The impact of metabolic syndrome components on urinary parameters and risk of stone formation.

PURPOSE: To investigate the relationship between metabolic syndrome (MS) and urinary abnormalities in stone-forming patients. Additionally, to delineate whether severity of urinary derangements is impacted by the number of co-occurring MS components. METHODS: Stone-forming patients who underwent initial metabolic workup prior to medical intervention at a comprehensive stone clinic were retrospectively reviewed and included in the study. Patients were given a six point (0-5) Metabolic Syndrome Severity Score (MSSS) based on the number of co-occurring MS components and split into six respective groups. Baseline clinical characteristics and metabolic profiles were compared between groups. RESULTS: Four-hundred-ninety-five patients were included in the study. Median age and median BMI was 58 years and 27.26 kg/m2, respectively. Several significant metabolic differences were noted, most notably a downward trend in median urinary pH (p < 0.001) and an upward trend in median urinary supersaturation uric acid (p < 0.001) across groups as MSSS increased. Multivariate analysis demonstrated an independent association between higher MSSS and increasing number of urinary abnormalities. A second multivariate analysis revealed that all MS components except hyperlipidemia were independently associated with low urinary pH. Additionally, obesity was independently associated with the greatest number of urinary abnormalities and had the strongest association with hyperuricosuria. CONCLUSIONS: Prior research has attributed the strong association of nephrolithiasis and MS to high prevalence of UA nephrolithiasis and low urinary pH. Our findings indicate that all MS components with the exception of hyperlipidemia were independently associated with low urinary pH suggesting a mechanism independent from insulin resistance.

Derivation and validation of genome-wide polygenic score for urinary tract stone diagnosis.

Urinary tract stones have high heritability indicating a strong genetic component. However, genome-wide association studies (GWAS) have uncovered only a few genome wide significant single nucleotide polymorphisms (SNPs). Polygenic risk scores (PRS) sum cumulative effect of many SNPs and shed light on underlying genetic architecture. Using GWAS summary statistics from 361,141 participants in the United Kingdom Biobank, we generated a PRS and determined association with stone diagnosis in 28,877 participants in the Mount Sinai BioMe Biobank. In BioMe (1,071 cases and 27,806 controls), for every standard deviation increase, we observed a significant increment in adjusted odds ratio of a factor of 1.2 (95% confidence interval 1.13-1.26). In comparison, a risk score comprised of GWAS significant SNPs was not significantly associated with diagnosis. After stratifying individuals into low and high-risk categories on clinical risk factors, there was a significant increment in adjusted odds ratio of 1.3 (1.12-1.6) in the low- and 1.2 (1.1-1.2) in the high-risk group for every standard deviation increment in PRS. In a 14,348-participant validation cohort (Penn Medicine Biobank), every standard deviation increment was associated with a significant adjusted odds ratio of 1.1 (1.03 - 1.2). Thus, a genome-wide PRS is associated with urinary tract stones overall and in the absence of known clinical risk factors and illustrates their complex polygenic architecture.

SGLT2 Inhibitors, Functional Capacity, and Quality of Life in Patients With Heart Failure: A Systematic Review and Meta-Analysis.

Importance: The associations of sodium glucose cotransporter-2 inhibitors (SGLT2is) with reduction in mortality and hospitalization rates in patients with heart failure (HF) are well established. However, their association with improving functional capacity and quality of life (QOL) has been variably studied and less reported. Objective: To provide evidence on the extent to which SGLT2is are associated with improvement on objective measures of functional capacity and QOL in patients living with HF. Data Sources: The MEDLINE, EMBASE, and Cochrane databases were systematically searched for relevant articles on July 31, 2023. Study Selection: Randomized, placebo-controlled clinical trials reporting the effect of SGLT2i on functional outcomes of exercise capacity (peak oxygen consumption [peak VO2] or 6-minute walk distance [6MWD]) and/or QOL using validated questionnaires for patients with HF were included. Data Extraction and Synthesis: Data were extracted by 2 authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020 guidelines, and a meta-analysis using the restricted maximum likelihood random-effects model was conducted. Main Outcomes and Measures: Outcomes of interest included changes in peak VO2, 6MWD, and Kansas City Cardiomyopathy Questionnaire-12 total symptom score (KCCQ-TSS), clinical summary score (KCCQ-CSS), and overall summary score (KCCQ-OSS). Results: In this meta-analysis of 17 studies, 23 523 patients (mean [range] age, 69 [60-75] years) were followed over a period ranging from 12 to 52 weeks. Four studies included peak VO2 as an outcome, 7 studies included 6MWD, and 10 studies reported KCCQ scores. Mean (SD) left ventricular ejection fraction was 43.5% (12.4%). Compared with controls, patients receiving SGLT2i treatment experienced significant increases in peak VO2 (mean difference [MD], 1.61 mL/kg/min; 95% CI, 0.59-2.63 mL/kg/min; P = .002) and 6MWD (MD, 13.09 m; 95% CI, 1.20-24.97 m; P = .03). SGLT2i use was associated with increased KCCQ-TSS (MD, 2.28 points; 95% CI, 1.74-2.81 points; P < .001), KCCQ-CSS (MD, 2.14 points; 95% CI, 1.53-2.74 points; P < .001), and KCCQ-OSS (MD, 1.90 points; 95% CI, 1.41-2.39 points; P < .001) scores. Subgroup analysis and meta-regression demonstrated almost all improvements were consistent across ejection fraction, sex, and the presence of diabetes. Conclusions and Relevance: These findings suggest that in addition to known clinical associations with mortality and hospitalization outcomes, SGLT2i use is associated with improvement in outcomes of interest to patients' everyday lives as measured by objective assessments of maximal exercise capacity and validated QOL questionnaires, regardless of sex or ejection fraction.

Severe functional mitral regurgitation and cardiogenic shock after transcatheter aortic valve replacement.

An 83-year-old woman with symptomatic severe aortic stenosis was referred for transcatheter aortic valve replacement. Diagnostic left heart catheterization documented diffuse 3-vessel coronary artery disease.

Is metformin use associated with changes in urinary parameters in stone formers?

INTRODUCTION: Diabetes mellitus (DM) is associated with an increased risk of nephrolithiasis and is often treated with metformin. The relationship between metformin and nephrolithiasis formation remains unclear, as studies have demonstrated conflicting results. METHODS: We conducted a cross-sectional analysis of stone-forming patients at our stone clinic prior to the initiation of stone-directed medical management. Patients were grouped based on diabetic status and diabetic medication regimen. Outcomes evaluated were 24-hour urinary parameters and specimen stone type using univariate Kruskal-Wallis and Chi-squared analyses. Multivariate analyses controlling for metabolic syndrome components and HbA1c were performed. RESULTS: Data were available for 505 patients, of whom 147 were diabetic and 358 were not. On multivariate analyses controlling for HbA1c and other comorbidities, diabetic patients on metformin still had worse urinary parameters, including urine pH, than non-diabetic patients (pH=-0.33, -0.37, p<0.05). Patients with DM on metformin did not exhibit significant differences in 24-hour urine findings compared to patients with DM not on metformin (p>0.05 for all urinary parameters). CONCLUSIONS: Stone-forming patients with DM on metformin were associated with urinary abnormalities similar to those not on metformin. Cohort studies comparing urinary parameters of patients prospectively started on metformin are necessary to further elucidate metformin's role, if any, in combatting nephrolithiasis.

Multi-Institutional Predictors of Antibiotic Resistance in Patients Presenting to the Emergency Department with Urosepsis Secondary to Ureteral Obstruction.

Introduction and Objective: Patients presenting with a urinary tract infection with kidney or ureteral stones is a urologic emergency often achieve early clinical stability but remain hospitalized while awaiting results from urine antibiotic sensitivity analyses. We aimed to identify clinical predictors of antibiotic resistance in patients who underwent urgent urinary tract decompression for sepsis and obstructive urolithiasis to facilitate early discharge on empiric oral antibiotics. Methods: Patients who underwent emergent urinary tract decompression for sepsis and an obstructing ureteral stone from 2014 to 2018 at two academic medical institutions were identified. Emergent stent placement was performed and patients were treated with broad-spectrum intravenous antibiotics. We assessed the association between clinical parameters at the time of presentation and resistance to at least one antibiotic from urine culture using the Wilcoxon test and Fisher exact test for continuous and categorical variables, respectively. Multivariate logistic regression was then performed using all significant variables from univariate analysis. Results: Out of 134 patients, 84 patients (62.7%) had urine cultures resistant to at least one antibiotic. On univariate analysis, patients with resistant cultures were significantly more likely to have had previous ureteroscopy, require postoperative intensive care unit-level care, have bacteremia, and a longer length of stay. In multivariate analysis using significant variables from univariate analysis, only previous ureteroscopy was significantly associated with antibiotic resistance with an increased odds of 6.95 (p = 0.011). Conclusions: In this study, we show that a history of ureteroscopy is significantly associated with antibiotic resistance in both univariate and multivariate analyses. Our findings suggest that patients with history of ureteroscopy should await urine culture results, while those without a history of ureteroscopy may be discharged early on empiric oral antibiotics. However, future studies are necessary to determine the effectiveness of this predictor.

Identifying challenges and recommendations for advancing global mental health implementation research: A key informant study of the National Institute of Mental Health Scale-Up Hubs.

OBJECTIVE: This study explored perspectives of researchers working with the National Institute of Mental Health (NIMH) Scale-Up Hubs, consisting of research partnerships for scaling up mental health interventions in low- and middle-income countries (LMICs), to: 1) identify common barriers to conducting impactful research on the implementation of evidence-based mental health services; and 2) provide recommendations to overcome these implementation challenges. METHODS: A sequential qualitative approach was employed. First, an open-ended survey was distributed to the 10 Scale-Up Hubs and NIMH program staff asking informants to identify challenges in conducting mental health implementation research in LMICs. Second, survey findings guided an in-person workshop to generate implementation recommendations to inform the field. RESULTS: In total, 46 respondents completed surveys, and 101 researchers attended the workshop. The workshop produced implementation recommendations for low-resource settings: 1) identifying impact of research on policy and practice; 2) sustaining careers of early researchers in global mental health; 3) engaging policymakers and donors to value mental health research; 4) supporting the workforce for delivering evidence-based treatments for mental disorders; and 5) promoting sustainability of programs. CONCLUSIONS: These findings can strengthen collaboration between researchers and key stakeholders, and highlight important targets for improving mental health implementation research in LMICs.

COVID-19 and forced alcohol abstinence in India: The dilemmas around ethics and rights.

In response to the COVID-19 pandemic, as with other countries across the world, the Central and State Governments of India initiated several measures to slow down the spread of the virus and to 'flatten the curve'. One such measure was a 'total lockdown' for several weeks across the country. A complex and unexpected outcome of the lockdown which has medical, ethical, economic, and social dimensions is related to alcohol consumption. The lockdown and consequent acute non-availability of alcohol resulted in people with alcohol dependence going into withdrawals, black marketing of alcohol, and in extreme cases suicide resulting from the alleged frustration of not having access to alcohol. The health dilemmas around this situation are biological (e.g. pushing people into risky situations-potentially fatal alcohol withdrawal, consumption of illicit or other non-consumable alcohol) and psychosocial (e.g. isolation increasing the risk of relapses, loss of control over the decision to abstain which can be detrimental to recovery, restriction of access to services for alcohol problems). The legal and rights-related dilemmas are centred around whether States have the right to impinge on individual autonomy on the grounds of public health, the capacity of the health systems to provide appropriate services to cope with those who will struggle with the unavailability of alcohol, the constitutionality of the Central government's impinging on jurisdiction of states under the guise of a health emergency caused by the pandemic, and the ability of the State to make unbiased decisions about this issue when it is highly dependent on the revenue from the sale of alcohol and associated industries. The way forward could be a pragmatic and utilitarian approach involving continued access to alcohol, while observing all physical distancing norms necessary during the pandemic, for those who want to continue drinking; and implementing innovative measures such as tele-counselling for those who wish not to return back to drinking.

Analysis of news media reports of suicides and attempted suicides during the COVID-19 lockdown in India.

BACKGROUND: Based on previous experience there is justifiable concern about suicidal behaviour and news media reporting of it during COVID-19 pandemic. METHODS: This study used a systematic search of online news media reports (versions of newspapers, magazine and other digital publications) of suicidal behaviour during India's COVID-19 lockdown and compared it to corresponding dates in 2019. Data was gathered using a uniform search strategy from 56 online news media publications 24 March to 3 May for the years 2019 and 2020 using keywords, suicide, attempted suicide, hangs self and kills self. Demographic variables and methods used for suicide were compared for suicide and attempts between the 2 years using chi-squared tests (χ2). RESULTS: There were online news media reports of 369 cases of suicides and attempted suicides during COVID lockdown vs 220 reports in 2019, a 67.7% increase in online news media reports of suicidal behaviour. Compared to 2019, suicides reported during lockdown were significantly older (30 vs 50 years, p < 0.05), men (71.2% vs 58.7%; p < 0.01), married (77.7% vs 49%; p < 0.01) and employed (82.9% vs 59.5%; p < 0.01). During the lockdown, significantly more suicides were by hanging (64.4% vs 42%), while poisoning (8.5% vs 21.5%) and jumping in front of a train (2% vs 9.4%) (p < 0.05) were significantly reduced. Comparison of COVID and non-COVID groups showed that online news media reports of COVID cases of suicide and attempted suicide were significantly more likely to be men (84.7% vs 60.4%; p < 0.01), older (31-50 years 52.9% vs 25.8%; p < 0.01) employed (91.5% vs 64.3%; p < 0.01), had poor mental (40.1% vs 20.8%; p < 0.01) and poor physical health (24.8% vs 7.9%;11.8, p < 0.01). CONCLUSION: Increase in online news media reports of suicides and attempts during COVID-19 lockdown may indicate an increase in journalists' awareness about suicide or more sensational media reporting or may be a proxy indicator of a real community increase in suicidal behaviour. It is difficult to attribute changes in demographic profile and methods used only to changes in journalists' reporting behaviour and should be further explored. We therefore call upon the Government of India to urgently release national suicide data to help devise a comprehensive suicide prevention strategy to address COVID-19 suicidal behaviour.

Evaluation of the SPIRIT Integrated Suicide Prevention Programme: study protocol for a cluster-randomised controlled trial in rural Gujarat, India.

BACKGROUND: Suicide is a major public health challenge globally and specifically in India where 36.6% and 24.3% of all suicides worldwide occur in women and men, respectively. The United Nations Sustainable Development Goals uses suicide rate as one of two indicators for Target 3.4, aimed at reducing these deaths by one third by 2030. India has no examples of large-scale implementation of evidence-based interventions to prevent suicide; however, there is a sizeable evidence base to draw on for suicide prevention strategies that have been piloted in India or proven to be effective regionally or internationally. METHOD: The SPIRIT study is designed as a cluster-randomized superiority trial and uses mixed methods to evaluate the implementation, effectiveness and costs of an integrated suicide prevention programme consisting of three integrated interventions including (1) a secondary-school-based intervention to reduce suicidal ideation among adolescents, (2) a community storage facility intervention to reduce access to pesticides and (3) training for community health workers in recognition, management, and appropriate referral of people identified with high suicidal risk. DISCUSSION: Combining three evidence-based interventions that tackle suicide among high-risk groups may generate a synergistic impact in reducing suicides at the community level in rural areas in India. Examination of implementation processes throughout the trial will also help to prepare a roadmap for policymakers and researchers looking to implement suicide prevention interventions in other countries and at scale. TRIAL REGISTRATION: Clinical Trial Registry of Indian Council of Medical Research, India: CTRI/2017/04/008313. Registered on 7 April 2017. http://ctri.nic.in/Clinicaltrials/pmaindet2.php?trialid=18256&EncHid=&userName=SPIRIT Trial registry was last modified on 28 June 2019.

Retrospective cohort study of clinical characteristics of 2199 hospitalised patients with COVID-19 in New York City.

OBJECTIVE: The COVID-19 pandemic is a global public health crisis, with over 33 million cases and 999 000 deaths worldwide. Data are needed regarding the clinical course of hospitalised patients, particularly in the USA. We aimed to compare clinical characteristic of patients with COVID-19 who had in-hospital mortality with those who were discharged alive. DESIGN: Demographic, clinical and outcomes data for patients admitted to five Mount Sinai Health System hospitals with confirmed COVID-19 between 27 February and 2 April 2020 were identified through institutional electronic health records. We performed a retrospective comparative analysis of patients who had in-hospital mortality or were discharged alive. SETTING: All patients were admitted to the Mount Sinai Health System, a large quaternary care urban hospital system. PARTICIPANTS: Participants over the age of 18 years were included. PRIMARY OUTCOMES: We investigated in-hospital mortality during the study period. RESULTS: A total of 2199 patients with COVID-19 were hospitalised during the study period. As of 2 April, 1121 (51%) patients remained hospitalised, and 1078 (49%) completed their hospital course. Of the latter, the overall mortality was 29%, and 36% required intensive care. The median age was 65 years overall and 75 years in those who died. Pre-existing conditions were present in 65% of those who died and 46% of those discharged. In those who died, the admission median lymphocyte percentage was 11.7%, D-dimer was 2.4 µg/mL, C reactive protein was 162 mg/L and procalcitonin was 0.44 ng/mL. In those discharged, the admission median lymphocyte percentage was 16.6%, D-dimer was 0.93 µg/mL, C reactive protein was 79 mg/L and procalcitonin was 0.09 ng/mL. CONCLUSIONS: In our cohort of hospitalised patients, requirement of intensive care and mortality were high. Patients who died typically had more pre-existing conditions and greater perturbations in inflammatory markers as compared with those who were discharged.

Clinical Characteristics of Hospitalized Covid-19 Patients in New York City.

BACKGROUND: The coronavirus 2019 (Covid-19) pandemic is a global public health crisis, with over 1.6 million cases and 95,000 deaths worldwide. Data are needed regarding the clinical course of hospitalized patients, particularly in the United States. METHODS: Demographic, clinical, and outcomes data for patients admitted to five Mount Sinai Health System hospitals with confirmed Covid-19 between February 27 and April 2, 2020 were identified through institutional electronic health records. We conducted a descriptive study of patients who had in-hospital mortality or were discharged alive. RESULTS: A total of 2,199 patients with Covid-19 were hospitalized during the study period. As of April 2 nd , 1,121 (51%) patients remained hospitalized, and 1,078 (49%) completed their hospital course. Of the latter, the overall mortality was 29%, and 36% required intensive care. The median age was 65 years overall and 75 years in those who died. Pre-existing conditions were present in 65% of those who died and 46% of those discharged. In those who died, the admission median lymphocyte percentage was 11.7%, D-dimer was 2.4 ug/ml, C-reactive protein was 162 mg/L, and procalcitonin was 0.44 ng/mL. In those discharged, the admission median lymphocyte percentage was 16.6%, D-dimer was 0.93 ug/ml, C-reactive protein was 79 mg/L, and procalcitonin was 0.09 ng/mL. CONCLUSIONS: This is the largest and most diverse case series of hospitalized patients with Covid-19 in the United States to date. Requirement of intensive care and mortality were high. Patients who died typically had pre-existing conditions and severe perturbations in inflammatory markers.

Section 377 and The Mental Healthcare Act, 2017: Breaking barriers.

The Supreme Court of India recently decriminalised homosexuality by passing a landmark judgment in the case of Navtej Johar and Others v. Union of India. In its judgment, the Court held that Section 377 of the Indian Penal Code, 1860 is unconstitutional in as much as it criminalises consensual sexual acts between two adults. The Court held that Section 377 discriminates against persons of the LGBTIQ community based on their sexual orientation and violates their fundamental rights guaranteed by the Constitution of India. The Court arrived at this conclusion after considering established principles of constitutional law, foreign precedents and expert opinions. However, a crucial part of the Court�s reasoning was based on a close reading of the Mental Healthcare Act, 2017. The Court relied on the anti-discriminatory provisions of the Mental Healthcare Act, 2017 to observe that homosexuality is not a mental illness or mental disorder, and that LGBTIQ persons cannot be discriminated against on the basis of their sexual orientation. The Court�s reading of the Mental Healthcare Act, 2017 and Section 377 is significant as its rationale can be extended further to challenge other laws which discriminate against persons with mental illness. The Court also highlights the responsibilities of mental health professionals and counsellors while providing mental healthcare to LGBTIQ persons. Finally, the Court�s reading of the Mental Healthcare Act, 2017 is also a recognition of its commitment as an anti-discrimination legislation which upholds constitutional values and protects the rights of persons with mental illness.