Hospital-wide ELectronic medical record evaluated computerised decision support system to improve outcomes of Patients with staphylococcal bloodstream infection (HELP): study protocol for a multicentre stepped-wedge cluster randomised trial.

BMJ Open. 2020 Feb 10;10(2):e033391

Authors: Hagel S, Gantner J, Spreckelsen C, Fischer C, Ammon D, Saleh K, Phan-Vogtmann LA, Heidel A, Müller S, Helhorn A, Kruse H, Thomas E, Rißner F, Haferkamp S, Vorwerk J, Deffge S, Juzek-Küpper MF, Lippmann N, Lübbert C, Trawinski H, Wendt S, Wendt T, Dürschmid A, Konik M, Moritz S, Tiller D, Röhrig R, Schulte-Coerne J, Fortmann J, Jonas S, Witzke O, Rath PM, Pletz MW, Scherag A

Abstract
INTRODUCTION: Staphylococci are the most commonly identified pathogens in bloodstream infections. Identification of Staphylococcus aureus in blood culture (SAB) requires a prompt and adequate clinical management. The detection of coagulase-negative staphylococci (CoNS), however, corresponds to contamination in about 75% of the cases. Nevertheless, antibiotic therapy is often initiated, which contributes to the risk of drug-related side effects. We developed a computerised clinical decision support system (HELP-CDSS) that assists physicians with an appropriate management of patients with Staphylococcus bacteraemia. The CDSS is evaluated using data of the Data Integration Cent ers (DIC) established at each clinic. DICs transform heterogeneous primary clinical data into an interoperable format, and the HELP-CDSS displays information according to current best evidence in bacteraemia treatment. The overall aim of the HELP-CDSS is a safe but more efficient allocation of infectious diseases specialists and an improved adherence to established guidelines in the treatment of SAB.
METHODS AND ANALYSIS: The study is conducted at five German university hospitals and is designed as a stepped-wedge cluster randomised trial. Over the duration of 18 months, 135 wards will change from a control period to the intervention period in a randomised stepwise sequence. The coprimary outcomes are hospital mortality for all patients to establish safety, the 90-day disease reoccurrence-free survival for patients with SAB and the cumulative vancomycin use for patients with CoNS bacteraemia. We will use a closed, hierarchical testing procedure and generalised linear mixed modelling to test for non-inferiority of the CDSS regarding hospital mortality and 90-day disease reoccurrence-free survival and for superiority of the HELP-CDSS regarding cumulative vancomycin use.
ETHICS AND DISSEMINATION: The study is approved by the ethics committee of Jena University Hospital and will start at each centre after local approval. Results will be published in a peer-reviewed journal and presented at scientific conferences.
TRIAL REGISTRATION NUMBER: DRKS00014320.

PMID: 32047014 [PubMed - in process]

History, Evolution and Current State of Ovarian Tissue Auto-Transplantation with Cryopreserved Tissue: a Successful Translational Research Journey from 1999 to 2020.

Reprod Sci. 2020 Jan 06;:

Authors: Marin L, Bedoschi G, Kawahara T, Oktay KH

Abstract
The loss of fertility and early menopause are common after gonadotoxic therapies and radical pelvic surgery. The strategy of ovarian tissue cryopreservation and auto-transplantation was introduced to prevent this significant quality of health issue. Ovarian transplantation with cryopreserved tissue has gone through remarkable evolution in the last 20 years. In this review, we detail the history and evolution of ovarian transplantation with cryopreserved tissue from its origins to the present. Ovarian cryopreservation and transplantation approach was first tested with animal models. The approach was then validated in human ovarian xenografting models before being applied to patients in pioneering clinical studies. The first orthotopic and heterotopic approaches to ovarian transplantation was developed by Oktay et al. who reported the first successful restoration of ovarian function with these approaches beginning in 2000 with first embryo development in 2004. Controversy remains on when the first live birth occurred after orthotopic ovarian transplantation with cryopreserved tissue as the patient was ovulating with elevated progesterone levels in the case reported in 2004; first live birth is likely to be the one reported by Meirow et al. in 2005. Nevertheless, the technique has evolved to reach a level where most recent live birth rates are exceeding 35% and the procedure is no longer considered experimental by many.

PMID: 32046442 [PubMed - as supplied by publisher]

Association of adverse drug reaction to anti-tuberculosis medication with quality of life in patients in a tertiary referral hospital.

Rev Soc Bras Med Trop. 2019;53:e20190207

Authors: Valadares RMC, Carvalho WDS, Miranda SS

Abstract
INTRODUCTION: Adverse drug reactions can develop when using anti-tuberculosis medication, and the effects of the drugs can also significantly hinder the treatment of patients.
METHODS: A cross-sectional survey was conducted in 73 patients using two standardized questionnaires and the World Health Organization Quality of Life-Bref.
RESULTS: All patients reported the presence of adverse drug reactions, 71.6% of which are minor and 28.3% both major and minor. The global quality of life analysis showed that patients with tuberculosis have a good average (67.3%).
CONCLUSIONS: There is an association between quality of life and adverse drug reaction, educational level, and vulnerability.

PMID: 31859946 [PubMed - indexed for MEDLINE]

Skin Doctor: Machine Learning Models for Skin Sensitization Prediction that Provide Estimates and Indicators of Prediction Reliability.

Int J Mol Sci. 2019 Sep 28;20(19):

Authors: Wilm A, Stork C, Bauer C, Schepky A, Kühnl J, Kirchmair J

Abstract
The ability to predict the skin sensitization potential of small organic molecules is of high importance to the development and safe application of cosmetics, drugs and pesticides. One of the most widely accepted methods for predicting this hazard is the local lymph node assay (LLNA). The goal of this work was to develop in silico models for the prediction of the skin sensitization potential of small molecules that go beyond the state of the art, with larger LLNA data sets and, most importantly, a robust and intuitive definition of the applicability domain, paired with additional indicators of the reliability of predictions. We explored a large variety of molecular descriptors and fingerprints in combination with random forest and support vector machine classifiers. The most suitable models were tested on holdout data, on which they yielded competitive performance (Matthews correlation coefficients up to 0.52; accuracies up to 0.76; areas under the receiver operating characteristic curves up to 0.83). The most favorable models are available via a public web service that, in addition to predictions, provides assessments of the applicability domain and indicators of the reliability of the individual predictions.

PMID: 31569429 [PubMed - indexed for MEDLINE]

Paracetamol overdose: limiting the potential for harm.

Med J Aust. 2019 09;211(5):211-212

Authors: Graudins A, Wong A

PMID: 31420865 [PubMed - indexed for MEDLINE]

Adverse Drug Reaction (ADR) as a Cause of Hospitalization at a Government Hospital in Saudi Arabia: A Prospective Observational Study.

Curr Drug Saf. 2019;14(3):192-198

Authors: Alayed N, Alkhalifah B, Alharbi M, Alwohaibi N, Farooqui M

Abstract
BACKGROUND: ADRs represent a substantial burden on health care resources worldwide and are considered as one of the leading causes of morbidity and mortality which significantly affects hospitalization rates. However, ADR related hospital admissions are not well explored in Saudi Arabia.
OBJECTIVE: The current study aims to evaluate ADR-related admissions at King Saud Hospital, Unaizah, Qassim, Saudi Arabia.
METHODS: A prospective, observational study was conducted at King Saud Hospital Unaizah. Over a period of 6 months, patients above 12 years of age who visited the Emergency Department (ED) with an ADR were included in this study. The investigators collected patient data by reviewing the patient's medical records and the ED records for admission. The Naranjo algorithm was used to assess the causality of the suspected ADR, and Hartwig's Severity Assessment Scale was used to assess the severity of the ADR.
RESULTS: Out of 4739 admissions to the wards, 38 (0.801%) were related to an ADR. The majority of patients were male (52.6%), with a mean age of ± 49.08 years. The total length of hospital stay was 565 days with a mean of ± 14.87 days. The causality assessment shows that 35 (92.1%) cases were probable ADRs, whereas 3 (7.9%) cases were possible ADRs. Moreover, the severity assessment showed that 6 (15.1%) cases were mild, and 27 (71.1%) and 5 (13.2%) cases were moderate and severe, respectively. In regard to the outcome of patients, most patients recovered after the ADR, and 2 ADRs resulted in the death of the patient.
CONCLUSION: Our study shows that ADRs as a cause of hospitalization in Qassim population is considerably low. However, ADRs may contribute to morbidity and mortality and result in a considerable financial burden.

PMID: 31109277 [PubMed - indexed for MEDLINE]

Immunogenicity and safety of a combined DTPa-IPV/Hib vaccine administered as a three-dose primary vaccination course in healthy Korean infants: phase III, randomized study.

Hum Vaccin Immunother. 2019;15(2):317-326

Authors: Kim KH, Kim CS, Kim HM, Kim JD, Ma SH, Kim DH, Hwang PH, Han JW, Lee TJ, Kim JH, Karkada N, Mesaros N, Sohn WY, Kim JH

Abstract
We assessed the immunogenicity and safety of a three-dose primary vaccination schedule with the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus/Haemophilus influenzae type b vaccine (DTPa-IPV/Hib) in Korean infants. In this phase III open-label, multicenter study (NCT01309646), healthy infants aged 42-69 days (randomized 1:1) received three doses of either pentavalent DTPa-IPV/Hib (DTPa-IPV/Hib group) or DTPa-IPV and Hib vaccines administered separately (DTPa-IPV+Hib group) at 2, 4, 6 months of age. The primary objective was to demonstrate non-inferiority of DTPa-IPV/Hib compared to DTPa-IPV+Hib vaccines in terms of immune responses to all vaccine antigens, 1 month post-dose 3. Solicited symptoms (local and general) were recorded during 4 days, and unsolicited adverse events (AEs) during 31 days, after each vaccination. Serious AEs (SAEs) were recorded throughout the study duration. The immunogenicity of the pentavalent DTPa-IPV/Hib vaccine was non-inferior compared to concomitant administration of DTPa-IPV+Hib vaccines. One month post-dose 3, nearly all infants had antibody levels above the seroprotective thresholds for anti-diphtheria toxoid, anti-tetanus toxoid, anti-polyribosyl-ribitol phosphate, and anti-poliovirus type 1, 2 and 3, and had antibody levels above the seropositive thresholds for anti-pertussis toxoid (PT), anti-filamentous hemagglutinin (FHA) and anti-pertactin (PRN) antibodies. A vaccine response for PT, FHA and PRN was observed in at least 96.7% of study participants. Anti-PRP geometric mean concentrations appeared lower for the DTPa-IPV/Hib group (8.456 µg/mL) than for the DTPa-IPV+Hib group (18.700 µg/mL). In both groups, the most common solicited symptoms were injection site redness and irritability. Fifty-seven SAEs were reported throughout the study; none were considered to be vaccination related.

PMID: 30431387 [PubMed - indexed for MEDLINE]

Do drug-related safety warnings have the expected impact on drug therapy? A systematic review.

Pharmacoepidemiol Drug Saf. 2020 Feb 11;:

Authors: Georgi U, Lämmel J, Datzmann T, Schmitt J, Deckert S

Abstract
PURPOSE: The need for drug-related safety warnings is undisputed, and their impact should also be evaluated. This systematic review investigates and assesses the impact of safety warnings on drug therapy.
METHODS: Studies published in English between January 1998 and December 2018 were searched in EMBASE and MEDLINE, complemented by manual search. Randomised controlled trials, cohort studies with a before/after component, and case-control studies were included, selected to predefined criteria, and assessed for their reporting and methodological quality.
RESULTS: Out of 7454 references identified, 72 studies were included. A total of 28/72 (39%) studies described the impact of safety warnings on drug therapy as being effective, whereas 12/72 (17%) studies did not. Further, 26/72 (36%) studies described a partial implementation of the warnings (one part of the warning had an impact on drug therapy and another did not). Unintended effects were investigated in 6/72 (8%) studies. While 34 (47%) studies examined safety warnings on psychotropic drugs using an interrupted time series (ITS) design (53%), a before/after (26%), and a time series design (21%), 38 (53%) studied other substances using an ITS design (34%), a before/after (40%), and a time series design (26%). The proportion of an effective impact on drug therapy was lower in the "psychotropic drugs" group (23%) than in the "others" group (53%).
CONCLUSION: Drug-related safety warnings induce intended and unintended effects. The included studies are of broadly varying methodological quality. To better compare their effectiveness, studies should be conducted using standardised procedures.

PMID: 32045502 [PubMed - as supplied by publisher]

Analysis of effectiveness and drug related problems of pain reliever for knee osteoarthritis: weighing clinical risk and benefit.

J Basic Clin Physiol Pharmacol. 2020 Feb 11;:

Authors: Khotib J, Setiawan HU, Nurhan AD, Rahadiansyah E, Ardianto C, Rahmadi M

Abstract
Background Osteoarthritis (OA) is a chronic degenerative joint disease, characterized by physiological disorders, such as cartilage degradation, bone remodeling, osteophyte formation, and joint inflammation, which results in pain. Several studies have reported problems with the use of pain medications in OA, such as the use of a combination of many drugs and their long-term use. Therefore, this study was designed to evaluate the use of pain medications in OA patients. The study focused on the analysis of effectiveness and drug related problems (DRPs) with the category of drug interactions and adverse drug events (ADEs) in knee OA patients in Orthopedic and Traumatology Clinic, Universitas Airlangga Teaching Hospital, Surabaya, Indonesia. Methods The study used a retrospective approach through tracking and recording of the medical data from the period of 1st January to 30th June, 2018. The potential of drug interactions was determined by analyzing data based on literature. The actual side effects of the drug were identified based on the patient's medical record through clinical data, laboratory data, and therapeutic data received by the patient. The study involved 143 subjects who met the inclusion criteria of 871 visits to the hospital. Results The results showed that women as much as 80.42% with an age distribution of at most 46-65 years are the most affected by OA cases. The predominant history of illness and comorbidities in OA patients was hypertension in 58.74% of patients. The use of analgesic meloxicam had a percentage of 26.06%, sodium diclofenac 20.21%, mefenamic acid 4.36% and paracetamol 4.25%. The effectiveness of the use of pain reliever was characterized by a decrease in VAS in each patient at the beginning and at the end of the study, where a decrease in pain intensity occurred in 79.72% of patients who received pain medications. Based on drug interactions, we were able to identify pharmacodynamic interactions of 43 events (4.94%) and onine events of pharmacokinetic interactions (1.03%), with a minor severity of 7 events (0.80%),44 moderate events (5.05%), and one major event (0.11%). Mostly identified side effects of the drugs were those due to the use of non-steroid anti inflammatory drugs, which occurred in 42 events (4.82%). Conclusions It can be concluded that OA therapy with a number of pain relievers shows an adequate therapeutic response with some side effects and interactions both pharmacokinetically and pharmacodynamically.

PMID: 32045352 [PubMed - as supplied by publisher]

Unilateral Tongue Angioedema Induced by Angiotensin Converting Enzyme Inhibitor: A Case Report.

Oman Med J. 2020 Jan;35(1):e92

Authors: Al-Hoqani ZK, Al-Kiyumi MH, Al-Tamemi SH, Al-Mahrezi AM

Abstract
Tongue angioedema is a well-recognized side effect of angiotensin-converting enzyme inhibitor particularly during the first few months of initiation. Unilateral tongue involvement is rarely encountered. We report the case of a 78-year-old woman who presented with unilateral right side tongue angioedema, which occurred after two years of lisinopril use. She did not have any respiratory distress and her symptoms had completely resolved after twelve hours of observation. Lisinopril was discontinued and no recurrence of angioedema was reported.

PMID: 32042467 [PubMed]

Severe hydralazine-induced lupus presenting as systemic lupus erythematosus.

Lupus. 2020 Feb 10;:961203320906265

Authors: Rubin RL, Haluptzok RF, Davila LM

Abstract
Despite its long history of untoward side effects of a systemic autoimmune disease, drug-induced lupus can be difficult to recognize because of the disconnect between chronic drug usage and onset of symptoms. In this case, the patient was treated with hydralazine for two years when symptoms were initially reported, but a diagnosis of hydralazine-induced lupus was not considered for another half year. Despite treatment with steroidal and nonsteroidal anti-inflammatory medications during this period, rheumatologic symptoms and signs continued to deteriorate, consistent with the diagnosis of systemic lupus erythematosus. Not until the patient voluntarily discontinued hydralazine did symptoms begin to improve, fully resolving over the subsequent 6-12 months largely in the absence of anti-inflammatory medication. This patient demonstrates that failure to recognize a drug-induced disease etiology can result in substantial worsening of rheumatologic symptoms over the subsequent six months, ultimately satisfying criteria for systemic lupus erythematosus. While symptoms and signs largely normalized, some laboratory abnormalities and occasional arthralgia remained two years after discontinuing hydralazine, suggesting smoldering inflammatory disease.

PMID: 32041503 [PubMed - as supplied by publisher]

Nivolumab efficacy in leptomeningeal metastasis of renal cell carcinoma: a case report.

Tumori. 2020 Feb 11;:300891620904411

Authors: Bonomi L, Bettini AC, Arnoldi E, Chirco A, Ghilardi L, Manara O, Roscigno M, Da Pozzo LF, Tondini CA

Abstract
BACKGROUND: Meningeal carcinomatosis is rare in patients with kidney cancer and treatment options are limited. Few patients treated with systemic approaches have been reported. We describe a case of complete remission of leptomeningeal metastasis in a patient with renal cell carcinoma treated with nivolumab. To our knowledge, this is the first report of nivolumab safety and efficacy in this particular site of metastasis.
CASE PRESENTATION: Our patient was a 60-year-old Caucasian man with bone and lung metastases from renal cell carcinoma. He developed leptomeningeal metastasis and progression of bone and lung lesions after only 2 months of his first-line treatment. He was then treated with nivolumab in second-line setting and experienced a rapid improvement of cancer-related symptoms, complete remission of leptomeningeal and lung lesions, and increased bone mineral density in bone metastasis. The patient did not experience any drug-related toxicity.
CONCLUSIONS: Meningeal carcinomatosis metastasis from renal cancer is a rare condition. Diagnosis is often challenging: the onset of nonspecific presenting symptoms could be initially attributed to bone involvement, side effects of oncologic therapy, or paraneoplastic syndromes. Our case suggests that nivolumab could be an effective and safe treatment option in patients with pretreated renal cancer with leptomeningeal metastasis.

PMID: 32041500 [PubMed - as supplied by publisher]

What is the Significance of Elevated Troponin I in Children and Adolescents? A Diagnostic Approach.

Pediatr Cardiol. 2019 Dec;40(8):1638-1644

Authors: Yoldaş T, Örün UA

Abstract
Troponin is a marker that displays cardiac injury quickly and accurately. In adults, troponin elevation is usually associated with coronary artery disease and requires urgent cardiac catheterization. In healthy children, myocardial injury is rare and may develop due to many different causes. Therefore, troponin elevation in children and adolescents does not usually require emergency cardiac catheterization. The aim of this study is to assess the most common causes of troponin elevation in children and adolescents and to show which diagnostic tests are helpful in assessing pediatric patients with elevated troponin. Patients who had been diagnosed with troponin I elevation (> 0.06 ng/ml) at Dr. Sami Ulus Maternity, Children's Health and Disease Training and Research Hospital between 2007 and 2018 were retrospectively evaluated. Patients undergoing cardiac surgery and those with severe congenital heart disease were excluded from the study. The medical records of the patients were examined and age, gender, diagnostic tests, and diagnosis were evaluated. During the study period, the records of 972 patients were obtained. 213 patients were excluded from the study because of heart surgery, congenital heart disease, and neonatal asphyxia or sepsis. Of the remaining 759 patients, 58% were male, 42% were female, and the median age was 4 years (3 days to 17 years). The most frequent causes are myopericarditis (n: 164), drug intoxications (n: 85), carbon monoxide poisoning (n: 74), perimyocarditis (n: 65), and intensive inhalation β agonist use in acute asthma and lower respiratory tract infections (n: 70). Patients diagnosed with myocarditis and myopericarditis were admitted with a complaint of chest pain, and the diagnosis was made by history, physical examination, ECG, and echocardiographic findings. Unlike adults, troponin I elevation may be associated with many cardiac and non-cardiac pathologies in children. The most common pathologies in cardiac etiology are myopericarditis and perimyocarditis and can be diagnosed by history, physical examination, ECG, and echocardiography. Cardiac catheterization is not necessary except for rare cardiac pathologies and does not alter the prognosis.

PMID: 31485699 [PubMed - indexed for MEDLINE]

Extensive Phenotyping for Potential Weight-Inducing Factors in an Outpatient Population with Obesity.

Obes Facts. 2019;12(4):369-384

Authors: Savas M, Wester VL, Visser JA, Kleinendorst L, van der Zwaag B, van Haelst MM, van den Akker ELT, van Rossum EFC

Abstract
BACKGROUND: Obesity has been associated with miscellaneous weight-inducing determinants. A comprehensive assessment of known obesity-related factors other than diet and physical activity within one cohort is currently lacking.
OBJECTIVES: To assess the prevalence of potential contributors to obesity and self-reported triggers for marked weight gain in an adult population with obesity and between obesity classes.
METHODS: In this observational cohort study, we assessed 408 persons with obesity (aged 41.3 ± 14.2 years, BMI 40.5 ± 6.2) visiting our obesity clinic. They were evaluated for use of weight-inducing drugs, hormonal abnormalities, menarcheal age, (high) birth weight, sleep deprivation, and obstructive sleep apnea syndrome (OSAS). We additionally assessed self-reported triggers for marked weight gain and performed genetic testing in patients suspected of genetic obesity.
RESULTS: Nearly half of the patients were using a potentially weight-inducing drug, which was also the most reported trigger for marked weight gain. For the assessed hormonal conditions, a relatively high prevalence was found for hypothyroidism (14.1%), polycystic ovary syndrome (12.0%), and male hypogonadism (41.7%). A relatively low average menarcheal age (12.6 ± 1.8 years) was reported, whereas there was a high prevalence of a high birth weight (19.5%). Sleep deprivation and OSAS were reported in, respectively, 14.5 and 13.7% of the examined patients. Obesity class appeared to have no influence on the majority of the assessed factors. Of the genetically analyzed patients, a definitive genetic diagnosis was made in 3 patients (1.9%).
CONCLUSIONS: A thorough evaluation of patients with obesity yields a relatively high prevalence of various potentially weight-inducing factors. Diagnostic screening of patients with obesity could therefore benefit these patients by potentially reducing the social stigma and improving the outcomes of obesity treatment programs by tackling, where possible, the weight-inducing factors in advance.

PMID: 31216558 [PubMed - indexed for MEDLINE]

Pharmacovigilance Systems in Arab Countries: Overview of 22 Arab Countries.

Drug Saf. 2019 07;42(7):849-868

Authors: Alshammari TM, Mendi N, Alenzi KA, Alsowaida Y

Abstract
Pharmacovigilance has received much attention in Arab countries recently due to the development of new regulations. However, there are differences in the progression of pharmacovigilance systems by regulatory agencies in these countries because only some are able to meet the requirements for conducting pharmacovigilance activities. Only 45% of Arab countries are official members of the World Health Organization (WHO) Collaborating Centre for International Drug Monitoring. Countries such as Morocco, Tunisia, Saudi Arabia, Egypt, and Jordan are considered to be advanced pharmacovigilance countries, whereas other countries such as Libya, Yemen, and Palestine remain in the very early stages of implementing and developing pharmacovigilance systems. Countries such as Somalia, Djibouti, Mauritania, and Comoros Island have no pharmacovigilance system or culture. Asian Arab countries have some advantages over those in Africa because 50% of them are a part of the Gulf Cooperation Council (GCC), meaning that most of them can utilize similar approaches for the application of the majority of activities related to the healthcare system, including pharmacovigilance. Thus, participating in the GCC enables increased connections among these countries. However, one of the strengths in Africa is that Morocco is partnering with the WHO through the WHO Collaborating Center to enhance and strengthen pharmacovigilance across the Eastern Mediterranean Region and the Francophone and Arab countries. This partnership could have a role in enhancing the pharmacovigilance culture among African Arab countries. This review provides a general overview of the current situation regarding regulatory agencies related to pharmacovigilance in Arab countries.

PMID: 31006085 [PubMed - indexed for MEDLINE]

Use of a Patient-Friendly Terms List in the Adverse Drug Reaction Report Form: A Database Study.

Drug Saf. 2019 07;42(7):881-886

Authors: de Vries ST, Harrison J, Revelle P, Ptaszynska-Neophytou A, Radecka A, Ragunathan G, Tregunno P, Denig P, Mol PGM

Abstract
INTRODUCTION: When reporting adverse drug reactions to pharmacovigilance centres, patients and consumers can describe adverse drug reactions experienced in free-text format. Recently, a patient-friendly adverse drug reaction terms list was introduced in the adverse drug reaction report form in the UK to facilitate this reporting.
OBJECTIVE: The objective of this study was to evaluate the actual use of the patient-friendly terms list in the adverse drug reaction report form and its association with the type of adverse drug reactions reported.
METHODS: We conducted a database study in which we reviewed the list's use for all reported adverse drug reactions by patients and consumers to the pharmacovigilance centre in the UK via the online report form between August and September 2017. Descriptive statistics were used. In addition, for adverse drug reactions reported more than 20 times, Chi-squared tests were used to test for differences in the number of reports in which the patient-friendly terms list was used and those in which the adverse drug reaction was entered as free text.
RESULTS: In total, 888 reports were received. In 185 reports (21%), the patient-friendly terms list was used to enter an adverse drug reaction. In total, the reports contained 3227 adverse drug reactions. Nausea, headache, diarrhoea, dizziness, insomnia, anxiety, depression, fatigue, tiredness, vomiting, appetite lost, joint pain, chest pain, constipation and pain were reported more than 20 times. Five of these adverse drug reactions (i.e. nausea, diarrhoea, dizziness, insomnia and constipation) were reported significantly more often in reports where the adverse drug reactions were selected from the patient-friendly terms list.
CONCLUSIONS: Most people chose to describe adverse drug reactions in their own words rather than selecting adverse drug reactions from a patient-friendly terms list. Although the patient-friendly terms list may be a useful feature for some patients or for some adverse drug reactions, it should not replace the option for patients to describe adverse drug reactions in their own words.

PMID: 30725337 [PubMed - indexed for MEDLINE]

Exploring the Association between Monoclonal Antibodies and Depression and Suicidal Ideation and Behavior: A VigiBase Study.

Drug Saf. 2019 07;42(7):887-895

Authors: Minnema LA, Giezen TJ, Souverein PC, Egberts TCG, Leufkens HGM, Gardarsdottir H

Abstract
INTRODUCTION: Several monoclonal antibodies (mAbs) have been linked to neuropsychiatric adverse effects in patients, including depression and suicidal ideation and behavior.
OBJECTIVE: The aim of this study was to quantify and characterize spontaneously reported adverse drug reactions (ADRs) of depression and suicidal ideation and behavior related to mAb users, and to explore a possible association with their mechanism of action.
METHODS: We included mAb ADRs that were reported in VigiBase, and identified those related to depression and suicidal ideation and behavior. Reporting odds ratios (RORs) were estimated for each mAb (bevacizumab as the reference) and according to their influence on the immune system (not directly targeting [reference], stimulating, or suppressing). Those suppressing the immune system were further divided into their intended indication (auto-immune diseases, cancer).
RESULTS: Overall, 2,924,319 ADRs for 44 mAbs were included; 9455 ADRs were related to depression and 1770 were related to suicidal ideation and behavior. The association was strongest for natalizumab and belimumab, both for depression (ROR 5.7, 95% confidence interval [CI] 5.0-6.4; and ROR 5.1, 95% CI 4.2-6.2) and suicidal ideation and behavior (ROR 12.0, 95% CI 7.9-18.3; and ROR 20.2, 95% CI 12.4-33.0). Those suppressing the immune system showed higher ROR, i.e. 1.9 (95% CI 1.8-2.0) for depression and 3.6 (95% CI 3.0-4.4) for suicidal ideation and behavior. This finding was only seen for mAbs used for treating autoimmune diseases.
CONCLUSION: Depression and suicidal ideation and behavior are seen in patients using mAbs, particularly mAbs used for treating autoimmune diseases that suppress the immune system. For interpretation of these data, the indications for use and other characteristics require further consideration.

PMID: 30617497 [PubMed - indexed for MEDLINE]

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Efficacy and safety of treatment with biologicals (benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab) for severe eosinophilic asthma.

Allergy. 2020 Feb 08;:

Authors: Agache I, Beltran J, Akdis C, Akdis M, Canelo-Aybar C, Canonica W, Casale T, Chivato T, Corren J, Del Giacco S, Eiwegger T, Firinu D, Gern JE, Hamelmann E, Hanania N, Mäkelä M, Martín IH, Nair P, O'Mahony L, Papadopoulos NG, Papi A, Park HS, Pérez de Llano L, Posso M, Rocha C, Quirce S, Sastre J, Shamji M, Song Y, Steiner C, Schwarze J, Alonso-Coello P, Palomares O, Jutel M

Abstract
Five biologicals have been approved for severe eosinophilic asthma, a well-recognised phenotype. Systematic reviews (SR) evaluated the efficacy and safety of benralizumab, dupilumab, mepolizumab, omalizumab and reslizumab (alphabetical order) compared to standard of care for severe eosinophilic asthma. Pubmed, EMBASE and Cochrane Library were searched to identify RCTs and health economic evaluations, published in English. Critical and important asthma-related outcomes were evaluated for each of the biologicals. The risk of bias and the certainty of the evidence were assessed using GRADE. 19 RCTs (3 RCTs for benralizumab, 3 RCTs for dupilumab, 3 RCTs for mepolizumab, 4 RCTs for omalizumab, and 5 RCTs for reslizumab), including subjects 12 to 75 years old (except for omalizumab including also subjects 6-11 years old), ranging from 12 to 56 weeks were evaluated. All biologicals reduce exacerbation rates with high certainty of evidence: benralizumab rate ratio (RR) 0.53 (95% CI 0.39 to 0.72), dupilumab RR 0.43 (95% CI 0.32 to 0.59), mepolizumab RR 0.49 (95% CI 0.38 to 0.66), omalizumab RR 0.56 (95% CI 0.40 to 0.77), and reslizumab RR 0.46 (95% CI 0.37 to 0.58). Benralizumab, dupilumab and mepolizumab reduce the daily dose of oral corticosteroids (OCS) with high certainty of evidence. All evaluated biologicals probably improve asthma control, QoL and FEV1 , without reaching the minimal important difference (moderate certainty). Benralizumab, mepolizumab and reslizumab slightly increase drug-related adverse events (AE) and drug-related serious AE (low to very low certainty of evidence). The incremental cost-effectiveness ratio per quality adjusted life-years value is above the willingness to pay threshold for all biologicals (moderate certainty). Potential savings are driven by decrease in hospitalisations, emergency and primary care visits. There is high certainty that all approved biologicals reduce the rate of severe asthma exacerbations and for benralizumab, dupilumab and mepolizumab for reducing OCS. There is moderate certainty for improving asthma control, QoL, FEV1 and cost-effectiveness. More data on long term safety are needed together with more efficacy data in the paediatric population.

PMID: 32034960 [PubMed - as supplied by publisher]

[Trends in Immunity and Adverse Drug Reactions Among People Newly Diagnosed With HIV].

Hu Li Za Zhi. 2020 Feb;67(1):55-65

Authors: Lin YC, Lai YY, Liu HY, Chen YC, Liu LF, Ko NY

Abstract
BACKGROUND: Early antiretroviral therapy (ART) is recommended as an intervention for HIV by the World Health Organization. However, the association between the CD4 count at ART initiation and the risk of adverse drug reactions (ADRs) remains unclear.
PURPOSE: This study aimed to describe the trends related to symptom number and intensity among patients newly diagnosed with HIV in three different CD4-count-based groups and then to investigate the ADR trends for these three groups at different points in time.
METHODS: This multi-center cohort study recruited newly diagnosed HIV/AIDS patients who had not previously used ART from AIDS-designated hospitals in Taiwan from March 2015 to December 2016. Study measures were assessed at the time of case enrollment (T0) and during the 1st month (T1), 4-6th month (T2), and 7-9th month (T3) of ART treatment. Patients were stratified into three groups according to initial CD4 count: ≤ 350 cells/mm3, >350-500 cells/mm3 and >500 cells/mm3. Repeated measures ANOVA and generalized estimating equations were used to estimate the relationships between the level of initial CD4 count and ADRs.
RESULTS: A total of 207 patients completed the study. Mean symptom numbers and symptom intensities decreased significantly over time in all three groups (p < .01). The largest mean reduction in both symptom number and intensity was achieved by the CD4 count >500 cells/mm3 group. Overall, at least one ADR was reported by 85.7% of the participants at the first month of ART use, and the incidence of ADR had decreased by an average of 22% at the 7-9th month assessment (p < .001). ARDs decreased significantly over time in the CD4 count > 500 cells/mm3 group, with the degrees of ADRs in systematic side effect most significantly decreased in this group (p = .03).
CONCLUSIONS / IMPLICATIONS FOR PRACTICE: Number and intensity of symptoms significantly improved over time in all three CD4 count groups. The percentage of systematic side effects was most reduced in the CD4 count > 500 cells/mm3 group. The results of this study may be referenced by HIV care providers when discussing with patients the initiation of ART and the potential risks of experiencing ADRs.

PMID: 31960397 [PubMed - indexed for MEDLINE]