Enhancing Agricultural Sustainability Through Rhizomicrobiome: A Review.

Sustainable agriculture represents the responsible utilization of natural resources while safeguarding the well-being of the natural environment. It encompasses the objectives of preserving the environment, fostering economic growth, and promoting socioeconomic equality. To achieve sustainable development for humanity, it is imperative to prioritize sustainable agriculture. One significant approach to achieving this transition is the extensive utilization of microbes, which play a crucial role due to the genetic reliance of plants on the beneficial functions provided by symbiotic microbes. This review focuses on the significance of rhizospheric microbial communities, also known as the rhizomicrobiome (RM). It is a complex community of microorganisms that live in the rhizosphere and influence the plant's growth and health. It provides its host plant with various benefits related to plant growth, including biocontrol, biofertilization, phytostimulation, rhizoremediation, stress resistance, and other advantageous properties. Yet, the mechanisms by which the RM contributes to sustainable agriculture remain largely unknown. Investigating this microbial population presents a significant opportunity to advance toward sustainable agriculture. Hence, this study aims to provide an overview of the diversity and applications of RM in sustainable agriculture practices. Lately, there has been growing momentum in various areas related to rhizobiome research and its application in agriculture. This includes rhizosphere engineering, synthetic microbiome application, agent-based modeling of the rhizobiome, and metagenomic studies. So, developing bioformulations of these beneficial microorganisms that support plant growth could serve as a promising solution for future strategies aimed at achieving a new green revolution.

A cross-sectional study on COVID-19 vaccine hesitancy in peri-urban areas in Kanpur, Uttar Pradesh, India.

Vaccination is a potential public health solution for the prevention of infection. It reduces the severity of symptoms in the case of COVID-19. Despite the availability of vaccines, some people are hesitant to be vaccinated. The objectives of this study were to measure the proportion of vaccine hesitancy among the peri-urban population and identify its determinants. An adult population of 303 from two peri-urban areas in the field practice area of the Urban Health Training Center, Rama Medical College, was interviewed from February 22 to March 25, 2021. Epicollect 5 was used for collecting data, and STATA 16 was used for analysis. Multivariable logistic regression was applied to compute the adjusted odds ratio (AOR) (95% confidence interval) to find out the determinants of vaccine hesitancy. The 3Cs model-guided tools were used for data collection and analysis. More than one-fourth (28%) of the participants were vaccine-hesitant, whereas 34.6% had no confidence in the vaccine. Other reasons were complacency (40.6%) and convenience (35.9%). Vaccine hesitancy was significantly associated with gender [AOR=2.40 (1.12-5.16)] and trust in government [AOR=0.18 (0.08-0.45)], but there was no association with age group, political affiliation, or source of information about the vaccine. It is important to build people's trust in vaccines, make them convenient, and resolve the issues that are making them complacent. The health system needs to involve non-governmental organizations to reach out to those for whom there are issues of availability and approach.

Ribociclib plus letrozole in male patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: subgroup analysis of the phase IIIb CompLEEment-1 trial.

PURPOSE: CompLEEment-1 (NCT02941926) is a single-arm, open-label, multicentre phase IIIb study investigating the safety and efficacy of ribociclib plus letrozole (RIB + LET) in a large, diverse cohort who have not received prior endocrine therapy (ET) for advanced disease. We present an exploratory analysis of male patients. METHODS: Eligible patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC), who had no prior ET and ≤ 1 line of prior chemotherapy for advanced disease, received RIB + LET. Male patients also received goserelin or leuprolide. Primary endpoint was safety and tolerability; efficacy was a secondary endpoint. RESULTS: In total, 39/3246 patients were male. Baseline characteristics were similar to the overall population. Male patients experienced fewer treatment-related adverse events (AEs) and treatment-related serious AEs compared with the overall population; fewer male patients had treatment-related AEs leading to discontinuation, adjustment/interruption, or additional therapy. One male patient died as a result of a serious AE that was not considered to be treatment-related. The most common AE was neutropenia; the incidence of grade ≥ 3 neutropenia in males (41.0%) was lower than in the overall population (57.2%). Median follow-up was 25.4 months; median time to progression was not reached in males versus 27.1 months for the overall population. CONCLUSION: The clinical benefit and overall response rates in males were consistent with the overall population. This analysis demonstrates the safety and efficacy of ribociclib in a close-to-real-world setting, supporting the use of RIB + LET in male patients with HR+, HER2- ABC. TRIAL REGISTRATION NUMBER: NCT02941926 (Registered 2016).

Full population results from the core phase of CompLEEment-1, a phase 3b study of ribociclib plus letrozole as first-line therapy for advanced breast cancer in an expanded population.

PURPOSE: CompLEEment-1 is a phase 3b trial in an expanded patient population with hormone receptor-positive (HR +), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (ABC), the largest current trial of cyclin-dependent kinase 4 and 6 inhibitors in ABC. METHODS: Patients treated with ≤ 1 line of prior chemotherapy and no prior endocrine therapy for ABC received ribociclib 600 mg/day (3-weeks-on/1-week-off) plus letrozole 2.5 mg/day and additionally monthly goserelin/leuprolide in men and pre-/perimenopausal women. Eligibility criteria allowed inclusion of patients with stable CNS metastases and an Eastern Cooperative Oncology Group performance status of 2. Primary objectives were safety and tolerability, and secondary objectives were efficacy and quality of life (QoL). RESULTS: Overall, 3,246 patients were evaluated (median follow-up 25.4 months). Rates of all-grade and grade ≥ 3 treatment-related adverse events (AEs) were 95.2% and 67.5%, respectively. Treatment-related discontinuations due to all grade and grade ≥ 3 AEs occurred in 12.9% and 7.3% of patients, respectively. Rates of all-grade AEs of special interest (AESI) were as follows: neutropenia (74.5%), increased alanine aminotransferase (16.2%), increased aspartate aminotransferase (14.1%), and QTcF prolongation (6.7%); corresponding values for grade ≥ 3 AESI were 57.2%, 7.7%, 5.7%, and 1.0%, respectively. Median time to progression was 27.1 months (95% confidence interval, 25.7 to not reached). Patient QoL was maintained during treatment. CONCLUSION: Safety and efficacy data in this expanded population were consistent with the MONALEESA-2 and MONALEESA-7 trials and support the use of ribociclib plus letrozole in the first-line setting for patients with HR + , HER2- ABC. TRIAL REGISTRATION: linicalTrials.gov NCT02941926.

Association of Continued Use of SGLT2 Inhibitors From the Ambulatory to Inpatient Setting With Hospital Outcomes in Patients With Diabetes: A Nationwide Cohort Study.

OBJECTIVE: Limited data are available on the continuation of outpatient sodium glucose cotransporter 2 inhibitors (SGLT2is) during hospitalization. The objective was to evaluate associations of SGLT2i continuation in the inpatient setting with hospital outcomes. RESEARCH DESIGN AND METHODS: This nationwide cohort study used Veterans Affairs health care system data of acute care hospitalizations between 1 April 2013 and 31 August 2021. A total of 36,505 admissions of patients with diabetes with an outpatient prescription for an SGLT2i prior to hospitalization were included. The exposure was defined as SGLT2i continuation during hospitalization. Admissions where SGLT2i was continued were compared with admissions where it was discontinued. The primary outcome was in-hospital mortality. Secondary outcomes were acute kidney injury (AKI) and length of stay (LOS). Negative binomial propensity score-weighted and zero-truncated analyses were used to compare outcomes and adjusted for multiple covariates, including demographics and comorbidities. RESULTS: Mean (SE) age was 67.2 (0.1) and 67.5 (0.1) years (P = 0.03), 97.0% and 96.6% were male (P = 0.1), 71.3% and 72.1% White, and 20.8% and 20.5% Black (P = 0.52) for the SGLT2i continued and discontinued groups, respectively. After adjustment for covariates (age, sex, race, BMI, Elixhauser Comorbidity Index, procedures/surgeries, and insulin use), the SGLT2i continued group had a 45% lower mortality rate (incidence rate ratio [IRR] 0.55, 95% CI 0.42-0.73, P < 0.01), no difference in AKI (IRR 0.96, 95% CI 0.90-1.02, P = 0.17), and decreased LOS (4.7 vs. 4.9 days) (IRR 0.95, 95% CI 0.93-0.98, P < 0.01) versus the SGLT2i discontinued group. Similar associations were observed across multiple sensitivity analyses. CONCLUSIONS: Continued SGLT2i during hospitalization among patients with diabetes was associated with lower mortality, no increased AKI, and shorter LOS.

Continuous glucose monitoring in the hospital: an update in the era of COVID-19.

PURPOSE OF REVIEW: Continuous glucose monitoring (CGM) systems are Food and Drug Administration approved devices for the ambulatory setting; however, they remain investigational systems for inpatient use. This review summarizes the most recent and relevant literature on the use of continuous glucose monitoring in the hospital setting. RECENT FINDINGS: CGM provides real-time glucose data that enable healthcare professionals to make proactive and timelier clinical decisions with regards to diabetes management. CGM devices appear to be safe and accurate systems for glucose monitoring in the hospital setting. Real-time CGM systems and glucose telemetry can decrease hypoglycemia and reduce hyperglycemia in hospitalized patients with diabetes. Remote glucose monitoring decreases the need of frequent Point-of-care checks and personal protective equipment use while also mitigating staff exposure risk which is timely in the advent of the COVID-19 pandemic. Although most nursing staff have limited exposure and training on CGM technology, early studies show that CGM use in the hospital is well received by nurses. SUMMARY: Given the evidence in the current literature regarding CGM use in the hospital, CGM devices may be incorporated in the inpatient setting.

Continuous Glucose Monitoring-Guided Insulin Administration in Hospitalized Patients With Diabetes: A Randomized Clinical Trial.

OBJECTIVE: The efficacy and safety of continuous glucose monitoring (CGM) in adjusting inpatient insulin therapy have not been evaluated. RESEARCH DESIGN AND METHODS: This randomized trial included 185 general medicine and surgery patients with type 1 and type 2 diabetes treated with a basal-bolus insulin regimen. All subjects underwent point-of-care (POC) capillary glucose testing before meals and bedtime. Patients in the standard of care (POC group) wore a blinded Dexcom G6 CGM with insulin dose adjusted based on POC results, while in the CGM group, insulin adjustment was based on daily CGM profile. Primary end points were differences in time in range (TIR; 70-180 mg/dL) and hypoglycemia (<70 mg/dL and <54 mg/dL). RESULTS: There were no significant differences in TIR (54.51% ± 27.72 vs. 48.64% ± 24.25; P = 0.14), mean daily glucose (183.2 ± 40 vs. 186.8 ± 39 mg/dL; P = 0.36), or percent of patients with CGM values <70 mg/dL (36% vs. 39%; P = 0.68) or <54 mg/dL (14 vs. 24%; P = 0.12) between the CGM-guided and POC groups. Among patients with one or more hypoglycemic events, compared with POC, the CGM group experienced a significant reduction in hypoglycemia reoccurrence (1.80 ± 1.54 vs. 2.94 ± 2.76 events/patient; P = 0.03), lower percentage of time below range <70 mg/dL (1.89% ± 3.27 vs. 5.47% ± 8.49; P = 0.02), and lower incidence rate ratio <70 mg/dL (0.53 [95% CI 0.31-0.92]) and <54 mg/dL (0.37 [95% CI 0.17-0.83]). CONCLUSIONS: The inpatient use of real-time Dexcom G6 CGM is safe and effective in guiding insulin therapy, resulting in a similar improvement in glycemic control and a significant reduction of recurrent hypoglycemic events compared with POC-guided insulin adjustment.

Ribociclib plus letrozole in subgroups of special clinical interest with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: Subgroup analysis of the phase IIIb CompLEEment-1 trial.

BACKGROUND: The phase IIIb CompLEEment-1 study evaluated ribociclib plus letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). Outcomes were investigated in the following subgroups: central nervous system (CNS) metastases, prior chemotherapy for advanced disease, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2, and visceral metastases plus prior chemotherapy for advanced disease or ECOG PS 2. PATIENTS AND METHODS: Patients with HR+, HER2- ABC without prior hormonal treatment for advanced disease received oral ribociclib (600 mg once daily, 3 weeks on/1 week off) plus letrozole (2.5 mg once daily, continuous). Primary endpoint was safety/tolerability, assessed via occurrence of adverse events (AEs); key secondary endpoints included time to progression (TTP), overall response rate, and clinical benefit rate. RESULTS: 51 patients had CNS metastases, 194 received prior chemotherapy for advanced disease, 112 had ECOG PS 2, 146 had visceral metastases plus prior chemotherapy, and 77 had visceral metastases plus ECOG PS 2. Safety results were consistent with those in the overall CompLEEment-1 population; no new safety concerns were identified. The AE profile was manageable with low rates of discontinuations due to AEs. TTP in patients with CNS metastases was consistent with the overall study population and shorter for other patient subgroups. Each patient subgroup achieved meaningful clinical benefit from treatment, consistent with the overall population. CONCLUSION: These findings confirm the clinical benefit of ribociclib plus endocrine therapy in high-risk patient subgroups of clinical interest commonly underrepresented in clinical trials.

Accuracy of Dexcom G6 Continuous Glucose Monitoring in Non-Critically Ill Hospitalized Patients With Diabetes.

OBJECTIVE: Advances in continuous glucose monitoring (CGM) have transformed ambulatory diabetes management. Until recently, inpatient use of CGM has remained investigational, with limited data on its accuracy in the hospital setting. RESEARCH DESIGN AND METHODS: To analyze the accuracy of Dexcom G6, we compared retrospective matched-pair CGM and capillary point-of-care (POC) glucose data from three inpatient CGM studies (two interventional and one observational) in general medicine and surgery patients with diabetes treated with insulin. Analysis of accuracy metrics included mean absolute relative difference (MARD), median absolute relative difference (ARD), and proportion of CGM values within 15, 20, and 30% or 15, 20, and 30 mg/dL of POC reference values for blood glucose >100 mg/dL or ≤100 mg/dL, respectively (% 15/15, % 20/20, % 30/30). Clinical reliability was assessed with Clarke error grid (CEG) analyses. RESULTS: A total of 218 patients were included (96% with type 2 diabetes) with a mean age of 60.6 ± 12 years. The overall MARD (n = 4,067 matched glucose pairs) was 12.8%, and median ARD was 10.1% (interquartile range 4.6, 17.6]. The proportions of readings meeting % 15/15, % 20/20, and % 30/30 criteria were 68.7, 81.7, and 93.8%, respectively. CEG analysis showed 98.7% of all values in zones A and B. MARD and median ARD were higher in the case of hypoglycemia (<70 mg/dL) and severe anemia (hemoglobin <7 g/dL). CONCLUSIONS: Our results indicate that CGM technology is a reliable tool for hospital use and may help improve glucose monitoring in non-critically ill hospitalized patients with diabetes.

Reducing Inpatient Hypoglycemia in the General Wards Using Real-time Continuous Glucose Monitoring: The Glucose Telemetry System, a Randomized Clinical Trial.

OBJECTIVE: Use of real-time continuous glucose monitoring (RT-CGM) systems in the inpatient setting is considered investigational. The objective of this study was to evaluate whether RT-CGM, using the glucose telemetry system (GTS), can prevent hypoglycemia in the general wards. RESEARCH DESIGN AND METHODS: In a randomized clinical trial, insulin-treated patients with type 2 diabetes at high risk for hypoglycemia were recruited. Participants were randomized to RT-CGM/GTS or point-of-care (POC) blood glucose testing. The primary outcome was difference in inpatient hypoglycemia. RESULTS: Seventy-two participants were included in this interim analysis, 36 in the RT-CGM/GTS group and 36 in the POC group. The RT-CGM/GTS group experienced fewer hypoglycemic events (<70 mg/dL) per patient (0.67 [95% CI 0.34-1.30] vs. 1.69 [1.11-2.58], P = 0.024), fewer clinically significant hypoglycemic events (<54 mg/dL) per patient (0.08 [0.03-0.26] vs. 0.75 [0.51-1.09], P = 0.003), and a lower percentage of time spent below range <70 mg/dL (0.40% [0.18-0.92%] vs. 1.88% [1.26-2.81%], P = 0.002) and <54 mg/dL (0.05% [0.01-0.43%] vs. 0.82% [0.47-1.43%], P = 0.017) compared with the POC group. No differences in nocturnal hypoglycemia, time in range 70-180 mg/dL, and time above range >180-250 mg/dL and >250 mg/dL were found between the groups. The RT-CGM/GTS group had no prolonged hypoglycemia compared with 0.20 episodes <54 mg/dL and 0.40 episodes <70 mg/dL per patient in the POC group. CONCLUSIONS: RT-CGM/GTS can decrease hypoglycemia among hospitalized high-risk insulin-treated patients with type 2 diabetes.

Association of glucose variability at the last day of hospitalization with 30-day readmission in adults with diabetes.

OBJECTIVE: To evaluate whether increased glucose variability (GV) during the last day of inpatient stay is associated with increased risk of 30-day readmission in patients with diabetes. RESEARCH DESIGN AND METHODS: A comprehensive list of clinical, pharmacy and utilization files were obtained from the Veterans Affairs (VA) Central Data Warehouse to create a nationwide cohort including 1 042 150 admissions of patients with diabetes over a 14-year study observation period. Point-of-care glucose values during the last 24 hours of hospitalization were extracted to calculate GV (measured as SD and coefficient of variation (CV)). Admissions were divided into 10 categories defined by progressively increasing SD and CV. The primary outcome was 30-day readmission rate, adjusted for multiple covariates including demographics, comorbidities and hypoglycemia. RESULTS: As GV increased, there was an overall increase in the 30-day readmission rate ratio. In the fully adjusted model, admissions with CV in the 5th-10th CV categories and admissions with SD in the 4th-10th categories had a statistically significant progressive increase in 30-day readmission rates, compared with admissions in the 1st (lowest) CV and SD categories. Admissions with the greatest CV and SD values (10th category) had the highest risk for readmission (rate ratio (RR): 1.08 (95% CI 1.05 to 1.10), p<0.0001 and RR: 1.11 (95% CI 1.09 to 1.14), p<0.0001 for CV and SD, respectively). CONCLUSIONS: Patients with diabetes who exhibited higher degrees of GV on the final day of hospitalization had higher rates of 30-day readmission. TRIAL REGISTRATION NUMBER: NCT03508934, NCT03877068.

Advancing the Use of CGM Devices in a Non-ICU Setting.

Improvements in glycemic control using continuous glucose monitoring (CGM) systems have been demonstrated in the outpatient setting. Among hospitalized patients the use of CGM is largely investigational, particularly in the non-ICU setting. Although there is no commercially available closed-loop system, it has recently been evaluated in the non-critical care setting. Both CGMs and closed-loop systems may lead to improved glycemic control, decreased length of stay, reduced risk of adverse events related to severe hypoglycemia or hyperglycemia. Limitations of inpatient use of CGM and closed-loop systems include lack of FDA approvals, inexperience with this technology, and costs related to supplies. Significant investment may be necessary for hospital staff training and for development of infrastructure to support inpatient use. Additional limitations for CGM systems includes potential inaccuracy of interstitial glucose measurements due to medication interferences, sensor lag, or sensor drift. Limitations for closed-loop systems also includes need for routine monitoring to detect infusion site issues as well as monitoring to ensure adequate insulin supply in reservoir to avoid abrupt cessation of insulin infusion leading to severe hyperglycemia. Hospital staff must be familiar with trouble-shooting and conversion to alternative mode of insulin delivery in the event of insulin pump malfunction. Given these complexities, implementation of closed-loop systems may require involvement of an endocrinology team, limiting widespread adoption. This article reviews current state of CGM and closed-loop system use in the non-ICU setting, available literature, advantages and limitations, as well as suggestions for future CGM design, specifically for the inpatient setting.

The Effect of Continuous Glucose Monitoring in Preventing Inpatient Hypoglycemia in General Wards: The Glucose Telemetry System.

BACKGROUND: Few studies have examined the use of continuous glucose monitoring (CGM) devices in the general wards. The aim of this pilot study was to examine whether CGM readings can be successfully transmitted from the bedside to a central monitoring device in the nursing station, and whether a glucose telemetry system can prevent hypoglycemic events. METHODS: We present pilot data on 5 consecutive insulin treated general medicine patients with type 2 diabetes (T2DM) whose glucose values were observed with CGM (DEXCOM) and the results were transmitted to a central nursing station monitoring system using DEXCOM Follow and Share 2 software. CGM alarms were set-up at glucose <85 mg/dl. RESULTS: Duration of CGM observation was 4.0 ± 1.6 days (mean ± SD). During CGM, the overall time spent within blood glucose (BG) target of 70-179 mg/dl was 64.68 ± 15% (mean ± SD), on hypoglycemia (<70 mg/dl) was 0.30% ± 0.39, and time spent on hyperglycemia (≥180 mg/dl) was 35.02% ± 15.5. Two patients had 3 actions of prevention of potential hypoglycemia (CGM BG <70 mg/dl for >20 minutes) captured by alarm. No patients had CGM glucose value <54 mg/dl. CONCLUSIONS: This pilot study indicates that the use of CGM values in hospitalized patients can be successfully transmitted to a monitoring device in the nursing station, improving patient surveillance in insulin treated patients with diabetes.

Implementation and outcomes of a pharmacist-managed clinical video telehealth anticoagulation clinic.

PURPOSE: The use of clinical video telehealth (CVT) technology to optimize the deployment of clinical pharmacy specialist resources in a community-based outpatient clinic (CBOC) is described. SUMMARY: In 2012, clinical pharmacy specialists at a Veterans Affairs (VA) medical center began using CVT technology to provide anticoagulation therapy management services to patients at a CBOC about 12 miles away. Using videoconferencing technology (video cameras and high-definition widescreen monitors), the remotely located pharmacists conduct patient interviews, evaluate International Normalized Ratio (INR) values, and gather other clinical data for use in therapeutic planning. Under the supervision of pharmacists, CBOC telehealth technicians perform targeted physical assessments (e.g., point-of-care INR values, measurements of vital signs), and the results are transmitted to the medical center for pharmacist evaluation. CVT policies and procedures jointly developed by pharmacy, telehealth, and CBOC nursing staff require focused training for clinic personnel and informed patient consent to receive CVT services. During the first few months of CVT clinic operations, the mean percentage of time patients' INR values were within the therapeutic range remained stable (about 81%, compared with about 77% under the previous face-to-face clinic model), and a high level of patient satisfaction was maintained. Implementation of CVT anticoagulation monitoring services enabled pharmacist resource reallocation to other duties. CONCLUSION: Through the use of CVT technology, high-quality anticoagulation services and patient satisfaction were maintained and the allocation of clinical pharmacy specialist resources was optimized.

Performance of fruit extract of Melastoma malabathricum L. as sensitizer in DSSCs.

Dye-sensitized solar cells (DSSCs) with fruit extracts, of Melastoma malabathricum L. as sensitizer, were fabricated. The fruit dye was extracted in two different solvents; de-ionized water (MMD) and ethanol (MME). The dye was subjected to UV-Vis and DSC studies. UV-Vis studies show absorption of light for a wider range of wavelength for MMD as compared to MME. Both MMD and MME were found to be stable till 121°C, as shown by DSC studies, beyond which MME showed unstable behavior. FTIR spectra of MMD and MME along with dye adsorbed TiO2 were recorded. MMD showed better adsorption with TiO2 than with MME. Voc, Jsc and efficiencies of the MMD sensitized solar cells were obtained in the ranges 420-430 mV, 1.25-1.50 mA cm(-2) and 1.11-1.37% respectively, while for MME sensitized solar cells they were in the ranges 370-380 mV, 0.63-0.87 mA cm(-2) and 0.41-0.72% respectively. Preliminary investigation on stability of DSSCs which were fabricated using both the extracts revealed sharp drop in efficiency of DSSC with MME in comparison to DSSC with MMD as sensitizer.