Evaluating therapeutic potential of AYUSH-64 constituents against omicron variant of SARS-CoV-2 using ensemble docking and simulations.

The COVID-19 pandemic in the later phase showed the presence of the B.1.1.529 variant of the SARS-CoV-2 designated as Omicron. AYUSH-64 a poly herbal drug developed by Central Council for Research in Ayurvedic Sciences (CCRAS) has been recommended by Ministry of Ayush in asymptomatic, mild to moderate COVID-19 patients. One of the earlier, in-silico study has shown the binding of the constituents of AYUSH-64 to the main protease (Mpro) of the SARS-CoV-2. This study enlisted four phytochemicals of AYUSH-64, which were found to have significant binding with the Mpro. In continuation to the same, the current study proposes to understand the binding of these four phytochemicals to main protease (Mpro) and receptor binding domain (RBD) of spike protein of the Omicron variant. An enhanced molecular docking methodology, namely, ensemble docking has been used to find the most efficiently binding phytochemical. Using molecular dynamics (MD) simulations and clustering approach it was observed that the Mpro and RBD Spike of Omicron variant of SARS-CoV-2 in complex with human ACE2 tends to attain 4 and 8 conformational respectively. Based on the docking studies, the best binding phytochemical of the AYUSH-64, akummicine N-oxide was selected for MD simulations. MD simulations of akummicine N-oxide bound to omicron variant of Mpro and RBD Spike-ACE complex was performed. The conformational, interaction and binding energy analysis suggested that the akummicine N-oxide binds well with Mpro and RBD Spike-ACE2 complex. The interaction between RBD Spike and ACE2 was observed to weaken in the presence of akummicine N-oxide. Hence, it can be inferred that, these phytochemicals from AYUSH-64 formulation may have the potential to act against the Omicron variant of SARS-CoV-2.

Hand-assisted laparoscopic retroperitoneal donor nephrectomy: A single-institution experience of over 500 cases-Operative technique and clinical outcomes.

OBJECTIVE: Although there are several variations of laparoscopic living-donor nephrectomies, there is no consensus as to the best technique. Our objective was to describe our technique and assess the outcomes of our approach to hand-assisted laparoscopic retroperitoneal donor nephrectomies. METHODS: From July 2001 to October 2015, 507 consecutive hand-assisted laparoscopic retroperitoneal donor nephrectomies were performed. Their clinical information was retrospectively reviewed including warm ischemia time, skin incision to kidney ready time, estimated blood loss, adverse intraoperative events, and postoperative complications. RESULTS: Mean incision time to kidney removal was 135 minutes (55-260), mean warm ischemia time was 125 seconds (30-390), and mean blood loss was 83 mL (20-500). Average length of stay was 3 days (1-6). There were no significant differences between left and right kidney donors based on demographics, length of hospital stay, or warm ischemia time. There were no conversions to open surgery. Complications occurred in 4.9% of patients (25/507), including 4 cases of perioperative bleeding. CONCLUSIONS: This is a single-center series describing the safety and efficacy of the hand-assisted laparoscopic retroperitoneal donor nephrectomy for both right and left sides. It does not require intraperitoneal manipulation and allows for safe extraction of either kidney with minimal warm ischemia time.

A Spatial Analysis of Acute Myocardial Infarction Rates in New York State in Relation to Hospitals Along State Jurisdictional Borders.

INTRODUCTION: Patients experiencing acute myocardial infarction (AMI) are likely to visit the nearest hospital providing appropriate services since timely care is a critical determinant in the treatment and progression of AMI. We comparatively examined AMI rates in border and nonborder census tracts. The New York State (NYS) Environmental Public Health Tracking (EPHT) program, in conjunction with the Statewide Planning and Research Cooperative System, will work on developing memoranda of understanding with neighboring states to be able to more comprehensively access NYS residents' out-of-state health records. OBJECTIVE: To determine whether AMI rates in the NYS border census tracts differ from AMI rates in nonborder census tracts as a preliminary exploration of the utilization of out-of-state care for acute health conditions by NYS border residents. DESIGN: We reviewed data on inpatient and emergency department visits in NYS with discharge dates from 2005 to 2014 retrospectively. We used the NYS EPHT tier 1 system database to locate hospitals. We geocoded all cases to NYS 2010 census tracts. We mapped differences between border and nonborder tracts and analyzed resulting spatial patterns. We computed tract-level AMI rates and differences between border and nonborder AMI rates. RESULTS: The age-adjusted AMI rates differed by 8.2 cases per 10 000 people (95% confidence interval, 6.94-12.60). Maps showed patterns of differences in AMI rates, especially along the NYS border with New England and other geographically closer out-of-state hospitals. CONCLUSIONS: AMI rates that were geographically closer to out-of-state hospitals were lower, suggesting that people residing in border census tracts are utilizing out-of-state care. Our study adds to literature on the geographical component of health care accessibility and utilization in the context of acute conditions such as AMI and lends impetus to access out-of-state health records to better understand health care facility access and utilization for NYS residents.

Human vascular progenitor cells derived from renal arteries are endothelial-like and assist in the repair of injured renal capillary networks.

Vascular progenitor cells show promise for the treatment of microvasculature endothelial injury. We investigated the function of renal artery progenitor cells derived from radical nephrectomy patients, in animal models of acute ischemic and hyperperfusion injuries. Present in human adventitia, CD34positive/CD105negative cells were clonal and expressed transcription factors Sox2/Oct4 as well as surface markers CXCR4 (CD184)/KDR(CD309) consistent with endothelial progenitor cells. Termed renal artery-derived vascular progenitor cells (RAPC), injected cells were associated with decreased serum creatinine after ischemia/reperfusion, reduced albuminuria after hyperperfusion, and improved blood flow in both models. A small population of RAPC integrated with the renal microvasculature following either experimental injury. At a cellular level, RAPC promoted local endothelial migration in co-culture. Profiling of RAPC microRNA identified high levels of miRNA 218; also found at high levels in exosomes isolated from RAPC conditioned media after cell contact for 24 hours. After hydrogen peroxide-induced endothelial injury, RAPC exosomes harbored Robo-1 transcript; a gene known to be regulated by mir218. Such exosomes enhanced endothelial cell migration in culture in the absence of RAPC. Thus, our work shows the feasibility of pre-emptive pro-angiogenic progenitor cell procurement from a targeted patient population and potential therapeutic use in the form of autologous cell transplantation.

Total trihalomethanes in public drinking water supply and birth outcomes: a cross-sectional study.

Reproductive effects of long-term, low-dose exposure to disinfectant by-products have not been consistently documented in large populations despite the known toxicity of high exposures and the wide-spread occurrence of low concentrations in public drinking water. We investigated the effect of low-dose exposure to total trihalomethanes (TTHM) on birth weight and gestational term in New York State. All singleton live births from 1998 through 2003 in 62 counties in New York State were linked with public water supply (PWS) system boundaries based on mother's residential address on birth certificate. Using the data from public water supply system, TTHM measurements were assigned geographically and temporally to each birth record linked with PWS boundary. Individual level maternal information including mother's race, ethnicity, education, employment status, smoking, age, along with adequacy of prenatal care utilization and infant's gender was used in a logistic model to adjust for potential confounding. A small non-linear association was detected between TTHM exposure and low birth weight (<2,500 g) births (OR 1.14; 95 % confidence interval (CI) 1.08-1.21), preterm births (OR 1.14; 95 % CI 1.08-1.20) and for small for gestational age births (OR 1.10; 95 % CI 1.04-1.16) suggesting a small increase in risk for these birth outcomes with chronic low maternal exposure to drinking water containing trihalomethanes. Maternal exposure to TTHMs during pregnancy may be associated with low birth weight, preterm births and small for gestational age births.

A multifaceted comparison of ArcGIS and MapMarker for automated geocoding.

Geocoding is increasingly being used for public health surveillance and spatial epidemiology studies. Public health departments in the United States of America (USA) often use this approach to investigate disease outbreaks and clusters or assign health records to appropriate geographic units. We evaluated two commonly used geocoding software packages, ArcGIS and MapMarker, for automated geocoding of a large number of residential addresses from health administrative data in New York State, USA to better understand their features, performance and limitations. The comparison was based on three metrics of evaluation: completeness (or match rate), geocode similarity and positional accuracy. Of the 551,798 input addresses, 318,302 (57.7%) were geocoded by MapMarker and 420,813 (76.3%) by the ArcGIS composite address locator. High similarity between the geocodes assigned by the two methods was found, especially in suburban and urban areas. Among addresses with a distance of greater than 100 m between the geocodes assigned by the two packages, the point assigned by ArcGIS was closer to the associated parcel centroid ("true" location) compared with that assigned by MapMarker. In addition, the composite address locator in ArcGIS allows users to fully utilise available reference data, which consequently results in better geocoding results. However, the positional differences found were minimal, and a large majority of addresses were placed on the same locations by both geocoding packages. Using both methods and combining the results can maximise match rates and save the time needed for manual geocoding.

Voluntary electronic reporting of laboratory errors: an analysis of 37,532 laboratory event reports from 30 health care organizations.

Laboratory testing is essential for diagnosis, evaluation, and management. The objective was to describe the type of laboratory events reported in hospitals using a voluntary electronic error reporting system (e-ERS) via a cross-sectional analysis of reported laboratory events from 30 health organizations throughout the United States (January 1, 2000, to December 31, 2005). A total of 37,532 laboratory-related events were reported, accounting for 14.1% of all reported quality events. Preanalytic laboratory events were the most common (81.1%); the top 3 were specimen not labeled (18.7%), specimen mislabeled (16.3%), and improper collection (13.2%). A small number (0.08%) of laboratory events caused permanent harm or death; 8% caused temporary harm. Most laboratory events (55%) did not cause harm. Laboratory errors constitute 1 of 7 quality events. Laboratory errors often are caused by events that precede specimen arrival in the lab and should be preventable with a better labeling processes and education. Most laboratory errors do not lead to patient harm.

What finance needs to know about using technology to improve value.

As the nation witnesses the unfolding of healthcare reform, value as an expression of reduced cost and improved quality will become the watchword for the healthcare industry. New, relatively inexpensive technologies have become more widely available that can help healthcare provider organizations more easily evaluate their performance around quality and safety, thereby contributing to improved value. Senior finance leaders should play a leading role in guiding their organizations toward measuring clinical quality and monitoring performance in monetary terms, which will be increasingly important with the growing focus on value.

Racial and ethnic disparities in kidney transplantation.

Success of renal transplantation, as a viable alternative to dialysis, has been tempered by long-standing racial disparities. Ethnic minorities have less access to transplantation, are less likely to be listed for transplantation, and experience a higher rate of graft failure. Reasons for the existing racial disparities at various stages of the transplantation process are complex and multi-factorial. They include a combination of behavioral, social, environmental, and occupational factors, as well as potential intended or unintended discrimination within the healthcare system. Immunologic factors such as human leukocyte antigen matching, composition of the organ donor pool, and patient immune response, all of which affect post-transplantation graft rejection rates and patient survival, also contribute to health disparities between ethnic groups.

Writing 'fatal care: survive in the U.S. health system'.

Preventing medical errors requires the participation of both providers and patients.

Development of an interactive environmental public health tracking system for data analysis, visualization, and reporting.

Healthcare providers and governmental agencies routinely collect and report data on health outcomes. In addition, governmental agencies and industry collect and report information on environmental hazards and exposures that may impact health. Use of these data for environmental public health tracking has been a challenge because these data are managed by different data stewards, may contain confidential information that must be protected, and have not been collected in a manner to facilitate linkages. Available tools for analysis, visualization, and reporting of these data are either difficult to use or not available through a common user interface. The New York State Department of Health has developed a user-friendly interactive system to access and link these data while protecting confidential information. The Environmental Public health tracking system provides tools for describing the geographic patterns, trends, and statistical associations between health, environmental exposure, and environmental hazard data. These tools provide descriptive statistics and automated techniques that smooth the data in order to protect patient confidentiality and reduce random fluctuations in rates due to small numbers. This article describes the user interface, data linkages, and analytic, visualization, and reporting tools.

Does error and adverse event reporting by physicians and nurses differ?

BACKGROUND: Some hospitals have instituted voluntary electronic error reporting systems (e-ERSs) to gather data on medical errors, adverse events, near misses, or environmental issues in a peer review-protected environment. An e-ERS allows for real-time review, oversight, and intervention and provides insight into hospital processes in need of modification to reduce the likelihood of adverse hospital events. In a descriptive study of a standardized, Web-based reporting system, the reporting practices of physicians and nurses were compared. METHODS: Twenty-nine acute care hospitals and one long-term care organization implemented an e-ERS between August 2000 and December 2005. The reporting system consisted of a secure, Web-based portal available on all hospital computers. Events were classified by the level of impact on the patient using a standard classification scheme. All reports that occurred from August 2000 through January 2006 were analyzed in aggregate analyses. Hospitals and patients were de-identified to study investigators. RESULTS: Some 266,224 events were reported over 7.3 million inpatient days--1 event per 27.5 days. Physicians were the reporters of 1.1% of total events, nurses 45.3%, and other hospital employees 53.6%. Physicians were more likely to be the reporter for events that caused permanent harm, near death, or death of a patient (p < .01). Nurses were more likely to be the reporter for events that caused no or temporary harm (p < .01). DISCUSSION: Physicians reported a narrower spectrum of events than nurses; they were more likely to report as the impact of events on patients increased but less likely to report fatal events. Nurses' reporting remained stable across impact levels. Differences exist between whether nurses and physicians report events; physicians must be encouraged to increase their reporting of adverse events.

Inpatient medical errors involving glucose-lowering medications and their impact on patients: review of 2,598 incidents from a voluntary electronic error-reporting database.

OBJECTIVE: To describe characteristics of inpatient medical errors involving hypoglycemic medications and their impact on patient care. METHODS: We conducted a cross-sectional analysis of medical errors and associated adverse events voluntarily reported by hospital employees and staff in 21 nonprofit, nonfederal health-care organizations in the United States that implemented a Web-based electronic error-reporting system (e-ERS) between August 1, 2000, and December 31, 2005. Persons reporting the errors determined the level of impact on patient care. RESULTS: The median duration of e-ERS use was 3.1 years, and 2,598 inpatient error reports involved insulin or orally administered hypoglycemic agents. Nursing staff provided 59% of the reports; physicians reported <2%. Approximately two-thirds of the errors (1,693 of 2,598) reached the patient. Errors that caused temporary harm necessitating major treatment or that caused permanent harm accounted for 1.5% of reports (40 of 2,598). Insulin was involved in 82% of reports, and orally administered hypoglycemic agents were involved in 18% of all reports (473 of 2,598). Sulfonylureas were implicated in 51.8% of reports involving oral hypoglycemic agents (9.4% of all reports). CONCLUSION: An e-ERS provides an accessible venue for reporting and tracking inpatient medical errors involving glucose-lowering medications. Results are limited by potential underreporting of events, particularly by physicians, and variations in the reporter perception of patient harm.

Prevalence of inadequate glycemic control among patients with type 2 diabetes in the United Kingdom general practice research database: A series of retrospective analyses of data from 1998 through 2002.

BACKGROUND: Since the mid-1990s, the development of new oral antidiabetic agents (OAs) and treatment guidelines have created an opportunity to improve glycemic control in patients with type 2 diabetes. OBJECTIVES: This study aimed to assess the prevalence of good and inadequate glycemic control across a 5-year period among patients with diabetes in the United Kingdom. It also investigated the factors associated with achieving glycemic targets. METHODS: This was a retrospective, cross-sectional analysis of data from the General Practice Research Database. Three limits were used to assess glycosylated hemoglobin (HbA1c): 6.5%, 7.0%, or 7.5%. Values above the cutoffs indicated inadequate control of HbA1c; those at or below the cutoffs indicated good control. The study evaluated clinical and pharmacy data from the years 1998 to 2002 for patients with type 2 diabetes, > or =2 years of follow-up, and > or =2 HbA1c measurements during the first year. Five independent cross-sectional analyses were conducted, grouping data by year. Statistical significance was determined by Student t and chi2 tests. RESULTS: Data were analyzed for 10,663 patients aged 17 to 98 years. The number of total eligible type 2 diabetes patients increased over the course of the study period: 5674 patients in 1998, 6553 in 1999, 7314 in 2000, 7323 in 2001, and 6192 in 2002. Overall, the study population had a mean (SD) age of 66 (11.0) years, was 53% male (3033/5674), and had a body mass index of 29 kg/m(2). Seventy-six percent of patients had HbA1c >7.0% and 37% were taking > or =2 oral agents. In 1998 and 2002, 79% (4482/5674) and 76% (4732/6192) of patients, respectively, had inadequate glycemic control, defined as HbA1c >7.0%. When defined as HbA1c >7.5%, 69% (3923/5674) and 62% (3814/6192) of patients, respectively, had inadequate control. Finally, when defined as HbA1c >6.5%, 88% (5011/5674) of patients in both 1998 and 2002 had inadequate control. Compared with patients with good disease control (HbA1c < or =7.0%), patients with inadequate control were approximately 2 years younger (P < 0.001) and had been prescribed more OAs: 41% received > or =2 OAs in 1998 and 52% in 2002, compared with 23% and 34% (both, P = 0.001), respectively, of patients with good glycemic control (P < 0.02). Sex, number of diabetes complications, and number of comorbidities did not differ between groups (P = NS). CONCLUSIONS: Despite the introduction of new OAs and treatment guidelines, the prevalence of inadequate glycemic control remains high (>60%) in patients with type 2 diabetes in the United Kingdom. Regardless of the HbA1c cutoff, patients with inadequate control were younger and received prescriptions for more OAs than patients with good control.

Voluntary electronic reporting of medical errors and adverse events. An analysis of 92,547 reports from 26 acute care hospitals.

OBJECTIVE: To describe the rate and types of events reported in acute care hospitals using an electronic error reporting system (e-ERS). DESIGN: Descriptive study of reported events using the same e-ERS between January 1, 2001 and September 30, 2003. SETTING: Twenty-six acute care nonfederal hospitals throughout the U.S. that voluntarily implemented a web-based e-ERS for at least 3 months. PARTICIPANTS: Hospital employees and staff. INTERVENTION: A secure, standardized, commercially available web-based reporting system. RESULTS: Median duration of e-ERS use was 21 months (range 3 to 33 months). A total of 92,547 reports were obtained during 2,547,154 patient-days. Reporting rates varied widely across hospitals (9 to 95 reports per 1,000 inpatient-days; median=35). Registered nurses provided nearly half of the reports; physicians contributed less than 2%. Thirty-four percent of reports were classified as nonmedication-related clinical events, 33% as medication/infusion related, 13% were falls, 13% as administrative, and 6% other. Among 80% of reports that identified level of impact, 53% were events that reached a patient ("patient events"), 13% were near misses that did not reach the patient, and 14% were hospital environment problems. Among 49,341 patient events, 67% caused no harm, 32% temporary harm, 0.8% life threatening or permanent harm, and 0.4% contributed to patient deaths. CONCLUSIONS: An e-ERS provides an accessible venue for reporting medical errors, adverse events, and near misses. The wide variation in reporting rates among hospitals, and very low reporting rates by physicians, requires investigation.

Relative importance of PSA in prostate cancer treatment.

METHODS AND MATERIALS: A retrospective study was conducted to (1) determine the relationship between baseline prostate-specific antigen (PSA) levels and initial treatment decisions for prostate cancer (surgery, hormone therapy, radiation, or watchful waiting) and (2) estimate the impact of PSA progression (doubling or three consecutive rises) on subsequent treatment decisions. Patient records (n=1116) from three community urology practices and a large academic health system were reviewed. Multivariate models were fitted to assess the relationship between initial treatment and baseline PSA, Gleason score, race, number of comorbid conditions and age and between PSA progression and time to subsequent therapy (adjusted for other factors). RESULTS: Baseline PSA was a significant predictor of initial treatment among men with localized disease with the likelihood of hormone therapy increasing with higher PSA levels and the likelihood of surgery decreasing steadily with higher PSA levels. PSA was the strongest predictor of hormone therapy as first choice followed by age. Age followed by PSA was the strongest predictor of surgery as first treatment as well as radiation therapy. Initial PSA levels did not predict the choice of watchful waiting. Patients with PSA progression were eight times (95% CI: 5.3-12.1) more likely to initiate a subsequent therapy than patients who did not have PSA progression when controlling for other predictors. CONCLUSIONS: In clinical practice, PSA significantly impacts the urologist's primary therapy choice and determines when they introduce subsequent treatments.

Late genitourinary and gastrointestinal toxicity after magnetic resonance image-guided prostate brachytherapy with or without neoadjuvant external beam radiation therapy.

BACKGROUND: This study was designed to estimate the rates of late genitourinary (GU) and rectal toxicity after magnetic resonance image (MRI)-guided prostate brachytherapy exclusively or in conjunction with external beam radiation therapy (EBRT). METHODS: Between November 1997 and April 2002, 201 patients with category T1C prostate carcinoma (according to the 2002 American Joint Committee on Cancer staging criteria), prostate specific antigen levels < 10 ng/mL, and biopsy Gleason score 3 + 4 disease were treated with MRI-guided brachytherapy exclusively or in conjunction with EBRT. The MRI-guided technique was designed to spare the urethra based on delivery of the prescription dose to the peripheral zone exclusively. The Kaplan-Meier method was used to estimate rates of freedom from late GU and rectal toxicity. Comparisons were made using a log-rank test. RESULTS: At a median follow-up of 2.8 years (range, 0.5-5.0 years), the 4-year estimates of rectal bleeding requiring coagulation for patients who underwent implantation therapy, compared with patients who received combined-modality therapy, were 8% versus 30%, respectively (log-rank P value = 0.0001). Although erectile dysfunction was common (range, 82-93%), with the use of sildenafil citrate (Viagra), it was estimated that at least two-thirds of patients had erectile function comparable to or superior to baseline function, independent of whether they received monotherapy or combined-modality therapy (P = 0.46). The 4-year estimate of freedom from radiation cystitis was 100% versus 95% (P = 0.01) for patients who received monotherapy and patients who received combined-modality therapy, respectively. No urethral strictures were observed, and no patients underwent postimplantation transurethral resection of the prostate. CONCLUSIONS: In the current study, rectal bleeding after MRI-guided prostate brachymonotherapy was infrequent, and urethral and bladder toxicity is reported to be rare and may be attributed to the urethral-sparing technique of the MRI-guided approach.