Comparative Safety Surveillance of Triple (IDA) Versus Dual Therapy (DA) in Mass Drug Administration for Elimination of Lymphatic Filariasis in Kenya: A Cohort Event Monitoring Study.

INTRODUCTION: Dual diethylcarbamazine and albendazole (DA) therapy is the standard mass drug administration (MDA) regimen for lymphatic filariasis in Kenya. Following the recent World Health Organization recommendation, Kenya piloted triple therapy with ivermectin, diethylcarbamazine, and albendazole (IDA) in MDA. OBJECTIVE: We conducted a community-based, observational, cohort event monitoring study to compare the types, frequency, severity, and predictors of adverse events following dual versus triple therapy in 20,421 eligible residents. METHODS: Residents in Kilifi (n = 10,010) and Mombasa counties (n = 10,411) received DA and IDA through MDA campaigns, respectively. Adverse events were actively monitored through house-to-house visits on days 1, 2, and 7 after MDA. Any clinical events reported before and after MDA were cross-checked and verified to differentiate pre-existing events from MDA-associated adverse events. RESULTS: Overall, 5807 and 3102 adverse events were reported by 2839 and 1621 individuals in the IDA and DA groups, respectively. The incidence of experiencing one or more adverse events was significantly higher (p < 0.0001) in the IDA group (27.3%; 95% confidence interval [CI] 26.4-28.2) than in the DA group (16.2%; 95% CI 15.5-16.9). Dizziness (15.9% vs 5.9%) and drowsiness (10.1% vs 2.6%) were the most common adverse events and significantly higher in the IDA group compared with the DA group (p < 0.0001). Most adverse events were mild or moderate with a few severe cases (IDA = 0.05%; 95% CI 0.35-0.78, DA = 0.03%; 95% CI 0.14-0.60). Female sex, obesity, taking three or more diethylcarbamazine or ivermectin tablets, and having pre-existing clinical symptoms were significant predictors of adverse events following IDA treatment. CONCLUSIONS: Ivermectin, diethylcarbamazine, and albendazole as a combination is as safe and well tolerated as DA to use in MDA campaigns with no serious life-threatening adverse events. Systemic mild-to-moderate adverse events with a few severe cases and transient adverse events are more common with IDA treatment than with DA treatment. Hence, integrating pharmacovigilance into a MDA program is recommended for the timely detection and management of adverse events.

Impact of educational interventions on utilization patterns of anticancer agents in patients with breast cancer at the specialty oncology care setting in South India.

Aims/Objectives: This study was conducted to assess the utilization patterns of anticancer agents in patients with breast cancer and to provide practice recommendations/educational interventions to optimize medication use in patients with breast cancer. Materials and Methods: This was an ambispective study conducted for a period of 3 years at a private, specialty oncology care hospital in South India. In the initial phase, the selection of anticancer agents, dosage of anticancer agents, and management of chemotherapy-induced nausea and vomiting (CINV) were reviewed retrospectively (using paper medical records) with respect to the National Cancer Comprehensive Network guidelines. The administration of anticancer agents and anti-emetics were reviewed with respect to the hospital drug administration policies. The deviations from the standards were reported, and practice recommendations/educational interventions were developed. Treatment patterns were reevaluated prospectively after providing educational interventions. Descriptive statistics were used to report and compare the results from both phases. Results: During retrospective phase, we observed 80% compliance in the selection of anticancer drugs, 74% compliance in drug dosing, and 63.5% compliance in the administration of anti-cancer agents. After the implementation of educational interventions, we observed 85% compliance in the selection of anticancer agents, 82.3% in their dosing, and 86.9% compliance in the administration of anticancer agents. For the management of CINV, we observed 75% compliance in the selection of drugs (vs. 53% during preintervention), 92% compliance in their dosing (vs. 90% during preintervention), 85.1% compliance in the administration of anti-emetics (vs. 50% during preintervention), and 80% compliance in the management of delayed CINV (vs. 60% during preintervention). Conclusions: Treatment patterns of breast cancer were improved with respect to treatment standards after educational interventions to oncology care team.

Impact of educational intervention on the best immunization practices among practicing health care professionals in a south Indian city.

BACKGROUND AND AIMS: Maintaining the quality and safety of immunization is as important as the efficacy of vaccines in vaccine-preventable diseases (VPD) programs. The aim of this study was to determine the problems associated with different stages of vaccine use and to assess the outcome of an educational intervention on safety and quality use of vaccines among health care providers. METHODS: A pilot prospective interventional study was conducted over a period of 2 years at 271 sites in Mysuru, India. The study population was health care professionals (HCPs) involved in immunization and a sample of parents (one per site). A validated questionnaire was used as a study tool. An educational intervention on best immunization practice was conducted for the enrolled HCPs and the impact of the educational intervention was assessed using the study tool after 3 weeks. RESULTS: The total number of the study population was 594 (323 HCPs and 271 parents). Of these, 41.49% were working at community health care facility and 33.13% were enrolled from primary care centers. There were statistically significant improvements in post interventional assessment of all stages of the immunization process including storage (p -0.001), transportation (p -0.001), administration (p 0.001), monitoring and reporting of adverse events following immunization (AEFIs) (p -0.001), knowledge of AEFIs (p 0.001), and HCP-parent communication (p 0.001). AEFI reporting improved by 30% in the post education phase. CONCLUSION: Continuous education and motivation can result in positive behavioral changes on best immunization practices amongst HCPs involved in immunization, which may help to improve and maintain the safety and quality use of vaccines in immunization centers irrespective of the type of facility.

Prevalence, Risk Factors, and Cost Burden of Fall-Related Hospital Admissions in india.

OBJECTIVE: To assess prevalence, risk factors, and cost burden of fall-related hospital admissions among older people in India. Previous studies conducted in India have not focused on the number of fall-related hospital admissions.
DESIGN: A prospective observational study was carried out over 12 months. Socio-demographic, medical and medication details were collected from the patients, medical records, and treating physicians.
SETTING: The study was conducted in internal medicine, orthopedics, and emergency departments of a tertiary care teaching hospital in Mysuru, Southern India.
PARTICIPANTS: Patients 60 years of age or older, of any gender, admitted to hospital were included in this study.
MAIN OUTCOME MEASURE: Prevalence of fall-related hospital admission, fall-related hospital admission associated with medication use, and direct cost incurred due to fall-related hospital admission.
RESULTS: A total of 1,036 patients [Males 53.6%] with a mean (SD) age of 69.3 (8.1) years were included in the study. A total of 188 patients were admitted due to falling with the prevalence of 18.1%. The majority of patients fell due to environmental factors [105 (55.8%)]. Among medication-related falls (20), the majority were associated with the use of antihyperglycemics and antihypertensives. Increasing age, female gender, and multiple comorbidities were identified as risk factors for fall-related hospital admissions.
CONCLUSIONS: Falls are a common reason for hospital admission among older populations. Clinicians need to focus on modifiable risk factors to reduce the prevalence of falls and advise patients and their caregivers about appropriate self-care behaviors.

What Future Healthcare Professionals Need to Know About Pharmacovigilance: Introduction of the WHO PV Core Curriculum for University Teaching with Focus on Clinical Aspects.

Adverse drug reactions (ADRs) can cause serious health problems, as shown in studies about drug-related hospitalizations. To build knowledge of and raise awareness about ADRs among healthcare professionals, more education in the field of ADRs and pharmacovigilance (PV) is needed. No standard exists for teaching PV at universities for medical, pharmacy, dentistry and nursing students, so a core curriculum needs to be developed to teach important aspects of PV to students. In September 2016, a stakeholders' meeting was initiated on behalf of the World Health Organization (WHO) and organized by the Netherlands Pharmacovigilance Centre Lareb. This meeting addressed and agreed on the PV competencies students need to develop and what key aspects of the subject should be taught. Five key aspects were identified: understanding the importance of PV in the context of pharmacotherapy, and preventing, recognizing, managing and reporting ADRs. Since time and resources for PV education are limited, elements of the WHO PV core curriculum for university teaching were designed to be integrated into existing courses but can be used as a stand-alone programme. The basis of and outline for the WHO PV core curriculum for university teaching are addressed in this paper. It is expected that PV competencies for students are vital for their contribution to safe use of medicines in the future. In addition, this article aims to stimulate discussion on this subject and promote collaboration between universities, national PV centres and other stakeholders to integrate key aspects of PV in their educational programmes.

A Prospective Surveillance of Pharmacovigilance of Psychotropic Medicines in a Developing Country.

AIMS/OBJECTIVES: Psychotropic drugs are associated with significant short-term and long-term safety issues which may affect patients' mental health, physical health and cost of care. EXPERIMENTAL DESIGNS: This was a prospective study conducted in psychiatry department of a tertiary care hospital. Study included patients of any age and either sex who presented with psychiatric illness as diagnosed by ICD-10 and were receiving at least one psychotropic agent. The study involved both intensive and spontaneous reporting methods to identify ADRs. Causality, Severity, Preventability of reported ADR was assessed using standard scales. PRINCIPLE OBSERVATION: Of 4321 patients reviewed, 1630 patients met study criteria, 990 ADRs were identified from 613 patients at an overall incidence rate of 37.6%. Antidepressants were the commonest group of agents implicated in ADRs (42%) followed by Antipsychotics (41%). Escitalopram (15.9%) and Olanzapine (12.1%) were the most commonly implicated medications. Most commonly involved system organ class was Gastrointestinal system (22.7%) followed by Central and peripheral nervous system (17.8%). Dry mouth (10.2%), weight gain (8.18%) and tremors (5.85%) were the commonly reported ADRs. Female gender (p = 0.002), Co-morbid conditions (p = 0.001) and drug- drug interactions (p = 0.000) were found as risk factors in developing ADRs in psychiatry patients. CONCLUSION: Patients receiving psychotropic medicines need routine monitoring to ensure their safety and adherence.

Impact of antidepressants use on risk of myocardial infarction: A systematic review and meta-analysis.

AIMS: The aim of the study was to perform a systematic review and meta-analysis to determine the association between antidepressants use and risk of myocardial infarction (MI), and whether this association differs between tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs). METHODS: A PubMed/MEDLINE search was conducted for studies published up to December 2013. Included studies were evaluated for publication bias and heterogeneity. Depending on the presence of heterogeneity, a random or fixed effects model was used to identify the pooled relative risk (RR) with 95% confidence intervals (CIs). Cumulative meta-analysis, subgroup and sensitivity analyses were also performed. All analyses were performed using comprehensive meta-analysis software. RESULTS: Fourteen (five cohort and nine case-control) studies were included. There was heterogeneity among the studies (P heterogeneity = 0.02; I (2) = 68%) but no publication bias (Begg's P = 0.30 and Egger's P = 0.45). Antidepressants use significantly increases the risk of myocardial infarction (MI) (RR = 2.03; 95% CI = 1.30-3.18; P < 0.01). On subgroup analysis by study design, cohort studies show significant positive association (RR = 2.16; 95% CI = 1.42-3.29; P < 0.01), but not case-control studies (RR = 2.47; 95% CI = 0.69-8.90; P = 0.17). Sensitivity analysis and cumulative meta-analysis confirmed the stability of results. TCAs users are having 36% increased risk of MI after excluding one outlier (RR = 1.36; 95% CI = 1.10-1.67; P < 0.01), but SSRIs showing no association (RR = 0.84; 95% CI = 0.57-1.22; P = 0.35). CONCLUSIONS: We found evidence that the use of antidepressants was associated with elevated risk of MI. Further research is needed to identify the underlying biological mechanisms.

An adverse drug interaction of haloperidol with levodopa.

Drug interactions are known to play a significant role in the incidence of adverse drug reactions (ADRs) both in the community and in hospitals. Both the newer atypical antipsychotics and their more traditional counterparts are subject to drug - drug interactions amongst themselves, with other psychotropics, and with the agents used in the treatment of various physical ailments. The most common interactions encountered in clinical practice are pharmacodynamic in nature. It is well established that antipsychotic drugs reduce the efficacy of levodopa in parkinson's disease by blockade of dopamine receptors in the corpus striatum. The case reported here illustrates a common pharmacodynamic drug interaction of haloperidol with levodopa in a 60-year-old female patient.

Identification and management of adverse effects of antipsychotics in a tertiary care teaching hospital.

OBJECTIVE: Antipsychotics have revolutionized psychiatry by allowing significant numbers of patients in long-term hospital settings to be discharged and successfully maintained in the community. However, these medications are also associated with a range of adverse events ranging from mostly annoying to rarely dangerous. This study is carried out to identify the adverse drug reactions (ADRs) to antipsychotics and its management in psychiatric patients. METHODS: Prospective interventional study was conducted in the psychiatric unit of a tertiary care hospital. Patients of any age and either sex prescribed with at least one antipsychotic were included and monitored for ADRs. FINDINGS: Among the 517 patients receiving antipsychotics, a total of 289 ADRs were identified from 217 patients at an overall incidence rate of 41.97%. Sixty-seven different kinds of ADRs were observed in the study patients. Central and peripheral nervous system was the most commonly affected system organ class (n = 59) and weight gain (n = 30) was the most commonly observed ADR. Olanzapine was most commonly implicated in reported ADRs (n = 92) followed by risperidone (n = 59). Of the 289 ADRs, 80% required interventions including cessation of drug and/or specific/symptomatic/nonpharmacological treatment. CONCLUSION: This post marketing surveillance study provides a representative data of the ADR profile of the antipsychotics likely to be encountered in psychiatric patients in an Indian tertiary care hospital.

Lorazepam-induced diplopia.

Diplopia - seeing double - is a symptom with many potential causes, both neurological and ophthalmological. Benzodiazepine induced ocular side-effects are rarely reported. Lorazepam is one of the commonly used benzodiazepine in psychiatric practice. Visual problems associated with administration of lorazepam are rarely reported and the frequency of occurrence is not established. We report a rare case of lorazepam-induced diplopia in a newly diagnosed case of obsessive compulsive disorder.

Health-related quality of life assessment using St. George's respiratory questionnaire in asthmatics on inhaled corticosteroids.

CONTEXT: Chronic diseases like asthma have significant effects on patients' health-related quality of life (HRQoL). HRQoL measures additional indices as compared to objective measurements like spirometry. AIMS: To assess and compare disease-specific quality of life in asthma patients using St. George's Respiratory Questionnaire (SGRQ) receiving fluticasone, beclomethasone, and budesonide (BUD). SETTINGS AND DESIGN: A prospective, open label, randomized, parallel group study conducted at a tertiary care teaching hospital in South India. MATERIALS AND METHODS: A 6-month follow-up of 277 patients with mild, moderate, and severe persistent asthma was randomized to receive fluticasone propionate (FP), BUD, or beclomethasone dipropionate (BDP) in equipotent doses according to their global initiative on asthma (GINA) severity. STATISTICAL ANALYSIS USED: Data analyzed using SPSS version: 13.0. General linear-repeated measures using the post-hoc bonferroni method assessed significance between treatment groups. RESULTS: Significant decrease (P < 0.05) in each SGRQ domains and total scores as well as improvement in FEV(1) (P < 0.05) was observed in all study subjects. A significant early response (P < 0.05) was noted after 15 days treatment in patients receiving FP with respect to SGRQ (activity, impact and total) scores and dyspnea indices, but not FEV(1). This improvement with FP was due to its greater effect in patients with moderate and severe persistent asthma. No difference was noted subsequently in all outcome measures studied until 6 months. CONCLUSIONS: There was evidence for an early QoL improvement to FP as compared to BUD or BDP in moderate and severe persistent asthma. Subsequently, the three ICS showed similar improvements in lung functions and dyspnea indices throughout the study.

Potentially inappropriate medication use in Indian elderly: comparison of Beers' criteria and Screening Tool of Older Persons' potentially inappropriate Prescriptions.

AIM: To compare Beers' criteria (BC) and Screening Tool of Older Persons' potentially inappropriate Prescriptions (STOPP) for prevalence, specificity, sensitivity and predictors for potentially inappropriate medication (PIM) use. METHODS: Patients aged ≥ 60 years from medicine wards of a tertiary care hospital were included. Comparisons between BC and STOPP were made using Pearson's χ(2) -test for categorical variables and Mann-Whitney U-test for continuous variables. Specificity and sensitivity were assessed by using 2 × 2 contingency table. Bivariate analysis and subsequent multivariate logistic regression was used to identify the predictors of PIM use. RESULTS: In the 540 patients included, prevalence of PIM use as per BC and STOPP was 24.6% and 13.3%, respectively. Sensitivity and specificity of BC in detecting PIM was 0.65 and 0.53, respectively. Considering the diagnoses/conditions, sensitivity and specificity of BC was 0.12 and 0.48, respectively, whereas independent of diagnoses/conditions, corresponding values were 0.75 and 0.54. PIM as per BC and STOPP accounted for 11 and 6 adverse drug reactions (ADR), respectively. Medications not listed in BC or STOPP were more likely to be associated with ADR. Multiple diseases (≥ 4) and use of more drugs during hospital stay (10-14) predicted PIM use as per BC, whereas age (60-74 years) predicted PIM use as per STOPP. CONCLUSION: Overall, BC is useful in the detection of PIM use independent of diagnoses/conditions, whereas STOPP is useful in detection of PIM use considering the diagnoses/conditions. There is a need for consensus on using the tool for detection of PIM use in Indian elderly.

Acute coronary syndrome in HIV patients: from pathophysiology to clinical practice.

A majority of human immunodeficiency virus (HIV) infected subjects in developed countries have access to highly active anti-retroviral therapy (HAART), which is associated with significantly improved long term survival. In this setting, clinical attention needs to be focused on the impact of premature atherosclerotic cardiovascular disease (CVD), which already represents a leading cause of morbidity and mortality in these patients. While the higher prevalence of traditional risk factors remains the main culprit of increased CVD risk, HIV infection itself and antiretroviral toxicity are confounding proatherogenic factors. It is therefore critical to treat modifiable risk factors, keeping close attention to drug interactions in these patients with high cardiovascular risk profile.

Prescribing patterns and predictors of high-level polypharmacy in the elderly population: A prospective surveillance study from two teaching hospitals in India.

BACKGROUND: Polypharmacy has been reported to increase the risks for inappropriate prescribing, adverse drug reactions, geriatric syndromes, and morbidity and mortality in elderly populations in the United States and Europe. Data on prescribing patterns and polypharmacy in the elderly population in India are limited. OBJECTIVES: The aims of this study were to assess prescribing patterns and to determine the predictors of high-level polypharmacy in the elderly population in 2 tertiary care hospitals in India. METHODS: This prospective surveillance study used medical records from patients aged 60 to 95 years admitted to the medicine wards of the 2 tertiary care hospitals between January 2008 and June 2009. Data on medication prescribing from admission through discharge were reviewed. Diseases were coded using the World Health Organization (WHO) International Classification of Diseases, 10th Revision, and medications were coded using the WHO Anatomical, Therapeutic, and Chemical classification. Concordance of prescribing with the indications in the product labeling as listed in the American Hospital Formulary Services Drug Information 2007 was determined. The prevalences of polypharmacy (5-9 medications) and high-level polypharmacy (>or=10 medications) were determined. Bivariate analysis and multivariate logistic regression analysis were used to determine the influential predictors of high-level polypharmacy during hospital stays. RESULTS: Data from 814 patients were included (493 [60.6%] men, 321 [39.4%] women; median age, 66 years [range, 60-95 years]). Systemic antibacterials were the most commonly prescribed therapeutic class of medications (574 [70.5%]), and pantoprazole was the most commonly prescribed medication (498 [61.2%]). The majority (7/10 [70.0%]) of the most commonly prescribed medications were prescribed as indicated. Medications prescribed "off-label" included pantoprazole (432/498 [86.7%]), ceftriaxone (212/259 [81.9%]), and atorvastatin (109/237 [46.0%]). Polypharmacy and high-level polypharmacy were prescribed in 366 (45.0%) and 370 (45.5%) patients, respectively. On multivariate logistic regression analysis, multiple (>or=3) diagnoses (odds ratio [OR] = 1.55; 95% CI, 1.16-2.08; P = 0.003), angina pectoris (OR = 2.58; 95% CI, 1.50-4.37; P < 0.001), and a length of stay >or=10 days (10-<15 days, OR = 3.14; 95% CI, 2.09-4.71; P < 0.001; and >or=15 days, OR = 5.74; 95% CI, 2.43-13.51; P < 0.001) were found to be predictors of high-level polypharmacy during hospital stays. CONCLUSIONS: The campaign for rational drug use in hospitalized elderly patients in India should promote pantoprazole, ceftriaxone, and atorvastatin prescribing in concordance with their indications. Interventions to reduce the high-level polypharmacy in the elderly during their stays in tertiary care hospitals in India should focus on patients with >/=3 diagnoses, angina pectoris, and/or >or=10 days of hospital stay.

Valproic acid-induced abnormal behavior.

A 12-year-old female was admitted to hospital with complaints of abnormal behavior. She was on valproic acid 200mg twice daily and clobazam 5mg at night for the past 13 weeks for her complex partial seizures with secondary generalized seizures. On day 60 of the treatment with valproic acid she developed behavioral disturbances and initiated treatment with tablet chlorpromazine, olanzapine and risperidone. During the present hospitalization, as there was no improvement in abnormal behavior, antipsychotics were discontinued and she was on observation for five days. On day 6, valproic acid was replaced with carbamazepine. Patient started recovering gradually from the abnormal behavior three days after the withdrawal of valproic acid and completely recovered after three months. Causality of valproic acid-induced abnormal behavior was 'possible'. Behavioral disturbances associated with valproic acid are rare and is reversible upon discontinuation of the drug. There is a need for vigilance on abnormal behavioral effects in patients receiving valproic acid.

Adverse drug reactions to antiretroviral therapy (ART): an experience of spontaneous reporting and intensive monitoring from ART centre in India.

PURPOSE: To assess the nature, severity, predictability and preventability of adverse drug reactions (ADRs) and to identify risk factors for antiretroviral ADRs. METHODS: Enrolled ambulatory patients were intensively monitored for ADRs. Spontaneously reported ADRs by clinicians were also included. Predictability was assessed based on history of previous exposure to the drug or literature incidence of ADRs. Preventability was assessed using Schumock and Thornton criteria and severity was assessed using modified Hartwig and Siegel scale. Bivariate analysis and subsequently multivariate logistic regression were used to identify the risk factors for ADRs. Data from spontaneous reporting was assessed using Bayesian neural network method for possible ADR signals. RESULTS: Monitoring by active surveillance indentified 159 (52.82%) ADRs from 400 patients. One hundred and forty-two (47.17%) reactions were spontaneously reported. Anaemia and vomiting were the most commonly observed ADRs. The ADRs were severe in 10.9% of cases. A total of 88% ADRs were definitely/probably preventable. Use of Zidovudine+Lamivudine with Nevirapine or Efavirenz, CD4 <200 cells/microl, female gender, tuberculosis and illiteracy were observed as risk factors for ADRs by bivariate analysis. Concurrent tuberculosis was the only influential risk factor for development of ADRs identified by multivariate logistic regression. CONCLUSION: Prevalence of ADRs in intensively monitored patients was found to be 39.7%. Tuberculosis in HIV patients is an influential risk factor for occurrence of ADRs. With the increasing access to antiretrovirals in India, ADRs to antiretrovirals require monitoring and reporting.

Clinical pharmacy in a South Indian teaching hospital.

OBJECTIVE: To describe how clinical pharmacy is helping to improve medication use at a South Indian teaching hospital by addressing medication use problems, which are commonly encountered in India. SUMMARY: Clinical pharmacy is practiced in many countries and makes a significant contribution to improved drug therapy and patient care. India is a country with significant problems with medication use, but until recently Indian pharmacists have not been educated for a patient-care role. Postgraduate pharmacy practice programs have been established at 2 pharmacy colleges in South India as a result of a joint Indo-Australian program of cooperation. At a teaching hospital associated with the colleges, clinical pharmacy services such as drug information, medication counseling, drug therapy review, adverse drug reaction reporting, and the preparation of antibiotic guidelines are assisting clinicians to improve drug therapy and patient care. Seven hundred twenty-seven requests for drug information were received from July 1997 to February 2001, and 543 suspected adverse drug reactions were evaluated from November 1997 to February 2001. The most common drug classes causing adverse drug reactions were antibiotics, nonsteroidal antiinflammatory drugs, and antitubercular agents. Physician opinion and service utilization have also been surveyed: 82% of respondents had sought drug information from the Clinical Pharmacy Department and 71% of respondents had sought advice on individual patient management. The success of this program is raising awareness of clinical pharmacy among pharmacy educators elsewhere in India and has led to the introduction of clinical pharmacy services at other Indian hospitals.