Balamurugan Tangiisuran

Development and validation of a risk model for predicting adverse drug reactions in older people during hospital stay: Brighton Adverse Drug Reactions Risk (BADRI) model

Background Older patients are at an increased risk of developing adverse drug reactions (ADR). Of particular concern are the oldest old, which constitute an increasingly growing population. Having a validated clinical tool to identify those older patients at risk of developing an ADR during hospital stay would enable healthcare staff to put measures in place to reduce the risk of such an event developing. The current study aimed to (1) develop and (2) validate an ADR risk prediction model. Methods We used a combination of univariate analysis and multivariate binary logistic regression to identify clinical risk factors for developing an ADR in a population of older people from a UK teaching hospital. The final ADR risk model was then validated in a European population (European dataset). Results Six-hundred-ninety patients (median age 85 years) were enrolled in the development stage of the study. Ninety-five reports of ADR were confirmed by independent review in these patients. Five clinical variables were identified through multivariate analysis and included in our final model; each variable was attributed a score of 1. Internal validation produced an AUROC of 0.74, a sensitivity of 80%, and specificity of 55%. During the external validation stage the AUROC was 0.73, with sensitivity and specificity values of 84% and 43% respectively. Conclusions We have developed and successfully validated a simple model to use ADR risk score in a population of patients with a median age of 85, i.e. the oldest old. The model is based on 5 clinical variables (≥8 drugs, hyperlipidaemia, raised white cell count, use of anti-diabetic agents, length of stay ≥12 days), some of which have not been previously reported.

Adverse drug reactions in elderly: Challenges in identification and improving preventative strategies

The use of medication among the elderly population has increased tremendously over the last decade. However, the benefits of medications are always accompanied by potential harm, even when prescribed at recommended doses based on approved guidelines. The elderly are particularly at increased risk of adverse drug reactions (ADR) [1] attributed in the main to polypharmacy and physiological changes affecting the pharmacokinetics and pharmacodynamics of many drugs or poor compliance due to cognitive impairment or depression. The reported prevalence of ADR has not changed over the past decade. The average rate of ADR-related hospital admission is 16.6% in the elderly compared to 4.1% in younger patients, with 88% considered preventable [2]. Studies specifically undertaken in the older age group have found that 24% of patients are admitted due to ADR [3] and 14% experience an ADR as an inpatient [4]. In 2004, the annual cost of ADR-related admissions to the NHS was estimated at £466 m [5]. There is increasing interest among clinicians and researchers to find ways to reduce the occurrence of ADR. The main determinant in this reduction is the correct identification of ADR. Not all clinicians, pharmacists, nurses or patients are able to accurately identify ADR and this is due to many reasons including education, expectations and previous experience. It is further complicated in the elderly where the presentation of an ADR is often atypical and non-specific. The ADR may be ascribed to ‘frailty’, to an already existing diagnosis or to the onset of a new medical problem. For example, falls, delirium, drowsiness, lethargy, light-headedness, apathy, urinary incontinence, chronic constipation and dyspepsia are often accepted as a primary diagnosis rather than secondary to medication. The inability to distinguish drug-induced symptoms from a definitive medical diagnosis often results in the addition of yet another drug to treat the symptoms, which increases drug–drug interactions and ADR, known as ‘the prescribing cascade’ [6]. The use of inappropriate medications in the elderly has also been described as a potential cause of ADR [7]. However, several studies failed to prove this association [8, 9]. In an attempt to improve identification of ADR in elderly patients, it is advisable for clinicians to always consider the (side) effects of medication high in the differential diagnosis of clinical symptoms. Knowledge of the most common ADR and the most frequently responsible agents in this age group along with the relationship of medication and symptoms will improve identification of the ADR and the ‘culprit’. There are 34 different methods available to evaluate the likelihood that observed adverse events are due to a particular drug [10]. One of the most widely used methods for evaluating causality is algorithms, e.g. Naranjo [11]. An algorithm is a clinical instrument in the form of a questionnaire that gives detailed operational criteria for ranking the probability of causation when an ADR is suspected [10]. These assessment tools focus clinical attention, but they have diagnostic limitations. Also, the availability of different algorithms contributes to the lack of congruency in achieving a clinical consensus. This is further confounded by interprofessional variability in assessments. So how can we prevent the occurrence of ADR if we do not agree on the diagnosis of the problem? There is also no single empirical method available at the moment to assess the likelihood that an ADR has taken place. When a drug is suspected as the cause of an acute change in a patient’s clinical condition, the clinician should initially consider the known adverse events of the particular drug. This is limited by the knowledge that not all events, especially rare events, are reported or documented, particularly for newly marketed drugs. If the suspected reactions are a known toxicity of a particular drug, then the link between the onset of the reaction and drug administration should be established. Other conditions that may predispose patients to such reactions should be considered, e.g. hypokalaemia in digoxin toxicity. Additional information should include comedication, previous experience by patients, disease exacerbations, dechallenge, rechallenge and objective evidence. An important risk factor for developing ADR is the previous occurrence of ADR. Re-exposure to offending drugs due to poor documentation can cause the patient to experience the same ADR again, thus emphasising the importance of accurate documentation of ADR at the time of the event and providing relevant information to the patient about ADR to help prevent further occurrence. Currently, the main mechanism for identifying drug or population factors associated with ADR is national pharmacovigilance systems, for example the Yellow Card System in the UK. Such records have evolved over recent years, to include electronic reporting as well as pilot schemes involving submissions from the general public. However, this may not

Adverse Drug Reactions in a Population of Hospitalized Very Elderly Patients

OBJECTIVES The aims of the study were to determine the rates, types, severity and preventability of adverse drug reactions (ADRs) in a hospitalized population of very elderly patients (over 80 years of age) and to identify factors that predispose the very elderly to an ADR. METHODS An observational study was conducted in patients over 80 years of age admitted to four care of the elderly wards in Brighton and Sussex University Hospitals NHS Trust. The main outcome measures were the incidence of ADRs during inpatient stay in older patients and the identification of the major drug classes involved and the risk factors contributing to the occurrence of ADRs. RESULTS A total of 560 very elderly patients were recruited, 74 of whom experienced one or more ADR (83 in total), representing an incidence of 13.2% (95% CI 10.4, 16). Sixty-three percent of all ADRs were considered preventable, with 57 classified as serious and three as life threatening. The drug classes frequently implicated in ADRs were cardiovascular agents (34%), analgesic medications (18%) and anti-diabetic drugs (10%). Five variables were established as independent predictors of ADRs: number of medications, use of hypoglycaemic agents, history of hyperlipidaemia, raised white cell count on admission, and length of stay. CONCLUSIONS The ADR incidence reported in this population was no greater than that seen in other studies for both general medical patients and those elderly patients over 65 years of age. A significant proportion of ADRs were preventable, and this suggests that closer monitoring of high-risk elderly patients is needed to address this problem.

The use of potentially inappropriate medications and changes in quality of life among older nursing home residents

Background Nursing home residents are mainly older people with multiple diseases and taking multiple medications. The quality use of medication and its association with health related quality of life (HRQoL) have not been reported in Malaysia. This study aims to investigate the association between the use of potentially inappropriate medications (PIMs) and the changes observed in the HRQoL among older nursing home residents. Methods A prospective follow up study was conducted at four nongovernmental organization nursing homes in Penang, Malaysia. Older residents (≥65 years old) taking at least one prescribed medication were included. Residents with PIMs were identified by using Screening Tool of Older Person’s potentially inappropriate Prescriptions (STOPP) criteria. HRQoL was assessed using EuroQol-5 dimension (EQ-5D) and EuroQol-visual analog scale (EQ-VAS) at baseline and after a 3-month follow up. The association of PIMs with HRQoL was analyzed using Mann-Whitney U test. Results The median age of the 211 participants was 77 years (interquartile range 72–82 years) and the median number of prescription medicines was four (interquartile range three to six). The prevalence of PIMs was 23.7% and 18.6% at baseline and 3 months later, respectively. The most commonly prescribed PIMs in decreasing order were first generation antihistamine, prescriptions of duplicate drug class, glibenclamide with type 2 diabetes mellitus, and anticholinergic to treat extrapyramidal side effects of neuroleptic medications. At baseline, there was no significant difference among residents with or without PIMs in each bracket of EQ-5D, EQ-5D index, or EQ-VAS scores. Comparison of the differences in the mean score index of EQ-5D between baseline and after 3 months also showed no statistically significant differences. Conclusion PIMs were found to be relatively common among older nursing home residents. However, no significant changes were observed in HRQoL among these residents. Further studies with a bigger sample size and longer follow up period are required to establish this association.

Adverse drug reactions in older people

Adverse drug reactions (ADR) pose significant health-related problems for the older person. Many studies from around the world report a significant incidence of ADR in general and in elderly people in particular, resulting in an increase in drug-related morbidity and mortality. Older people appear to be particularly at risk of experiencing an ADR due to a range of factors, which include polypharmacy, altered drug pharmacokinetic profiles and pharmacodynamic responses, drug interactions and cognitive problems that increase the risk in this patient group. Certain drug classes, such as hypoglycaemic agents and cardiovascular active medicines, have been identified as common causes of ADR. Many studies suggest that the majority of ADR are preventable, so that several different approaches have been tried in an attempt to limit this problem, such as the use of computerized systems to communicate routine issues of patient care, interventions made by pharmacists, spontaneous reporting and continuous education of health care professionals. Whilst all have been shown to reduce drug-related events, identifying individuals at high risk of developing ADR at the point of prescribing by using a risk stratification model could improve the identification and prevention of ADR. This article discusses the clinical impact of ADR in older people and the relative merits of the various approaches tested to date before suggesting areas that require further research.

Barriers and facilitators of adherence to antidepressants among outpatients with major depressive disorder: A qualitative study

Background One of the major challenges in treating major depressive disorder (MDD) is patients’ non-adherence to medication. This study aimed to explore the barriers and facilitators of patients’ adherence to antidepressants among outpatients with MDD. Methods Semi-structured and individual in-depth interviews were conducted among patients with MDD who were taking antidepressants, in the psychiatric clinic of a government-run hospital in Malaysia. Participants were purposively sampled from different genders and ethnicities. Interviews were conducted using a validated topic guide, and responses were audio-recorded, transcribed verbatim, checked, and analyzed using the grounded theory approach. Results A total of 30 patients were interviewed. Forty different themes and sub-themes were identified which were conceptually divided into two distinct categories related to barriers and facilitators to adherence. The barriers were: patient-specific, medication-specific, healthcare provision and system, social-cultural, and logistics. The facilitators were: having insight, perceived health benefits, regular activities, patient-provider relationship, reminders, and social support networks. Conclusions Patient-specific barriers and medication side effects were the major challenges for adhering to treatment. Perceived health benefits and having insight on the need for treatment were the most frequently cited facilitators. Targeted interventions should be developed to address the key barriers, and promote measures to facilitate adherence in this group of patients.

Determinants of functional status among survivors of severe sepsis and septic shock: One-year follow-up.

RATIONALE: Sepsis is a leading cause of intensive care unit (ICU) admissions worldwide and a major cause of morbidity and mortality. Limited data exist regarding the outcomes and functional status among survivors of severe sepsis and septic shock. OBJECTIVES: This study aimed to determine the functional status among survivors of severe sepsis and septic shock a year after hospital discharge. METHODS: Adult patients admitted between April 2007 and March 2010 to the medical-surgical ICU of a tertiary hospital in Saudi Arabia, were included in this study. The ICU database was investigated for patients with a diagnosis of severe sepsis or septic shock. Survival status was determined based on hospital discharge. Patients who required re-admission, stayed in ICU for less than 24 hours, had incomplete data were all excluded. Survivors were interviewed through phone calls to determine their functional status one-year post-hospital discharge using Karnofsky performance status scale. RESULTS: A total of 209 patients met the eligibility criteria. We found that 38 (18.1%) patients had severe disability before admission, whereas 109 (52.2%) patients were with severe disability or died one-year post-hospital discharge. Only one-third of the survivors had good functional status one-year post-discharge (no/mild disability). After adjustment of baseline variables, age [adjusted odds ratio (aOR) = 1.03, 95% confidence interval (CI) = 1.01-1.04] and pre-sepsis functional status of severe disability (aOR = 50.9, 95% CI = 6.82-379.3) were found to be independent predictors of functional status of severe disability one-year post-hospital discharge among survivors. CONCLUSIONS: We found that only one-third of the survivors of severe sepsis and septic shock had good functional status one-year post-discharge (no/mild disability). Age and pre-sepsis severe disability were the factors that highly predicted the level of functional status one-year post-hospital discharge.

Knowledge and perceptions of physicians from private medical centres towards generic medicines in the State of Perak, Malaysia: Findings and implications

ObjectiveTo evaluate the knowledge and perceptions of physicians from private medical centres towards generic medicines.Method and settingA cross-sectional questionnaire-based mail survey involving 172 physicians in 16 private medical centres in Perak, Malaysia was conducted.ResultsA total of 105 physicians participated in the study, giving a response rate of 61.0%. Most participants were male (81.9%), had a median age of 47 years (range 34–72 years), obtained their medical degree from Malaysia (56.2%) and had been practicing for a median of 21 years (range 8–49 years). Although only 5.7% of the participants correctly identified the bioequivalence regulatory standards for generic medicines, 48.6% believed that generic medicines are bioequivalent to their counterpart innovator brands. In this study, 35.3% of participants had doubts about efficacy of generic medicines and 58.1% had doubts about their safety. In this study, 47.6% of physicians believed that advertisements by pharmaceutical companies affect t...

Inter-rater reliability of the assessment of adverse drug reactions in the hospitalised elderly

BackgroundThe identification and assessment of adverse drug reactions (ADRs) is very challenging especially among the older person. Inter observer reliability of an ADR classification system by different healthcare providers is vital to establish the validity of the reaction.ObjectiveTo assess the inter-rater reliability of an ADR classification system in hospitalised elderly patients and to investigate the differences in reliability by different professions.MethodsFrom a cohort of 330 elderly patients, patients who experienced a suspected medication related incident (n=87) were selected. The data were analysed by four healthcare professionals (2 pharmacists and 2 physicians) who independently classified the events into event type, types of adverse drug reactions, severity and preventability after a standardised induction based on previously published criteria. Fleiss’ kappa was used to assess the level of agreement between the four raters. The difference in level of agreement between the professions was assessed using the weighted least-squares approach for comparing correlated kappa of Barnhart et al.ResultsPharmacists and physicians showed high agreement in the identification and on the type and causality of ADRs. However there was lower (moderate) agreement for the severity (kappa = 0.61) and preventability of ADR (kappa = 0.48). Statistically significant differences were also noted between the professions; pharmacists have higher agreement in the classification of preventability (p=0.03) whereas the physicians pairs showed stronger agreement for classifying severity (p<0.001).ConclusionDespite the high agreement in the identification, type and causality of ADRs, physicians and pharmacists have difficulties in classifying preventability and severity in a reliable way. A multi-disciplinary approach would enable each profession to share their expert knowledge in order to facilitate better or safer patient care.

Perceptions among general medical practitioners toward implementation of medication reconciliation program for patients discharged from hospitals in Penang, Malaysia.

Objective This study aims to explore the perceptions of general practitioners (GPs) from the state of Penang toward the feasibility of implementing the medication reconciliation program in Malaysia. Methods A cross-sectional descriptive study using a validated, self-completed anonymous 18-item questionnaire was undertaken over a period of 2 months in 2010. The study was conducted in the state of Penang, Malaysia. A letter consisting of survey questionnaires and prepaid return envelope were mailed to 429 GPs identified from the Private Medical Practice Control Department Registry. Results A total of 86 responses were received with response rate of 20.1%. Majority (90.1%) of the respondents agreed that medication reconciliation can be a feasible strategy to improve medication safety, and 97.7% confirmed that having an accurate up-to-date list of the patient’s previous medication will be useful in the rational prescribing process. However, about half (56.9%) of them felt that standardization of the medication reconciliation process in all clinics will be difficult to achieve. Three quarters (73.2%) of the respondents believed that the involvement of GPs alone is insufficient, and 74.5% agreed that this program should be expanded to community pharmacy setting. More than 90% of the respondents agreed upon the medication reconciliation card proposed by the researchers. Conclusions General practitioners in Penang are generally in favor of the implementation of medication reconciliation program in their practice. Because medication reconciliation has been shown to reduce many medicine-related problems, it is thus worth considering the feasibility of nationwide implementation of such program.