There are no "side" effects, just "core" effects of antipsychotic pharmacotherapy.

Acta Psychiatr Scand. 2021 02;143(2):99-100

Authors: Fornaro M

PMID: 33452692 [PubMed - indexed for MEDLINE]

Applying the Medications at Transitions and Clinical Handoffs Toolkit in a Rural Primary Care Clinic: Implications for Nursing, Patients, and Caregivers.

J Nurs Care Qual. 2020 Jul/Sep;35(3):233-239

Authors: Jarrett T, Cochran J, Baus A

Abstract
BACKGROUND: Adequate medication reconciliation is related to patients' safety. Rural populations are at increased risk of adverse drug events due to errors in medication reconciliation and often receiving medical care across multiple health care entities and across long distances with separate electronic medical records.
METHODS: This study examined the implementation of Medications at Transitions and Clinical Handoffs Toolkit (MATCH) in a rural primary care clinic and assessed the acceptability and feasibility of implementation.
INTERVENTION: MATCH was developed as a workflow process intervention to improve medication reconciliation.
RESULTS: Findings from MATCH implementation indicate that the process improved medication reconciliation workflow. A shared definition of current medications across providers and patients was essential.
CONCLUSIONS: Empowering patients and caregivers with tools and language to work with providers, particularly nurses, to conduct medication reconciliation during primary care clinic visits is key to improving patient medication reconciliation in rural settings.

PMID: 32433146 [PubMed - indexed for MEDLINE]

Association of DNA repair gene variants with colorectal cancer: risk, toxicity, and survival.

BMC Cancer. 2020 May 12;20(1):409

Authors: Salimzadeh H, Lindskog EB, Gustavsson B, Wettergren Y, Ljungman D

Abstract
BACKGROUND: Single nucleotide polymorphisms (SNPs) in DNA repair genes have a potential clinical value in predicting treatment outcomes. In the current study, we examined the association of SNPs in the genes XRCC1-rs25487, ERCC1-rs11615, ERCC2-rs238406, and ERCC2-rs13181 with colorectal cancer (CRC) risk, relapse-free survival (RFS), overall survival (OS), and toxicity during chemotherapy.
METHODS: SNPs were analysed in 590 CRC cases and 300 controls using TaqMan technology. The association of SNPs with CRC risk and toxicity during chemotherapy was analysed using Chi2 test. The Kaplan-Meier method and log-rank test was used to measure the effects of the SNPs on RFS and OS.
RESULTS: The CC genotype of ERCC2-rs238406 and the ERCC2-rs13181 C allele were associated with a significantly increased risk of CRC. The ERCC1-rs11615 genotype T/T was associated with stomatitis in adjuvant chemotherapy (p = 0.03). Also, more patients with the ERCC2-rs13181 C allele needed dose reduction compared to patients with the A/A genotype (p = 0.02). In first line chemotherapy, more patients with the ERCC1-rs11615 C allele suffered from nausea compared to those with the T/T genotype (p = 0.04) and eye reactions and thrombocytopenia were more common in patients with the ERCC2-rs13181 C allele compared to the A/A genotype (p = 0.006 and p = 0.004, respectively). ERCC2- rs238406 C/C was also associated with a higher frequency of thrombocytopenia (p = 0.03). A shorter 5-year OS was detected in stage I & II CRC patients with the ERCC2- rs238406 C allele (p = 0.02). However, there was no significant association between the SNPs and 5-year RFS.
CONCLUSIONS: Both SNPs in ERCC2 were associated with risk of CRC as well as toxicity during first line treatment. In addition, ERCC2- rs238406 was linked to OS in early stage CRC. The ERCC1-rs11615 variant was associated with toxicity during adjuvant chemotherapy. The results add support to previous findings that SNPs in ERCC1 and ERCC2 have a prognostic and predictive value in clinical management of CRC.

PMID: 32397974 [PubMed - indexed for MEDLINE]

Treatment and its side effects in ANCA-associated vasculitides - Study based on POLVAS registry data.

Adv Med Sci. 2020 Mar;65(1):156-162

Authors: Biedroń G, Włudarczyk A, Wawrzycka-Adamczyk K, Wójcik K, Sznajd J, Zdrojewski Z, Masiak A, Czuszyńska Z, Majdan M, Jeleniewicz R, Klinger M, Jakuszko K, Rowaiye OO, Brzosko M, Brzosko I, Dębska-Ślizień A, Storoniak H, Tłustochowicz W, Kur-Zalewska J, Wisłowska M, Madej M, Hawrot-Kawecka A, Głuszko P, Kucharz EJ, Musiał J, Szczeklik W

Abstract
PURPOSE: The aim of this study is to present the treatment modalities and associated side effects in a Polish nation-wide ANCA-associated vasculitides (AAV) patients' cohort.
MATERIALS AND METHODS: Retrospective analysis of patients diagnosed with AAV between 1990 and 2016, included in the POLVAS registry was performed. Standard descriptive statistic methods were used with an emphasis on the treatment modalities.
RESULTS: There were 625 patients diagnosed with AAV included in this study: 417 cases of granulomatosis with polyangiitis (GPA; 66.7%), 106 cases of microscopic polyangiitis (MPA; 17.0%) and 102 cases of eosinophilic granulomatosis with polyangiitis (EGPA; 16.3%). The mean age at the date of diagnosis was 50.4 (±15.7) years and the median observational period amounted to 4.0 (2.0-8.0) years. Glucocorticosteroids (GCs) were the medicaments most frequently used for remission induction (593/622; 95.3%), followed by cyclophosphamide (487/622; 78.3%), rituximab (44/622; 7.1%), and methotrexate (39/622; 6.3%). GCs were also most frequently administered for maintenance therapy (499/592; 84.3%), followed by azathioprine (224/592; 37.8%), methotrexate (136/592; 23.0%) and mycophenolate mofetil (99/592; 16.7%). The median cumulative doses of cyclophosphamide and rituximab equalled 7.99 g (4.18-14.0) and 2000 mg (1500-2800), respectively. The most commonly observed adverse events included: infections - 214/551 cases (38.8%), which were associated with the time of observation (OR = 1.05; 95% CI 1.01-1.10), the use of GCs intravenous pulses (OR = 2.76; 95% CI 1.68-4.54) and need for haemodialysis (OR = 1.73; 95% CI 1.10-2.71).
CONCLUSIONS: Polish patients with AAV were predominantly treated according to appropriate guidelines. The most frequent adverse events were typical for usually administered immunosuppressive treatment.

PMID: 31958704 [PubMed - indexed for MEDLINE]

Safety, efficacy and cost of two direct-acting antiviral regimens: A comparative study in chronic hepatitis C Egyptian patients.

J Clin Pharm Ther. 2020 Jun;45(3):539-546

Authors: Ibrahim Mohammed Ebid AH, Ashraf Ahmed O, Hassan Agwa S, Mohamed Abdel-Motaleb S, Mohamed Elsawy A, Hagag RS

Abstract
WHAT IS KNOWN AND OBJECTIVE: Direct-acting antivirals (DAAs) have become the most widely used treatment of chronic hepatitis C infection. Comparative studies on DAAs regimens approved by the Egyptian Ministry of Health for easy-to-treat genotype 4 (G4) Egyptian patients are still deficient. In this prospective study, we compared the efficacy and cost of two DAA regimens that are used in the treatment of Egyptian chronic hepatitis C virus (HCV) G4. The cost-saving regimen is determined.
METHODS: Eligible patients were randomized into 2 groups. Group 1 (Gp 1) received sofosbuvir plus daclatasvir, and group 2 (Gp 2) received ombitasvir, paritaprevir and ritonavir plus ribavirin (RBV) for 12 weeks. Data were collected and evaluated at baseline and at weeks 4, 8 and 12. Sustained virologic response 12 weeks after the end of treatment (SVR12 ) was evaluated. Cost-minimization analysis (CMA) was performed.
RESULTS AND DISCUSSION: Eligibility was achieved in 107 patients, Gp1 included 57 patients, and Gp 2 included 50 patients. Two patients dropped out from Gp 2 due to non-compliance. All patients in the two groups showed negative HCV blood levels at the end of treatment. At the 24th week, 3 relapsers (5.2%) were detected in Gp1 and 2 relapsers (4.1%) were detected in Gp 2. SVR12 was 54/57 (94.7%) and 46/48 (95.8%) for Gp 1 and Gp 2, respectively. After the 12th week of treatment, a significant decrease in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and haemoglobin levels were observed in both groups. Albumin levels declined in Gp 2 only. CMA showed higher cost in Gp 2 than Gp 1, although similar efficacy and safety.
WHAT IS NEW AND CONCLUSION: The two DAA regimens showed high SVR12 and safety in Egyptian HCV G4 patients. Sofosbuvir plus daclatasvir is the cost-saving regimen.

PMID: 31889322 [PubMed - indexed for MEDLINE]

Assessment of factors associated with completeness of spontaneous adverse event reporting in the United States: A comparison between consumer reports and healthcare professional reports.

J Clin Pharm Ther. 2020 Jun;45(3):462-469

Authors: Toki T, Ono S

Abstract
WHAT IS KNOWN AND OBJECTIVE: The objectives of this study were to explore completeness of direct adverse event (AE) reports from consumers and healthcare professionals (HCPs), and to discuss the reasons completeness varied among reporters with different occupations.
METHODS: We used a total of 5475 direct AE reports to the United States (US) Food and Drug Administration (FDA) from the first and second quarters of 2016 and assessed completeness of basic information (eg, patient sex, age, weight) and information relevant to AEs (eg, suspect and concomitant drugs). Logistic regression analysis was conducted to evaluate the associations between report completeness and reporting backgrounds.
RESULTS AND DISCUSSION: The completeness of AE reports from consumers was generally greater than that of reports from HCPs. Completeness of specific items varied among different occupations, which may reflect accessibility to, and/or availability of, relevant information for each type of reporter. There was a clear association between the proportion of 'known' ADRs in a report and completeness, suggesting that consumers and HCPs are likely to consult labelling information when reporting AEs.
WHAT IS NEW AND CONCLUSION: The quality of AE reports seemed to depend on information costs accrued to potential reporters. Researchers should consider the impact of database heterogeneity and possible sample selection bias when using spontaneous AE reports as a sample of events in the United States.

PMID: 31765498 [PubMed - indexed for MEDLINE]

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JAMA. 2021 Feb 2;325(5):482-483. doi: 10.1001/jama.2020.17308.

NO ABSTRACT

PMID:33528524 | DOI:10.1001/jama.2020.17308

Sleep Med. 2021 Jan 5;79:145-151. doi: 10.1016/j.sleep.2021.01.005. Online ahead of print.

ABSTRACT

BACKGROUND: Under-diagnosis of obstructive sleep apnea (OSA) is common because of the demanding and time-consuming nature of polysomnography (PSG). Herein, we assessed the utility of a short daytime dexmedetomidine-induced PSG for diagnosis of OSA in adults.

METHODS: This was a single-center, prospective, diagnostic trial. We evaluated 86 patients using a full overnight PSG and a short diurnal drug-induced PSG (DIPSG). DIPSG was induced by continuous intravenous dexmedetomidine infusion. Sedation depth was monitored and maintained using the Narcotrend index (50-70). Diagnostic performance for DIPSG with different apnea-hypopnea index (AHI) cut-off values were calculated. Bland-Altman plots used for analysis. Sleep architecture and position were compared.

RESULTS: We studied 47 OSA patients and 39 healthy volunteers. Sensitivity and specificity for detection of OSA by DIPSG were 92% and 79%, respectively, for an AHI cut-off value of 5, 90% and 77%, respectively, for an AHI cut-off value of 15, and 95% and 85%, respectively, for an AHI cut-off value of 30. The DIPSG bias was -5 (-25; 15) for AHI and -3 (-13; 7) for minimal oxygen saturation. N2 sleep was increased (32.9% vs. 50.75%, respectively; p < 0.01) and REM sleep was decreased (21.35% vs. 1.24%, respectively; p < 0.01) during DIPSG. Twenty-eight (33%) participants had postural shifts during DIPSG. No significant adverse events were observed during DIPSG.

CONCLUSIONS: Dexmedetomidine-induced PSG had a good sensitivity and specificity, and can be used as a screening tool for diagnosis of OSA in adults.

CHINESE CLINICAL TRIAL REGISTRATION: ChiCTR1900024044.

PMID:33524840 | DOI:10.1016/j.sleep.2021.01.005

Endocrinol Diabetes Metab Case Rep. 2021 Jan 27;2021:20-0123. doi: 10.1530/EDM-20-0123. Online ahead of print.

ABSTRACT

SUMMARY: A 62-year-old patient with metastatic hypopharyngeal carcinoma underwent treatment with nivolumab, following which he developed symptoms suggestive of diabetes insipidus. Nivolumab was stopped and therapy with methylprednisolone was started. During corticosteroid therapy, the patient presented himself in poor health condition with fungal infection and glycemic decompensation. Methylprednisolone dose was tapered off, leading to the resolution of mycosis and the restoration of glycemic compensation, nevertheless polyuria and polydipsia persisted. Increase in urine osmolarity after desmopressin administration was made diagnosing central diabetes insipidus as a possibility. The neuroradiological data by pituitary MRI scan with gadolinium was compatible with coexistence of metastatic localization and infundibulo-neurohypophysitis secondary to therapy with nivolumab. To define the exact etiology of the pituitary pathology, histological confirmation would have been necessary; however, unfortunately, it was not possible. In the absence of histological confirmation, we believe it is likely that both pathologies coexisted.

LEARNING POINTS: A remarkable risk of endocrine immune-related adverse events (irAEs) during therapy with checkpoint inhibitors exsists. In order to ensure maximum efficiency in the recognition and treatment of endocrine iRAes related to immune checkpoint inhibitors, multidisciplinary management of oncological patients is critical. The pituitary syndrome in oncological patients who underwent immunotherapy represents a challenge in the differential diagnosis between pituitary metastasis and drug-induced hypophysitis. This is the first case, described in the literature of diabetes insipidus in a patient suffering from nivolumab-induced infundibulo-neurohypophysitis and anterohypophyseal metastasis.

PMID:33522491 | PMC:PMC7849457 | DOI:10.1530/EDM-20-0123

Cureus. 2020 Dec 27;12(12):e12325. doi: 10.7759/cureus.12325.

ABSTRACT

Acute pancreatitis is an acute inflammatory process of the pancreas that is associated with multiple etiologies. The two most common causes are gallstones and acute alcohol intoxication. However, medications are often overlooked when determining the cause. Empagliflozin is a type of sodium-glucose transport protein 2 (SGLT-2) inhibitor used for the treatment of type 2 diabetes mellitus. Given that this medication is new, the adverse effects have not been fully reported in the literature. Currently, the most commonly reported side effects are genitourinary infections such as cystitis or yeast infection although acute pancreatitis as a result of empagliflozin is very rare. Here, we discuss a case of a 64-year-old female who presented with severe pancreatitis after recently initiating the use of empagliflozin. Based on the timing of her presentation and her hospital workup to rule out many of the common etiologies, it was concluded that empagliflozin was the likely cause of her acute pancreatitis. With SGLT-2 inhibitors such as empagliflozin, becoming popular as first-line in the management of diabetes, this case may hope to raise awareness of the possible adverse effects related to it. Additionally, this case also emphasizes the importance of identifying iatrogenic related pancreatitis.

PMID:33520523 | PMC:PMC7837635 | DOI:10.7759/cureus.12325

Yakugaku Zasshi. 2021;141(2):179-185. doi: 10.1248/yakushi.20-00196-4.

ABSTRACT

Industrial reforms utilizing artificial intelligence (AI) have advanced remarkably in recent years. The application of AI to big data analysis in the medical information field has also been advancing and is expected to be used to find drug adverse effects that cannot be predicted by conventional methods. We have developed an adverse drug reactions analysis system that uses machine learning and data from the Japanese Adverse Drug Event Report (JADER) database. The system was developed using the C# programming language and incorporates the open source machine learning library Accord.Net. Potential analytical capabilities of the system include discovering unknown drug adverse effects and evaluating drug-induced adverse events in pharmaceutical management. However, to apply the system to pharmaceutical management, it is important to examine the characteristics and suitability of the level of AI used in the system and to select statistical methods or machine learning when appropriate. If these points are addressed, there is potential for pharmaceutical management to be individualized and optimized in the clinical setting by using the developed system to analyze big data. The system also has the potential to allow individual healthcare facilities such as hospitals and pharmacies to contribute to drug repositioning, including the discovery of new efficacies, interactions, and drug adverse events.

PMID:33518637 | DOI:10.1248/yakushi.20-00196-4

J Pharm Pract. 2021 Feb 1:897190021989931. doi: 10.1177/0897190021989931. Online ahead of print.

ABSTRACT

Neurological toxicity is a relatively rare adverse reaction reported in elderly patients treated with cephalosporins. We present a case of ceftazidime-induced encephalopathy in the context of acute kidney injury in an 80-year-old female treated for a Pseudomonas aeruginosa prosthetic joint infection. During the course of treatment, the patient developed sudden confusion and disorientation. The patient's mental state progressively worsened, eventually leading to intubation and admission to the intensive care unit. As imaging and laboratory analyses revealed no alternative causes explaining the patient's symptoms, ceftazidime was stopped under the suspicion of drug-induced neurotoxicity. Shortly after ceftazidime discontinuation, the patient's condition drastically improved and returned to baseline within 5 days. This case reveals the potential severity of cephalosporin-induced neurotoxicity in elderly patients and highlights the importance of quickly detecting such adverse events in order to prevent dire outcomes.

PMID:33517818 | DOI:10.1177/0897190021989931

Risk of bleeding complications and atrial fibrillation associated with ibrutinib treatment: a systematic review and meta-analysis.

Crit Rev Oncol Hematol. 2021 Jan 27;:103238

Authors: Pellegrini L, Novak U, Andres M, Suter T, Nagler M

Abstract
The use of ibrutinib is hampered by major bleeding events and atrial fibrillation. Speculating whether randomized controlled trials might underestimate the risk of adverse events in clinical practice, we conducted a systematic review and meta-analysis studying patients treated in any setting and indication. We systematically searched the literature using MEDLINE and EMBASE databases for case series, cohort studies, or randomized controlled trials and retrieved all data in parallel. Proportions of patients with adverse events were pooled in relevant subgroups using the binominal distribution and Freeman-Tukey double arcsine transformation. Among 2'537 records screened, 85 were finally included, comprising 7'317 patients. Methodological quality according to the Newcastle-Ottawa Scale was rated as moderate to poor with regard to bleeding events and atrial fibrillation; 106 studies were excluded because of missing data at all. Reported events varied substantially between 0% and 78% (any bleedings), 0% and 25% (major bleedings), and 0% and 38% (new-onset atrial fibrillation). Pooled estimates were 28% (95% confidence interval 22%, 34%), 3% (2%, 4%), and 8% respectively (7%, 10%). The risk of events was higher in studies with an older population, high ibrutinib dosage, thrombocytopenia, antithrombotic treatment, and retrospective studies. In conclusions, reporting of bleeding events and atrial fibrillation varied substantially among studies. These observations, in combination with the estimates obtained, suggest a relevant risk in clinical practice.

PMID: 33515702 [PubMed - as supplied by publisher]

A Randomized, Placebo-controlled Study to Evaluate the Efficacy and Safety of Adding Omarigliptin to Insulin Therapy in Japanese Patients with Type 2 Diabetes and Inadequate Glycemic Control.

Diabetes Obes Metab. 2021 Jan 29;:

Authors: Kadowaki T, Seino Y, Kaku K, Okamoto T, Kameya M, Sato A, Hirano T, Oshima N, Gantz I, O'Neill EA, Engel SS, Omarigliptin Study 039 Group

Abstract
AIMS: To evaluate the efficacy and safety of adding the once-weekly oral DPP-4 inhibitor omarigliptin to treatment of Japanese patients with type 2 diabetes and inadequate glycemic control on insulin monotherapy.
MATERIALS AND METHODS: In a 52-week clinical trial, Japanese patients on insulin monotherapy were randomized to once-weekly omarigliptin 25 mg (N=123) or placebo (N=61) for a 16-week, double-blind, placebo-controlled period. After Week 16, patients continued or switched to omarigliptin for a 36-week open-label period.
RESULTS: From a mean baseline of approximately 8.8%, the Week 16 least squares mean changes in HbA1c were -0.61% (omarigliptin) and 0.29% (placebo); the between-group difference was -0.90%, p<0.001. At Week 52, the mean change from baseline in HbA1c was -0.57% in both the group on omarigliptin for 52 weeks and the group on omarigliptin for 36 weeks (switched from placebo at Week 16). During the first 16 weeks of treatment, the incidences of adverse events (AEs), serious AEs, drug-related AEs, and discontinuation from trial medication due to an AE were similar in both groups. A slight increase in incidence of symptomatic hypoglycaemia was observed in the omarigliptin group (n=13 [10.6%]) compared with placebo (n=4 [6.6%]). No severe hypoglycaemia was reported during the study. No new safety signals emerged with treatment beyond Week 16 through Week 52.
CONCLUSION: The addition of once-weekly omarigliptin to insulin therapy for up to 52 weeks was generally well tolerated and provided clinically meaningful improvement in glycemic control throughout the trial period. (ClinicalTrials.gov: NCT02906709). This article is protected by copyright. All rights reserved.

PMID: 33512755 [PubMed - as supplied by publisher]

A Phase 1 Study of KHK4083: A Single-Blind, Randomized, Placebo-Controlled Single-Ascending-Dose Study in Healthy Adults and an Open-Label Multiple-Dose Study in Patients With Ulcerative Colitis.

Clin Pharmacol Drug Dev. 2021 Jan 29;:

Authors: Furihata K, Ishiguro Y, Yoshimura N, Ito H, Katsushima S, Kaneko E, Shimabe M, Mukai M, Watanabe R, Morishige T

Abstract
OX40 plays an essential role in maintaining late T-cell proliferation and survival by suppressing apoptosis and by inducing T-cell memory formation. Here, we report the results of the phase 1 study of KHK4083, a fully human antimonoclonal antibody specific for OX40. In this study, we aimed to assess the safety and tolerability of a single intravenous or subcutaneous administration of KHK4083 compared with placebo in healthy Japanese and Caucasian subjects and determined the pharmacokinetics (PK) and immunogenicity. Also, we assessed the preliminary efficacy and pharmacodynamics of multiple intravenous doses in Japanese patients with moderate to severe ulcerative colitis (UC). Drug-related treatment emergent adverse events occurred in 21 healthy subjects (58.3%) and 5 patients with UC (62.5%) after administration of KHK4083. There were no serious adverse events. The PK profile of a single intravenous dose of 10 mg/kg KHK4083 was similar in healthy Japanese and Caucasian subjects. Of 8 UC patients, a clinical response was observed in 3 patients (37.5%) and clinical remission in 2 patients (25.0%) in week 6. Our study demonstrated the safety and tolerability of single and multiple administrations of KHK4083 in healthy Japanese and Caucasian subjects and Japanese patients with moderate to severe UC. It also indicated favorable pharmacological properties of the drug.

PMID: 33512065 [PubMed - as supplied by publisher]

Suspected cholestatic liver injury induced by favipiravir in a patient with COVID-19.

J Infect Chemother. 2021 Feb;27(2):390-392

Authors: Yamazaki S, Suzuki T, Sayama M, Nakada TA, Igari H, Ishii I

Abstract
Favipiravir is an antiviral drug that is expected to have a therapeutic effect on SARS-CoV2 infection. Teratogenicity and hyperuricemia are known as the main side effects of favipiravir, but little is known about other side effects. This report describes a case of cholestatic liver injury induced by favipiravir. A 73-year-old Japanese with a history of alcoholic hepatitis was infected with SARS-CoV2. Drug therapy was instituted with lopinavir/ritonavir combined with interferon β-1b. However, his condition worsened despite additional support with continuous hemodiafiltration and veno-venous extracorporeal membrane oxygenation. We suspected complications of bacterial pneumonia and started favipiravir in addition to antimicrobial therapy. Favipiravir was administered at 6000 mg/day on the first day and 2400 mg/day for the second and subsequent days for 14 days. After the initiation of antibiotics, transaminase and total bilirubin were elevated, suggesting a transient cholestasic liver dysfunction. The liver dysfunction in this case may have been triggered by antibacterial treatment, and high dose of favipiravir may have promoted the deterioration of liver function. Monitoring of liver function is vital and close attention should be paid when using favipiravir at high doses or in patients with impaired liver function.

PMID: 33402301 [PubMed - indexed for MEDLINE]

Impact of Adverse Drug Reactions in Patients with End Stage Renal Disease in Greece.

Int J Environ Res Public Health. 2020 12 06;17(23):

Authors: Spanakis M, Roubedaki M, Tzanakis I, Zografakis-Sfakianakis M, Patelarou E, Patelarou A

Abstract
BACKGROUND: Patients with end-stage renal disease (ESRD) require specialized therapeutic interventions. The decreased renal function that modulates the physiology and presence of comorbidities is often associated with variations in the pharmacological response, thus increasing the risk of adverse drug events or reactions (ADE/ADRs) from co-administered drugs.
METHODS: A cross-sectional study to record comorbidities, drug-drug interactions (DDIs), ADE/ADRs in patients with chronic kidney disease of stage five in Greece. The study enrolled 60 patients of mean age 64.8 ± 12.9 years, undergoing hemodialysis three times a week. Demographic and social factors, comorbidities, laboratory test data, medication regimens, DDIs and the reporting of ADE/ADRs were analyzed.
RESULTS: Cardiovascular diseases and diabetes were the main comorbidities. In total, 50 different DDIs of various clinical significance were identified. CNS, GI-track, and musculoskeletal-system-related ADE/ADRs were most often reported by patients. ADE/ADRs as clinical outcome from DDIs were associated in 64% of the total identified DDIs. There was a positive trend between number of medications, ADE/ADRs report and DDIs.
CONCLUSIONS: The impact of ADE/ADRs in ESRD patients should be always considered. Guidelines as well as continuous training in the context of evidence-based clinical practice by healthcare personnel on therapy administration and prevention of adverse events are important.

PMID: 33291233 [PubMed - indexed for MEDLINE]

Body mass index and immune-related adverse events in patients on immune checkpoint inhibitor therapies: a systematic review and meta-analysis.

Cancer Immunol Immunother. 2021 Jan;70(1):89-100

Authors: Guzman-Prado Y, Ben Shimol J, Samson O

Abstract
BACKGROUND: As a result of the growing use of immune checkpoint inhibitors (ICIs) for treating malignancy, immune-related adverse events (irAEs) have been increasingly reported. Higher body mass index (BMI) has been highlighted as a potential risk factor for the development of irAEs. However, there are no meta-analyses summarizing the association between BMI and irAEs in patients on ICI therapies.
METHODS: PubMed, MEDLINE, EMBASE, Cochrane and grey literature were searched up to January 2020. Odds ratios (ORs) 95% and confidence intervals (CIs) were summarized using the random-effects model. Heterogeneity test, subgroup and sensitivity analyses were conducted. The protocol was registered on PROSPERO (number registration: CRD42020168790).
RESULTS: Five studies (n = 1937) met eligibility criteria for inclusion. Being overweight or obese was associated with an increased odds of developing irAEs (OR 2.62, 95% CI 1.70-4.03, P ≤ 0.00001, I2 = 53%). In subgroup analyses, higher BMI was associated with irAEs in patients using anti-CTLA-4 single agents or in combination with anti-PD-1/PD-L1 (OR 1.87, 95% CI 1.17-2.98, P = 0.009, I2 = 0%) and in patients using anti-PD-1/PD-L1 (OR 3.22, 95% CI 2.06-5.01, P = 0.00001, I2 = 32%) monotherapy. The increased odds of irAEs in patients with higher BMI was comparable (test for subgroup differences, P = 0.72, I2 = 0%) between studies with adjusted OR (OR 2.21, 95% CI 1.44-3.38, P = 0.0003, I2 = 4%) and unadjusted OR (OR 2.65, 95% CI 1.08-6.50, P = 0.03, I2 = 66%).
CONCLUSION: Our meta-analysis provides evidence of a relationship between higher BMI (overweight-obesity) and increased risk of irAEs in patients on ICI therapies. Further research is needed to strengthen this association.

PMID: 32648164 [PubMed - indexed for MEDLINE]

Meta-analysis examining overall survival in patients with pancreatic cancer treated with second-line 5-fluorouracil and oxaliplatin-based therapy after failing first-line gemcitabine-containing therapy: effect of performance status and comparison with other regimens.

BMC Cancer. 2020 Jul 08;20(1):633

Authors: Wainberg ZA, Feeney K, Lee MA, Muñoz A, Gracián AC, Lonardi S, Ryoo BY, Hung A, Lin Y, Bendell J, Hecht JR

Abstract
BACKGROUND: Pancreatic cancer has a poor prognosis and few choices of therapy. For patients with adequate performance status, FOLFIRINOX or gemcitabine plus nab-paclitaxel are preferred first-line treatment. 5-Fluorouracil (5-FU)-based therapy (e.g. FOLFIRI, OFF, or FOLFOX) are often used in patients who previously received gemcitabine-based regimens. A systematic review was conducted of the safety and efficacy of FOLFOX for metastatic pancreatic cancer following prior gemcitabine-based therapy. A Bayesian fixed-effect meta-analysis with adjustment of patient performance status (PS) was conducted to evaluate overall survival (OS) and compare outcomes with nanoliposomal irinotecan combination therapy.
METHODS: PubMed.gov , FDA.gov , ClinicalTrials.gov , congress abstracts, Cochrane.org library, and EMBASE database searches were conducted to identify randomized controlled trials of advanced/metastatic disease, prior gemcitabine-based therapy, and second-line treatment with 5-FU and oxaliplatin. The database search dates were January 1, 1990-June 30, 2019. Endpoints were OS and severe treatment-related adverse events (TRAEs). Trial-level PS scores were standardized by converting Karnofsky grade scores to Eastern Cooperative Oncology Group (ECOG) Grade, and overall study-weighted PS was calculated based on weighted average of all patients.
RESULTS: Of 282 studies identified, 11 randomized controlled trials (N = 454) were included in the meta-analysis. Baseline weighted PS scores predicted OS in 10 of the 11 studies, and calculated PS scores of 1.0 were associated with a median OS of 6.3 months (95% posterior interval, 5.4-7.4). After adjusting for baseline PS, FOLFOX had a similar treatment effect profile (median OS, range 2.6-6.7 months) as 5-FU/leucovorin plus nanoliposomal irinotecan therapy (median OS, 6.1 months; 95% confidence interval 4.8-8.9). Neutropenia and fatigue were the most commonly reported Grade 3-4 TRAEs associated with FOLFOX.
CONCLUSIONS: Baseline PS is a strong prognostic factor when interpreting the efficacy of 5-FU and oxaliplatin-based therapy of pancreatic cancer after progression on first-line gemcitabine-based regimens. When baseline PS is considered, FOLFOX has a similar treatment effect as 5-FU and nanoliposomal irinotecan therapy and a comparable safety profile. These findings suggest that 5-FU and oxaliplatin-based therapies remain an acceptable and alternative second-line treatment option for patients with pancreatic cancer and adequate PS (e.g. ECOG 0-1) following gemcitabine treatment.

PMID: 32641104 [PubMed - indexed for MEDLINE]