Effect of α-blockers on Handgrip Test Response of Diastolic Blood Pressure in Hypertensive, Benign Hypertrophy of Prostate Patients in a Therapeutics Clinic, Kolkata: A Cross-sectional Study.

BACKGROUND: The isometric handgrip (IHG) test is commonly used to detect sympathetic autonomic dysfunction. Tamsulosin, approved for the management of symptomatic benign prostatic hyperplasia (BPH), acts as an antagonist for α1-adrenergic receptors (α1-AR), whereas prazosin, an α1 receptor blocker, being less selective than tamsulosin, is used as an antihypertensive agent clinically. Our objective was to investigate if there is a distinction in blood pressure (BP) increase during IHG exercise between individuals with essential hypertension taking tamsulosin compared to those taking prazosin. MATERIALS AND METHODS: A cross-sectional observational study was performed on 50 subjects receiving tablet prazosin and 47 subjects receiving tamsulosin, who were asked to undergo an IHG test. Pre- and posttest BP was recorded for both the groups, and the difference in diastolic BP (DBP) (delta DBP) was compared between the groups and to their respective baseline values. RESULTS: Post-IHG test, mean DBP was found to be 93.98 ± 9.13 mm Hg in the prazosin group and 101.00 ± 12.05 mm Hg in the tamsulosin group, respectively. The change of delta DBP in the tamsulosin group was significant, but the prazosin group showed an insignificant rise in DBP. CONCLUSION: Prazosin, being less selective than tamsulosin in terms of α1 receptor antagonism, showed suppression of BP during IHG. Tamsulosin demonstrates high selectivity for prostatic receptors while showing minimal affinity for vascular receptors. As a result, its impact on BP is expected to be minimal.

Sympathetic Neurofunction Testing in Gestational Hypertension and Relationship with Developing Preeclampsia and Eclampsia: Real-world Evidences from Clinical Pharmacology Clinics.

BACKGROUND: Gestational hypertension carries a high-risk for adverse maternal and fetal outcomes, and it can also develop into preeclampsia. A relative decrease in parasympathetic and increase in sympathetic activity has been seen in normal pregnancy which returns to baseline after delivery. The present study aimed to detect any abnormality in sympathetic neurofunction in gestational hypertension and to identify its possible association with the development of preeclampsia/eclampsia. METHODS: A prospective, observational study was carried out among gestational hypertensive patients between 24 and 26 weeks of gestation, who were sent to clinical pharmacology clinics for autonomic neurofunction testing, along with their 24-hour urinary protein testing reports. Preisometric handgrip (IHG) and post-IHG differences in diastolic blood pressure (DBP) were noted. The association between Δ DBP and the development of eclampsia/preeclampsia was probed. RESULTS: A total of 52 pregnancy-induced hypertension (PIH) participants, both multigravida (n = 15) and primigravida (n = 37) were included in one arm (PIH arm), and 52 matched (age and gravida) pregnant women, those do not have PIH included in another arm for comparative analysis. On comparing the PIH arm and normal arm, prehand grip DBP (p ≤ 0.0001), posthand grip DBP, and Δ DBP were significantly higher in the PIH arm. Correlation between Δ DBP and 24 hours' proteinuria was observed in the PIH arm, with a significant positive correlation. CONCLUSION: A high-rise in DBP post-IHG exercise is associated with gestational hypertensive mothers and this rise is strongly correlated with the development of preeclampsia and eclampsia, which suggests that addressing sympathetic hyperactivity could be a potential area to target therapeutics while managing gestational hypertension.

Safety incident reporting and barriers (SIRaB) study: Strategies and approaches for investigating patient safety events in a hospital set-up.

BACKGROUND: Unsafe patient events not only entail a clinical impact but also lead to economic burden in terms of prolonged hospitalization or unintended harm and delay in care delivery. Monitoring and time-bound investigation of patient safety events (PSEs) is of paramount importance in a healthcare set-up. OBJECTIVES: To explore the safety incident reporting behaviour and the barriers in a hospital set-up. METHODS: The study had two sections: (a) Retrospective assessment of all safety incidents in the past 1 year, and (b) Understanding the barriers of safety reporting by interviewing the major stakeholders in patient safety reporting framework. Further root cause analysis and failure mode effect analysis were performed for the situation observed. Results were statistically analyzed. RESULTS: Of the total of 106 PSEs reported voluntarily to the system, the highest reporting functional group was that of nurses (40.57%), followed by physicians (18.87%) and pharmacists (17.92%). Among the various factors identified as barriers in safety incident reporting, fear of litigation was the most observed component. The most commonly observed event was those pertaining to medication management, followed by diagnostic delay. Glitches in healthcare delivery accounted for 8.73% of the total reported PSEs, followed by 5.72% of events occurring due to inter-stakeholder communication errors. 4.22% of the PSEs were attributed to organizational managerial dysfunctionalities. Majority of medication-related PSE has moderate risk prioritization gradation. CONCLUSION: Effective training and sensitization regarding the need to report the patient unsafe incidents or near misses to the healthcare system can help avert many untoward experiences. The notion of 'No Blame No Shame' should be well inculcated within the minds of each hospital unit such that even if an error occurs, its prompt reporting does not get harmed.

Real-world Clinical Effectiveness on Glycaemic Parameters, Safety and Additional Benefits of Glargine U300 (Toujeo®) Initiation after Oral Antidiabetic Drug Failure in Insulin-naïve Patients with type 2 Diabetes Mellitus.

Background: Several studies have proved the advantages of second-generation insulin analogs in lowering intra-individual variability in plasma insulin levels, flexibility in dosing, a sustained glucose-lowering effect, and decreasing the risk of hypoglycemia. Glargine 300 is one of the newer second-generation basal insulin analogs to have been approved for both type 1 and 2 diabetes. The present study aims to assess the real-world clinical effectiveness and safety of Glargine U300 (Toujeo®) initiation after oral antidiabetic drug failure in insulin-naïve patients with T2DM. Methods: A prospective, observational study was conducted where participants were interviewed regarding their basic demographics, body weight, and treatment details. Glycemic parameters (HbA1C%, Fasting Plasma Glucose, and Post Prandial Blood Glucose) were observed in the initial 6 months, and changes were noted and compared. Any hypoglycemic events or other complications were also noted. Data collected were statistically analyzed. Results: The study included a total of 188 patients. Treatment with glargine 300 significantly reduced the mean HbA1C level from 9.78% at baseline to 7.90% at the end of 6 months of treatment (p < 0.001). 10.60% of patients achieved the glycemic target of ≤7.0% by the end of 6 months, while only 6.90% were within the target range at baseline. Similarly, significant reduction in FPG was observed at the end of 6 months treatment period with Glargine U300. A significant increase in dose requirement was observed throughout the study phase (p < 0.001). Incidence of hypoglycemia was noted in 2.12% of subjects. Conclusion: The lower incidence statistics of hypoglycemia coupled with sustained positive glycemic effects, stands out to be a prominent advantage of Glargine U300 over its other congeners.

Effectiveness of budesonide formoterol fixed-dose combination MDI in reducing cough symptoms in COVID-19 patients: A real-world evidence study.

Background: Cough is a wearisome and exasperating symptom affecting the daily life of the infected patient. Cough due to coronavirus disease 2019 (COVID-19) causes excessive morbidity in human populations globally. Apart from the morbidity associated with cough, it also enhances the transmission of this viral infection through droplets. Therefore, curbing cough is crucial to limit its spread. Patients often administer over-the-counter products and antitussive agents, which have no proven benefit. The present study was undertaken to find out if cough associated with COVID-19 and other indicative clinical outcomes is alleviated with a budesonide/formoterol fixed-dose combination (FDC) metered-dose inhaler (MDI). Materials and Methods: A prospective observational study was conducted in mild COVID-19 patients who presented with a cough score ≥8 at presentation. Patients who were initiated on ICS-LABA MDI were observed as group A and those who were not initiated on MDI were observed as Group B. Cough symptom score (at baseline and on day 3 and day 7), the incidence of hospital admission and/or death, and need for mechanical ventilation were documented. Prescribing patterns of anti-cough medications were also noted and analysed. Results: Compared to group B, a higher mean cough score reduction was noted for group A patients at day 3 and day 7 when compared to the baseline, and this was significant at P < 0.001. A significant negative correlation was also observed between mean latency of MDI initiation from the symptom onset and mean cough score reduction. Analysis of the proportion of patients prescribed medications to treat cough showed that overall, 10.78% did not require these, with a greater proportion in group A compared to group B. Conclusion: Patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 who were treated with ICS-LABA MDI along with usual care benefitted significantly in terms of symptom reduction compared to usual care.

Efficacy and safety of lobeglitazone, a new Thiazolidinedione, as compared to the standard of care in type 2 diabetes mellitus: A systematic review and meta-analysis.

AIM: This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of lobeglitazone as compared to the standard of care (SOC) in patients with type 2 diabetes mellitus (T2DM). METHODS: Databases were searched for relevant randomized controlled trials. The primary outcome was the comparison of the glycated hemoglobin (HbA1C) level after 24 weeks. Pooled mean differences and odds ratios were calculated using random-effects models. RESULTS: Of 267 studies that were screened, four were included. Treatment with adjunct lobeglitazone showed a reduction in the HbA1C level [mean difference: -0.23% (95% CI: -0.62 to 0.16); p = 0.24; i2: 87%; moderate GRADE (Grading of Recommendations Assessment, Development and. Evaluation) of evidence], fasting blood glucose level [mean difference: -7.12 mg/dl (95% CI: -20.09 to 5.85); p = 0.28; i2: 87%; moderate GRADE of evidence], and lipid profile as compared to those following treatment with the SOC; however, the changes were not statistically significant. The risk of hypoglycemia was significantly lower [odds ratio: 0.24 (95% CI: 0.08 to 0.70); p < 0.05; i2: 0%; moderate GRADE of evidence] without any significant difference in the risk of drug-related adverse events [odds ratio: 1.59 (95% CI: 0.87 to 2.93); p = 0.13; i2: 0%; moderate GRADE of evidence] following treatment with lobeglitazone as compared to those following treatment with the SOC. CONCLUSION: Treatment with adjunct lobeglitazone showed changes in the blood glycemic status and lipid profile similar to SOC in patients with T2DM, and the results were not statistically significant. Lobeglitazone was well tolerated; its safety profile was comparable to SOC.

Association between Polypharmacy and Cardiovascular Autonomic Function among Elderly Patients in an Urban Municipality Area of Kolkata, India: A Record-Based Cross-Sectional Study.

We assessed the association between polypharmacy and cardiovascular autonomic function among community-dwelling elderly patients having chronic diseases. Three hundred and twenty-one patients from an urban municipality area of Kolkata, India were studied in August 2022. The anticholinergic burden and cardiac autonomic function (Valsalva ratio, orthostatic hypotension, change in diastolic blood pressure after an isometric exercise, and heart rate variability during expiration and inspiration) were evaluated. Binary logistic regression analysis was performed to find out the association of polypharmacy and total anticholinergic burden with cardiac autonomic neuropathy. A total of 305 patients (age, 68.9 ± 3.4; 65.9% male) were included. Of these patients, 81 (26.6%) were on polypharmacy. Out of these 81 patients, 42 patients were on ninety-eight potential inappropriate medications. The anticholinergic burden and the proportion of patients with cardiac autonomic neuropathy were significantly higher among patients who were on polypharmacy than those who were not (8.1 ± 2.3 vs. 2.3 ± 0.9; p = 0.03 and 56.8% vs. 44.6%; p = 0.01). The presence of polypharmacy and a total anticholinergic burden of > 3 was significantly associated with cardiac autonomic neuropathy (aOR, 2.66; 95% CI, 0.91−3.98 and aOR, 2.51; 95% CI, 0.99−3.52, respectively). Thus, polypharmacy was significantly associated with cardiac autonomic neuropathy among community-dwelling elderly patients.

Issues and challenges of polypharmacy in the elderly: A review of contemporary Indian literature.

The aging population is of growing concern all across the globe as well as in India. Polypharmacy has been defined as the simultaneous use of multiple medications by an individual and the clinical suitability of such use. Polypharmacy is found more frequently in the geriatric population. Researches in India have also reiterated the fact. Polypharmacy in the geriatric population leads to many negative consequences such as increased adverse drug reactions, falls, frailty, and even increased mortality. Moreover, it leads to increased out-of-pocket expenditure. Polypharmacy also poses risk of poor treatment adherence and missed dose in the geriatric population. Mitigation measures in this regard may include increased awareness among physicians, improved medication management and adherence, efforts to reduce self-medication, and improper crosspathy.

Ivermectin and Hydroxychloroquine for Chemo-Prophylaxis of COVID-19: A Questionnaire Survey of Perception and Prescribing Practice of Physicians vis-a-vis Outcomes.

BACKGROUND: Chemoprophylaxis (CP) along with masking and physical distancing seem an undeniable alternative. Considering the significant but uncertain role of CP for the current COVID-19 pandemic situation, we aimed to determine the various aspects of CP prescribing practices among physicians across India. METHODS: An online survey was conducted among prescribing physicians across India where physicians were assessed for their prescribing practices on COVID-19 CP. Responses to the questionnaire were obtained via telephone, email and WhatsApp messages. Responses were duly analyzed thereafter. RESULT: Ivermectin was the preffered choice in 44% individuals followed by hydroxychloroquine in 34% individuals. Odds of COVID contact among those using HCQ and / or IVR prophylaxis was less than 1 of which IVR was found more protective. The present study also made a survey among 309 community dwellers, where odds of contacted COVID among those with any prophylaxis was 0.46 times than those without any prophylaxis. CONCLUSION: The HCPs found IVR to have a greater risk reduction than with HCQ; while the combination showed the greatest reduction and lack of CP use was associated with a high risk of SARS-CoV-2 infection.

Deprescribing for Better Patient Outcomes in Chronic Long Term Care and Role of Clinical Pharmacological Review.

Prescribing is always a risky proposition with a varied degree of vulnerability embedded in the act. It is therefore important to do a perfect balancing in favor of benefit against harm. Deprescribing is the planned and supervised process of dose reduction or stopping of prescribed medications, aimed at correcting inappropriate polypharmacy and improving patient outcomes. Informed reconciliation for potential deprescribing need should be a norm in all patients receiving many medications for multiple chronic comorbidities and is best done in partnership with the prescribing physician. Judicious deprescribing through clinical pharmacological review ensures better patient outcomes. We present here a case series from our experience in clinical pharmacology outpatients' department (OPD), highlighting how de-prescribing helps achieving better patient outcomes.

Leukocytoclastic vasculitis secondary to clozapine.

Leukocytoclastic vasculitis (LCV) may be secondary to drugs, underlying infection, collagen vascular disorders, or malignancy. Drug-induced vasculitis contributes to 10% of vasculitic skin lesions cases usually developing within 7-21 days of treatment initiation. The present case highlights a report of LCV in a 59-year-old male with a history of paranoid schizophrenia on clozapine therapy. The report upsurges the need to promote awareness and expedite diagnosis and treatment of drug-induced LCVs.

Etoricoxib-induced toxic epidermal necrolysis: A fatal case report.

Cyclooxygenase inhibitors were developed in the quest of enhanced analgesic efficacy devoid of gastric side effects. High usage of etoricoxib by prescription as well as self-administered routes has led to increasing reports of side effects and adverse reactions including dermatologic reactions in 0.1%-0.3% of cases. The present report enumerates a case of toxic epidermal necrolysis induced by etoricoxib.

Adverse drug reaction monitoring in patients on antiretroviral therapy in a tertiary care hospital in Eastern India.

BACKGROUND: Besides unparalleled benefits, highly active antiretroviral therapy is also associated with wide range of potential adverse drug reactions (ADRs), which hinders treatment adherence. The present study was thus designed to monitor and explore the pattern of occurrence of ADRs to various antiretroviral therapy (ART) regimens in a tertiary care ART setup. MATERIALS AND METHODS: A prospective, observational clinical study was carried out in the outpatient setting of nodal ART center of Eastern India. A total of 610 patients on various ART regimens were studied for suspected ADRs over 12 months. Adverse event history, medication history, and other relevant details were captured. Causality and severity of each reported ADR were duly assessed. RESULTS: 32.45% patients of total study participants presented with a total of 330 ADRs. Patients from zidovudine-based regimens presented with majority of ADRs such as anemia (up to 36%), central nervous system (CNS), and gastrointestinal (GI) side effects. Tenofovir-based regimens were, however, found to be mildly safer. The combination with Efavirenz was associated with majorly CNS side effects while that of nevirapine was associated with rash and pigmentation of nails. Atazanavir boosted second-line regimens were notably associated with increased serum lipid levels followed by other GI and CNS adverse effects. Increased liver enzymes were found in atazanavir-based second-line ART. CONCLUSION: The study enables to obtain information on the incidence and pattern of ADRs associated with various antiretroviral regimens, thereby reducing its occurrence and protecting the patient population from avoidable harm. Need of intensive monitoring for ADRs in ARTs thus seems to be a mandate.

Pedal edema associated with atypical antipsychotics.

This study describes a patient diagnosed as a case of bipolar affective disorder complaining of bothersome incidence of pedal edema 1 month after the initiation of atypical antipsychotic regimen with risperidone and quetiapine. All hematological and biochemical profiles were found to be normal. On discontinuation of risperidone, the condition remained unresolved even after 2 weeks, and the edema progressed reaching her calves. On tapering the dose of quetiapine, she started showing gradual improvement in edematous condition. Quetiapine was slowly discontinued. No further recurrence of edema occurred, and hence, no further medication changes were implemented. Pedal edema was found to be resolved within weeks of dechallenge of the regimen. Naranjo adverse drug reaction probability scale gave a score of 7 which denotes "probable" adverse drug reaction with quetiapine.

Impact on behavioral changes due to chronic use of sertraline in Wistar albino rats.

AIM: Despite having better tolerability and a wide range of clinical applications over other antidepressants, selective serotonin reuptake inhibitors (SSRIs) are also known to be associated with serious adverse effects like suicidal ideation on chronic use. The present study had explored the impact of the chronic use of sertraline, an SSRI, on the behavioral changes in Wistar albino rats. MATERIALS AND METHODS: The study was conducted on 30 Wistar albino rats of either sex; divided into five groups. Four groups were subjected to chronic mild stress induced by using various stressors randomly scheduled in a week and continued for a period of 3 weeks. The stressed rodents were subjected to sertraline treatment for 9 weeks in different human therapeutic doses extrapolated to animal doses. Behavioral changes were monitored, assessed, and evaluated throughout the treatment phase with the help of tests such as locomotor activity test, forced swim test, tail suspension test, antianxiety test, and sucrose preference test (SPT). RESULTS: All tests except SPT, demonstrated significant (P < 0.05) reduction in depressive-like activity in the stressed rodents by the mid-treatment phase, followed by an abrupt onset of the depressive state by the end of the treatment phase. SPT showed a significant (P < 0.05) increase in sucrose consumption throughout the treatment phase. CONCLUSION: Behavioral changes following chronic sertraline administration conferred gradual remission of depression state on initial treatment phase, followed by a reversal of effect on chronic use.

Polysaccharide-rich fraction of Termitomyces eurhizus accelerate healing of indomethacin induced gastric ulcer in mice.

The current study aims to determine the healing activity of water soluble polysaccharide-rich fraction of a wild mushroom, Termitomyces eurhizus (TEps) against the indomethacin induced gastric ulceration in mice model. Gastric tissue histology, myeloperoxidase (MPO) activity, cyclooxygenases (COX) 1 and 2 expression, prostaglandin E2 (PGE2) synthesis, and modulation of pro/anti inflammatory cytokines expression were studied for this purpose. Histological study shows that TEps (20 mg/kg) effectively healed the gastric ulceration. Based on biochemical results, the healing capacities of TEps could be attributed to reduction of MPO activity and protection of mucosal mucin content. Enhanced synthesis of PGE2 by modulation of COX-1 and COX-2 expression and a prominent shift of cytokines expression from pro (TNF-α, IL-1ß) to anti inflammatory (IL-10) side are also held responsible for ulcer healing. The preliminary study highlights the anti-ulcerogenic property of polysaccharide-rich fraction of Termitomyces eurhizus and opens an alternative cure for NSAID induced gastroduodenal diseases.