Effectiveness of pediatric drug-induced sleep endoscopy for REM-predominant obstructive sleep apnea.

STUDY OBJECTIVES: Because dexmedetomidine (DEX)-induced sedation mimics non-rapid eye movement (NREM) sleep, its utility in sedating children with REM-predominant disease is unclear. We sought to determine the effectiveness of pediatric drug-induced sleep endoscopy (DISE) using DEX and ketamine for children with REM-predominant OSA, specifically whether or not at least one site of obstruction could be identified. METHODS: A retrospective case series of children without tonsillar hypertrophy undergoing DISE at a tertiary pediatric hospital from 10/2013 through 9/2015 who underwent subsequent surgery to address OSA with polysomnography (PSG) before and after. RESULTS: We included 56 children, mean age 5.6±5.4 years, age range 0.1-17.4 years, mean BMI 20.3±7.4 kg/m2 (76±29 percentile). At least one site of obstruction was identified in all patients, regardless of REM- or NREM-predominance. The mean obstructive apnea-hypopnea index (oAHI) improved (12.6 ± 10.7 to 9.0 ± 14.0 events/h) in children with REM-predominant (P = 0.013) and NREM-predominant disease (21.3 ± 18.9 to 10.3 ± 16.2 events/h) (P = 0.008). The proportion of children with a postoperative oAHI < 5 was 53% and 55% for REM- and NREMpredominant OSA, respectively. Unlike children with NREM-predominant disease, children with REM-predominant disease had significant improvement in the mean saturation nadir (P < 0.001), total sleep time (P = 0.006), and sleep efficiency (P = 0.015). CONCLUSIONS: For children with OSA without tonsillar hypertrophy, DISE using DEX/ketamine was useful to predict at least one site of obstruction, even for those with REM-predominant OSA. DISE-directed outcomes resulted in significant improvements in mean oAHI, total sleep time, sleep efficiency, saturation nadir, and the proportion with oAHI < 5, after surgery for some children with REM-predominant disease.

A case of invasive cytomegalovirus duodenitis in an immunosuppressed patient 15 months after renal transplantation.

Cytomegalovirus (CMV) remains one of the most important infections in kidney transplantation. Only a handful of images have been reported in the literature thus far. We present classic pathologic and gross images of CMV duodenitis in an immunosuppressed patient more than one year post-renal transplantation.

Disclosure of Leprosy by Health Care Providers in South-India: Patients' Perception and Relevance to Leprosy Control, Tamil Nadu.

Stigma, isoIation and discrimination are typically associated with diagnosis of leprosy and its disclosure. Health care providers (HCPs) find it challenging to disclose the diagnosis of leprosy to patients and their family members. A qualitative study was done in a rural community near Chennai in Tamil Nadu, from August 2011 to March 2012, covering 155 out of 648 (23.9%) purposively selected leprosy patients from 53 out of 148 panchayats, representing 264 villages in the study area; Out of these 155 patients, 59% were males; 30% were illiterates; 70% were married; 56% were living in nuclear families; half the leprosy patients were either agricultural labourers or skilled workers (50%).Thirty two percent were multibacillary (MB) cases and 68% were pauci bacillary (PB) cases; 77% were old patients and 23% were new patients; 22% had leprosy deformity 12% had disfiguration; 23% had anaesthesia and 3% were with lagophthalmous. Of the 155 patients, 31 (20%) reported that they were not informed about diagnosis of their disease by the concerned HCPs. They were informed to be having a skin disease or a skin patch. Of these 31 patients, 22 (71%) were women; all except one with PB leprosy. Seven patients (23%) had not yet started on treatment 3 patients (10%) were given treatment when they were young and neither, them nor their parents were informed about this disease. Seven (33%) of the married patients who had the disease during their child had or when they were young, were not informed of the diagnosis by the HCPs. Ten respondents (32%) were neither bothered nor concerned about non disclosure of the disease by HCPs. Now, after knowing the diagnosis of the disease 4 females (13%) mentioned that they were having some fear, worry or stigma. As non-disclosure of leprosy by HCPs may adversely affect acceptance and adherence, to treatment by the patients, appropriate communication strategies should be developed and implemented.

Prognostic implications of recipient or donor hepatitis B seropositivity in thoracic transplantation: analysis of 426 hepatitis B surface antigen-positive recipients.

BACKGROUND: Prognostic data on survival of hepatitis B surface antigen-positive (HBsAg+) recipients and of hepatitis B core antibody-positive (HBcAb+) donors are limited in the thoracic transplantation (TT) cohort. Improved understanding of risks could potentially expand the recipient and donor pools. METHODS: Post-hoc analysis of limited-access dataset of the United Network for Organ Sharing database from January 2000-September 2010 was performed. Analyses were performed for all TT, including single and bilateral lung, orthotopic heart, and simultaneous heart-lung transplants. The primary analyzed outcome was overall survival. A Cox proportional multivariate hazards model was used to adjust for significant risk predictors. RESULTS: Of 24,817 patients included, 426 recipients were HBsAg+, of whom 106 (25%) died during a mean follow-up of 3.6 years. On multivariate analysis, recipient HBsAg+ (hazard ratio [HR] = 0.88, 95% confidence interval [CI]: 0.69-1.32; P = 0.80), and donor HBcAb+ (HR = 0.91, 95% CI: 0.68-1.22; P = 0.53) were not associated with increased overall mortality in the entire TT cohort, with similar results for each individual transplant cohort. Unadjusted survival analysis using Kaplan-Meier curves in individual transplant cohorts did not show significant differences between HBsAg+ and HBsAg- recipients. No statistically significant differences were found between causes of mortality in the 2 groups. CONCLUSION: HBsAg+ status of recipients or HBcAb+ status of donors does not significantly affect overall survival of TT recipients. These data add to the scant literature on this subject and could potentially increase the donor and recipient pools.

Liver transplantation of hepatitis B surface antigen positive donors to hepatitis B core antibody recipients: analysis of 27 patients.

AIM: Shortage of donor livers is the major limiting factor for liver transplantation (LT). While livers from patients with past infection of Hepatitis-B (HBcAb+) are commonly used as donors, scant data exists on outcomes following transplantation of HBsAg+ donor livers. The impact of donor HBsAg positivity on recipient survival is currently analyzed. METHODS: Post hoc analysis of all adults undergoing LT from October 1987-September 2010 registered in United Network for Organ Sharing/Organ Procurement and Transplantation Network, a concurrent, limited access database of all American LT recipients. Only recipients who were HBcAb+ were analyzed. LTs with missing donor or recipient serologic parameters for Hepatitis-B were excluded. Significant predictors of survival were determined by univariate analysis. Cox proportional hazards model was used to determine independent risk predictors in the multivariate analysis. RESULTS: The population consisted of 13,329 LT recipients. The mean age of donors and recipients were 40±16 years and 52±9 years respectively. The mean follow-up was 3.7 years. Study population included 27 recipients transplanted with HBsAg+ grafts, of whom 7 (28%) died. Outcomes were adjusted for donor age, recipient age, donor gender, recipient gender, type of LT, MELD score, HCV status, previous LT, and cold ischemic time. On multivariate analysis, LT recipient outcomes were not significantly different for HBsAg+ donors versus donors without prior hepatitis B infection (HR: 1.14, 95% CI: 0.93-1.39, P=0.17). Kaplan-Meier curves revealed no significant survival difference between the two groups. CONCLUSION: These results suggest that donor HBsAg positivity did not affect overall survival of LT recipients. These findings could potentially expand the pool of liver donors.

Risk factors associated with death among influenza A (H1N1) patients, Tamil Nadu, India, 2010.

BACKGROUND: Limited information is available about the risk factors associated with death among patients of influenza A (H1N1) in India. AIMS: To describe the epidemiology of laboratory-confirmed influenza A (H1N1) patients and identify risk factors associated with death. SETTINGS AND DESIGN: We reviewed the surveillance data of laboratory-confirmed patients in Tamil Nadu, India, for the year 2010. We conducted a case-control study by comparing 70 laboratory-confirmed A (H1N1) patients who died (cases) with 210 A (H1N1) patients who recovered (controls) to identify the risk factors for deaths. MATERIALS AND METHODS: We interviewed the controls and immediate care-takers of the influenza patients who died to collect information about socio-demographic details and co-morbid conditions. We used an abstraction form to collect the information about the clinical details from the case records of the hospitals where the cases and controls received treatment. STATISTICAL ANALYSIS: We analysed the surveillance data by time, place and person. We conducted univariate and multivariate logistic regression analysis for identifying factors associated death. RESULTS: During 2010, 1302 laboratory-confirmed cases were reported to the Tamil Nadu surveillance unit. Of these, 72 patients died (case fatality=5.5%). About 2/3 of the cases and 40% of the deaths were from three districts. On multivariate analysis, past history of diabetes, treatment in private hospitals, treatment with corticosteroids during illness, visit to >1 healthcare facility before laboratory confirmation and delay of >48 h in starting antivirals were found to be independently associated with the deaths. CONCLUSIONS: Influenza patients with previous history of diabetes, who had treatment with corticosteroids during illness, and started with antivirals after 48 h of onset of symptoms, were at higher risk of adverse outcome. In order to reduce the risk of death during future waves of influenza in Tamil Nadu, the physicians need to be sensitised regarding (1) higher risk of adverse outcomes among A (H1N1) patients with diabetes; (2) adherence to the national protocol for categorisation of cases; (3) prompt initiation of antivirals for severe cases; and (4) avoidance of systemic corticosteroids during management.

Somatic mutation of the MEN1 gene in parathyroid tumours.

Primary hyperparathyroidism is a common disorder with an annual incidence of approximately 0.5 in 1,000 (ref. 1). In more than 95% of cases, the disease is caused by sporadic parathyroid adenoma or sporadic hyperplasia. Some cases are caused by inherited syndromes, such as multiple endocrine neoplasia type 1 (MEN1; ref. 2). In most cases, the molecular basis of parathyroid neoplasia is unknown. Parathyroid adenomas are usually monoclonal, suggesting that one important step in tumour development is a mutation in a progenitor cell. Approximately 30% of sporadic parathyroid tumours show loss of heterozygosity (LOH) for polymorphic markers on 11q13, the site of the MEN1 tumour suppressor gene. This raises the question of whether such sporadic parathyroid tumours are caused by sequential inactivation of both alleles of the MEN1 gene. We recently cloned the MEN1 gene and identified MEN1 germline mutations in fourteen of fifteen kindreds with familial MEN1 (ref. 10). We have studied parathyroid tumours not associated with MEN1 to determine whether somatic mutations in the MEN1 gene are present. Among 33 tumours we found somatic MEN1 gene mutation in 7, while the corresponding MEN1 germline sequence was normal in each patient. All tumours with MEN1 gene mutation showed LOH on 11q13, making the tumour cells hemi- or homozygous for the mutant allele. Thus, somatic MEN1 gene mutation for the mutant allele. Thus, somatic MEN1 gene mutation contributes to tumorigenesis in a substantial number of parathyroid tumours not associated with the MEN1 syndrome.

The association between body mass index, abdominal fatness, and weight change and the risk of adult asthma: a systematic review and meta-analysis of cohort studies.

Obesity has been associated with increased risk of adult asthma, however, not all studies have found a clear association between overweight and the incidence of asthma, and data on other adiposity measures have been limited. Hence, we aimed to summarize evidence on association between adiposity and adult asthma. Relevant studies were retrieved through searches conducted in PubMed, and EMBASE up to March 2021. A total of sixteen studies (63,952 cases and 1,161,169 participants) were included in the quantitative synthesis. The summary RR was 1.32 (95% CI 1.21-1.44, I2 = 94.6%, pheterogeneity < 0.0001, n = 13) per 5 kg/m2 increase in BMI, 1.26 (95% CI 1.09-1.46, I2 = 88.6%, pheterogeneity < 0.0001, n = 5) per 10 cm increase in waist circumference and 1.33 (95% CI 1.22-1.44, I2 = 62.3%, pheterogeneity= 0.05, n = 4) per 10 kg increase in weight gain. Although the test for nonlinearity was significant for BMI (pnonlinearity < 0.00001), weight change (pnonlinearity = 0.002), and waist circumference (pnonlinearity = 0.02), there was a clear dose-response relationship between higher levels of adiposity and asthma risk. The magnitude of the associations and the consistency of the results across studies and adiposity measures provide strong evidence that overweight and obesity, waist circumference and weight gain increases asthma risk. These findings support policies to curb the global epidemic of overweight and obesity.

Bacteriological results and leprosy reactions among MB leprosy patients treated with uniform multidrug therapy in China.

OBJECTIVES: To investigate the changes of bacteriological index and leprosy reactions among Multi-bacillary (MB) patients treated with uniform multi-drug therapy (UMDT). METHODS: Newly diagnosed leprosy patients were recruited after taking informed consent in three districts in Guizhou Province and one district in Yunnan Province China during November 2003 to June 2005 and were treated with Uniform Multidrug Therapy. All patients were followed up once a year for 3 years after completion of treatment. All data on bacteriological index (BI) and the frequencies of leprosy reaction were collected and analysed. RESULTS: A total of 166 patients were recruited for UMDT trial. Among them 114 patients had positive BI smear, and 83 patients had been followed up for 42 months. The mean BI of 83 patients decreased from 2.84 before treatment to 0.33 at the end of 42 months follow-up. At the end of this period, 61 patients (73.5%) had become BI negative. There were 13 (14.6%) patients who had a Type I reaction during 24 months of follow-up. One patient in the study group relapsed 13 months after stopping treatment of the UMDT. CONCLUSION: There was a significant decrease in the mean BI and 73.5% of patients treated with UMDT became BI negative during 3 years' follow-up. The frequency of Type I reaction seemed a little higher among patients treated with UMDT, but the numbers of patients enrolled were too few to determine statistical significance. Future studies on U-MDT should also study Type I reactions in these patients.

Awareness, social acceptance and community views on leprosy and its relevance for leprosy control, Tamil Nadu.

As the leprosy burden has declined considerably, we need to understand the current social status of the disease and patients. A qualitative study was conducted in a rural community near Chennai in Tamil Nadu, between March and October 2011. In-depth interviews with 72 leprosy patients from 25 villages and 3 focus group discussions (FGDs) with 26 women from 3 villages were conducted using a guide. The qualitative data were grouped into different domains and analysed. Most of them did not have basic knowledge on leprosy; instead there were misconceptions on cause and spread of leprosy. Nearly one third of the patients had not disclosed about the disease to their spouse, family members, relatives or friends for fear of social rejection, discrimination and ill treatment. In all, more than half of them had self-stigma and, most of them who had deformity faced actual stigma by way of disowning, isolation and social rejection. Many patients, particularly PB cases had the behavior of "denial". FGD women reported of self and actual stigma, particularly towards deformity and disfigurement, for fear of getting infected. Stigma among patients with deformity, and denial of the disease among PB cases, were highlighted. Importance of awareness programmes to remove misconceptions related to cause and spread of the disease was stressed. Need for person-centered social treatment was suggested for increased case detection.

Stakeholders perspectives on perceived needs and priorities for leprosy control and care, Tamil Nadu, India.

Although leprosy has been declared as eliminated in India, treated patients with persisting disabilities still require care. With the shift from vertical to integrated services, questions remain about case detection and maintaining the quality of patient care. We conducted a qualitative study to clarify the perceived status of elimination, patient care and other aspects of leprosy control from the perspective of various stakeholders. We interviewed leprosy programme managers, Non-governmental organization directors, healthcare providers, patients and community leaders from Kanchipuram district, Tamil Nadu. Consensus endorsed the current approach to integration of leprosy in primary healthcare, but healthcare personnel acknowledged problems from shortage of medicines and failure to fill key positions. Patients were concerned about limited clinic hours, long waits and delayed treatment. Disabled patients indicated how they were troubled by stigmatization of their condition. Programme managers mentioned limited support for needed research and some emphasized the potential threat of emerging drug resistance. Although consensus supports an integrated approach for leprosy services in primary care, the relative priority of different aspects of leprosy control vary among stakeholders. Perspectivist approaches to methodologically sound operational research could guide planning for effective case detection and patient care during the post-elimination era.

Efficacy of single-dose chemotherapy (rifampicin, ofloxacin and minocycline-ROM) in PB leprosy patients with 2 to 5 skin lesions, India: randomised double-blind trial.

UNLABELLED: We conducted randomized double-blind trial for single-dose of Rifampicin, Ofloxacin and Minocycline (ROM) compared to WHO-PB-MDT among paucibacillary (PB) leprosy patients with 2-5 skin lesions. We enrolled 1526 patients from five centres (ROM=762; WHO-PB-MDT=764) and followed them for 36 months posttreatment during 1998-2003. We generated information on clearance of skin lesions and relapse rates per 100 person-years (PY) for all the five centres. At base-line, the patients in the two arms were comparable. Complete clearance of skin lesions was similar (72% vs. 72.1%; p=0.95) in both the arms. Clinical scores declined steadily and equally. Difference in relapse rates was statistically highly significant (ROM=1.13 and WHO-PB-MDT=0.35 per 100 PY; mid-p exact=0.001016). Twenty eight of 38 of these relapses occurred within 18 months. In all, 10 suspected adverse drug reactions were.observed (ROM=2; WHO-PB-MDT=8). We extended the follow-up to 48 months for 1082 of 1526 patients from two programme-based centres. No further relapses occurred. Decline in clinical score was not dependent on age, gender, number of lesions or affected body parts. Single dose ROM, though less effective than the standard WHO-PB-MDT regimen conceptually offers an alternative treatment regimen for PB leprosy patients with 2-5 lesions only when careful follow-up for relapse is possible. Registered at the Clinical Trials Registry of India; REGISTRATION NUMBER: CTRI/2012/05/002645

Safety and efficacy of a Siddha Medicine fixed regimen for the treatment of asymptomatic and mild COVID-19 patients.

Background: The Coronavirus disease 2019 (COVID-19) pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a massive threat to public health worldwide. Siddha system of medicine is one of the traditional medicines of South India. The recommended formulations in Siddha Sasthric Medicines- Fixed Regimen (SSM-FiRe) are Amukkura tablets, Kaba Sura Kudineer (KSK) for asymptomatic COVID-19 positive (RT-PCR) patients, and Athimathuram tablets, Adathodai Manappagu syrup, Thippili Rasayanam, Brahmananda Bairavam tablet, and Notchi Kudineer for mild symptomatic patients. The core objective of the trial was to document the efficacy of SSM-FiRe in the prevention of asymptomatic and mild COVID-19 disease progression to the next level of severity, reduce the severity of symptoms and revert to RT-PCR Negative. Methods: An exploratory, prospective, open-labeled, single-arm, non-randomized trial was designed as per GCP guidelines to assess the efficacy of SSM-FiRe. Sixty RT-PCR positive participants who were asymptomatic or with mild COVID-19 symptoms were recruited for the study at the Siddha COVID Care Centre, Vyasarpadi, Chennai from June to August 2020. Nasal and oropharyngeal swab tests were performed on the 0, 7th, and 14th days. All participants were treated with SSM - FiRe regimen. All the participants were also assessed based on Siddha Yakkkaiyin Ilakkanam, which included Clinical symptoms and vitals. Laboratory investigations such as Haemogram, Liver Function Test, Renal Function Test, HbA1C, Electrolytes, Inflammatory markers, Cardiac profile, Immunoglobulins, and anti-SARS-CoV-2 antibody tests were performed. Results: 83% of COVID-19 patients turned RT-PCR negative on the 7th day and in most of the cases, symptoms were reduced within the first 5 days of admission. The RT-PCR cycle threshold (ct) value increased significantly (<0.001) after treatment and all the participants were RT-PCR negative, except one, who was positive even after 14 days. Anti-SARS-CoV-2 antibodies developed significantly (p-value - 0.006). LFT, RFT, CBC, Total proteins, and electrolytes continued to be in the normal range after treatment, indicating the safety of the intervention. Conclusion: Asymptomatic and mild COVID-19 disease can be well managed by SSM - FiRe treatment, Further studies could be taken up to strengthen the findings.

Programmatic and beneficiary-related factors for low vaccination coverage in Papum Pare district, Arunachal Pradesh, India.

Vaccination coverage in Papum Pare district, Arunachal Pradesh was observed to be low. We evaluated the universal immunization programme (UIP) through survey of health facilities in the district and collected data about inputs and processes for childhood vaccination, cold-chain maintenance, supervision and monitoring. Using cluster sampling methodology, we selected 697 children aged 12-23 months from 41 clusters and interviewed their mothers to collect information about vaccination status, socio-demographic factors, knowledge, attitude and practices. Only 50% health facilities in the district were conducting fixed-day immunizations. Of the children surveyed, 55% were fully vaccinated. Mothers who were informed about next due date by health workers, possessed immunization card, attended antenatal clinics, or who delivered in hospital were likely to complete the vaccination schedule of their children. In order to increase the vaccination coverage, all health facilities in the district need to be made functional for conducting immunization. Educating health workers to remind mothers about due date of vaccination will also help increasing the vaccination coverage.

Evaluation through outbreak simulation exercise points to the need for considerable improvement in the capacity of peripheral health workers for outbreak detection and response, South India, 2018.

BACKGROUND: Outbreaks are emergencies, requiring skilled peripheral health workers in the health system. Given the lack of evaluation of the knowledge and practices of peripheral health workers regarding outbreak investigation and response, we surveyed to estimate the performance level of health workers in outbreak detection and response. METHODS: We developed a simulation exercise based on hepatitis and fever outbreak to ascertain knowledge and skills in outbreak detection and response. Following a pilot test and with inputs from public health experts, we finalized the instrument in the local language. The simulation exercise was self-administered among all health inspectors (HI) (n = 39) from a district in South India responsible for outbreak investigation. We collected sociodemographic factors, training, education level, awareness about the surveillance program, outbreak triggers, and prior experience with an outbreak. We assigned a score of 0.25 for each correct response (range 0 to 10.75). We categorized a score of <75% as poor performance. The academic ethics committee of ICMR-National Institute of Epidemiology approved the protocol. RESULTS: All the HIs were male except one. Median age is 51 years (Range: 37.5-54). The median years of service is 12 (range 5.3 to 23). Twenty-two received training, and fifteen had prior exposure to an outbreak in the previous year. The overall performance of HIs was poor, with the highest mark being below 40%. The median score in the section of history taking was 0.25 [interquartile range (IQR) 0-0.5], 31% (n = 12) scored zero. The median score in the section of data entry, analysis, and outbreak detection was 0.25 (0-0.25), 28% (n = 11) scored zero. The median score in the section of outbreak response was 0.75 (IQR 0.75-1.13), 5% (n = 2) scored zero. CONCLUSION: The HIs performed poorly in outbreak preparedness and response. We recommend improving their performance through field-epidemiology training and regular field or facility-based evaluations.

Kabasura Kudineer (KSK), a poly-herbal Siddha medicine, reduced SARS-CoV-2 viral load in asymptomatic COVID-19 individuals as compared to vitamin C and zinc supplementation: findings from a prospective, exploratory, open-labeled, comparative, randomized controlled trial, Tamil Nadu, India.

INTRODUCTION: Despite several ongoing efforts in biomedicine and traditional medicine, there are no drugs or vaccines for coronavirus disease 2019 (COVID-19) as of May 2020; Kabasura Kudineer (KSK), a polyherbal formulation from India's Siddha system of medicine, has been traditionally used for clinical presentations similar to that of COVID-19. We explored the efficacy of KSK in reducing viral load and preventing the disease progression in asymptomatic, COVID-19 cases. METHODS: A prospective, single-center, open-labeled, randomized, controlled trial was conducted in a COVID Care Centre in Chennai, India. We recruited reverse-transcription polymerase chain reaction (RT-PCR)-confirmed COVID-19 of 18 to 55 years of age, without clinical symptoms and co-morbidities. They were randomized (1:1 ratio) to KSK (60 mL twice daily for 7 days) or standard of care (7 days supplementation of vitamin C 60,000 IU morning daily and zinc 100 mg evening daily) groups. The primary outcomes were reduction in the SARS-CoV-2 load [as measured by cyclic threshold (CT) value of RT-PCR], prevention of progression of asymptomatic to symptomatic state, and changes in the immunity markers including interleukins (IL-6, IL-10, IL-2), interferon gamma (IFNγ), and tumor necrosis factor (TNF α). Siddha clinical assessment and the occurrence of adverse effects were documented as secondary outcomes. Paired t-test was used in statistical analysis. RESULTS: Viral load in terms of the CT value (RdRp: 95% CI = 1.89 to 5.74) declined significantly on the seventh day in the KSK group and that of the control group, more pronounced in the study group. None progressed to the symptomatic state. There was no significant difference in the biochemical parameters. We did not observe any changes in the Siddha-based clinical examination and adverse events in both groups. CONCLUSION: KSK significantly reduced SARS-CoV-2 viral load among asymptomatic COVID-19 cases and did not record any adverse effect, indicating the use of KSK in the strategy against COVID-19. Larger, multi-centric trials can strengthen the current findings. TRIAL REGISTRATION: Clinical Trial Registry of India CTRI2020/05/025215 . Registered on 16 May 2020.

The efficacy of Siddha Medicine, Kabasura Kudineer (KSK) compared to Vitamin C & Zinc (CZ) supplementation in the management of asymptomatic COVID-19 cases: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: The primary objectives of this study are to determine efficacy of Siddha medicine, Kabasura kudineer in reduction of SARS-CoV-2 viral load and reducing the onset of symptoms in asymptomatic COVID-19 when compared to Vitamin C and Zinc (CZ) supplementation. In addition, the trial will examine the changes in the immunological markers of the Siddha medicine against control. The secondary objectives of the trial are to evaluate the safety of the Siddha medicine and to document clinical profile of asymptomatic COVID-19 as per principles of Siddha system of Medicine. TRIAL DESIGN: A single centre, open-label, parallel group (1:1 allocation ratio), exploratory randomized controlled trial. PARTICIPANTS: Cases admitted at non-hospital settings designated as COVID Care Centre and managed by the State Government Stanley Medical College, Chennai, Tamil Nadu, India will be recruited. Eligible participants will be those tested positive for COVID-19 by Reverse Transcriptase Polymerase Chain reaction (RT-PCR) aged 18 to 55 years without any symptoms and co-morbidities like diabetes mellitus, hypertension and bronchial asthma. Those pregnant or lactating, with severe respiratory disease, already participating in COVID trials and with severe illness like malignancy will be excluded. INTERVENTION AND COMPARATOR: Adopting traditional methods, decoction of Kabasura kudineer will be prepared by boiling 5g of KSK powder in 240 ml water and reduced to one-fourth (60ml) and filtered. The KSK group will receive a dose of 60ml decoction, orally in the morning and evening after food for 14 days. The control group will receive Vitamin C (60000 IU) and Zinc tablets (100mg) orally in the morning and evening respectively for 14 days. MAIN OUTCOMES: The primary outcomes are the reduction in the SARS-CoV-2 load [as measured by cyclic threshold (CT) value of RT-PCR] from the baseline to that of seventh day of the treatment, prevention of progression of asymptomatic to symptomatic state (clinical symptoms like fever, cough and breathlessness) and changes in the immunity markers [Interleukins (IL) 6, IL10, IL2, Interferon gamma (IFNγ) and Tumor Necrosis Factor (TNF) alpha]. Clinical assessment of COVID-19 as per standard Siddha system of medicine principles and the occurrence of adverse effects will be documented as secondary outcomes. RANDOMISATION: The assignment to the study or control group will be allocated in equal numbers through randomization using random number generation in Microsoft Excel by a statistician who is not involved in the trial. The allocation scheme will be made by an independent statistician using a sealed envelope. The participants will be allocated immediately after the eligibility assessment and informed consent procedures. BLINDING (MASKING): This study is unblinded. The investigators will be blinded to data analysis, which will be carried out by a statistician who is not involved in the trial. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Sample size could not be calculated, as there is no prior trial on KSK. This trial will be a pilot trial. Hence, we intend to recruit 60 participants in total using a 1:1 allocation ratio, with 30 participants randomised into each arm. TRIAL STATUS: Protocol version 2.0 dated 16th May 2020. Recruitment is completed. The trial started recruitment on the 25th May 2020. We anticipate study including data analysis will finish on November 2020. We also stated that protocol was submitted before the end of data collection TRIAL REGISTRATION: The study protocol was registered with clinical trial registry of India (CTRI) with CTRI/2020/05/025215 on 16 May 2020. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Risk factors for typhoid in Darjeeling, West Bengal, India: evidence for practical action.

OBJECTIVE: To identify risk factors for typhoid and propose prevention measures. METHODS: Case-control study; we compared hospital-based typhoid cases defined as fever>38 degrees C for >or=3 days with four-fold rise in 'O' antibodies on paired sera (Widal) with community, age and neighbourhood matched controls. We obtained information on drinking water, fruits, vegetables, milk products and sanitation; and calculated matched odds ratios (MOR) and attributable fractions in the population (AFP) for the risk factors or failure to use prevention measures. RESULTS: The 123 typhoid cases (median age: 25 years, 47% female) and 123 controls did not differ with respect to baseline characteristics. Cases were less likely to store drinking water in narrow-mouthed containers (MOR: 0.4, 95% CI: 0.2-0.7, AFP 29%), tip containers to draw water (MOR: 0.4, 95% CI: 0.2-0.7, AFP 33%) and have home latrines (MOR: 0.5, 95% CI: 0.3-0.8, AFP 23%). Cases were more likely to consume butter (OR: 2.3, 95% CI: 1.3-4.1, AFP 28%), yoghurt (OR: 2.3, 95% CI: 1.4-3.7, AFP 34%) and raw fruits and vegetables, including onions (MOR: 2.1, 95% CI: 1.2-3.9, AFP 34%), cabbages (OR: 2.8, 95% CI: 1.7-4.8, AFP 44%) and unwashed guavas (OR: 1.9, 95% CI: 1.2-3, AFP 25%). CONCLUSION: Typhoid was associated with unsafe water and sanitation practices as well as with consumption of milk products, fruits and vegetables. We propose to chlorinate drinking water at the point of use, wash/cook raw fruits and vegetables and ensure safer preparation/storage of local milk products.

Positional cloning of the gene for multiple endocrine neoplasia-type 1.

Multiple endocrine neoplasia-type 1 (MEN1) is an autosomal dominant familial cancer syndrome characterized by tumors in parathyroids, enteropancreatic endocrine tissues, and the anterior pituitary. DNA sequencing from a previously identified minimal interval on chromosome 11q13 identified several candidate genes, one of which contained 12 different frameshift, nonsense, missense, and in-frame deletion mutations in 14 probands from 15 families. The MEN1 gene contains 10 exons and encodes a ubiquitously expressed 2.8-kilobase transcript. The predicted 610-amino acid protein product, termed menin, exhibits no apparent similarities to any previously known proteins. The identification of MEN1 will enable improved understanding of the mechanism of endocrine tumorigenesis and should facilitate early diagnosis.

Risk factors associated with leptospirosis during an outbreak in Middle Andaman, India.

BACKGROUND & OBJECTIVE: Leptospirosis outbreaks occur frequently in North and South Andaman Islands but not in Middle Andaman. In 2002, an outbreak appeared in Middle Andaman for the first time. Although a study on risk factors was conducted in North Andaman, it used seropositivity to define leptospirosis. Since seropositivity might not indicate current leptospiral infection and as no study on risk factors was conducted in Middle Andaman, we carried out this study to identify the risk factors during the outbreak. METHODS: A suspected outbreak of leptospirosis occurred in Rangat of Middle Andaman during October - November 2002. Suspected cases were screened for leptospirosis using microscopic agglutination test (MAT). Fifty two patients confirmed to have leptospirosis based on rising titres in MAT on paired sera, and 104 age, sex and neighbourhood seronegative matched controls, were included in the study. A conditional multiple regression by backward elimination process was carried out with acute leptospirosis as the dependent factor and various environmental, occupational and behavioural factors as independent factors. A stratified analysis was also carried out. RESULTS: The presence of cattle in the house, drinking stream water, contact with garbage, walking barefoot and standing in water while working were identified as significant factors associated with leptospirosis. Stratified analysis showed a dose response relationship between number of cattle in the house and the risk of leptospiral infection suugesting that cattle could be a source of infection. INTERPRETATION & CONCLUSION: Identification of the potential risk factors would help understand the transmission dynamics of the disease and formulate public health interventions.