Rate Of Adverse Drug Reactions Research Articles

Consensus guidelines for antifungal stewardship, surveillance and infection prevention, 2021.

Invasive fungal diseases (IFD) are serious infections associated with high mortality, particularly in immunocompromised patients. The prescribing of antifungal agents to prevent and treat IFD is associated with substantial economic burden on the health system, high rates of adverse drug reactions, significant drug-drug interactions and the emergence of antifungal resistance. As the population at risk of IFD continues to grow due to the increased burden of cancer and related factors, the need for hospitals to employ antifungal stewardship (AFS) programmes and measures to monitor and prevent infection has become increasingly important. These guidelines outline the essential components, key interventions and metrics, which can help guide implementation of an AFS programme in order to optimise antifungal prescribing and IFD management. Specific recommendations are provided for quality processes for the prevention of IFD in the setting of outbreaks, during hospital building works, and in the context of Candida auris infection. Recommendations are detailed for the implementation of IFD surveillance to enhance detection of outbreaks, evaluate infection prevention and prophylaxis interventions and to allow benchmarking between hospitals. Areas in which information is still lacking and further research is required are also highlighted.

Adverse Drug Reactions of Multiple Sclerosis Disease-modifying Drugs.

High frequency of adverse drug reactions (ADRs) challenges multiple sclerosis (MS) treatment. This study aims to assess the nature and frequency of ADRs induced by MS medications in an observational cross-sectional study. ADRs of all outpatients who had seen a neurologist and had received at least one disease-modifying therapy (DMT) for MS during the last three months were investigated. A total of 484 ADRs were detected in these patients. The preventability rate was 5.9%, and 0.61% of reactions were serious. The high frequency of adverse drug reactions in this study shows a strong need for strategy planning to increase patients' adherence to treatment. Adverse drug reactions (ADRs) are common in MS patients using disease modifying therapies.Such ADRs are more common in women than men.Various brand names of biosimilar disease-modifying therapy (DMT)s may have a different ADR profile. Multiple sclerosis (MS) is a condition that can be managed by using disease modifying medications. Such medication could trigger an adverse reaction in the patients., affecting their commitment to the treatment. By identifying these adverse reactions and educating the MS patients about these reactions and how the adverse effects can be managed, healthcare providers can improve the treatment process. This study recorded the adverse drug reactions in 250 MS patients who were receiving the medication for at least three months. Most of the patients (76.4%) experienced some kind of adverse reaction. A bigger proportion of women experienced adverse reactions than men. About 84% of these reactions occurred within the first 3 hours of receiving the medication. Depending on the medication's brand name, the rate of adverse drug reactions were different in some cases. The results of this study point out the fact that experiencing adverse drug reactions is common in MS patients and these experiences could be different for each medication with a different brand name. Therefore, it is important for the healthcare providers to inform the patients about such reactions and the patients should seek all the information they need to manage these adverse effects by consulting their physician.

Status and Safety Signals of Cephalosporins in Children: A Spontaneous Reporting Database Study.

Introduction: Cephalosporins are widely used in clinical treatment of children, but it is difficult to carry out clinical trials and there is no strong evidence of their safety. Therefore, adverse drug reactions (ADR) of cephalosporins can be a public health problem that deserves attention. Methods: ADR reports collected by the Hubei Adverse Drug Reaction Monitoring Center from 2014 to 2019 were analysed. The safety of Cephalosporins was described by descriptive analysis and three signal mining methods, including the reporting odd ratio (ROR), proportional reporting ratio (PRR), and comprehensive standard method (MHRA). Results: The findings indicated that the age groups of 0–1 and 2–3 years had the highest rates of reporting ADRs. Children aged 0–4 years reported more ADRs, while the proportion of severe ADRs was lower than the average (6.63%). Among the 37 cephalosporins, the severe ADRs of ceftezole, ceftazidime, cefoperazone/sulbactam, cefotaxime, ceftriaxone were reported more and the proportion of severe ADRs was higher. The proportion of severe ADRs of most cephalosporin compound preparations was higher than that of corresponding single components. A total of 99.18% of the cases improved after treatment. There were four deaths whose ADRs were mainly anaphylactic shock, dyspnoea, and anaphylactoid reaction. In signal mining, the three methods produced 206 signals that were the same, and 73 of them were off-label ADRs. Conclusion: ADRs were common but not serious in children aged 0–4 years. And the reported rate of serious ADRs in children aged over 4 years increased with age. ADR reports of ceftezole, ceftazidime, cefoperazone/sulbactam, cefotaxime, ceftriaxone were numerous and serious, and the safety of cephalosporin compound preparations in children was doubtful. Ceftezole may cause off-label ADRs including tremor, face oedema, cyanosis, pallor, rigors, and palpitation. The labeling of ADRs in children in cephalosporin instructions and the record of allergic history need to be improved.

Effectiveness and safety of traditional Chinese herbs in children with cough variant asthma: a systematic review and Meta-analysi.

To systematically investigate the clinical effectiveness and safety of traditional Chinese herbs (TCHs) as an alternative to conventional medicine (CM) in children with cough variant asthma(CVA). Randomized controlled trial (RCT) studies that were published from their inceptions to March 31, 2020, were identified from the electronic databases of China National Knowledge Infrastructure, Wangfang, PubMed, and Cochrane Central Library. The primary outcome of the review was the total effective rate (TER), and the secondary outcomes were immunoglobulin E (IgE), peak expiratory flow (PEF), adverse drug reactions, and relapse rates of interventions. For the Meta-analysis, 13 studies involving 992 children with CVA were included. In terms of TER and IgE, the experimental interventions of TCH, when compared with the control interventions of CM, on pediatric CVA were found to be significantly effective (P < 0.0001), whereas for spirometry, PEF was not significantly improved in the TCH group (P = 0.48). The incident rates of adverse drug reaction and relapse were found to be significantly lower in the TCH group than those in the CM group (P = 0.02 and P < 0.0001, respectively). Compared with CM therapy, the effects of TCH therapy on pediatric CVA were significantly beneficial in terms of TER and IgE, but not for PEF, and the methodological quality of included studies was poor. Therefore, the results should be interpreted with caution. More randomized controlled trials with rigorous experimental methodologies are required for objectivity in the future.

Adverse Drug Reactions to First-line Anti-tubercular Drugs Based on Individual Case Safety Report in a Single Tertiary Hospital

Background/Aims: Tuberculosis has incidence and mortality rates that are among the highest for all communicable diseases. Adverse drug reactions (ADRs) to anti-tubercular drugs are common, and have a major impact on treatment maintenance and prognosis. It is important to understand the characteristics of ADRs and establish a suitable management plan. Methods: We retrospectively reviewed patients with ADRs during treatment with first-line antitubercular drugs such as isoniazid, rifampicin, ethambutol, and pyrazinamide from 2009 to 2018. Age, sex, and total treatment period, and the onset, severity, seriousness, and system organ class of ADRs, were analyzed to understand the characteristics of first-line anti-tubercular drug-related ADRs. Results: A total of 1,606 of 5,482 patients (29.3%) experienced ADRs after administration of first-line anti-tubercular drugs. The incidence of ADRs related to isoniazid, rifampicin, ethambutol, and pyrazinamide was 22.2%, 21.3%, 24.5%, and 29.6%, respectively. A total of 2,098 ADR reports were made (mean of 1.3 ± 0.6 per patient). The rates of mild, moderate, and severe ADRs were 32.4%, 61.1%, and 6.5%, respectively. There were 127 reports (6.1%) of serious ADRs. Skin and appendage disorders were most frequently reported (27.5%), followed by gastrointestinal disorders (17.5%), and liver and biliary system disorders (13.1%). The total treatment period was longer in patients who experienced ADRs (224.0 ± 3.1 days vs. 247.0 ± 4.7 days, &lt;i&gt;p&lt;/i&gt; = 0.009). Conclusions: The incidence of ADRs to first-line anti-tuberculosis drugs was 29.3%, and 6.5% were severe ADRS. ADRs prolonged the overall treatment duration, indicating the importance of their detection and management.

Polypharmacology of clinical sodium glucose co-transport protein 2 inhibitors and relationship to suspected adverse drug reactions.

Sodium glucose co‐transporter 2 inhibitors (SGLT2i) are a promising second‐line treatment strategy for type 2 diabetes mellitus (T2DM) with a developing landscape of both beneficial cardio‐ and nephroprotective properties and emerging adverse drug reactions (ADRs) including diabetic ketoacidosis (DKA), genetic mycotic infections, and amputations among others. A national register study (MHRA Yellow Card, UK) was used to quantify the SGLT2i's suspected ADRs relative to their Rx rate (OpenPrescribing, UK). The polypharmacology profiles of SGLT2i were data‐mined (ChEMBL) for the first time. The ADR reports (n = 3629) and prescribing numbers (Rx n = 5,813,325) for each SGLT2i in the United Kingdom (from launch date to the beginning December 2019) were determined. Empagliflozin possesses the most selective SGLT2/SGLT1 inhibition profile at ~2500‐fold, ~10‐fold more selective than cangliflozin (~260‐fold). Canagliflozin was found to also inhibit CYP at clinically achievable concentrations. We find that for overall ADR rates, empagliflozin versus dapagliflozin and empagliflozin versus canagliflozin are statistically significant (χ 2, p < .05), while dapagliflozin versus canagliflozin is not. In terms of overall ADRs, there is a greater relative rate for canagliflozin > dapagliflozin > empagliflozin. For fatalities, there is a greater relative rate for dapagliflozin > canagliflozin > empagliflozin. An organ classification that resulted in a statistically significant difference between SGLT2i was suspected infection/infestation ADRs between empagliflozin and dapagliflozin. Our findings at this stage of SGLT2i usage in the United Kingdom suggest that empagliflozin, the most selective SGLT2i, had the lowest suspected ADR incident rate (relative to prescribing) and in all reported classes of ADRs identified including infections, amputations, and DKA.

What Are the Barriers and Enablers to the Implementation of Pharmacogenetic Testing in Mental Health Care Settings?

In psychiatry, the selection of antipsychotics and antidepressants is generally led by a trial-and-error approach. The prescribing of these medications is complicated by sub-optimal efficacy and high rates of adverse drug reactions (ADRs). These both contribute to poor levels of adherence. Pharmacogenetics (PGx) considers how genetic variation can influence an individual’s response to a drug. Pharmacogenetic testing is a tool that could aid clinicians when selecting psychotropic medications, as part of a more personalized approach to prescribing. This may improve the use of and adherence to these medications. Yet to date, the implementation of PGx in mental health environments in the United Kingdom has been slow. This review aims to identify the current barriers and enablers to the implementation of PGx in psychiatry and determine how this can be applied to the uptake of PGx by NHS mental health providers. A systematic searching strategy was developed, and searches were carried out on the PsychInfo, EmBase, and PubMed databases, yielding 11 appropriate papers. Common barriers to the implementation of PGx included cost, concerns over incorporation into current workflow and a lack of knowledge about PGx; whilst frequent enablers included optimism that PGx could lead to precision medicine, reduce ADRs and become a more routine part of psychiatric clinical care. The uptake of PGx in psychiatric care settings in the NHS should consider and overcome these barriers, while looking to capitalize on the enablers identified in this review.

Long-term safety of growth hormone treatment in childhood: two Large observational studies: nordiNet IOS and ANSWER

Context: Growth hormone (GH) treatment has a generally good safety profile; however, concerns about increased mortality risk in adulthood have been raised. Objective: This work aims to assess the long-term safety of GH treatment in clinical practice. Methods: Data were collected from 676 clinics participating in 2 multicenter longitudinal observational studies: the NordiNet International Outcome Study (2006-2016, Europe) and ANSWER Program (2002-2016, USA). Pediatric patients treated with GH were classified into 3 risk groups based on diagnosis. Intervention consisted of daily GH treatment, and main outcome measures included incidence rates (events/1000 patient-years) of adverse drug reactions (ADRs), serious adverse events (SAEs), and serious ADRs, and their relationship to GH dose. Results: The combined studies comprised 37702 patients (68.4% in low-risk, 27.5% in intermediate-risk, and 4.1% in high-risk groups) and 130476 patient-years of exposure. The low-risk group included children born small for gestational age (SGA; 20.7%) and non-SGA children (eg, with GH deficiency; 79.3%). Average GH dose up to the first adverse event (AE) decreased with increasing risk category. Patients without AEs received higher average GH doses than patients with more than one AE across all groups. A significant inverse relationship with GH dose was shown for ADR and SAE incidence rates in the low-risk group (P=.003 and P=.001, respectively) and the non-SGA subgroup (both P=.002), and for SAEs in the intermediate-and high-risk groups (P=.002 and P=.05, respectively). Conclusions: We observed no indication of increased mortality risk nor AE incidence related to GH dose in any risk group. A short visual summary of our work is available (1).

Long-term safety and effectiveness of abatacept in Japanese patients with rheumatoid arthritis: 3-year follow-up of a postmarketing surveillance.

To analyse the long-term safety and effectiveness of abatacept for rheumatoid arthritis using real-world, Japanese, postmarketing surveillance data, focusing on serious infections and malignancies as priority events. This 3-year, multicentre surveillance registered patients undergoing abatacept treatment by intravenous infusion between July 2011 and October 2012. The safety and effectiveness analysis sets included 647 and 596 patients, respectively. The total observation period for the safety analysis was 1280 patient-years. Over the 3-year follow-up, the incidence rates of adverse drug reactions (ADRs) and serious ADRs were 19.92 per 100 patient-years (22.87% of patients) and 4.06 per 100 patient-years (6.65% of patients), respectively. Infections and infestations were the most common ADRs (14.68%), followed by respiratory, thoracic, and mediastinal disorders (3.09%). Incidence rates of serious infections as ADRs and malignancy as adverse events were 1.95 and 1.02 per 100 patient-years, respectively. Retention rates at 1 and 3 years were 67.4% and 43.9%, respectively. Significant decreases from baseline were observed in Disease Activity Score (DAS) 28-erythrocyte sedimentation rate and DAS28-C-reactive protein, as well as Health Assessment Questionnaire-Disability Index (HAQ-DI) and modified HAQ scores. No new safety signals were detected during the 3-year observation period and effectiveness was maintained over time.

Rituximab Desensitization in Liver Transplant Recipients With Preformed Donor-specific HLA Antibodies: A Japanese Nationwide Survey.

Background.The significance of preformed donor-specific anti-HLA antibodies (DSAs) in liver transplant recipients is controversial. Moreover, there has been no established desensitization protocol for DSA-positive recipients.Methods.A Japanese nationwide survey was performed to investigate the clinical practice among preformed DSA-positive patients with special reference to rituximab desensitization.Results.There was a total of 47 cases, including 2 pediatric cases, in which rituximab (287 ± 159 mg [319 (50–916)/m2]) was administered to desensitize preformed DSA. The decision for the indication of rituximab desensitization was based on a single-antigen assay in the majority of cases (83%, 39/47), and the most frequent protocol was rituximab monotherapy (n = 12) followed by quadruple treatment with rituximab tacrolimus, mycophenolate mofetil, and plasmapheresis (n = 11). The overall 1-, 3-, and 5-y graft and patient survival rates among adult patients were 85%, 83%, 83%, and 81%, 77%, 74%, respectively, while neither graft loss nor death was observed in the 2 pediatric cases. The 1-, 3-, and 12-mo cumulative incidence of antibody-mediated rejection (AMR) was 11%, 13%, and 13%, respectively. The incidence of AMR was significantly higher in the lower rituximab dose group than in the higher rituximab dose group (cutoff 300 mg/m2, 4% versus 24%, P = 0.041). The rate of infusion-related adverse drug reactions (ADRs) was 4.4%, and all ADRs were mild and self-limiting. A total of 99 ADRs among 27 patients were reported, none of which were severe adverse events associated with rituximab.Conclusions.The rituximab induction was well tolerated among DSA-positive liver transplant recipients with a satisfactory outcome. A rituximab dose >300 mg/m2 was observed to achieve less incidence of the development of AMR.

The Efficacy and Safety of Chinese Herbal Medicine Xianling Gubao Capsule Combined With Alendronate in the Treatment of Primary Osteoporosis: A Systematic Review and Meta-Analysis of 20 Randomized Controlled Trials.

Objective: Herein, we purposed to evaluate the efficacy along with the safety of Xianling Gubao capsule (XLGB) combined with alendronate (ALE) for primary osteoporosis (POP) from the current literature. Materials and Methods: We carried out a search for electronic literature in the PubMed, Chinese National Knowledge Infrastructure, EMBASE, Wanfang Web of Science, Chinese Biomedical Literature Database, Cochrane Library, as well as Chinese VIP databases targeting articles published from inception to December 2020. Only randomized controlled trials (RCTs) were enrolled into the study. Alkaline phosphatase (ALP), visual analogue scale (VAS), serum phosphorus (S-P), bone gla protein (BGP), serum calcium (S-Ca) and bone mineral density (BMD) were the primary outcome variable. The total clinical effective rate along with the adverse drug reaction (ADR) were the secondary outcome variables. The meta-analysis was conducted using RevMan 5.3 and STATA 12.0. GRADE pro3.6.1 software was used for the assessment of evidence quality. Results: Overall, 20 RCTs focusing on 1911 patients were enrolled into the study. Our meta-analysis demonstrated that XLGB combined with ALE remarkably increased BMD (p < 0.001), BGP (p < 0.001), S-Ca (p < 0.001), S-P (p < 0.001) and effective rate (p < 0.001) than ALE alone in patients with POP. Moreover, ALP (p < 0.001) and VAS (p < 0.001) were overtly by decreased XLGB. However, XLGB combined with ALE would not markedly increase the rate of ADR in contrast with ALE alone (p = 0.499). Conclusion: The results of our study demonstrated that XLGB is a potential candidate for OP treatment. We recommend that rigorous, as well as high-quality trials involving large samples sizes should be conducted to confirm our findings.

Psychotropic Drugs Prescription and Use among Children with Mental Disorders at a Tertiary Hospital in Vietnam.

Background: Awareness of psychotropic medication and its adverse drug reactions (ADRs) can promote safe and rational use of medications, particularly in children and adolescents with mental problems. This study examined the prescription of psychotropic drugs and actual drug-drug interaction (DDI) and ADR for children with mental disorders under 18 years of age in a tertiary hospital in Vietnam. Methods: A cross-sectional descriptive study was performed on 257 psychiatric inpatients under 18 years of age at the National Mental Health Institute-Bach Mai Hospital in 2017. Information about the course of treatment included prescribed medications, drug interactions, side effects, drug combination, and modifications to the regimen was collected. Results: 14.8% and 59.5% of patients received a single-drug regimen and a 2-drug combination regimen upon admission, respectively. The most used regimen was antipsychotics + tranquilizers, accounting for 38.1%. Haloperidol was the most commonly prescribed drug (40.5%). Most patients were given the recommended dosage of the drug (>90%). There were 20.6% of patients having drug interactions with the largest proportion of the combination of diazepam and olanzapine (62.3%). ADRs of psychotropic drugs were detected in 46.3% of patients, with the highest rate of ADRs from antipsychotic drugs. Antipsychotics had the highest rate of replacement (91.3%), mostly replaced from a first-generation antipsychotic (FGA) to a second-generation antipsychotic (SGA). Conclusion: The appointment of psychotropic drugs to patients under 18 years of age has to comply with the recommendations, and carefully balance the benefits and risks of ADRs as well as the risk of DDI in case of the drug combination.

Effectiveness and safety of apremilast in biologic-naïve patients with moderate psoriasis treated in routine clinical practice in Greece: the APRAISAL study.

Apremilast is an oral phosphodiesterase-4 inhibitor indicated for patients with moderate-to-severe chronic plaque psoriasis and active psoriatic arthritis. To examine the effectiveness of apremilast on Dermatology Life Quality Index (DLQI), Psoriasis Area and Severity Index (PASI) and nail, scalp and palmoplantar involvement, when administered prior to biologics. This 52-week real-world study included biologic-naive adults with moderate psoriasis (psoriasis-involved body surface area 10% to <20%, or PASI 10 to <20 and DLQI 10 to <20). Apremilast was initiated ≤7days before enrolment. Data from the first 100 eligible patients who completed 24weeks (W24) of observation (or were prematurely withdrawn) are presented in this interim analysis using the last-observation-carried-forward imputation method. Eligible patients (mean age: 49.9years; 71.0% males; median disease duration: 8.0years) were consecutively enrolled between April and October 2017, by 18 dermatology specialists practising in hospital outpatient settings in Greece. Baseline DLQI (median: 12.0) and PASI (median: 11.7) scores improved (P<0.001) at all postbaseline timepoints (Weeks 6, 16 and 24; W24 median decreases: 9.0 and 9.4 points respectively). At W24, DLQI ≤5, DLQI 0 or 1, and PASI-75 response rates were 63.0%, 25.0% and 48.0% respectively. The Nail Psoriasis Severity Index score in patients with baseline nail involvement (n=57) decreased at all postbaseline timepoints (P<0.001; W24 median decrease: 20.0 points). At W24, 50.0% and 51.7% of patients with baseline scalp (n=76) and palmoplantar (n=29) involvement respectively achieved postbaseline Physician's Global Assessment (PGA) score of 0 or 1 if baseline score was ≥3, or 0 if baseline score was 1 or 2. The adverse drug reaction rate was 21.0% (serious: 2.0%). These interim results indicate that through 24weeks, apremilast improved quality of life and reduced disease severity in biologic-naive patients with moderate plaque psoriasis, while demonstrating safety consistent with the known safety profile.

Effectiveness of medical therapy for treatment of idiopathic frequent premature ventricular complexes.

The relative effectiveness of medical therapy compared with a conservative approach of monitoring in patients with idiopathic frequent premature ventricular complexes (PVCs) is uncertain. We evaluated the effectiveness of medical versus conservative therapy for frequent PVCs. Patients with frequent PVCs (≥5%) were prospectively enrolled in this cohort study between 2016 and 2020. In patients with normal cardiac function and no structural heart disease, those receiving medical therapy were compared with controls without therapy. Patients were followed longitudinally for change in PVC burden and with serial echocardiography. Overall, 120 patients met inclusion criteria (mean: 56.5 ± 14.6 years, 54.2% female) with 53 on beta-blockers or calcium channel blockers (BBs/CCBs), 27 on Class I or III antiarrhythmic drugs (AADs), and 40 patients treated conservatively. Median initial PVC burden ranged from 15.5% to 20.6%. The median relative reduction of PVCs was 32.7%, 30.5%, and 81.3%, in the conservative therapy, BBs/CCBs, and AADs cohorts, respectively. AADs had greater PVC reduction compared with BBs/CCBs (p = 0.017) and conservative therapy (p = 0.045). PVC reduction to <1% was comparable across groups at 35.0%, 17.0%, 33.3%, respectively. Four patients (4/120, 3.3%) developed left ventricular dysfunction. Rates of adverse drug reactions and medication discontinuation were similar between groups, with no serious adverse events noted. In patients with idiopathic frequent PVCs, BB, and CCBhave limited effectiveness in PVC reduction. Class I and III AADs have superior effectiveness for medical therapy in symptomatic patients, but only achieved complete PVC resolution suppression in one-third of patients.

Safety and Persistence of Nalmefene Treatment for Alcohol Dependence. Results from Two Post-authorisation Safety Studies.

AimsTwo post-authorisation studies assessed the safety and persistence of patients’ use of nalmefene.MethodsThe START study (EUPAS5678) was a non-interventional, multi-country, prospective, 18-month (8 follow-up visits) cohort study including outpatients initiating nalmefene for the first time. The multi-database retrospective cohort study (MDRC, EUPAS14083) included baseline and follow-up data from German, Swedish and UK healthcare databases. Both studies permitted ‘all comers’ without explicit exclusion criteria; predefined subgroups of interest included the elderly (≥65 years) as well as patients with significant psychiatric and/or somatic comorbidities.ResultsSTART study: Overall, the mean duration of nalmefene treatment was 10.3 ± 7.3 months (N = 1348), with 49.0% of patients treated for ≥1 year; frequent reasons for treatment discontinuation were ‘goal reached’ and ‘drug cost’. The most frequently reported adverse drug reactions (ADRs) were nausea (4.7%), dizziness (3.2%) and insomnia (2.0%). ADR rates appeared higher in the elderly subpopulation (18.6% reported ≥1 ADR vs. 12.0% in the total population) but were not higher in the other predefined subgroups.MDRC study: The database follow-up analysis followed 2892 patients over 18 months for whom the duration of nalmefene treatment was between 2 and 3 months and <5% of patients used nalmefene for ≥1 year.ConclusionsDespite the inclusion of a wider patient population (e.g. elderly patients and those with relevant co-morbidities), the safety and tolerability profile of nalmefene given in routine practice was consistent with previous clinical studies. The differing rates of persistence beyond 1 year likely reflect the different methodologies and highlight the relevance of psychosocial support at follow-up visits.

Annual Costs Incurred in Managing Adverse Drug Reactions Attributable to Fixed-Dose Combination Highly Active Antiretroviral Therapy in an Outpatient Antiretroviral Clinic in Gauteng: A Budget Impact Analysis

ObjectivesThis study aimed to identify adverse drug reactions (ADRs) attributable to tenofovir (TDF)- and zidovudine (AZT)-based fixed-dose combinations of highly active antiretroviral (ARV) therapy and subsequently determine the annual costs incurred in managing these ADRs and the budget implications in an outpatient ARV clinic in Mamelodi, Pretoria. MethodsThis retrospective cohort study reviewed deidentified clinical data for ADRs. Medical charts of human immunodeficiency virus–positive patients, who were receiving either TDF- or AZT-based fixed-dose combinations of ARV therapy, were analyzed. Costs were converted to US dollars using the rate of US$1 equivalent to ZAR14.3853. Based on the costs and the incidence rates of ADRs observed in the analysis, a decision tree model was established to estimate the cost impact of ADR management on the clinic’s budget. ResultsA total of 469 patient files were analyzed (62% female vs 38% male). The mean age at the start of ARV therapy for the cohort was 36.6 years (95% confidence interval 35.74-37.45), and the mean baseline CD4 count was 380 (95% confidence interval 343-418). The incidence of ADRs to TDF- or AZT-based fixed-dose combinations of ARV therapy was found to be 24.95%. The study revealed that US$29.70 was the cost attributed to ADRs owing to TDF-based regimens, whereas US$32.53 was the cost attributed to ADRs owing to AZT-based regimens, per patient, annually. Costs attributed to gastrointestinal-related ADRs were the highest in comparison with other ADRs. The estimated total cost of ADRs attributed to AZT-based therapy was US$556.40, and the estimated total cost of ADRs attributed to TDF-based ARV therapy per annum was US$2348.80 for the 1221 patients who started receiving ARV therapy between July 2017 and June 2018 at the clinic. ConclusionsDespite the estimated costs related to ADRs in the study being lower than those in similar studies, there remains a notable budget impact, particularly in a resource-limited setting. The study findings allow for improved budget forecasts in an ARV clinic setting.

Incidence and Predictors of Severe Adverse Drug Reaction Among Patients on Antiretroviral Therapy in Tigray, Ethiopia: A Retrospective Cohort Study.

BackgroundThe aim of the present study was to assess the incidence and predictors of severe adverse drug reactions among patients on antiretroviral therapy (ART) in Tigray, North Ethiopia.MethodsWe employed four years retrospective cohort study using a structured data extraction sheet. The study populations were HIV patients on ART follow-up from January 2017 to February 2020 in the study area. Severe adverse drug reaction (ADR) was an outcome variable and defined as having any one of the complaints related to ARV drug reaction due to regimen change, discontinuation, and/or in-patient care. Data were collected using a structured data extraction sheet. A Cox proportional hazard regression model was used to determine the relationship between the predictors and the outcome variable. The mean survival time of the cohort was estimated using the Kaplan–Meier method.ResultsThe incidence rate of ADRs was 3.6 (95%CI: 2.9–4.35) per 100-person years. HIV patients with no formal education (adjusted hazard ratio=1.58, 95%CI: 1.03–2.41), with experience of regimen change (adjusted hazard ratio=1.59, 95%CI: 1.12–2.91), who ever took other medication (adjusted hazard ratio=1.49, 95%CI: 1.05–2.15) and with lower body mass index (adjusted hazard ratio=3.24, 95%CI: 1.18–4.91) were more likely to develop severe adverse drug reaction.ConclusionADRs were diagnosed an inconsiderable number of HIV patients on ART and factors were patient and drug-related. To minimize it, special attention is sought for patients with no formal education, previous regime change, whoever took other medication, and who have lower body mass index levels.

A questionnaire based study-assessment of knowledge, attitude and practice of pharmacovigilance among health care professionals, pre and post educational intervention

Background: Pharmacovigilance (PV) is an important tool in generating adverse drug reaction (ADR) data. However, the practice of PV is still very low among health care professionals due to lack of knowledge and awareness. This study was conducted to assess the level of knowledge, awareness and practice of PV among health care professionals and to assess subsequent change in these after PV training session.Methods: A cross sectional questionnaire based study was conducted among health care professionals of a tertiary health care and teaching institute. Participants were given a questionnaire. They completed it before and after undergoing training programme in PV. Impact of effectiveness of educational intervention (continuing medical education-CME (pharmacovigilance workshop) was evaluated by paired t-test.Results: Out of 110 participants, 96 participants completely filled the questionnaire before and after the educational intervention (CME). CME on PV was found to increase knowledge and positive attitudes towards various aspects of PV.Conclusions: Training programme on PV will help increase the knowledge as well as awareness about principles and techniques of PV and improve the rate of spontaneous ADR reporting. Organising frequent CME programmes and workshops will increase the credibility of health care in the country.

Barriers to adverse drug reaction reporting in Malaysia: a narrative review based on theoretical domains framework

Abstract Objectives This review aims to determine the common barriers to adverse drug reaction (ADR) reporting in Malaysia based on theoretical domains framework (TDF). Methods Three online databases, PubMed (Medline), Scopus and Web of Science, were searched from 2000 to 2020 to identify related quantitative and qualitative studies. Key findings Eleven articles were reviewed – nine quantitative and two qualitative studies. Three domains from TDF were identified as the most common: (1) knowledge, (2) skills and (3) environmental context and resources. Lack of awareness of an ADR reporting system, lack of clinical and ADR knowledge and lack of time were identified as the main barriers. Additionally, assumption of healthcare professionals (HCPs) of ADR to be too insignificant or too well known and unavailability of the ADR form were also reported as barriers for reporting an ADR. Conclusions The findings from this narrative review could be useful for the policymakers in planning strategies at the national level to improve the reporting rate of ADR in Malaysia. It is necessary to promote and publicize pharmacovigilance activities and to enhance communication and engagement between the Malaysian ADR Advisory Committee and the HCPs and consumers. There is also a need to increase training and continuous education related to ADR and pharmacovigilance system and making ADR reporting compulsory for all HCPs.

Treatment of Children with Primary Immunodeficiencies with a Subcutaneous Immunoglobulin 16.5% (Cutaquig ® [Octanorm

Background: Subcutaneous human immunoglobulin (16.5%; octanorm/cutaquig®) was efficacious and well tolerated in patients with primary immunodeficienciesin a Phase IIIstudy. A subanalysis of pediatric data is presented here. Materials & methods: Children (2-16years) previously treated with intravenous human immunoglobulin received weekly subcutaneous human immunoglobulin infusions over 64weeks. The main objective was to assess the efficacy of cutaquigin preventing serious bacterial infections. Results:38children received 2213 infusions of cutaquig. No serious bacterial infections developed during the study. The rate of other infections was 3.1 per person-year and the rate of adverse drug reactions was 0.083 per infusion. Higher immunoglobulin Gtrough levels were achieved with cutaquigcompared with previous intravenous therapy. Conclusion: Once-weekly infusions of cutaquigwere efficacious and well tolerated in children with primary immunodeficiencies.