Front Pharmacol. 2022 Jan 27;12:728908. doi: 10.3389/fphar.2021.728908. eCollection 2021.

ABSTRACT

Background: Although multiple randomized controlled trials (RCTs) and systematic review and meta-analysis were performed to investigate the efficiency and safety of nonsteroidal anti-inflammatory drugs (NSAIDs) and opioids in the treatment of acute renal colic, the therapeutic regimen of renal colic is still controversial. Therefore, the aim of this study was to derive a more concise comparison of the effectiveness and safety between NSAIDs and opioids in the treatment for patients with acute renal colic by a systematic review and meta-analysis. Design: We searched PubMed, Embase, and Cochrane Central Register of controlled trials for seeking eligible studies. The pooled mean difference (MD) or risk ratio (RR) with 95% confidence interval (CI) was calculated using the random effects model. The primary outcome was assessed according to the Grading of Recommendations Assessment, Development and Evaluation. Results: A total of 18 studies involving 3,121 participants were included in the systematic review and meta-analysis. No significant difference between the NSAID and opioid groups was observed, with changes in the visual analog scale (VAS) at 0-30 min (MD = 0.79, 95% CI: -0.51, 2.10). NSAIDs in the form of intravenous administration (IV) had no better effect on the changes in the VAS at 0-30 min, when compared to opioids (MD = 1.25, 95% Cl: -4.81, 7.3). The NSAIDs group in the form of IV had no better outcome compared to the opioids group, as well as the VAS at 30 min (MD = -1.18, 95% Cl: -3.82, 1.45; MD = -2.3, 95% Cl: -5.02, 0.42, respectively). Moreover, similar results of this outcome were also seen with the VAS at 45 min (MD = -1.36, 95% Cl: -5.24, 2.52). Besides, there was a statistical difference in the incidence of later rescue (RR = 0.76, 95% CI: 0.66, 0.89), drug-related adverse events (RR = 0.44, 95% CI: 0.27, 0.71), and vomiting (RR = 0.68, 95% CI: 0.49, 0.96). Conclusion: There is no significant difference between the NSAIDs and opioids in the treatment of renal colic in many outcomes (e.g., the VAS over different periods using different injection methods at 30 and 60 min), which has been focused on in this study. However, the patients who were treated using NSAIDs by clinicians can benefit from fewer side effects.

PMID:35153734 | PMC:PMC8828916 | DOI:10.3389/fphar.2021.728908

J Coll Physicians Surg Pak. 2022 Mar;32(3):407-408. doi: 10.29271/jcpsp.2022.03.407.

ABSTRACT

COVID-19 pandemic has exaggerated the role of steroids in the standard of care despite minimum direct evidence of their efficacy in COVID-19 patients and their well-known adverse effects. The literature abounds on the side effects of steroids affecting different organ systems of the body. COVID-19 patients, who are on long-term steroids, are more susceptible to their adverse effects. We, herein, briefly review the potential uses and the adverse effects of steroids on different organ systems of the body. Key Words: Steroids, COVID-19, Adverse effects.

PMID:35148604 | DOI:10.29271/jcpsp.2022.03.407

Rev Prat. 2021 Oct;71(8):871.

NO ABSTRACT

PMID:35147343

Rev Prat. 2021 Nov;71(9):1021-1024.

NO ABSTRACT

PMID:35147325

Rev Prat. 2021 Nov;71(9):1018-1020.

NO ABSTRACT

PMID:35147324

Cureus. 2022 Jan 4;14(1):e20928. doi: 10.7759/cureus.20928. eCollection 2022 Jan.

ABSTRACT

Denosumab, a receptor activator of nuclear factor kappa-Β ligand (RANK-L) monoclonal antibody used in osteoporosis and various malignancies, has been shown to cause hypocalcemia shortly after initiation of treatment. There have been few case reports of electrolyte abnormalities in patients managed with long-term treatment with this medication. This report presents the case of a 43-year-old male with metastatic prostate cancer who presented with severe hypophosphatemia and hypocalcemia, initially resistant to repletion. After more aggressive and persistent repletion with IV calcium, phosphorus, and vitamin D, as well as time for the denosumab to dissipate, the patient's electrolytes stabilized and he was able to be discharged with oral replacement and close follow-up. Therefore, long-term monitoring of electrolytes for patients on denosumab should be carefully considered.

PMID:35145817 | PMC:PMC8812272 | DOI:10.7759/cureus.20928

J Ethnopharmacol. 2022 Feb 7:115090. doi: 10.1016/j.jep.2022.115090. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Tripterygium glycosides tablets (TGT) and Tripterygium wilfordii tablets (TWT) have been used to treat autoimmune diseases clinically, however, the side effects of TWT are higher than TGT, especially for hepatotoxicity.

THE AIM OF THE STUDY: This study aims to determine the mechanism of TWT-induced liver injury.

MATERIALS AND METHODS: We performed metabolomic analysis of samples from mice with liver injury induced by TGT and TWT. Ppara-null mice were used to determine the role of PPARα in TGT-induced liver injury.

RESULTS: The results indicated that TWT induced the accumulation of medium- and long-chain carnitines metabolism, which was associated with the disruption of PPARα-IL6-STAT3 axis. PPARα agonists fenofibrate could reverse the liver injury from TWT and TP/Cel, and its protective role could be attenuated in Ppara-null mice. The toxicity difference of TWT and TGT was due to the different ratio of triptolide (TP) and celastrol (Cel) in the tablet in which TP/Cel was lower in TWT than TGT. The hepatotoxicity induced by TP and Cel also inhibited PPARα and upregulated IL6-STAT3 axis, which could be alleviated following by PPARα activation.

CONCLUSIONS: These results indicated that PPARα plays an important role in the hepatotoxicity of Tripterygium wilfordii, and PPARα activation may offer a promising approach to prevent hepatotoxicity induced by the preparations of Tripterygium wilfordii.

PMID:35143937 | DOI:10.1016/j.jep.2022.115090

CPT Pharmacometrics Syst Pharmacol. 2022 Feb 10. doi: 10.1002/psp4.12765. Online ahead of print.

ABSTRACT

Promising drug development efforts may frequently fail due to unintended adverse reactions. Several methods have been developed to analyze such data, aiming to improve pharmacovigilance and drug safety. In this work, we provide a brief review of key directions to quantitatively analyzing adverse events and explore the potential of augmenting these methods using additional molecular data descriptors. We argue that molecular expansion of adverse event data may provide a path to improving the insights gained through more traditional pharmacovigilance approaches. Examples include the ability to assess statistical relevance with respect to underlying biomolecular mechanisms, the ability to generate plausible causative hypotheses and/or confirmation where possible, the ability to computationally study potential clinical trial designs and/or results, as well as the further provision of advanced features incorporated in innovative methods, such as machine learning. In summary, molecular data expansion provides an elegant way to extend mechanistic modeling, systems pharmacology, and patient centered approaches for the assessment of drug safety. We anticipate that such advances in real world data informatics and outcome analytics will help to better inform public health, via the improved ability to prospectively understand and predict various types of drug-induced molecular perturbations and adverse events.

PMID:35143713 | DOI:10.1002/psp4.12765

J Nepal Health Res Counc. 2021 Dec 15;19(3):644-646. doi: 10.33314/jnhrc.v19i3.3433.

ABSTRACT

Drug-induced arthritis is not an uncommon scenario. DPP-4 inhibitors could potentially cause adverse-events mediated by cytokine-induced inflammation leading to arthritis. The activity of the DPP-4 enzyme could be inversely related to the development of rheumatoid arthritis, explaining the increased inflammatory activity with its inhibition by a drug. We discuss a 72-year-old gentleman with twenty-three years of history of type 2 diabetes mellitus, who after 6 years of treatment with a DPP-4 inhibitor, developed features of inflammatory arthritis and fulfilled the criteria for seronegative rheumatoid; which eventually subsided after stopping the drug. Keywords: DDP-4 inhibitor; diabetes mellitus; Nepal; rheumatoid arthritis; seronegative.

PMID:35140448 | DOI:10.33314/jnhrc.v19i3.3433

Zhonghua Jie He He Hu Xi Za Zhi. 2022 Feb 12;45(2):227-232. doi: 10.3760/cma.j.cn112147-20210610-00413.

ABSTRACT

Isoniazid(INH, H) has been a key drug for treating drug-susceptible tuberculosis (TB) for nearly seventy years. The differences in the pharmacokinetic(PK) might affect INH absorption. Low plasma concentration is related to less treatment outcomes and vice versa, but higher plasma concentrations can induce hepatotoxicity or death. Factors that can cause fluctuations in blood concentration include INH absorption (i.e. drug-drug or drug-food interactions and other diseases such as gastrointestinal problems, diabetes or TB) and abnormal metabolization by the liver. N-acetyltransferase 2 (NAT2) genetic polymorphism significantly affects the plasma concentrations of INH. However, there is a lack of guidelines for the management of adverse drug reactions caused by isoniazid therapy, and the only measures taken to address adverse reactions to isoniazid are abrupt discontinuation of the drug or reduction in the dose of isoniazid based on clinical experience, but such measures could lead to the development of drug resistance in Mycobacterium tuberculosis. Therefore, further clarification of the correlation between the host NAT2 genotype and its phenotypic polymorphisms, plasma isoniazid concentration and adverse effects can help to improve the efficacy and minimize the adverse effects.

PMID:35135095 | DOI:10.3760/cma.j.cn112147-20210610-00413

Ned Tijdschr Geneeskd. 2021 Dec 23;165:D6111.

ABSTRACT

Gurwitz and colleagues showed that a complex intervention, aimed at a reduction of drug-related adverse events and medication errors immediately after hospital discharge, did not result in a significant outcome difference between the intervention and control groups. We feel that the intervention lacked standardization, that a better outcome might have been achieved by intervening prior to hospital discharge, that more details about the nature of observed medication errors and acceptance of the intervenor recommendations should have been reported. Also, the number of unpreventable adverse drug events was higher in the intervention (n = 37) than in the control group (n = 27), suggesting a Hawthorne effect. The small number of adverse drug events detected overall points to a low sensitivity of the detection method used. We recommend that future studies be designed differently, including a stronger focus on physician-pharmacist collaboration, patient participation and improved communication between the hospital and general practice.

PMID:35138704

Syst Rev. 2022 Feb 8;11(1):23. doi: 10.1186/s13643-022-01890-y.

ABSTRACT

BACKGROUND: The use of thiazide (T) diuretics for the treatment of hypertension may be associated with adverse metabolic effects, which can be minimized by combining thiazides with potassium-sparing (PS) diuretics. The additional blood pressure (BP)-lowering effect provided by the addition of a PS diuretic is unclear. Due to a large number of drugs in the T diuretics class, and the possible difference between them, there is a need to identify the best available evidence for health decision-making. This systematic review with network meta-analysis aims to compare the antihypertensive efficacy of T diuretics alone or in combination with a PS diuretic in patients with primary hypertension, as well as the safety of such drugs through the measurement of drug-related adverse events.

METHODS: A comprehensive electronic search will be conducted in six electronic bibliographic databases (PubMed/MEDLINE, Cochrane Library, Embase, Web of Science, Scopus, Lilacs), a registration database ( ClinicalTrials.gov ), and Educational Resources Information Center (ERIC [ProQuest]), published from inception to the date of the search. The search will be updated towards the end of the review. A hand search of the reference sections of the included studies and cited studies will also be performed. In case of missing data, authors will be contacted by e-mail or academic social networking sites whenever possible. To be included in the review, studies must be double-blind randomized controlled trials evaluating T diuretics alone or in combination with PS diuretics in patients with primary hypertension. The primary outcome measure will be office BP. Ambulatory BP monitoring (ABPM), non-melanoma skin cancer, major adverse cardiovascular events, laboratory parameters, and the number of withdrawals will be included as secondary outcomes. The results will be quantitatively summarized using differences between the mean change from baseline or differences between means for quantitative outcomes and relative risk for dichotomous outcomes. Results will be presented as mean or relative risk with credible intervals through a league table. The treatments will also be ranked using the surface under the cumulative ranking curve method. The risk of bias will be assessed through the RoB 1.0 tool.

DISCUSSION: To the best of our knowledge, this review will be the first to synthesize currently available evidence on the antihypertensive efficacy of different T diuretics alone or in combination with PS diuretics in adults with hypertension. The goals of hypertension treatment are to control high BP and to reduce associated cardiovascular morbidity and mortality, using the most appropriate therapy. Thiazides are widely used for pharmacological treatment due to their demonstrated effectiveness in reducing BP, favorable safety profile, and low cost. The results of this study will provide evidence regarding the best therapeutic strategies with T and PS diuretics, evidencing interventions with better antihypertensive efficacy and safety profile.

TRIAL REGISTRATION: This systematic review and network meta-analysis was prospectively registered at the PROSPERO database ( CRD42018118492 ).

PMID:35135630 | DOI:10.1186/s13643-022-01890-y

Global Spine J. 2022 Feb 7:21925682211060043. doi: 10.1177/21925682211060043. Online ahead of print.

ABSTRACT

STUDY DESIGN: Randomised control study.

OBJECTIVE: Different parenteral analgesics are used to alleviate post-operative pain after transforaminal lumbar interbody fusion (TLIF) but limited by their efficacy and side effects. We performed a RCT to evaluate the safety and efficacy of epidural Morphine-Bupivacaine on post-operative pain management after TLIF.

METHODS: Consecutive patients (n=100) of TLIF were divided randomly into study (SG) and control groups (CG). At the end of procedure, SG (n=50) received epidural instillation of morphine 5 mg and bupivacaine .25% - 2 mL, along with 6 mL of .25% bupivacaine infiltration in the deep fascia before wound closure. The functional outcomes were assessed at regular intervals (4, 8, 12, 24, 36, 48, 72, 96 hours) with VAS, nausea and vomiting scale, Ramsay sedation scale and breakthrough analgesia needed, time to ambulation and other complications.

RESULTS: The mean VAS score at 4 hours in SG was significantly less (1.16 ± .88) than the CG (3.32 ± 1.0) (P = .000). This significant difference was maintained at each time point during the first 48 hours (P < .004). Similarly, the mean NRS score in SG at 4 hours was 1.02 ± .89, and in CG 3.3 ± .69 (P = .0000) which was maintained at all intervals of assessment till 48 hours (P = .0137). The mean time to first ambulation was significantly less in the SG (4.46 ± 1.04 hours) than CG (11.64 ± 2.3 hours) (P < .001). There were no drug-related complications.

CONCLUSION: Epidural instillation of bupivacaine and morphine is safe and enables better pain relief in the initial 48 hours which helps in early mobilisation, and enhanced functional recovery.

PMID:35130086 | DOI:10.1177/21925682211060043

Antimicrob Agents Chemother. 2022 Feb 7:AAC0205721. doi: 10.1128/AAC.02057-21. Online ahead of print.

ABSTRACT

Long-acting (LA) cabotegravir demonstrated superior efficacy versus daily oral standard-of-care for HIV-1 pre-exposure prophylaxis. This Phase 1 study assessed safety, tolerability, pharmacokinetics, and acceptability of cabotegravir in 47 HIV-negative adult Chinese men at low risk of acquiring HIV-1. Participants received once-daily oral cabotegravir 30 mg for 4 weeks and, after a 1-week washout, five 600-mg (3-mL) intramuscular cabotegravir LA injections at Weeks 5, 9, 17, 25, and 33. Pharmacokinetic plasma samples were intensively collected on Day 27 (n=17) and sparsely collected before each injection until 56 weeks after final injection (n=47). Cabotegravir LA injections were acceptable and well tolerated. Common adverse events included injection site pain, injection site swelling, and upper respiratory tract infection. No drug-related serious adverse events or deaths occurred. Mean cabotegravir concentration remained above 1.33 μg/mL (8× in vitro protein-adjusted concentration for 90% of the maximum inhibition of viral growth [PA-IC90]) before each injection and above 0.166 μg/mL (PA-IC90) for >32 weeks after final injection. Trough concentrations remained above PA-IC90 in nearly all participants and showed minimal accumulation. Non-compartmental pharmacokinetic analysis was performed. Geometric mean of terminal half-life was 1.89 and 47 days after oral and LA dosing, respectively. Cabotegravir concentrations were estimated to remain quantifiable for 48.7 weeks after final injection. Steady-state AUC, peak concentration, trough concentration, terminal half-life, time to peak concentration, and apparent clearance after cabotegravir oral and LA dosing were similar to those estimated in non-Asian men in historical studies. These results support further clinical development of cabotegravir LA in China. (NCT03422172).

PMID:35129374 | DOI:10.1128/AAC.02057-21

Immunotherapy. 2022 Feb 7. doi: 10.2217/imt-2021-0074. Online ahead of print.

ABSTRACT

Aim: The emergence of antitumor immunotherapy has been beneficial for patients with tumors, but more attention should be paid to the toxic side effects of chemoimmunotherapy. Here we describe a patient with NK/T-cell lymphoma who developed toxic epidermal necrolysis (TEN) during treatment with a regimen consisting of sintilimab combined with pegaspargase, gemcitabine and oxaliplatin (P-GemOx). Case presentation: A patient received six cycles of P-GemOx chemotherapy as first-line treatment; 1 year later, he received the same dose of P-GemOx combined with sintilimab as chemoimmunotherapy due to recurrence of NK/T-cell lymphoma. He developed a massive rash that quickly developed into TEN after the fourth chemoimmunotherapy. Conclusion: Although rare, cases of fatal TEN caused by single-agent PD-1 inhibitor or gemcitabine have been reported. Careful attention to drug-related cutaneous toxicities is needed when these two agents are combined. This report highlights the significance of TEN as a rapid and serious adverse event induced by chemoimmunotherapy.

PMID:35128931 | DOI:10.2217/imt-2021-0074

Ther Adv Infect Dis. 2022 Jan 30;9:20499361211073248. doi: 10.1177/20499361211073248. eCollection 2022 Jan-Dec.

ABSTRACT

BACKGROUND: Despite the severity and frequency of streptococcal bloodstream infections (BSIs), the effectiveness of oral definitive therapy remains unknown. The objective of this study was to evaluate the clinical outcomes of step-down oral antibiotics for the treatment of uncomplicated streptococcal BSIs.

METHODS: In this retrospective cohort study, adult patients admitted with uncomplicated streptococcal BSI between June 2015 and June 2017 were included. Patients were excluded if they received <48 h of antibiotic therapy; therapy was started >48 h after first positive culture; had complicated infections of endocarditis, bone and joint infections, or central nervous system infections; Pitt bacteremia score (PBS) ⩾ 4; or failed to respond to effective therapy necessitating continued intravenous (IV) therapy. Patients were grouped by receipt of step-down oral antibiotic therapy (PO group) versus continued IV therapy (IV group). Outcomes included hospital length of stay (LOS), 30-day recurrence of BSI, 30-day readmission, 30-day all-cause mortality, and catheter-related or drug-related adverse events (AEs).

RESULTS: Of 244 patients included, 40% received step-down oral therapy (n = 98). Overall, the most common source of BSI was pneumonia (22%), followed by skin and soft tissue infections (SSTI) (18%). Severity of illness measured by intensive care unit (ICU) admission and PBS was similar. The IV group had significantly longer LOS [median 10 (interquartile range [IQR] = 5-21) versus 5 (4-6) days, p < 0.01] compared with the PO group. BSI recurrence, readmission, all-cause mortality within 30 days, and AEs were similar between the groups (p = ns).

CONCLUSION: In uncomplicated streptococcal BSI, patients treated with step-down oral antibiotic therapy had significantly shorter LOS compared with continued IV therapy without compromise of clinical outcomes.

PMID:35127081 | PMC:PMC8808041 | DOI:10.1177/20499361211073248

Front Pharmacol. 2022 Jan 19;12:786174. doi: 10.3389/fphar.2021.786174. eCollection 2021.

ABSTRACT

In the last 5 years, the landscape of oncologic treatment has been deeply modified with the development and use of immune checkpoint inhibitors (ICIs) that exert their antitumoral effect by reverting the exhausted phenotype of tumor-infiltrating lymphocytes. This innovative therapeutic strategy has widely changed the prognosis of some advanced neoplastic diseases such as melanoma and lung cancer, providing durable remission for a significant number of patients. Unfortunately, immune-related adverse events (irAEs), especially ICI-induced hepatitis, may be very severe in some cases, impairing the prognosis of the patient. Guidelines available today on the diagnosis and management of ICI-induced hepatitis are mainly based on expert opinions and case series. This lack of large data is explained not only by the low incidence of hepatic adverse events but also by their clinical heterogeneity and variable severity. In this article, we will review the clinical, biological, and histological characteristics of ICI-induced liver injury. We will discuss the current knowledge on their pathological mechanisms and their therapeutic strategy based on immunosuppressive treatment for more severe cases. Regarding severity assessment, we will discuss the gap between the oncologist and the hepatologist's point of view, highlighting the need for multidisciplinary management. While initially developed for notably less frequent diseases than neoplastic ones, gene therapy is going to be a revolution for the treatment of diseases not responding to pharmacological therapy. Limited but growing data describe liver injury after the administration of such therapy whose exact physiopathology remains unknown. In this article, we will discuss the available data supporting the role of gene therapies in the onset of drug-induced liver injury and related mechanisms. We will describe the clinical context, the biological and histological features, and the management currently proposed.

PMID:35126126 | PMC:PMC8807695 | DOI:10.3389/fphar.2021.786174

Drug Ther Bull. 2022 Feb 4:dtb-2022-000004. doi: 10.1136/dtb.2022.000004. Online ahead of print.

ABSTRACT

Overview of: Abrilla AA, Pajes ANNI, Jimeno CA. Metformin extended-release versus metformin immediate-release for adults with type 2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials. Diabetes Res Clin Pract 2021;178:108824.

PMID:35121575 | DOI:10.1136/dtb.2022.000004

Drug Ther Bull. 2022 Feb 4:dtb-2022-000005. doi: 10.1136/dtb.2022.000005. Online ahead of print.

ABSTRACT

Overview of: Speirs TP, Tuffin N, Mundy-Baird F, et al Long-term nitrofurantoin: an analysis of complication awareness, monitoring, and pulmonary injury cases. BJGP Open 2021;5:BJGPO.2021.0083.

PMID:35121574 | DOI:10.1136/dtb.2022.000005

Clin Transl Sci. 2022 Feb 4. doi: 10.1111/cts.13244. Online ahead of print.

ABSTRACT

The immunosuppressant drug azathioprine is associated with a 4% risk of acute pancreatitis in patients with inflammatory bowel disease. Studies have demonstrated an increased risk in carriers of HLA-DQA1*02:01 and HLA-DRB1*07:01. We investigated whether these HLA types were associated with azathioprine-induced pancreatitis also in Swedish patients with inflammatory bowel disease, and whether the type of disease affected the association. Nineteen individuals with inflammatory bowel disease who developed acute pancreatitis after initiation of azathioprine were genotyped and compared with a population control cohort (n=4891) and a control group matched for disease (n=81). HLA-DQA1*02:01 and HLA-DRB1*07:01 were in full linkage disequilibrium, and were significantly associated with acute pancreatitis both when cases were compared with population controls (OR 3.97 [95% CI 1.57-9.97], p=0.0035) and matched controls (OR 3.55 [95% CI 1.23-10.98], p=0.0275). In a disease-specific analysis, the correlation was positive in patients with Crohn's disease vs matched controls (OR 9.27 [95% CI 1.86 - 46.19], p=0.0066), but not in those with ulcerative colitis vs matched controls (OR 0.69 [95% CI 0.07 - 6.74], p=0.749). In patients with Crohn's disease, we estimated the conditional risk of carriers of HLA-DQA1*02:01-HLA-DRB1*07:01 to 7.3%, and the conditional risk of a non-carrier to 2.2%. We conclude that HLA-DQA1*02:01-HLA-DRB1*07:01 is a marker for increased risk of acute pancreatitis in individuals of Swedish genetic origin, treated with azathioprine for Crohn's disease.

PMID:35120281 | DOI:10.1111/cts.13244