Rev Prat. 2021 Jun;71(6):587-596.

ABSTRACT

Side effects of long-term oral corticosteroid therapy. Systemic corticosteroid therapy has been used for over 70 years, and is still the cornerstone of the treatment of many conditions, in particular systemic, autoimmune or inflammatory diseases. Side effects of corticosteroids are numerous, and for most of them well known by prescribers. Nonetheless, guidelines for the prevention of corticosteroids toxicity are scarce, and the implementation of protective measures by prescribers is heterogenous. Hence, corticosteroids related complications entail a significant morbidity, which, importantly, could be largely prevented. We conducted therefore a systematic literature, through the Medline database, the Cochrane database and the grey literature until January 2021. After recalling the history of the discovery of corticosteroid therapy and its main pharmacological properties, we present the various complications associated with long-term corticosteroid therapy, and discuss the relevance of the preventive measures that may be proposed in daily practice in the light of available scientific evidence. This work highlights the importance of multidisciplinary follow-up, but above all of a thorough screening of the risk factors of complications at treatment initiation, and of a repeated evaluation of the complications all along the treatment course, in order to reduce the significant burden of morbidity associated with long-term corticosteroid therapy and to improve patient quality of life.

PMID:34553543

Otolaryngol Pol. 2021 Feb 16;75(5):9-15. doi: 10.5604/01.3001.0014.7445.

ABSTRACT

In the daily practice of an otolaryngologist, we encounter cases where the symptoms are not the result of disease but result from pharmacotherapy. In the case of symptoms such as hearing loss, tinnitus, or dizziness, polytherapy may be used as the basis for their occurrence, which, due to the lack of rationality in combining drugs, leads to symptoms that the patient and the doctor very often interpret as a new disease syndrome. The aim of the study is to show and to raise awareness of the fact that the symptoms of hearing organ impairment are frequently drug-related and only a modification of the currently used pharmacotherapy is a rational procedure in such cases. This paper describes 30 cases who developed side effects of polypharmacy in the form of hearing disorders, dizziness, and tinnitus. The causes of drug-related complications were discussed, as well as effective methods of their prevention.

PMID:34552021 | DOI:10.5604/01.3001.0014.7445

Curr Drug Saf. 2021 Sep 22. doi: 10.2174/1574886316666210922153059. Online ahead of print.

ABSTRACT

Drug-induced QTc prolongation is a concerning electrocardiogram (ECG) abnormality. This cardiac disturbance carries a 10% risk of sudden cardiac death due to the malignant arrhythmia, Torsades de Pointes. The Arizona Center for Education and Research on Therapeutics (AzCERT) has classified QTc prolonging therapeutic classes such as antiarrhythmics, antipsychotics, anti-infectives, and others. AzCERT criteria categorizes medications into three risk categories: "known," "possible," and "conditional risk" of QTc prolongation and Torsades de Pointes. The list of QTc prolonging medications continues to expand as new drug classes are approved and studied. Risk factors for QTc prolongation can be delineated into modifiable or non-modifiable. A validated risk scoring tool may be utilized to predict the likelihood of prolongation in patients receiving AzCERT classified medication. The resultant risk score may be applied to a clinical decision support system which offers mitigation strategies. Mitigation strategies including discontinuation of possible offending agents with selection of an alternative agent, assessment of potential drug interactions or dose adjustments through pharmacokinetic and pharmacodynamic monitoring, and initiation of both ECG and electrolyte monitoring are essential to prevent a drug-induced arrhythmia. The challenges presented by the COVID-19 pandemic have led to the development of innovative continuous monitoring technology, increasing protection for both patients and healthcare workers. Early intervention strategies may reduce adverse events and improve clinical outcomes in patients identified to be at risk of QTc prolongation.

PMID:34551700 | DOI:10.2174/1574886316666210922153059

Drug Ther Bull. 2021 Sep 21:dtb-2021-000054. doi: 10.1136/dtb.2021.000054. 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:34548393 | DOI:10.1136/dtb.2021.000054

Front Pharmacol. 2021 Sep 2;12:738577. doi: 10.3389/fphar.2021.738577. eCollection 2021.

ABSTRACT

Herbal medicine is widely used in Asia as well as the west. Hepatotoxicity is one of the most severe side effects of herbal medicine which is an increasing concern around the world. Reynoutria multiflora (Thunb.) Moldenke (Polygonum multiflorum Thunb., PM) is the most common herb that can cause herb-induced liver injury (HILI). The recent scientific and technological advancements in clinical and basic research are paving the way for a better understanding of the molecular aspects of PM-related HILI (PM-HILI). This review provides an updated overview of the clinical characteristics, predisposing factors, hepatotoxic components, and molecular mechanisms of PM-HILI. It can also aid in a better understanding of HILI and help in further research on the same.

PMID:34539416 | PMC:PMC8443768 | DOI:10.3389/fphar.2021.738577

World J Gastroenterol. 2021 Aug 28;27(32):5376-5391. doi: 10.3748/wjg.v27.i32.5376.

ABSTRACT

The application of immune checkpoint inhibitors (ICI) in advanced cancer has been a major development in the last decade. The indications for ICIs are constantly expanding into new territory across different cancers, disease stages and lines of therapy. With this increased use, adverse events including immune checkpoint inhibitor-related hepatotoxicity (ICH) have emerged as an important clinical problem. This along with the introduction of ICI as first- and second-line treatments for advanced hepatocellular carcinoma makes ICH very relevant to gastroenterologists and hepatologists. The incidence of ICH varies between 1%-20% depending on the number, type and dose of ICI received. Investigation and management generally involve excluding differential diagnoses and following a stepwise escalation of withholding or ceasing ICI, corticosteroid treatment and adding other immunosuppressive agents depending on the severity of toxicity. The majority of patients with ICH recover and some may even safely recommence ICI therapy. Guideline recommendations are largely based on evidence derived from retrospective case series which highlights a priority for future research.

PMID:34539139 | PMC:PMC8409159 | DOI:10.3748/wjg.v27.i32.5376

Dig Liver Dis. 2021 Sep 16:S1590-8658(21)00761-1. doi: 10.1016/j.dld.2021.08.020. Online ahead of print.

ABSTRACT

BACKGROUND: Adalimumab is used to treat ulcerative colitis, but additional effectiveness and safety data are needed.

PATIENTS AND METHODS: This retrospective study considered adults with ulcerative colitis treated with adalimumab at 19 hospitals. Clinical data were collected from the start of treatment, after 2, 6 and 12 months, and at the last visit. Outcome measures of effectiveness were treatment duration, reasons for discontinuation and colectomy.

RESULTS: We studied 381 patients treated with adalimumab for a median of 12.1 months. Disease activity at the start of treatment was moderate to severe in 262 cases (68.8%) and endoscopic activity was moderate to severe in 339 cases (89.0%). At week 8, clinical responses were observed in 177 cases (46.5%) and clinical remission in 136 cases (35.7%). At 12 months, remission was observed in 128 cases (33.6%). Overall, 44 patients required colectomy, and 170 patients (44.6%) were still taking adalimumab when data were collected. Variables associated with adalimumab discontinuation were concomitant steroid treatment, severe clinical-endoscopic activity at baseline, need for adalimumab intensification and drug-related adverse events. Variables associated with colectomy were concomitant steroid treatment and high baseline C-reactive protein.

CONCLUSION: Adalimumab is safe and effective for the treatment of ulcerative colitis.

PMID:34538764 | DOI:10.1016/j.dld.2021.08.020

Wiad Lek. 2021;74(8):1970-1974.

ABSTRACT

OBJECTIVE: The aim of the article is to establish the interrelation of human biological rhythms and circadian hormones producement as well as to determine their impact on the medicine usage.

PATIENTS AND METHODS: Materials and methods: The review and latest data analysis of scientific and medical literature were performed.

CONCLUSION: Conclusions: Proceeding from the literature sources there is a firm interrelation between human biological rhythms and circadian hormones producement. Following chronotherapy principles will allow to increase effectiveness of diseases treatment, including dental ones. It will also allow to reduce dosage of prescribed medicines as well as their side effects. Prospects for a further research are to identify a clear relationship between circadian biorhythms in patients with chronic generalized periodontitis in order to increase the effectiveness of therapeutic measures.

PMID:34537752

J Med Case Rep. 2021 Sep 19;15(1):462. doi: 10.1186/s13256-021-03075-y.

ABSTRACT

BACKGROUND: Moxifloxacin is a fourth-generation fluoroquinolone used as a second-line treatment for multiple bacterial infections. Uveitis has been described as an adverse effect related to this medication. Although several case reports have been published describing uveitis and bilateral acute iris transillumination syndrome related to moxifloxacin, we present a unique case of a patient with severe sequelae associated with bilateral acute iris transillumination syndrome secondary to the use of oral moxifloxacin.

CASE PRESENTATION: A 45-year-old Colombian hispanic female presented bilateral conjunctival hyperemia, decreased visual acuity, blurred vision, photophobia, and ocular pain after 15 days of treatment with systemic moxifloxacin for an upper tract respiratory infection. The patient presented unilateral anterior chamber pigment dispersion, mydriatic and nonreactive pupils, extensive iris transillumination defects, and secondary glaucoma. Blood and aqueous humor tests were negative for infectious and autoimmune diseases. Moxifloxacin-induced bilateral acute iris transillumination syndrome was diagnosed. Permanent sequelae such as ocular pain, photophobia, and focus difficulty secondary to severe bilateral iridian atrophy and inability of synkinetic reflex were left. Additionally, glaucoma was diagnosed, and Ahmed valve implantation was required.

CONCLUSIONS: We should be aware of the possible association between moxifloxacin and bilateral acute iris transillumination syndrome. A detailed anamnesis, adequate examination, and laboratory tests are necessary to reach an early diagnosis and treatment to avoid unnecessary therapies. Larger studies should be carried out to understand the pathophysiology, diagnosis, management, and sequelae of the disease.

PMID:34537056 | DOI:10.1186/s13256-021-03075-y

J Clin Pharmacol. 2021 Sep 18. doi: 10.1002/jcph.1969. Online ahead of print.

ABSTRACT

Immunostimulants are gradually being used in the prevention and treatment of recurrent respiratory tract infections in susceptible children, but their drug effects have not been quantified. The purpose of this study was to confirm the efficacy of immunostimulants in the prevention and treatment of recurrent respiratory tract infections in susceptible children. A model-based meta-analysis (MBMA) was used to describe the time course of placebo and immunostimulants in the prevention of respiratory tract infections in children. The cumulative number of respiratory tract infections was used as an indicator of efficacy. A meta-analysis was used to analyze the incidence of drug-related adverse events. Fourteen articles with 2,400 pediatric subjects were finally included in the analysis. The results showed that the cumulative number of respiratory tract infections increased linearly with time, with the incidence of respiratory tract infections in the placebo group being 0.65 (95% CI: 0.55, 0.75) per month. OM-85 BV and pidotimod reduced the incidence of respiratory tract infections by 0.21 (95% CI: 0.16, 0.26) and 0.19 (95% CI: 0.17, 0.21) compared to placebo per month, respectively. Pidotimod and OM-85 BV can effectively reduce the incidence of respiratory tract infections in susceptible children, with no significant increase in the incidence of drug-related adverse events when compared with placebo [RR values were 1.07 (95% CI: 0.66, 1.71) and 1.31 (95% CI: 0.54, 3.19), respectively]. This study provides quantitative support for the application of immunostimulants for the prevention of recurrent respiratory tract infections in children. This article is protected by copyright. All rights reserved.

PMID:34535904 | DOI:10.1002/jcph.1969

Reg Anesth Pain Med. 2021 Sep 17:rapm-2021-102845. doi: 10.1136/rapm-2021-102845. Online ahead of print.

ABSTRACT

BACKGROUND: Multiple myeloma is a cancer of plasma cells that often leads to complications including osteolytic bone lesions, nephropathy and neuropathy. Multiple myeloma is only one etiology of many cancer pain conditions that may necessitate interventional pain treatment when refractory to multimodal medications. Notably, local anesthetic systemic toxicity is a rare but life-threatening complication of local anesthetic administered for these interventions.

CASE PRESENTATION: A 50-60-year-old woman presented with multiple myeloma complicated by chronic bone pain and in an acute pain crisis. A fluoroscopic-guided L4-5 epidural catheter was placed with clinical doses of bupivacaine for comfort to undergo MRI of the spine. Soon after, she became tachycardic, tachypneic and hypoxic requiring non-invasive positive pressure airway support. As this respiratory distress was attributed to a large pleural effusion, a pigtail catheter was inserted in the intensive care unit with submaximally dosed lidocaine infiltration. She then developed a left bundle branch block followed by cardiovascular collapse minimally responsive to high-dose inotrope and vasopressor support. Lipid emulsion was started with dramatic therapeutic response and recovery to baseline. A CT of the thoracolumbar spine showed worsening extensive lytic lesions throughout all vertebral bodies and ribs from diffuse myeloma.

CONCLUSIONS: Patients with oncologic lesions focal to the thoracolumbar spine may be at higher risk for local anesthetic systemic toxicity from palliative epidurals due to increased cancer-related angiogenesis. Likewise, local anesthetic infiltration for procedures near any malignant sites could have a similar risk and may require lower initial fractionated dosages with increased vigilance.

PMID:34535547 | DOI:10.1136/rapm-2021-102845

JAMA Netw Open. 2021 Sep 1;4(9):e2125524. doi: 10.1001/jamanetworkopen.2021.25524.

ABSTRACT

IMPORTANCE: As of May 2021, more than 32 million cases of COVID-19 have been confirmed in the United States, resulting in more than 615 000 deaths. Anaphylactic reactions associated with the Food and Drug Administration (FDA)-authorized mRNA COVID-19 vaccines have been reported.

OBJECTIVE: To characterize the immunologic mechanisms underlying allergic reactions to these vaccines.

DESIGN, SETTING, AND PARTICIPANTS: This case series included 22 patients with suspected allergic reactions to mRNA COVID-19 vaccines between December 18, 2020, and January 27, 2021, at a large regional health care network. Participants were individuals who received at least 1 of the following International Statistical Classification of Diseases and Related Health Problems, Tenth Revision anaphylaxis codes: T78.2XXA, T80.52XA, T78.2XXD, or E949.9, with documentation of COVID-19 vaccination. Suspected allergy cases were identified and invited for follow-up allergy testing.

EXPOSURES: FDA-authorized mRNA COVID-19 vaccines.

MAIN OUTCOMES AND MEASURES: Allergic reactions were graded using standard definitions, including Brighton criteria. Skin prick testing was conducted to polyethylene glycol (PEG) and polysorbate 80 (P80). Histamine (1 mg/mL) and filtered saline (negative control) were used for internal validation. Basophil activation testing after stimulation for 30 minutes at 37 °C was also conducted. Concentrations of immunoglobulin (Ig) G and IgE antibodies to PEG were obtained to determine possible mechanisms.

RESULTS: Of 22 patients (20 [91%] women; mean [SD] age, 40.9 [10.3] years; 15 [68%] with clinical allergy history), 17 (77%) met Brighton anaphylaxis criteria. All reactions fully resolved. Of patients who underwent skin prick tests, 0 of 11 tested positive to PEG, 0 of 11 tested positive to P80, and 1 of 10 (10%) tested positive to the same brand of mRNA vaccine used to vaccinate that individual. Among these same participants, 10 of 11 (91%) had positive basophil activation test results to PEG and 11 of 11 (100%) had positive basophil activation test results to their administered mRNA vaccine. No PEG IgE was detected; instead, PEG IgG was found in tested individuals who had an allergy to the vaccine.

CONCLUSIONS AND RELEVANCE: Based on this case series, women and those with a history of allergic reactions appear at have an elevated risk of mRNA vaccine allergy. Immunological testing suggests non-IgE-mediated immune responses to PEG may be responsible in most individuals.

PMID:34533570 | PMC:PMC8449279 | DOI:10.1001/jamanetworkopen.2021.25524

N Engl J Med. 2021 Sep 18. doi: 10.1056/NEJMoa2112431. Online ahead of print.

ABSTRACT

BACKGROUND: Human epidermal growth factor receptor 2 (HER2)-targeted therapies have not been approved for patients with non-small-cell lung cancer (NSCLC). The efficacy and safety of trastuzumab deruxtecan (formerly DS-8201), a HER2 antibody-drug conjugate, in patients with HER2-mutant NSCLC have not been investigated extensively.

METHODS: We conducted a multicenter, international, phase 2 study in which trastuzumab deruxtecan (6.4 mg per kilogram of body weight) was administered to patients who had metastatic HER2-mutant NSCLC that was refractory to standard treatment. The primary outcome was objective response as assessed by independent central review. Secondary outcomes included the duration of response, progression-free survival, overall survival, and safety. Biomarkers of HER2 alterations were assessed.

RESULTS: A total of 91 patients were enrolled. The median duration of follow-up was 13.1 months (range, 0.7 to 29.1). Centrally confirmed objective response occurred in 55% of the patients (95% confidence interval [CI], 44 to 65). The median duration of response was 9.3 months (95% CI, 5.7 to 14.7). Median progression-free survival was 8.2 months (95% CI, 6.0 to 11.9), and median overall survival was 17.8 months (95% CI, 13.8 to 22.1). The safety profile was generally consistent with those from previous studies; grade 3 or higher drug-related adverse events occurred in 46% of patients, the most common event being neutropenia (in 19%). Adjudicated drug-related interstitial lung disease occurred in 26% of patients and resulted in death in 2 patients. Responses were observed across different HER2 mutation subtypes, as well as in patients with no detectable HER2 expression or HER2 amplification.

CONCLUSIONS: Trastuzumab deruxtecan showed durable anticancer activity in patients with previously treated HER2-mutant NSCLC. The safety profile included interstitial lung disease that was fatal in two cases. Observed toxic effects were generally consistent with those in previously reported studies. (Funded by Daiichi Sankyo and AstraZeneca; DESTINY-Lung01 ClinicalTrials.gov number, NCT03505710.).

PMID:34534430 | DOI:10.1056/NEJMoa2112431

AIDS. 2021 Sep 15. doi: 10.1097/QAD.0000000000003070. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess efficacy and safety of dolutegravir (DTG) + lamivudine (3TC) vs DTG + tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) in treatment-naive adults with HIV-1 in the prespecified 144-week secondary analyses of GEMINI-1 and GEMINI-2.

DESIGN: Identical, multicenter, phase III, randomized, non-inferiority studies (double-blind through 96 weeks).

METHODS: Participants with HIV-1 RNA ≤500,000 copies/mL and no major viral resistance mutations to nucleoside reverse transcriptase inhibitors, non-nucleoside reverse transcriptase inhibitors, or protease inhibitors were randomized 1:1 to once-daily DTG + 3TC or DTG + TDF/FTC.

RESULTS: At Week 144, DTG + 3TC (N = 716) was non-inferior to DTG + TDF/FTC (N = 717) in proportion of participants achieving HIV-1 RNA <50 copies/mL (Snapshot algorithm) in the pooled analysis (82% vs 84%, respectively; adjusted treatment difference [95% CI], -1.8% [-5.8, 2.1]), GEMINI-1 (-3.6% [-9.4, 2.1]), and GEMINI-2 (0.0% [-5.3, 5.3]). Twelve DTG + 3TC participants and 9 DTG + TDF/FTC participants met protocol-defined confirmed virologic withdrawal (CVW) criteria; none developed treatment-emergent resistance. One DTG + 3TC participant who did not meet CVW criteria developed M184 V at Week 132 and R263R/K at Week 144, conferring a 1.8-fold change in susceptibility to DTG; non-adherence to therapy was reported. Significantly fewer drug-related adverse events occurred with DTG + 3TC vs DTG + TDF/FTC (20% vs 27%; relative risk [95% CI], 0.76 [0.63-0.92]). Renal and bone biomarker changes favored DTG + 3TC.

CONCLUSIONS: Three-year durable efficacy, long-term tolerability, and high barrier to resistance support first-line use of DTG + 3TC for HIV-1 treatment (see Supplemental Digital Content 1, video abstract, http://links.lww.com/QAD/C297).

PMID:34534138 | DOI:10.1097/QAD.0000000000003070

Cochrane Database Syst Rev. 2021 Sep 17;9:CD009806. doi: 10.1002/14651858.CD009806.pub3.

ABSTRACT

BACKGROUND: Mucopolysaccharidosis type VI (MPS VI) or Maroteaux-Lamy syndrome is a rare genetic disorder caused by the deficiency of arylsulphatase B. The resultant accumulation of dermatan sulphate causes lysosomal damage. The clinical symptoms are related to skeletal dysplasia (i.e. short stature and degenerative joint disease). Other manifestations include cardiac disease, impaired pulmonary function, ophthalmological complications, hepatosplenomegaly, sinusitis, otitis, hearing loss and sleep apnea. Intellectual impairment is generally absent. Clinical manifestation is typically by two or three years of age; however, slowly progressive cases may not present until adulthood. Enzyme replacement therapy (ERT) with galsulfase is considered a new approach for treating MPS VI.

OBJECTIVES: To evaluate the effectiveness and safety of treating MPS VI by ERT with galsulfase compared to other interventions, placebo or no intervention.

SEARCH METHODS: Eletronic searches were performed on the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register. Date of the latest search: 09 June 2021. Further searches of the following databases were also performed: CENTRAL, MEDLINE, LILACS, the Journal of Inherited Metabolic Disease, the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov. Date of the latest search: 20 August 2021.

SELECTION CRITERIA: Randomized and quasi-randomized controlled clinical studies of ERT with galsulfase compared to other interventions or placebo.

DATA COLLECTION AND ANALYSIS: Two authors independently screened the studies, assessed the risk of bias, extracted data and assessed the certainty of the the evidence using the GRADE criteria.

MAIN RESULTS: One study was included involving 39 participants who received either ERT with galsulfase (recombinant human arylsulphatase B) or placebo. This small study was considered overall to have an unclear risk of bias in relation to the design and implementation of the study, since the authors did not report how both the allocation generation and concealment were performed. Given the very low certainty of the evidence, we are uncertain whether at 24 weeks there was a difference between groups in relation to the 12-minute walk test, mean difference (MD) of 92.00 meters (95% confidence interval (CI) 11.00 to 172.00), or the three-minute stair climb, MD 5.70 (95% CI -0.10 to 11.50). In relation to respiratory tests, we are uncertain whether galsulfase makes any difference as compared to placebo in forced vital capacity in litres (FVC (L) (absolute change in baseline), given the very low certainty of the evidence. Cardiac function was not reported in the included study. We found that galsulfase, as compared to placebo, may decrease urinary glycosaminoglycan levels at 24 weeks, MD -227.00 (95% CI -264.00 to -190.00) (low-certainty evidence). We are uncertain whether there are differences between the galsulfase and placebo groups in relation to adverse events (very low-certainty evidence). In general, the dose of galsulfase was well tolerated and there were no differences between groups. These events include drug-related adverse events, serious and severe adverse events, those during infusion, drug-related adverse events during infusion, and deaths. More infusion-related reactions were observed in the galsulfase group and were managed with interruption or slowing of infusion rate or administration of antihistamines or corticosteroids drugs. No deaths occurred during the study. AUTHORS' CONCLUSIONS: The results of this review are based only on one small study (a 24-week randomised phase of the study and prior to the open-label extension). We are uncertain whether galsulfase is more effective than placebo, for treating people with MPS VI, in relation to the 12-minute walk test or the three-minute stair climb, as the certainty of the evidence has been assessed as very low. We found that galsulfase may reduce urinary glycosaminoglycans levels. We are also uncertain whether there are any differences between treatment groups in relation to cardiac or pulmonary functions, liver or spleen volume, overnight apnea-hypopnea, height and weight, quality of life and adverse effects. Further studies are needed to obtain more information on the long-term effectiveness and safety of ERT with galsulfase.

PMID:34533215 | DOI:10.1002/14651858.CD009806.pub3

Sci Rep. 2021 Sep 16;11(1):18467. doi: 10.1038/s41598-021-98069-7.

ABSTRACT

Proton pump inhibitors (PPIs), followed by histamine 2 receptor antagonists (H2RAs), are the most commonly used drugs to prevent gastrointestinal bleeding in critically ill patients through stress ulcer prophylaxis. The relative efficacy and drug-related adverse events of PPIs and H2RAs remain unclear. In this retrospective, observational, comparative cohort study, PPIs and H2RAs for stress ulcer prophylaxis in critically ill patients were compared using a common data model. After propensity matching, 935 patients from each treatment group (PPI or H2RA) were selected. The PPI group had a significantly higher 90-day mortality than the H2RA group (relative risk: 1.28; P = 0.01). However, no significant inter-group differences in the risk of clinically important gastrointestinal bleeding were observed. Moreover, there were no significant differences between the groups concerning the risk of pneumonia or Clostridioides difficile infection, which are known potential adverse events related to these drugs. Subgroup analysis of patients with high disease severity were consistent with those of the total propensity score-matched population. These findings do not support the current recommendations, which prefer PPIs for gastrointestinal bleeding prophylaxis in the intensive care unit.

PMID:34531488 | DOI:10.1038/s41598-021-98069-7

Science. 2021 Sep 17;373(6561):1304-1306. doi: 10.1126/science.abc3734. Epub 2021 Sep 16.

ABSTRACT

[Figure: see text].

PMID:34529479 | DOI:10.1126/science.abc3734

Am J Manag Care. 2021 Sep;27(16 Suppl):S280-S291. doi: 10.37765/ajmc.2021.88753.

ABSTRACT

OBJECTIVES: Older patients are especially vulnerable to drug-related problems due to multiple prescription drugs, which increases their risk of drug-drug interactions and adverse drug events (ADEs). This study aimed to examine outcomes associated with the MedWise Risk Score (MRS) in a Medicare Part D population, including total medical expenditures, ADEs, falls, mortality, emergency department (ED) visits, hospital admissions, and length of stay (LOS).

STUDY DESIGN: Retrospective observational study.

METHODS: The association between MRS and patient health outcomes was derived using drug claims data from 213,561 beneficiaries and medication risk stratification using outcomes data in 2018 with 1 year of follow-up. Analyses were conducted with the Max MRS and the Mean MRS calculated over the year. Analyses utilizing the Max MRS performed better, and results using the Max MRS are presented. Statistical analyses were performed using linear regression, logistic regression, negative binomial regression, and zero-inflated Poisson (ZIP) models.

RESULTS: Of 203,630 patients studied (mean ± SD age, 76.0 ± 8.0 years), 4.9%, 9.8%, 24.5%, and 15.5% experienced at least 1 ADE, fall, ED visit, and hospital admission, respectively, in 2018. The MRS was associated with an 8.5% change in total medical expenditure per 1-unit increase. The adjusted odds ratio (OR) of ADE was 1.058 (95% CI, 1.055-1.06)/unit MRS. ADEs, falls, and death were more likely in elevated MRS categories (eg, OR of 4.45 for ADEs [95% CI, 4.10-4.83], 5.51 for falls [95% CI, 5.17-5.87], and 4.42 for death [95% CI, 3.82-5.12], respectively forSevere MRS group). Our model predicts 7000 ED visits for every 100,000 patients per unit increase of the MRS. The ZIP models estimated ORs of 1.03 and 1.01 for hospital admissions and increase in hospital LOS, respectively, per MRS unit.

CONCLUSIONS: This study shows that MRS was associated with health outcomes and therefore could be used to identify patients at increased risk of negative outcomes based primarily on their medication regimens.

PMID:34529367 | DOI:10.37765/ajmc.2021.88753

Drugs Real World Outcomes. 2021 Sep 16. doi: 10.1007/s40801-021-00275-2. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with chronic or acute/postoperative pain frequently use opioids. However, opioids may cause considerable adverse reactions (ARs), such as respiratory depression, which could be lethal. Unfortunately, only 5% of drug-related ARs (including those to opioids) are reported to health authorities. Therefore, little is known regarding the occurrence of opioid-related ARs at the population level.

OBJECTIVE: The aim of this study was to investigate how the rates of reported opioid-related ARs have changed in Canada since 1965.

METHODS: Our retrospective study examined trends of reported opioid-related ARs occurring in hospitalized and outpatients. Data on opioid-related ARs and mortality between 1965 and 2019 were obtained from the Canada Vigilance and Statistics Canada databases. Descriptive and Joinpoint regression analyses were performed.

RESULTS: Oxycodone and normethadone were the most and least involved opioid agents, respectively, among the 18,407 reported ARs. The highest rate of reported opioid ARs (3.8 per 100,000 person-years) was recorded in 2012, whereas the lowest was recorded in 1965 (0.1 per 100,000 person-years). Between 1965 and 2019, annual rates climbed by 4.2% (95% confidence interval [CI] 3.1-5.2), and many fluctuations were observed: 1965-1974: +22.3% (95% CI 12.0-33.6); 1974-2000: - 4.1% (95% CI - 5.3 to - 2.9); 2000-2008: +30.3% (95% CI 22.6-38.4); 2008-2014: +4.1% (95% CI - 1.5 to 10.1); 2014-2017: -26.0% (95% CI - 44.7 to - 0.9); and, finally, 2017-2019: +35.4% (95% CI 3.8-76.7).

CONCLUSION: Reported opioid-related ARs have increased since 1965, although fluctuations were observed in recent decades. The absolute number of opioid-related ARs might be seriously underestimated. Future studies should look into how to close this gap.

PMID:34529224 | DOI:10.1007/s40801-021-00275-2

J R Coll Physicians Edinb. 2021 Sep;51(3):237-245. doi: 10.4997/JRCPE.2021.306.

ABSTRACT

Conventional disease-modifying antirheumatic drugs (DMARDs) have been used in the management of rheumatoid arthritis for a long time. Whereas methotrexate (MTX) is the anchor drug, leflunomide, hydroxychloroquine and sulfasalazine are used along with MTX either in combination or sequentially. Together these four drugs are the most commonly used DMARDs. They are also used in combination with biological DMARDs (bDMARDs) to enhance their efficacy and MTX in particular to reduce antibodies against anti-tumour necrosis factor. Despite their widespread use, concerns regarding their safety especially when used long-term hinder their optimum use in clinical medicine. In this narrative review we have critically appraised the available literature regarding the safety of these four DMARDs when used long-term.

PMID:34528610 | DOI:10.4997/JRCPE.2021.306