Front Psychiatry. 2021 Feb 24;12:579448. doi: 10.3389/fpsyt.2021.579448. eCollection 2021.

ABSTRACT

Background: Efavirenz (EFV) is widely used in antiretroviral therapy (ART), but the incidence and risk factors of neuropsychiatric adverse events (NPAEs) after EFV treatment have rarely been studied in Chinese ART naïve patients. Methods: This prospective cohort study assessed HIV-infected patients initiating antiretroviral treatment with EFV to determine prevalence of and factors associated with NPAEs over a 12-month follow-up period using the Hospital Anxiety and Depression Scale (HADS) and the Pittsburgh Sleep Quality Index (PSQI). Results: A total of 546 patients were enrolled. Prevalence of anxiety, depression, and sleep disturbances at baseline were 30.4, 22.7, and 68.1%, respectively. Six patients discontinued treatment due to drug related NPAEs. Treatment was associated with improvements in HADS-A, HADS-D, and PSQI scores over the 12-month follow-up, and the frequencies of patients with anxiety, depression, and sleep disturbances significantly decreased after 12 months. Abnormal baseline HADS-A, HADS-D, and PSQI scores and other factors, including high school education or lower income, unemployment, divorce, and WHO III/IV stages, were associated with severe neuropsychiatric disorders over the 12 months. Conclusions: These findings suggested EFV discontinuation due to NAPEs was low, and the HADS-A, HADS-D, and PSQI scores after 12 months of EFV treatment were associated with several risk factors. The clinicians should keep in mind and routinely screen for the risk factors associated with neuropsychiatric disorders in HIV-infected patients.

PMID:33716807 | PMC:PMC7943719 | DOI:10.3389/fpsyt.2021.579448

Intern Med. 2021 Mar 15. doi: 10.2169/internalmedicine.6370-20. Online ahead of print.

ABSTRACT

Objective This study examined whether or not the Digestive Disease Week-Japan (DDW-J) 2004 scale proposed over 15 years ago can be applied to current cases of drug-induced liver injury (DILI). Patients and Methods The new patients group included 125 patients from 2012 to 2019 and was divided into 2 subgroups: 96 patients in the new DILI group and 29 patients in the new non-DILI group. Similarly, the old patients group included 105 patients from 1997 to 2002 and was divided into 2 subgroups: 59 patients in the old DILI group and 46 patients in the old non-DILI group. Patients were assessed by the DDW-J 2004 scale; those with a score ≥3 were defined as having DILI. Results The total score of the new DILI group was significantly lower than that of the old DILI group (6 [1-11] vs. 6 [3-9], p=0.004). The sensitivity, specificity, positive predictive value, and negative predictive value (NPV) were 94.8%, 65.6%, 90.1%, and 79.2%, respectively, in the new patients group and 100%, 91.4%, 93.7%, and 100%, respectively, in the old patients group. The specificity and NPV of the new patients group were significantly lower than those of the old patients group. Conclusion The DDW-J 2004 scale maintains a stable diagnostic ability for DILI, regardless of differences in eras and verification methods. However, differential diagnoses can affect the scoring, and new types of DILI, such as immune-related adverse events, must be addressed. Therefore, upgrading the scale should be considered.

PMID:33716281 | DOI:10.2169/internalmedicine.6370-20

Transplant Proc. 2021 Mar 10:S0041-1345(21)00121-4. doi: 10.1016/j.transproceed.2021.02.010. Online ahead of print.

ABSTRACT

A 35-year-old male patient with end-stage renal disease due to vesicoureteral reflux preemptively received a renal graft from his father. The patient had a history of allergy to contrast-enhancing media. He received oral tacrolimus (TAC) and mycophenolate mofetil without any problems for 2 days before kidney transplantation. During the induction period of the surgery, his systolic blood pressure (sBP) decreased to 60 mmHg approximately 1 hour after initiating intravenous tacrolimus (TAC-IV) and intravenous piperacillin (PIPC), and the anesthesiologist suspected drug-induced anaphylaxis and stopped administration of the medications. Because TAC had been administered preoperatively without any adverse events, PIPC was suspected as the causative agent of the anaphylaxis. After the patient's hemodynamics returned to baseline, TAC-IV was restarted. However, his sBP rapidly decreased to 40 mmHg and the patient developed wheezing. He was diagnosed with drug-induced anaphylaxis due to castor oil derivatives in the TAC-IV formulation. The patient's sBP was restored with the administration of some vasopressors, and kidney transplantation was then performed without difficulty. Two days after kidney transplantation, oral TAC was administered without anaphylaxis. Clinicians should consider that not only the drug itself but also its additives or metabolites could induce anaphylaxis.

PMID:33714607 | DOI:10.1016/j.transproceed.2021.02.010

J Am Med Inform Assoc. 2021 Mar 13:ocab019. doi: 10.1093/jamia/ocab019. Online ahead of print.

ABSTRACT

OBJECTIVE: We developed and evaluated Drug-Drug Interaction Wide Association Study (DDIWAS). This novel method detects potential drug-drug interactions (DDIs) by leveraging data from the electronic health record (EHR) allergy list.

MATERIALS AND METHODS: To identify potential DDIs, DDIWAS scans for drug pairs that are frequently documented together on the allergy list. Using deidentified medical records, we tested 616 drugs for potential DDIs with simvastatin (a common lipid-lowering drug) and amlodipine (a common blood-pressure lowering drug). We evaluated the performance to rediscover known DDIs using existing knowledge bases and domain expert review. To validate potential novel DDIs, we manually reviewed patient charts and searched the literature.

RESULTS: DDIWAS replicated 34 known DDIs. The positive predictive value to detect known DDIs was 0.85 and 0.86 for simvastatin and amlodipine, respectively. DDIWAS also discovered potential novel interactions between simvastatin-hydrochlorothiazide, amlodipine-omeprazole, and amlodipine-valacyclovir. A software package to conduct DDIWAS is publicly available.

CONCLUSIONS: In this proof-of-concept study, we demonstrate the value of incorporating information mined from existing allergy lists to detect DDIs in a real-world clinical setting. Since allergy lists are routinely collected in EHRs, DDIWAS has the potential to detect and validate DDI signals across institutions.

PMID:33712848 | DOI:10.1093/jamia/ocab019

Internist (Berl). 2021 Mar 12. doi: 10.1007/s00108-021-00993-3. Online ahead of print.

ABSTRACT

The need for a long-term pharmacological treatment of osteoporosis, the problem of potential compliance issues and also potentially severe side effects during the treatment are of central interest not only for patients but also for medical guidelines and prescribers. This review summarizes the current knowledge about the pharmacological substances used and the current scientifically based guidelines and approaches for the long-term use as well as the monitoring and potential treatment changes with a special focus on future developments.

PMID:33710362 | DOI:10.1007/s00108-021-00993-3

Eur J Hosp Pharm. 2021 Mar 11:ejhpharm-2020-002542. doi: 10.1136/ejhpharm-2020-002542. Online ahead of print.

ABSTRACT

OBJECTIVES: The objectives were to compare clinical pharmacist interventions between two care groups: COVID-19-positive and COVID-19-negative patients, and to identify drugs that require particular attention, especially those involved in COVID-19 management.

METHODS: A prospective cohort study was conducted on patients with positive and negative COVID-19 statuses admitted to Lille University Hospital over 1 month. Pharmaceutical analysis instigated interventions to rectify drug-related errors. For each pharmaceutical intervention (PI), the anatomical therapeutic chemical classification of the drug and the outcome of such an intervention were specified.

RESULTS: The study included 438 patients. Prescription analysis led to 188 PIs performed on 118 patients (64 COVID-19-positive patients and 54 COVID-19-negative patients). Most drug-related problems were incorrect dosage representing 36.7% (69/188) of all interventions: 27.9% (29/104) for the COVID-19-positive group and 47.6% (40/84) for the COVID-19-negative group. The most frequent PI in 34% (64/188) of cases was terminating a drug: 27.9% (29/104) for the COVID-19-positive group and 47.6% (40/84) for the COVID-19-negative group. The main drug classes involved were antithrombotic agents (20.7%, 39/188), antibacterials for systemic use (13.8%, 26/188) and drugs for gastric acid-related disorders (6.4%, 12/188). Study population was limited to a single centre over 1 month.

CONCLUSION: No difference in PI was noted between the two groups. The presence of pharmacists led to a reduction in drug-related prescription problems, especially for antithrombotic and antibacterial drugs for both groups. Clinical pharmacy commitment in such a pandemic is therefore important.

PMID:33707185 | DOI:10.1136/ejhpharm-2020-002542

Hematology. 2021 Dec;26(1):312-320. doi: 10.1080/16078454.2021.1875600.

ABSTRACT

OBJECTIVES: The present meta-analysis was performed to evaluate the efficacy, toxicities of both hypomethylating agents (decitabine and azaciticine) in the treatment of CMML patients.

METHODS: All available cohort studies of patients with CMML treated with decitabine and azacitidine were identified. The primary endpoints of this meta-analysis were response to hypomethylating agents. Pooled estimates of treatment response and drug-related adverse events were calculated using fixed or random effect models.

RESULTS: Fourteen studies with 600 CMML patients (decitabine: n=196; azacitidine: n=404) were identified and included for meta-analysis. HMAs yielded a pooled ORR estimate of 43% (95% CI: 36%-50%) in patients with CMML. Patients received either azacitidine or decitabine exhibited comparable incidence of ORR (43% vs. 45%, P=0.810), while significantly higher incidence of mCR was observed in patients treated with decitabine (23% vs. 10%, P=0.000). Decitabine treatment was also associated with higher incidence of transfusion independence (42% vs. 20%, P=0.044). Both HMAs led to objective hematologic or non-hematologic AEs (27%-43%), while dosage modification/delay were more frequent in patients treated with azacitidine (81% vs. 67%, P=0.021).

CONCLUSION: This current study may provide preliminary data in evaluating the efficacy and safety of HMAs in patients with CMML. Decitabine and azacitidine are comparable effective and safe in treating CMML. However, it is necessary to point out that any comparison of decitabine and azacitidine with respect to clinical outcomes can only be done in the context of a randomized controlled trial.

PMID:33706667 | DOI:10.1080/16078454.2021.1875600

Neurosci Lett. 2021 Mar 8:135800. doi: 10.1016/j.neulet.2021.135800. Online ahead of print.

ABSTRACT

Epilepsy, a common neurological disorder, affects about 50 million people around the world. The prevalence of epilepsy is approximately 6.8 per 1000 in the US [1].Since it is a chronic disease, it often requires lifelong treatment. The severity of epilepsy may vary from well controlled seizure on monotherapy to refractory seizures on polytherapy with many comorbidities and several drug related side effects and interactions [2]. Although there are many alternative treatment options for for epilepsy, such as vagus nerve stimulation (VNS), surgery, and a ketogenic diet, antiepileptic drugs (AEDs) are accepted as the first choice [2].Common adverse effects of AEDs include dizziness, drowsiness, mental slowing, skin rashes, hepatotoxicity, movement and behavioral disorders, and metabolic disturbances, such as weight gain, metabolic acidosis, and nephrolithiasis [3].Although some of AED side effects may be cosmetic changes such as weight gain, hair loss, acne, or masculine hair distribution in women, hormonal effects of antiepileptic drugs can have a significant impact on the life quality of patients. AEDs can affect hormonal balance in different areas, from bone health to fertility, sexual dysfunction,and thyroid abnormalities [4].

PMID:33705937 | DOI:10.1016/j.neulet.2021.135800

Drug Ther Bull. 2021 Mar 10:dtb-2021-000011. doi: 10.1136/dtb.2021.000011. Online ahead of print.

ABSTRACT

The BNF is jointly published by the Royal Pharmaceutical Society and BMJ. BNF is published in print twice a year and interim updates are issued and published monthly in the digital versions. The following summary provides a brief description of some recent key changes that have been made to BNF content.

PMID:33692150 | DOI:10.1136/dtb.2021.000011

Kardiol Pol. 2021 Mar 4. doi: 10.33963/KP.15860. Online ahead of print.

ABSTRACT

BACKGROUND: Hypertension is one of the most common chronic diseases. The need to undergo indefinite treatment combined with the risk of developing complications affecting the cardiovascular system impose significant psychological and somatic burdens on the patient. Arterial hypertension (AH) is rarely an isolated disease. Its most commonly observed comorbidities include metabolic disorders, as well as clinically apparent complications associated with polypharmacy, which increases the risk of drug-induced adverse events.

AIMS: To determine those factors that have an impact on illness acceptance in patients with AH.

METHODS: The study was conducted on a group of 532 patients who had been diagnosed with AH, the study made use of a standardized Acceptance of Illness Scale (AIS) questionnaire and a questionnaire prepared by the authors. The AIS scale allows to classify the illness acceptance as high (30-40 points), average (19-29 points) or low (8-18 points).

RESULTS: A high level of illness acceptance was noted in 45% of participants, while average acceptance was observed in 46%. Patients with different levels of illness acceptance showed disparities in: duration of arterial hypertension, number of cardiovascular and all diseases, the frequency of mental disorders, and the number of drugs taken. The number of cardiovascular diseases was significantly lower in patients with high acceptance than in those with poor acceptance. Disease duration in patients with a high level of illness acceptance was significantly shorter than in patients with average acceptance.

CONCLUSIONS: Acceptance of illness is correlated with duration of illness, number of diseases and number of medications taken.

PMID:33687869 | DOI:10.33963/KP.15860

Infect Dis Ther. 2021 Mar 9. doi: 10.1007/s40121-021-00419-5. Online ahead of print.

ABSTRACT

INTRODUCTION: We report the 48-week results of an ongoing study to assess the efficacy and safety of switching older people with HIV to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF).

METHODS: This was a 96-week, phase 3b, open-label, single-arm study (GS-US-380-4449; NCT03405935). Virologically suppressed individuals aged ≥ 65 years receiving elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or a tenofovir disoproxil fumarate-based regimen were switched to B/F/TAF. Primary endpoint was the percentage of participants with HIV-1 RNA < 50 copies/ml at week 24.

RESULTS: Eighty-six participants (median age 69 [range 65-80] years; 87% male; 95% white) were enrolled and treated in five European countries. Rates of virologic suppression were 97.7% at week 24 and 90.7% at week 48; none had HIV-1 RNA ≥ 50 copies/ml, and 100% had virologic suppression by missing = excluded analysis at both time points. No treatment-emergent resistance was observed. There were no grade 3-4 study drug-related adverse events (AEs) or study drug-related serious AEs or deaths. Three AEs led to premature discontinuation; one (moderate abdominal discomfort) was attributed to the study drug by the investigator. At week 48, median changes from baseline in weight and estimated glomerular filtration rate were + 0.1 kg (interquartile range [IQR] - 1.0, 2.3) and - 6.0 ml/min (IQR - 10.2, 0.0), respectively. There were no clinically relevant changes from baseline to week 48 in fasting lipid parameters. Treatment satisfaction improved, and health-related quality of life was maintained from baseline through week 48. Median adherence to the study drug was 98.6% (IQR 96.0, 100).

CONCLUSIONS: Switching to B/F/TAF was effective and well tolerated through 48 weeks in virologically suppressed adults aged ≥ 65 years.

TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03405935.

PMID:33686573 | DOI:10.1007/s40121-021-00419-5

BMJ Evid Based Med. 2021 Mar 8:bmjebm-2020-111661. doi: 10.1136/bmjebm-2020-111661. Online ahead of print.

NO ABSTRACT

PMID:33685948 | DOI:10.1136/bmjebm-2020-111661

Sex Med. 2021 Mar 5:100337. doi: 10.1016/j.esxm.2021.100337. Online ahead of print.

ABSTRACT

INTRODUCTION: The incidence of erectile dysfunction (ED) increases with age in mainland China and phosphodiesterase 5 inhibitors (PDE5i) are the major drugs used for its treatment.

AIM: To determine the efficacy and safety of Chinese developed avanafil as therapy for ED in China.

METHODS: This phase III trial was carried out in 7 medical centers in China. Eligible subjects suffering from ED were allocated randomly into 3 groups (ratio 1:1:1) and orally received a placebo, 100 or 200 mg avanafil for a total of 12 weeks.

MAIN OUTCOME MEASURES: The primary endpoint was changes in erectile function (EF) domain scores according to the International Index of EF (IIEF) questionnaire from baseline to week 12 of therapy. Secondary endpoints assessments were changes in the response rates of SEP, Q2 and Q3; changes in IIEF other domain scores. Safety evaluation monitored treatment-emergent adverse events (TEAEs), serious TEAEs, laboratory test results, vital signs and electrocardiographs.

RESULTS: Of 218 randomized ED subjects, 182 (83.5%) completed the study. After 12-week therapy, alterations from baseline of the mean IIEF-EF domain scores in the 100 mg and 200 mg groups were greater than for the placebo (all P < .05) group. The changes in mean SEP Q2 response rates from baseline to week 12 in the placebo, 100 mg and 200 mg groups were 5.4%, 22.3% and 22.1%, and SEP Q3 response rate were 22.7%, 42.6% and 38.1%, respectively. Avanafil treatment (regardless of dose) improved EF vs placebo for most of other secondary efficacy endpoints studied (all P < .05). No differences were detected in efficacy endpoints between the 100 and 200 mg dosage groups (all P > .05) or in the incidence of TEAEs and drug-related TEAEs among the 3 groups (all P > .05).

CONCLUSION: Avanafil (100 or 200 mg) was effective and generally well tolerated in Chinese subjects with ED.

PMID:33685839 | DOI:10.1016/j.esxm.2021.100337

Br J Clin Pharmacol. 2021 Mar 8. doi: 10.1111/bcp.14800. Online ahead of print.

ABSTRACT

Emerging data are linking coronavirus disease 2019 (COVID-19) with an increased risk of developing new-onset diabetes. The gut has been so far out of the frame of the discussion on the pathophysiology of COVID-19-induced diabetes, with the pancreas, liver, and adipose tissue being under the spotlight of medical research. Sodium-glucose co-transporters (SGLT) 1 represent important regulators of glucose absorption, expressed in the small intestine where they mediate almost all sodium-dependent glucose uptake. Similar to what happens in diabetes and other viral infections, SGLT1 upregulation could result in increased intestinal glucose absorption and subsequently promote the development of hyperglycaemia in COVID-19. Considering the above, the question whether dual SGLT (1 and 2) inhibition could contribute to improved outcomes in such cases sounds challenging, deserving further evaluation. Future studies need to clarify whether putative benefits of dual SGLT inhibition in COVID-19 outweigh potential risks, particularly with respect to drug-induced euglycaemic diabetic ketoacidosis, gastrointestinal side effects, and compromised host response to pathogens.

PMID:33684969 | DOI:10.1111/bcp.14800

Med J Aust. 2021 Mar 8. doi: 10.5694/mja2.50973. Online ahead of print.

NO ABSTRACT

PMID:33684959 | DOI:10.5694/mja2.50973

Invest New Drugs. 2021 Mar 8. doi: 10.1007/s10637-020-01056-4. Online ahead of print.

ABSTRACT

BI 836826 is a chimeric immunoglobulin G1 antibody targeting CD37, a transmembrane protein expressed on normal and malignant B cells. This open-label, phase Ib, dose-escalation study was conducted to determine the recommended phase II dose (RP2D) of BI 836826 + ibrutinib in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Eligible patients received 420 mg/day of ibrutinib with escalating doses of BI 836826. BI 836826 was administered in 4-week cycles. After Cycle 12, patients achieving complete response (CR), CR with incomplete marrow recovery, or minimal residual disease-negative partial response could continue to receive BI 836826 + ibrutinib every 4 weeks for ≤ 12 additional cycles. Patients received either 100 mg (n = 3) or 200 mg (n = 3) BI 836826 + ibrutinib. In the 100 mg BI 836826 cohort, one patient received two cycles and two patients received 22 cycles of BI 836826. In the 200 mg BI 836826 cohort, patients received 12, 16 and 20 cycles of BI 836826, respectively. All patients discontinued BI 836826 and continued ibrutinib outside the trial. No dose-limiting toxicities were reported in the maximum tolerated dose (MTD) evaluation period. As the trial was discontinued before the MTD was reached, the RP2D was not determined. Grade 3/4 adverse events (AEs) were predominantly hematological. Pseudomonal bacteremia was the only drug-related AE of special interest. BI 836826 + ibrutinib did not exceed the MTD at doses up to 200 mg in patients with CLL. However, RP2D and MTD were not formally established, as the sponsor discontinued the trial.

PMID:33683501 | DOI:10.1007/s10637-020-01056-4

Proc (Bayl Univ Med Cent). 2020 Dec 23;34(2):316-317. doi: 10.1080/08998280.2020.1855922.

ABSTRACT

Linezolid is a frequently prescribed antibiotic for chronic infection suppression, such as in prosthetic joint infections. While well tolerated, its prolonged use can increase the risk of rare and serious side effects. We present a case of linezolid toxicity presenting with a constellation of adverse effects including bone marrow suppression, lactic acidosis, and drug-induced liver injury. Our case highlights the increased risk of acute multiorgan failure in patients using the antibiotic for extended durations, notably those with preexisting comorbidities.

PMID:33678977 | PMC:PMC7901438 | DOI:10.1080/08998280.2020.1855922

Diabetes Res Clin Pract. 2021 Mar 4:108732. doi: 10.1016/j.diabres.2021.108732. Online ahead of print.

ABSTRACT

Acute bacterial skin and skin structures infections (ABSSSIs) are associated with high morbidity, costs and mortality in patients with diabetes mellitus. Their appropriate management should include several figures and a well-organized approach. This review aims to highlight the interplay between diabetes and ABSSSIs and bring out the unmet clinical needs in this area. Pathogenetic mechanisms underlying the increased risk of ABSSSIs in diabetes mellitus are multifactorial: high glucose levels play a crucial pathogenetic role in the tissue damage and delayed clinical cure. Moreover, the presence of diabetes complications (neuropathy, vasculopathy) further complicates the management of ABSSSIs in patients with diabetes. Multidrug resistance organisms should be considered in this population based on patient risk factors and local epidemiology and etiological diagnosis should be obtained whenever possible. Moreover, drug-drug interactions and drug-related adverse events (such as nephrotoxicity) should be considered in the choice of antibiotic therapy. Reducing unnecessary hospitalizations and prolonged length of hospital stay is of primary importance now, more than ever. To achieve these objectives, a better knowledge of the interplay between acute and chronic hyperglycemia, multidrug resistant etiology, and short and long-term outcome is needed. Of importance, a multidisciplinary approach is crucial to achieve full recovery of these patients.

PMID:33676996 | DOI:10.1016/j.diabres.2021.108732

Eur J Radiol. 2021 Feb 25;138:109617. doi: 10.1016/j.ejrad.2021.109617. Online ahead of print.

ABSTRACT

PURPOSE: Cancer treatments with immune checkpoint inhibitors (ICI) are associated with a unique set of drug toxicities called immune-related adverse events (irAES). The aim of the present study was to describe the radiological manifestation of irAES detectable by CT.

METHOD: Retrospective analysis of 284 patients treated with ICI for various types of advanced cancer; of them, 129 patients were selected, all having been treated with single-agent ICI, and all with a baseline CT scan and follow-up scans available at our Institute. CT examinations were reviewed by two radiologists involved in the study with a consensus reading. Imaging findings consistent with irAES were reported and correlated with clinical-laboratory data.

RESULTS: Immune-related adverse events were found in 25/129 (19.4 %) patients. No statistically significant differences were found in either the prevalence of irAES or in the time of onset of tumour type. Thoracic complications were detected in 14/25 (56.0 %) patients consisting in: 3 radiation recall pneumonia, 3 Transient Asymptomatic Pulmonary Opacities (TAPOs), 3 hypersensitivity pneumonia, 2 diffuse alveolar damage, 2 organizing pneumonia, 1 sarcoid-like reaction. In the remaining 11/25 (44.0 %), there were extra-pulmonary complications: 3 colitis, 4 cholecystitis, 2 pancreatitis and 2 cases of visceral ischemia.

CONCLUSIONS: Radiologists should be aware of the wide spectrum of irAES as they could affect the outcome. Pneumonia is the most frequent irAES; however, the international classification for interstitial lung disease does not seem to be capable of describing all possible drug-related pulmonary toxicities. Additional findings included TAPOs, radiation recall pneumonia and sarcoid-like reaction.

PMID:33676358 | DOI:10.1016/j.ejrad.2021.109617

Crit Rev Oncol Hematol. 2021 Mar 3:103296. doi: 10.1016/j.critrevonc.2021.103296. Online ahead of print.

ABSTRACT

We systematically reviewed the quality of AEs reports in published oncology trials analyzing also the bias in the attribution process. We searched MEDLINE, PubMed (2000-2019) selecting randomized, double-blind, placebo-controlled, and phase 3 cancer trials using exclusively targeted therapy or immunotherapy-related drugs. The proportion of publications with complete AE reports (including both all-cause and drug-related AE data) and the AEs attribution ratio (patients with drug-related over all-cause AE) were investigated. Among 60 trials (38,174 patients) included, 40 (66.6%) presented an incomplete report of AEs attribution. Journals with the lowest impact factor were significantly associated with deficient reports of grade 3-4 AEs (p = 0.02). Under placebo administration, the median incidence of all-grade drug-related AEs was 49% (IQR 39-56). The median attribution ratio for all-grade AEs in the active and placebo arms was 88.9% (IQR 79.8-93) and 53.9% (IQR 43.4-60.9), respectively. The AEs reporting and attribution process appear to be more unreliable than expected.

PMID:33675904 | DOI:10.1016/j.critrevonc.2021.103296