, the CFI was valued by clinicians, patients and relatives in out-patient psychiatric assessment in urban Pune, India. Though relatives may add information and other value, their presence in the interview may impose additional demands on clinicians. Our findings contribute to cross-cultural evaluation of the CFI.

Stresses and Disability in Depression across Gender.

Depression, though generally episodic, results in lasting disability, distress, and burden. Rising prevalence of depression and suicide in the context of epidemiological transition demands more attention to social dimensions like gender related stresses, dysfunction, and their role in outcome of depression. Cross-sectional and follow-up assessment of men and women with depression at a psychiatric tertiary centre was undertaken to compare their illness characteristics including suicidal ideation, stresses, and functioning on GAF, SOFAS, and GARF scales (N = 107). We reassessed the patients on HDRS-17 after 6 weeks of treatment. Paired t-test and chi-square test of significance were used to compare the two groups, both before and after treatment. Interpersonal and marital stresses were reported more commonly by women (P < 0.001) and financial stresses by men (P < 0.001) though relational functioning was equally impaired in both. Women had suffered stresses for significantly longer duration (P = 0.0038). Men had more impairment in social and occupational functioning compared to females (P = 0.0062). History of suicide attempts was significantly associated with more severe depression and lower levels of functioning in case of females with untreated depression. Significant cross-gender differences in stresses, their duration, and types of dysfunction mandate focusing on these aspects over and above the criterion-based diagnosis.

Interpreting "statistical hypothesis testing" results in clinical research.

Difference between "Clinical Significance and Statistical Significance" should be kept in mind while interpreting "statistical hypothesis testing" results in clinical research. This fact is already known to many but again pointed out here as philosophy of "statistical hypothesis testing" is sometimes unnecessarily criticized mainly due to failure in considering such distinction. Randomized controlled trials are also wrongly criticized similarly. Some scientific method may not be applicable in some peculiar/particular situation does not mean that the method is useless. Also remember that "statistical hypothesis testing" is not for decision making and the field of "decision analysis" is very much an integral part of science of statistics. It is not correct to say that "confidence intervals have nothing to do with confidence" unless one understands meaning of the word "confidence" as used in context of confidence interval. Interpretation of the results of every study should always consider all possible alternative explanations like chance, bias, and confounding. Statistical tests in inferential statistics are, in general, designed to answer the question "How likely is the difference found in random sample(s) is due to chance" and therefore limitation of relying only on statistical significance in making clinical decisions should be avoided.

Evaluating higher doses of Shunthi - Guduchi formulations for safety in treatment of osteoarthritis knees: A Government of India NMITLI arthritis project.

BACKGROUND: Results of an exploratory trial suggested activity trends of Zingiber officinale-Tinopsora cordifolia (platform combination)-based formulations in the treatment of Osteoarthritis (OA) Knees. These formulations were "platform combination+Withania somnifera+Tribulus terrestris" (formulation B) and "platform combination+Emblica officinale" (formulation C). This paper reports safety of these formulations when used in higher doses (1.5-2 times) along with Sallaki Guggul and Bhallataka Parpati (a Semecarpus anacardium preparation). MATERIALS AND METHODS: Ninety-two patients with symptomatic OA knees were enrolled in a 6 weeks investigator blind, randomized parallel efficacy 4-arm multicenter drug trial. The 4 arms were (I) formulation B, 2 t.i.d.; (II) formulation B, 2 q.i.d.; (III) platform combination+Sallaki Guggul; (IV) Bhallataka Parpati+formulation C. A detailed enquiry was carried out for adverse events (AE) and drug toxicity as per a priori check list and volunteered information. Laboratory evaluation included detailed hematology and metabolic parameters. Patients were examined at baseline, first and fourth weeks, and on completion. Standard statistical program (SPSS version 12.5) was used for analysis. RESULTS: None of the patients reported serious AE or withdrew due to any drug-related toxicity. Mild gut-related (mostly epigastric burning) AE was reported. A mild increase in liver enzymes [serum glutamic pyruvate transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT)] without any other hepatic abnormality was reported in 2 patients (group IV). Other laboratory parameters remained normal. The mean improvement in active pain visual analog scale (1.4, CI 0.5-2.22), WOMAC (functional activity questionnaire) pain score (1.37, CI 0.22-2.5), and urinary C-TAX (cartilage collagen breakdown product) assay was maximum (NS) in group IV. Lower dose group I showed numerically superior improvement compared with higher dose group II. CONCLUSION: The results suggested that despite higher doses, standardized Ayurvedic formulations demonstrated a good safety profile. An improved efficacy and likely chondroprotective effect was shown by group IV intervention. A confirmatory drug trial with adequate power and sample size was planned based on the learning from this trial.

Comparable efficacy of standardized Ayurveda formulation and hydroxychloroquine sulfate (HCQS) in the treatment of rheumatoid arthritis (RA): a randomized investigator-blind controlled study.

Hydroxychloroquine sulfate (HCQS) is a popular disease-modifying antirheumatic drug (DMARD) despite modest efficacy and toxicity. Ayurveda (ancient India medicinal system) physicians treat rheumatoid arthritis (RA) with allegedly safer herbal formulations. We report a head-to-head comparison in an exploratory drug trial. The objective is to compare standardized Ayurvedic formulations and HCQS in the treatment of RA. One hundred twenty-one patients with active moderately severe RA (ACR 1988 classified) were randomized into a 24-week investigator-blind, parallel efficacy, three-arm (two Ayurvedic and HCQS) multicenter drug trial study; polyherb (Tinospora cordifolia and Zingiber officinale based) and monoherb (Semecarpus anacardium). Study measures included joint counts (pain/tenderness and swelling), pain visual analogue scale, global disease assessments, and health assessment questionnaire. Oral meloxicam (fixed-dosage schedule) was prescribed to all patients during the initial 16 weeks. Patients on prednisolone could continue a fixed stable dose (<7.5 mg daily). Rescue oral use of paracetamol was permitted and monitored. All groups matched well at baseline. An intent-to-treat analysis (ANOVA, significance P < 0.05) did not show significant differences by treatment groups. In the polyherb, monoherb, and HCQS arms, 44%, 36%, and 51%, respectively, showed ACR 20 index improvement. Several efficacy measures improved significantly in the HCQS and polyherb groups with no difference between the groups (corrected P). However, the latter was individually superior to monoherb. Only mild adverse events (gut and skin, and none withdrew) were reported with no differences between the groups. Forty-two patients dropped out. This preliminary drug trial controlled for HCQS demonstrated a standardized Ayurvedic polyherb drug to be effective and safe in controlling active RA. A better-designed study with a longer evaluation period is recommended.

Cultural epidemiology of neurasthenia spectrum disorders in four general hospital outpatient clinics of urban Pune, India.

Disorders emphasizing symptoms of fatigue and/or weakness, collectively termed Neurasthenia Spectrum Disorders (NSDs), typically emphasize a biological basis in the West and social origins in East Asia. In India, explanatory concepts are diverse. To clarify, 352 outpatients in Psychiatry, Medicine, Dermatology, and Ayurved clinics of an urban hospital were interviewed with a version of the Explanatory Model Interview Catalogue. Comparisons of categories and narratives of illness experience and meaning across clinics indicated both shared and distinctive features. Explanatory models of NSDs highlighted social distress, ''tensions,'' and both general and clinic-specific physical, psychological, and cultural ideas. Findings indicate the importance of social contexts and cultural meaning in explanatory models of neurasthenia, as well as the potential clinical relevance of the construct of Neurasthenia Spectrum Disorder.

A Randomized Controlled Exploratory Evaluation of Standardized Ayurvedic Formulations in Symptomatic Osteoarthritis Knees: A Government of India NMITLI Project.

The multidisciplinary "New Millennium Indian Technology Leadership Initiative" Arthritis Project was undertaken to validate Ayurvedic medicines. Herbal formulations in popular use were selected by expert consensus and standardized using modern tools. Our clinical strategy evolved from simple exploratory evaluations to better powered statistically designed drug trials. The results of the first drug trial are presented here. Five oral formulations (coded A, B, C, D and E), with a common base of Zingiber officinale and Tinospora cordifolia with a maximum of four plant extracts, were evaluated; with placebo and glucosamine as controls. 245 patients suffering from symptomatic OA knees were randomized into seven arms (35 patients per arm) of a double blind, parallel efficacy, multicentric trial of sixteen weeks duration. The groups matched well at baseline. There were no differences for patient withdrawals (17.5%) or adverse events (AE) of mild nature. Intention-to-treat efficacy analysis, demonstrated no significant differences (P < .05) for pain (weight bearing) and WOMAC questionnaire (knee function); placebo response was high. Based on better pain relief, significant (P < .05) least analgesic consumption and improved knee status, "C" formulation was selected for further development. Controlled exploratory drug trials with multiple treatment arms may be used to economically evaluate several candidate standardized formulations.

Efficacy and safety of Ayurvedic medicines: Recommending equivalence trial design and proposing safety index.

Ayurvedic drugs have begun to be evaluated in controlled clinical trials. The trials, often placebo controlled, are usually designed to demonstrate superiority. Though the results have been usually reported as encouraging, statistical significance has been elusive. In this melee to show efficacy, several positive results related to safety and other purported advantages with Ayurvedic drugs, including improved quality of life, easy drug availability and less cost, get drowned. Though safety is the prime concern, efficacy ultimately matters in trials. Excellent safety profile offset modest efficacy, especially for long-term management of chronic difficult to treat disorders. There is a trade-off between efficacy and safety but we have no means to put them together in a mathematical evaluation to judge the overall performance of a drug. However, we need more suitable modern science methods/techniques to unravel the true therapeutic role of Ayurvedic drugs. We propose "equivalence trials" using modern medicine benchmark as a comparator and a "safety/tolerability index" on this perspective. We believe that several Ayurvedic drugs are capable of demonstrating equal efficacy but superior safety. Our concept may also be applicable for pragmatic trials that are more suitable for Ayurvedic therapy.

Diagnostic concordance of neurasthenia spectrum disorders in Pune, India.

BACKGROUND: Clinically significant fatigue or weakness is a common but understudied clinical problem in India. The applicability and relevance of Western clinical criteria in this setting are not studied. Alternative criteria sets used in different clinical contexts suggest a range of conditions constituting neurasthenia spectrum disorders (NSDs). We therefore aimed to determine frequency of patients with these complaints in four specialty outpatient clinics of an urban general hospital. We compared the concordance of four diagnostic criteria sets of fatigue disorders among the same patients. METHODS: Patients from the clinics of Psychiatry, Medicine, Dermatology, and Ayurved were screened for clinically significant fatigue or weakness and assessed for CFS, ICD-10 neurasthenia, DSM-IV draft criteria for neurasthenia, and CCMD-2 neurasthenia. RESULTS: For 352 patients, sensitivity of CDC criteria for CFS (13.4%) was poorest. CFS was most frequent in the Medicine clinic. CCMD-2 criteria were the most frequently met (77.6%) with no significant difference across clinics. Two-way concordance of neurasthenia categories was no better than fair (< or =0.4) and few patients (8.0%) met criteria for all four categories. DISCUSSION: Four NSD criteria sets identified different clinical subgroups. CFS, considering fatigue and ignoring weakness, was least relevant for identifying NSD patients in these clinics. Poor concordance among the four diagnostic systems studied indicates the need for reviewing the nosology of these disorders. Focus on clinical significance alone is likely to avoid the discordant confusion arising from cross-cultural differences.