UNDERSTANDING THE ADAPTATION AND SENSITIVITY OF THE MICROBIOME: MICROBIAL RESILIENT AND HUMAN WELL-BEING.

The term microbiome describes the assortment of microbes that dwell in and on a person's body, particularly in the gut, comprising fungi, bacteria, infectious agents and additional microbes. According to research, numerous elements of human well-being, such as digestion, immunological response and psychological well-being, have been linked to the microbiome. Preserving human wellness requires knowledge of the microbiome's stability and how it reacts to perturbations. According to preliminary research, adults' microbial ecosystems are considered stable with no signs of significant disturbances. This stability is not preserved by inertia and the system's interaction with restorative forces keeps the processes stable. Short antibiotic doses can result in quick and substantial microbiome alterations. However, there is confirmation that the taxonomic structure of the microbiome has at least recovered after such disruptions. The effect of antibiotics is individualized and can be altered by earlier exposure to a similar drug, which is a crucial aspect to remember. These results suggest that the individual's microbiome has adaptable qualities. Examining the microbiome's reactions to perturbations might be helpful in the prediction of potential instabilities and illness by revealing important features of function, microbial connections, and important species in the native microbiota. This information can benefit the management of the individual microbial community and the promotion of better health conditions.

2-deoxy-D-glucose as an adjunct to standard of care in the medical management of COVID-19: a proof-of-concept and dose-ranging randomised phase II clinical trial.

BACKGROUND: At present, no single efficacious therapeutic exists for acute COVID-19 management and a multimodal approach may be necessary. 2-deoxy-D-glucose (2-DG) is a metabolic inhibitor that has been shown to limit multiplication of SARS-CoV-2 in-vitro. We evaluated the efficacy and safety of 2-DG as adjunct to standard care in the treatment of moderate to severe COVID-19 patients. METHODS: We conducted a randomized, open-label, phase II, clinical study to evaluate the efficacy, safety, and tolerability of 2-DG administered as adjunct to standard of care (SOC). A total of 110 patients between the ages of 18 and 65 years with moderate to severe COVID-19 were included. Patients were randomized to receive 63, 90, or 126 mg/kg/day 2-DG in addition to SOC or SOC only. Times to maintaining SpO2 ≥ 94% on room air, discharge, clinical recovery, vital signs normalisation, improvement by 1 and 2 points on WHO clinical progression scale, negative conversion on RT-PCR, requirement for intensive care, and mortality were analyzed to assess the efficacy. RESULTS: Patients treated with 90 mg/kg/day 2-DG plus SOC showed better outcomes. Time to maintaining SpO2 ≥ 94% was significantly shorter in the 2-DG 90 mg compared to SOC (median 2.5 days vs. 5 days, Hazard ratio [95% confidence interval] = 2.3 [1.14, 4.64], p = 0.0201). Times to discharge from isolation ward, to clinical recovery, and to vital signs normalization were significantly shorter for the 2-DG 90 mg group. All three doses of 2-DG were well tolerated. Thirty-three (30.3%) patients reported 65 adverse events and were mostly (86%) mild. CONCLUSIONS: 2-DG 90 mg/kg/day as adjunct to SOC showed clinical benefit over SOC alone in the treatment of moderate to severe COVID-19. The promising trends observed in current phase II study is encouraging for confirmatory evaluation of the efficacy and safety of 2-DG in a larger phase III trial. TRIAL REGISTRATION: CTRI, CTRI/2020/06/025664. Registered 5th June 2020, http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=44369&EncHid=&modid=&compid=%27,%2744369det%27 .

Systemic lupus erythematosus presenting with holocord myelitis.

This is a report of a case of a 25-year-old woman, who presented with a rapidly progressive sensory-motor flaccid quadriparesis which had developed over a few days along with bladder and bowel involvement. She had a past history of photosensitive rash and joint pains along with mild-to-moderate grade fever; for which she had never been evaluated. Serological markers for systemic lupus erythematosus (SLE) were strongly positive and helped in establishing the diagnosis of SLE-related holocord myelitis. High-dose intravenous glucocorticoid followed by intravenous pulse cyclophosphamide was used to treat her and there was a significant improvement. In this case report, the diagnosis of SLE was made for the first time in a patient presenting with holocord myelitis.

Photobiomodulation therapy in neuroischaemic diabetic foot ulcers: a novel method of limb salvage.

OBJECTIVE: Low-level laser therapy (also known as photobiomodulation therapy, PBMT) promotes accelerated healing of diabetic foot ulcers (DFUs), thereby preventing the risk of future complications and amputation. The aim of this study was to determine the effect of PBMT, with structured, graded mobilisation and foot care, on DFU healing dynamics. METHOD: Patients diagnosed with type 2 diabetes, diabetic peripheral neuropathy and presenting with a chronic neuroischaemic DFU, were treated with PBMT using scanning and non-contact probe methods. The DFU was clinically observed and the area measured every seven days until complete healing. Neuropathic parameters were also measured. The PBMT was administered until complete closure of the DFU and patients also undertook a programme of graded mobilisation. RESULTS: A total of 17 participants were recruited, with a mean age of 69±8 years, and a mean duration of diabetes of 13±5 years. Mean complete closure time was 26±11days. In addition, a mean reduction of the semi-quantitative vibration pressure threshold from 49±2 volts to 20±4 volts was observed in all participants. CONCLUSION: PBMT can be effectively used as a treatment mode for neuroischaemic DFUs in patients with type 2 diabetes. Graded mobilisation with focused foot care could improve the function of people living with type 2 diabetes with a chronic DFU.

Risk Factors associated with defaulting from visceral leishmaniasis treatment: analysis under routine programme conditions in Bihar, India.

OBJECTIVE: To assess the rate of default from treatment in the visceral leishmaniasis (VL) elimination programme and to identify risk factors and its underlying causes. METHODS: Case-control study conducted between December 2009 and June 2012 in three primary health centres (PHCs) of Muzaffarpur district, India. Patients who defaulted from treatment from the PHCs were considered as 'cases' and those who completed their treatment as 'controls'. Two controls were included in the study for each case. Respondents' opinion and satisfaction with the services provided at the PHCs were also elicited. Logistic regression was performed to assess the contribution of sociodemographic variables on patient status, and a discriminant analysis was used (after decomposing the original data) to identify factors that can predict the patient status as defaulter or not, based on factor scores of the components as predictor variables. RESULTS: During the study period, 16.3% (89/544) of patients defaulted; 87 cases and 188 controls were interviewed through a semistructured questionnaire. Women tended to be more at risk for default (OR, 1.6, 95% CI (0.9 -2.9). Treatment received was miltefosine in 55.6% and sodium stibogluconate (SSG) in 44.4%. Most (86%) defaulters completed their treatment at other healthcare facilities; 70% of them preferred non-governmental institutions. Most cited reasons for default were seeking a second opinion for VL treatment and preferring to be treated in specialised VL centres. Discriminant analysis showed only one significant predictor: dissatisfaction with the medical care received in PHCs. CONCLUSION: Efforts are needed to enhance the quality of VL care at PHC level, which will be beneficial in increasing treatment completion rates.

Blood Pressure Variability in Patients with Diabetes Mellitus with Hypertension: Treatment Recommendations and Role of Amlodipine.

Recently, blood pressure variability (BPV) has gained focus owing to its role in predicting cardiovascular (CV) outcomes. Additionally, alterations in BPV contribute to the progression of end organ damage and trigger vascular events in hypertensive patients. Therefore, amelioration of BPV is considered a potentially important target and different classes of drugs are used to achieve the desired blood pressure (BP) goal. Based on several studies and clinical trials, treatments with CCB such as amlodipine have been found to be most effective in the management of BPV in hypertensive patients with diabetes. Growing evidence substantiates the role of amlodipine in significant reduction of BPV, thus, lowering the risk of diabetes related complications. This review sheds light on the importance of BPV reduction and the effectiveness of amlodipine in preventing cardiovascular morbidity and mortality in hypertensive patients with diabetes.

Cost of hospitalisation for non-communicable diseases in India: are we pro-poor?

OBJECTIVES: To estimate out-of-pocket (OOP) expenditure due to hospitalisation from NCDs and its impact on households in India. METHODS: The study analysed nationwide representative data collected by the National Sample Survey Organisation in 2014 that reported health service utilisation and healthcare-related OOP expenditure by income quintiles and by type of health facility (public or private). The recall period for inpatient hospitalisation expenditure was 365 days. Consumption expenditure was collected for a recall period of 1 month. OOP expenditure amounting to >10% of annual consumption expenditure was termed as catastrophic. Weighted analysis was performed. RESULTS: The median expenditure per episode of hospitalisation due to NCDs was USD 149 - this was ~3 times higher among the richest quintile compared to poorest quintile. There was a significantly higher prevalence of catastrophic expenditure among the poorest quintile, more so for cancers (85%), psychiatric and neurological disorders (63%) and injuries (63%). Mean private-sector OOP hospitalisation expenditure was nearly five times higher than that in the public sector. Medicines accounted for 40% and 27% of public- and private-sector OOP hospitalisation expenditure, respectively. CONCLUSION: Strengthening of public health facilities is required at community level for the prevention, control and management of NCDs. Promotion of generic medicines, better availability of essential drugs and possible subsidisation for the poorest quintile will be measures to consider to reduce OOP expenditure in public-sector facilities.

The Impact of Preventive Dental Services on Subsequent Dental Treatment for Children in Medicaid.

OBJECTIVE: The goal of this study was to use claims data linked with community-level measures to evaluate the impact of preventive services on the time to subsequent restorative, advanced restorative, and complex dental treatment among children enrolled in the Virginia Medicaid program. METHODS: Four data sources were used (dental claims, eligibility files, American Community Survey, and Area Health Resource Files) for fiscal years 2011 to 2018. The outcomes of interest were time to first treatment services from birth. The treatment outcomes were basic restorative treatment, advanced restorative treatment, or complex treatment. The independent variable was a preventive service prior to a treatment service. Time-to-event curves were estimated and compared using a log-rank test. Propensity score-matched univariate and multivariate Cox proportional hazards frailty models with an inverse probability censoring weighting correction estimated hazard ratios (HRs) for treatment outcomes comparing use of preventive services while controlling for patient demographic, geospatial, and county-level socioeconomic status measures. RESULTS: The analysis included 430,594 children (10,204,182 claims). A log-rank test showed significant differences (P < 0.001) between the times to treatment of those who had a preventive service and those who did not have a preventive service prior to a treatment service. Both Kaplan-Meier curves and the adjusted HR (1.88; 95% confidence interval [CI], 1.46-2.15) indicated that children without preventive services were more likely to have basic restorative treatment at an earlier age along with advanced restorative treatment (HR, 1.52; 95% CI, 1.28-1.80) and complex treatment (HR, 2.13; 95% CI, 1.68-2.61). CONCLUSIONS: In a population of Medicaid-enrolled children, children who did not receive preventive services were significantly more likely to have treatment at an earlier age than those who did receive preventive services. KNOWLEDGE TRANSFER STATEMENT: This study examines the impact of the utilization of preventive dental services since birth and the subsequent dental treatment for children enrolled in a dental Medicaid program. This study also examines the influence of preventive care on dental complexity of treatment for these children. Findings can inform federal and state policy planning of dental Medicaid programs as well as interventions to improve referral systems for the early use of preventive dental services and the establishment of a dental home.

Waste-Derived Fuels and Renewable Chemicals for Bioeconomy Promotion: A Sustainable Approach.

Bio-based fuels and chemicals through the biorefinery approach has gained significant interest as an alternative platform for the petroleum-derived processes as these biobased processes are noticed to have positive environmental and societal impacts. Decades of research was involved in understanding the diversity of microorganisms in different habitats that could synthesize various secondary metabolites that have functional potential as fuels, chemicals, nutraceuticals, food ingredients, and many more. Later, due to the substrate-related process economics, the diverse low-value, high-carbon feedstocks like lignocellulosic biomass, industrial byproducts, and waste streams were investigated to have greater potential. Among them, municipal solid wastes can be used as the source of substrates for the production of commercially viable gaseous and liquid fuels, as well as short-chain fattyacids and carboxylic acids. In this work, technologies and processes demanding the production of value-added products were explained in detail to understand and inculcate the value of municipal solid wastes and the economy, and it can provide to the biorefinery aspect.

Towards achievement of universal health care in India by 2020: a call to action.

To sustain the positive economic trajectory that India has had during the past decade, and to honour the fundamental right of all citizens to adequate health care, the health of all Indian people has to be given the highest priority in public policy. We propose the creation of the Integrated National Health System in India through provision of universal health insurance, establishment of autonomous organisations to enable accountable and evidence-based good-quality health-care practices and development of appropriately trained human resources, the restructuring of health governance to make it coordinated and decentralised, and legislation of health entitlement for all Indian people. The key characteristics of our proposal are to strengthen the public health system as the primary provider of promotive, preventive, and curative health services in India, to improve quality and reduce the out-of-pocket expenditure on health care through a well regulated integration of the private sector within the national health-care system. Dialogue and consensus building among the stakeholders in the government, civil society, and private sector are the next steps to formalise the actions needed and to monitor their achievement. In our call to action, we propose that India must achieve health care for all by 2020.

Human resources for health in India.

India has a severe shortage of human resources for health. It has a shortage of qualified health workers and the workforce is concentrated in urban areas. Bringing qualified health workers to rural, remote, and underserved areas is very challenging. Many Indians, especially those living in rural areas, receive care from unqualified providers. The migration of qualified allopathic doctors and nurses is substantial and further strains the system. Nurses do not have much authority or say within the health system, and the resources to train them are still inadequate. Little attention is paid during medical education to the medical and public health needs of the population, and the rapid privatisation of medical and nursing education has implications for its quality and governance. Such issues are a result of underinvestment in and poor governance of the health sector--two issues that the government urgently needs to address. A comprehensive national policy for human resources is needed to achieve universal health care in India. The public sector will need to redesign appropriate packages of monetary and non-monetary incentives to encourage qualified health workers to work in rural and remote areas. Such a policy might also encourage task-shifting and mainstreaming doctors and practitioners who practice traditional Indian medicine (ayurveda, yoga and naturopathy, unani, and siddha) and homoeopathy to work in these areas while adopting other innovative ways of augmenting human resources for health. At the same time, additional investments will be needed to improve the relevance, quantity, and quality of nursing, medical, and public health education in the country.

Stellate ganglion block for the management of hot flashes and sleep disturbances in breast cancer survivors: an uncontrolled experimental study with 24 weeks of follow-up.

BACKGROUND: We studied the stellate ganglion block (SGB) recently suggested for the treatment of severe vasomotor symptoms and sleep disturbances in breast cancer survivors. Following an initial pilot study, which focused on the acceptability and safety of SGB for this important problem, we evaluated its short- and long-term efficacy. MATERIALS AND METHODS: Postmenopausal breast cancer survivors with severe vasomotor symptoms resistant to standard nonhormonal pharmacological intervention were eligible. Diaries were used to measure daily hot flash scores (frequency and intensity) and sleep quality (Pittsburgh Sleep Quality Index) during scheduled visits at baseline, 1, 4, 12 and 24 weeks following the SGB. Efficacy data were analyzed using longitudinal regression models. RESULTS: Thirty-four patients participated and none refused the SGB procedure. Most patients received more than one SGB. The pilot study found SGB to be safe. In the main study, hot flash scores were reduced from baseline by 64% [95% confidence interval (CI) -74% to -49%] and 47% (95% CI -62% to -27%) at weeks 1 and 24, respectively. The odds ratio of better sleep quality relative to baseline was 3.4 at week 1 (95% CI 1.6-7.2) and 4.3 at week 24 (95% CI 1.9-9.8). CONCLUSION: In the short term, SGB appears to be an effective treatment with acceptable morbidity for some breast cancer survivors with therapy-resistant vasomotor symptoms and/or sleep disturbances. Although sleep quality was maintained out to 24 weeks the efficacy of SGB for hot flashes was reduced over time. A randomized controlled trial is needed to confirm these findings.

The non specialist paediatric training registrar in the healthcare system.

This study evaluated the experiences of non Specialist Paediatric Training Registrars (nonSPTR) in the Irish Healthcare system. The survey explored their adaptation to the healthcare system, skill development, perceptions of training and career development inclusive of working conditions. Thirty nine (53%) doctors responded. The time spent in Paediatrics ranged from 3 to 19 years with a mean of 8.9 years. Nineteen (49%) had only worked in non regional hospitals and for 20 (51%) the mean time spent in regional hospitals was 2.6 years. The very positives experiences (likert scores 5/6) included journal appraisal for 19 (49%), clinical skill development for 17 (44%) and consultant feedback for 11 (28%).The very negative experiences were difficulty obtaining desired clinical posts for 16 (43%) doctors and only 5 (13%) were happy with their career progression. Thirty one (79.5%) cited specific barriers to career progression, with only 10 (25%) making an application to the Specialist Paediatrics Registrar (SPR) training programme. Solutions for the non SPTR difficulties include the expansion of the SPR programme and the utilization of a criterion based portfolio system to integrate the nonSPTR into formal training.

Restrictions on contraceptive services for unmarried youth: a qualitative study of providers' beliefs and attitudes in India.

Sexual and reproductive health (SRH) of unmarried youth is an important issue, particularly in Indian society, where premarital sex is socially restricted. It is an uncomfortable subject for most people, including healthcare providers, who are responsible for catering to the reproductive health needs of youth. This is because of the prevailing social norms, where sex outside marriage is discouraged and stigmatised. These social norms give importance to virginity, and children outside marriage are not welcome. The present qualitative study was conducted in public health facilities (primary and secondary) to explore the attitudes of healthcare providers in providing contraceptive services to unmarried youth. In-depth interviews were conducted with family planning (FP) service providers (frontline healthcare workers [ASHAs] nurses and FP counsellors) between October 2017 and September 2018. Almost a quarter of the providers were either hesitant or against providing contraceptives to unmarried youth. Providers stated that they preferred emergency contraceptive pills for unmarried girls if they had already engaged in unprotected sex. Providers expressed strong personal views against premarital sex because they believed it was against existing social norms. Some providers were concerned about the possible negative reactions of the community if they recommended any contraceptive to unmarried youth. A few providers even considered it illegal to provide contraceptives to unmarried youth, though there is no such law in the country. Findings further indicated that though the country had launched programmes for improving adolescents and youth SRH, service providers were still conflicted between medical eligibility and social beliefs.

Topical fluoride-antibacterial agent combined therapy versus topical fluoride monotherapy in preventing dental caries: a systematic review and meta-analysis.

PURPOSE: To compare the effectiveness of topical fluoride-antibacterial agent combined therapy versus topical fluoride monotherapy in preventing dental caries among 1- to 16-year-old children. METHODS: PubMed, EbscoHost, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials were searched for randomised controlled trials. The trials should have assessed the caries-preventive effectiveness of topical fluoride-antibacterial agent (Povidone Iodine/Chlorhexidine/Xylitol/Triclosan/Cetylpyridinium Chloride) combined therapy versus topical fluoride monotherapy among children. Out of 3475 records that were screened, full text of 41 articles was assessed for potential inclusion. Sixteen trials that fulfilled the eligibility criteria were subjected to qualitative synthesis. The risk of bias was assessed using the Cochrane Collaboration's tool. Continuous data from nine trials were pooled using Inverse Variance test in meta-analysis function of Review Manager (version 5.4). GRADE approach was used to analyse the certainty of evidence. Statistical heterogeneity was quantified using the I2 statistic. A p-value of < 0.05 was considered as statistically significant. RESULTS: With respect to the caries increment, combined therapy showed superior caries-preventive effectiveness than topical fluoride monotherapy [SMD - 0.12, 95% CI (- 0.2 to - 0.04), p = 0.004; (I2 = 20%, p = 0.29)]. No significant difference was noted between the two groups for the post-intervention salivary S mutans count [SMD - 0.11, 95% CI (- 0.33 to 0.1), p = 0.3; (I2 = 0%, p = 0.77)]. CONCLUSION: The pooled analysis indicates towards an added benefit of topical fluoride-antibacterial agent combined therapy over topical fluoride monotherapy in preventing dental caries incidence among children. However, the results may be interpreted with caution since the evidence generated is of low certainty and is driven by two studies on Xylitol, thus it demands further good quality trials.

Lead loadings in household dust in Delhi, India.

Lead in household dust is dangerous to children who ingest lead from playing close to the ground, and having frequent hand-to-mouth contact. Although there have been several investigations of lead levels in India in air, blood and new paint, the literature is sparse on the levels of lead in household dust. This study analyzed 99 samples of dust taken from bare floors and 49 samples of dust taken from windowsills in a cross-section of Delhi, India houses for lead loadings. The arithmetic mean of lead loading for floor samples and windowsill dust samples was found to be 36.24 microg/ft(2) and 129.5 microg/ft(2), respectively. The geometric mean of dust lead loading for floor and interior windowsill samples was found to be 19.7 microg/ft(2) and 75.5 microg/ft(2), respectively. Comparing the results with US geometric mean dust lead levels from a national cross-section of US housing, which in 2000 were 1.1 microg/ft(2) and 9.4 microg/ft(2) on floors and windowsills, respectively as reported by Jacobs et al. (2002) suggests that the lead content of the dust in Delhi homes is much higher than that in the national data in the US and that the levels pose a hazard to children. Practical Implications The present study is first of its kind in this part of the world. In the context of ongoing efforts to eliminate lead from paints worldwide this research will help the scientists and policy makers in assessing the Children's exposure to lead in developing country as well. Since more than one half of the housing units tested had at least one dust lead sample exceeding US health-based standards, health care providers and public health officials need to give attention to possible lead poisoning in Delhi children. Routine blood lead screening of children should follow recommended public health practice for children at risk. Additional larger-scale studies are needed in Delhi and elsewhere to determine how representative these findings are and to attempt to delineate the sources of the high dust lead which are expected to vary depending on the location. Knowledge of the sources is needed to appropriately allocate resources. From other studies performed in India it is likely that lead-based paint is one of the sources and its continued use should be discontinued.