PLoS One. 2022 Feb 4;17(2):e0262212. doi: 10.1371/journal.pone.0262212. eCollection 2022.

ABSTRACT

BACKGROUND: Transplant related toxicity is a major therapeutic challenge. We have previously reported that the toxicity of chemotherapy is largely not directly because of the drugs themselves; rather it is mainly due to DNA damage, apoptosis and hyper-inflammation triggered by cell-free chromatin particles that are released because of drug-induced host cell death. Cell-free chromatin particles can be inactivated by free-radicals which are generated when the nutraceuticals resveratrol and copper are administered orally. We investigated if a combination of resveratrol and copper would reduce transplant related toxicities in an exploratory, prospective dose-escalation study.

PATIENTS AND METHODS: Twenty-five patients with multiple myeloma were enrolled between March 2017 to August 2019. Patients were divided into 3 groups: control (Group 1, N = 5) received vehicle alone; group 2 (N = 15) received resveratrol-copper at dose level I (resveratrol = 5.6 mg and copper = 560 ng); group 3 (N = 5) received resveratrol-copper at dose level II (resveratrol = 50 mg and copper = 5 μg). The dose was given twice daily with the first dose administered 48 hours before administering melphalan and continued until day +21 post-transplant. Common Terminology Criteria for Adverse Events version 4.02 was used to assess toxicities which included oral mucositis, nausea, vomiting and diarrhea. Measurement of inflammatory cytokines was done by ELISA.

RESULTS: All patients (100%) in the control group developed grade 3/4 oral mucositis compared to 8/20 (40%) in both resveratrol-copper group 2 plus group 3 combined (P = 0.039). Reduction in inflammatory cytokines: salivary TNF - α (p = 0.012) and IL-1β (p = 0.009) in dose level I but not in dose level II was observed.

CONCLUSIONS: A combination of resveratrol-copper reduced transplant related toxicities in patients with multiple myeloma receiving high dose melphalan. We conclude that relatively inexpensive nutraceuticals may be useful as adjuncts to chemotherapy to reduce its toxicity.

REGISTRATION: The trial was registered under Clinical Trial Registry of India (no.CTRI/2018/02/011905).

PMID:35120140 | DOI:10.1371/journal.pone.0262212

Br J Clin Pharmacol. 2022 Feb 2. doi: 10.1111/bcp.15256. Online ahead of print.

ABSTRACT

AIM: This trial (NCT04013048) investigated the metabolite profiles, mass balance and pharmacokinetics of fuzuloparib, a novel poly (ADP-ribose) polymerase (PARP) inhibitor, in subjects with advanced solid cancers.

METHODS: A single dose of 150 mg [14 C]fuzuloparib was administered to five subjects with advanced solid cancers. Blood, urine and fecal samples were collected, analyzed for radioactivity, unchanged fuzuloparib and profiled for metabolites. The safety of the medicine was assessed during the study.

RESULTS: The maximum concentration (Cmax ) of the total radioactivity (TRA) and unchanged fuzuloparib in plasma was 5.39 μg eq/mL and 4.19 μg/mL, respectively, at approximately 4 h post dose. The exposure (AUC0-t ) of fuzuloparib accounted for 70.7% of the TRA in plasma, and no single metabolite was observed accounting for more than 10% of the plasma TRA. The recovery of TRA in excreta was 103.3±3.8% in 288 h, including 59.1±9.9% in urine and 44.2±10.8% in feces. Sixteen metabolites of fuzuloparib were identified, including mono-oxidation (M1), hydrogenation (M2), di-oxidation (M3), trioxidation (M4), glucuronidation (M5, M7, M8) and de-ethylation (M6) products, and there was no specific binding between these metabolites and blood cells. Aliphatic hydroxylated fuzuloparib (M1-1) was the primary metabolite in the excreta, accounting for more than 40% of the dose for subjects. There were no serious adverse events observed in the study.

CONCLUSION: Fuzuloparib was widely metabolized and excreted completely through urine and feces in subjects with advanced solid cancer. Unchanged fuzuloparib was indicated to be the primary drug-related compound in circulation. [14 C]fuzuloparib was well-tolerated at the study dose.

PMID:35112382 | DOI:10.1111/bcp.15256

Reprod Sci. 2022 Feb 2. doi: 10.1007/s43032-021-00787-w. Online ahead of print.

ABSTRACT

Several clinical trials in women with endometriosis demonstrated that dienogest reduces endometrial lesions and improves health-related quality of life (HRQoL). To assess HRQoL in dienogest-treated patients in real-world setting, we conducted a prospective, non-interventional study in 6 Asian countries. Women aged ≥18 years with clinical or surgical diagnosis of endometriosis, presence of endometriosis-associated pelvic pain (EAPP) and initiating dienogest therapy were enrolled. The primary objective was to evaluate HRQoL using the Endometriosis Health Profile-30 (EHP-30) questionnaire. The secondary objectives included analysis of EAPP, satisfaction with dienogest, endometriosis symptoms and bleeding patterns. 887 patients started dienogest therapy. Scores for all EHP-30 scales improved with the largest mean changes at month 6 and 24 in scale pain (-28.9 ± 27.5 and - 34 ± 28.4) and control and powerlessness (-23.7 ± 28.2 and - 28.5 ± 26.2). Mean EAPP score change was -4.6 ± 3.0 for both month 6 and 24 assessments. EAPP decrease was similar in surgically and only clinically diagnosed patients. From baseline to month 24, rates of normal bleeding decreased (from 85.8% to 17.5%) while rates of amenorrhea increased (from 3.5% to 70.8%). Majority of patients and physicians were satisfied with dienogest. Over 80% of patients reported symptoms improvement. 39.9% of patients had drug-related treatment-emergent adverse events, including vaginal hemorrhage (10.4%), metrorrhagia (7.3%) and amenorrhea (6.4%). In conclusion, dienogest improves HRQoL and EAPP in the real-world setting in women with either clinical or surgical diagnosis of endometriosis. Dienogest might be a promising first-line treatment option for the long-term management of debilitating endometriosis-associated symptoms.NCT02425462, 24 April 2015.

PMID:35112299 | DOI:10.1007/s43032-021-00787-w

Case Rep Nephrol Dial. 2021 Dec 30;11(3):376-383. doi: 10.1159/000518304. eCollection 2021 Sep-Dec.

ABSTRACT

Immune checkpoint inhibitors (ICIs) have revolutionized solid organ and hematologic cancer treatments by improving overall prognoses. However, they can lead to overactivation of the immune system and several immune-related adverse events and sometimes affecting the renal system. Although acute interstitial nephritis is well described, we know little about ICI-associated glomerular injury. Herein, we report an exceptional case of renal ANCA positive-associated vasculitis (AAV) after nivolumab therapy. Three weeks after the last nivolumab injection, the patient presented with proteinuria at 1.73 g/g of creatininuria, hematuria, and acute kidney injury needing dialysis associated with lung hemorrhage; anti-neutrophil cytoplasmic antibody (ANCA titer ≥1,280 with myeloperoxidase specificity of 780 U/mL) was positive, and kidney biopsy confirmed glomerular injury with crescents. The patient underwent treatment with steroid pulses, rituximab, and plasmapheresis, resulting in an improvement of the renal function and lung hemorrhage and produced a negative ANCA titer. Despite the results of the PEXIVAS study and the absence of clear benefit of plasmapheresis demonstrated in idiopathic AAV, we suggest that drug-induced AAV may be effectively treated by plasmapheresis, steroids, and rituximab.

PMID:35111820 | PMC:PMC8787507 | DOI:10.1159/000518304

N Engl J Med. 2022 Feb 3;386(5):463-477. doi: 10.1056/NEJMra2111003.

NO ABSTRACT

PMID:35108471 | DOI:10.1056/NEJMra2111003

Cancer Med. 2022 Feb 2. doi: 10.1002/cam4.4478. Online ahead of print.

ABSTRACT

The poor prognosis of acute T-cell lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) in older adults and patients with relapsed/refractory illness is an unmet clinical need, as there is no defined standard of care and there are few treatment options. Abnormally elevated CD38 expression in T-ALL and T-LBL is associated with tumor expansion and disease development, making CD38 a potential target for anti-T-ALL and T-LBL treatment. Isatuximab is a monoclonal antibody that binds to a specific epitope on CD38. The purpose of the study was to assess the efficacy and safety of isatuximab monotherapy in a phase 2, multicenter, one-arm, open-label study in patients with relapsed or refractory T-ALL or T-LBL (Clinical Trials.gov identifier NCT02999633). The primary endpoint was to assess the efficacy of isatuximab by overall response rate (ORR). An interim analysis based on the efficacy and safety of isatuximab in the first 19 patients enrolled was scheduled, however only 14 patients were enrolled in the study. No patient achieved complete response (CR) or CR with incomplete peripheral recovery. Most patients (11 [78.6%]) developed progressive disease and had progressive disease as their best response. A total of 10 (71.4%) patients had treatment emergent adverse events considered treatment-related, with infusion reactions as the most frequent drug-related TEAE, occurring in 8 (57.1%) patients. Despite the low efficacy of isatuximab in the current study, it is likely that the use of immunotherapy medication in T-ALL will be expanded through logically targeted approaches, together with advances in the design of T-cell therapy and clinical experience and will provide restorative options beyond chemotherapy and targeted treatments.

PMID:35106962 | DOI:10.1002/cam4.4478

Am J Hypertens. 2022 Feb 1:hpac013. doi: 10.1093/ajh/hpac013. Online ahead of print.

ABSTRACT

BACKGROUND: Drug-related adverse events associated with antihypertensive therapy may result in subsequent prescribing of other potentially harmful medications, known as prescribing cascades. The aim of this study was to assess the magnitude and characteristics of a beta-blocker - edema - loop diuretic prescribing cascade.

METHODS: A prescription sequence symmetry analysis (PSSA) was used to assess loop diuretic initiation before and after initiation of beta-blockers among patients 20 years or older without heart failure, atrial fibrillation, other arrythmias, or use of calcium channel blocker within a US private insurance claims database (2005 to 2018). The temporality of loop diuretic initiation relative to a beta-blocker or negative control (renin-angiotensin system blocker) initiation was tabulated. Secular trend-adjusted sequence ratios (aSRs) with 95% CIs compared the initiation of loop diuretic 90 days before and after initiation of beta-blockers.

RESULTS: Among 988,675 beta-blocker initiators, 9,489 patients initiated a new loop diuretic prescription 90 days after and 5,245 patients before beta-blocker initiation, resulting in an aSR of 1.78 (95% CI, 1.72-1.84). An estimated 1.72 beta-blocker initiators per 100 patient-years experienced the prescribing cascade in the first 90 days. The aSR was disproportionately higher among older adults (aSR 1.97), men (aSR 2.25), and patients who initiated metoprolol tartrate (aSR 2.48), labetalol (aSR 2.18), or metoprolol succinate (aSR 2.11). Negative control results (aSR 1.09, 95% 1.05-1.13) generally corroborated our findings, but suggested modest within-person time-varying confounding.

CONCLUSIONS: We observed excess use of loop diuretics following beta-blocker initiation that was only partially explained by secular trends or hypertension progression.

PMID:35106529 | DOI:10.1093/ajh/hpac013

Oncotarget. 2022 Jan 24;13:198-213. doi: 10.18632/oncotarget.28180. eCollection 2022.

ABSTRACT

DNA double strand breaks (DSBs) have been highly studied in the context of cancers, as DSBs can lead to apoptosis or tumorigenesis. Several pharmaceuticals are widely used to target DSBs during cancer therapy. Amifostine (WR-2721) and etoposide are two commonly used drugs: amifostine reduces DSBs, whereas etoposide increases DSBs. Recently, a novel role for DSBs in immediate early gene expression, learning, and memory has been suggested. Neither amifostine nor etoposide have been assessed for their effects on learning and memory without confounding factors. Moreover, sex-dependent effects of these drugs have not been reported. We administered amifostine or etoposide to 3-4-month-old male and female C57Bl/6J mice before or after training in fear conditioning and assessed learning, memory, and immediate early genes. We observed sex-dependent baseline and drug-induced differences, with females expressing higher cFos and FosB levels than males. These were affected by both amifostine and etoposide. Post-training injections of amifostine affected long-term contextual fear memory; etoposide affected contextual and cued fear memory. These data support the hypothesis that DSBs contribute to learning and memory, and that these could play a part in cognitive side effects during common treatment regimens. The sex-dependent effects also highlight an important factor when considering treatment plans.

PMID:35106123 | PMC:PMC8794536 | DOI:10.18632/oncotarget.28180

Pediatr Emerg Care. 2022 Feb 1;38(2):e529-e533. doi: 10.1097/PEC.0000000000002372.

ABSTRACT

OBJECTIVE: This study aimed to compare the traditional bulb aspirator with a nasal-oral aspirator in the treatment of bronchiolitis.

METHODS: This was a single-center, single-blind, randomized controlled trial. Patients with bronchiolitis discharged from the emergency department were randomized to receive a bulb or nasal-oral aspirator for home use.Data regarding return visits, hydration, respiratory relief, parental satisfaction, device preference, and adverse events were gathered using a predistribution questionnaire, diary, poststudy questionnaire, and chart review.

RESULTS: There was not a statistically significant difference in the rate of unscheduled return visits (bulb vs nasal-oral, 28.2% vs 20.7%; P = 0.26). No difference was seen in hydration or respiratory relief in either the diary or poststudy questionnaire. The nasal-oral aspirator had higher satisfaction rates (bulb vs nasal-oral, 68.8% vs 93.9%; P < 0.01). When asked which device was preferred with regard to all devices ever tried, 57.2% of respondents reported the nasal-oral aspirator. More adverse events were seen with the bulb compared with the nasal-oral aspirator (bulb vs nasal-oral, 50.0% vs 17.5%; P < 0.01).

CONCLUSIONS: No difference was appreciated between the bulb and nasal-oral aspirators in unscheduled return rates. The nasal-oral aspirator demonstrated higher parental satisfaction and preference rates, and fewer adverse effects compared with the bulb aspirator. Medical providers should have a cost-benefit discussion with caregivers when recommending home aspirators for the treatment of bronchiolitis.Registry ClinicalTrials.gov Identifier: NCT03288857. Comparison of the Bulb Aspirator With a Nasal-Oral Aspirator in the Treatment of Bronchiolitis.

PMID:35100758 | DOI:10.1097/PEC.0000000000002372

Pain Med. 2022 Feb 1:pnac010. doi: 10.1093/pm/pnac010. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the effectiveness of Δ9-tetrahydrocannabinol (dronabinol, DRO), as an add-on treatment in patients with refractory chronic pain (CP).

METHODS: An exploratory retrospective analysis of 12-week data provided by the German Pain e-Registry (GPeR) on adult patients with treatment refractory CP who received DRO.

RESULTS: Between March 10, 2017 and June 30, 2019 the GPeR collected information on 89,095 pain patients of whom 1,145 patients (1.3%; 53.8% female, mean ± SD age: 56.9 ± 10.6 years) received DRO, and 70.0% documented use for the entire 12-week evaluation period. Average DRO daily dose was 15.8±7.5mg, typically in three divided doses (average DRO dose of 5.3±2.1mg). Average 24-hr. pain intensity decreased from 46.3±16.1 to 26.8±18.7 mm VAS, (absolute VAS difference -19.5 ± 17.3; p < 0.001). A 50% improvement from baseline was documented among patients who completed follow up for pain (46.5%), activities of daily living (ADL) (39%), quality-of-life (QoL) (31.4%), and sleep (35.3%). A total of 536 patients (46.8%) reported at least one of 1617 drug related adverse events (DRAEs), of which none was serious, and 248 (21.7%) stopped treatment. Over the 12-week period, 59.0% of patients reported a reduction of other pain treatments and 7.8% a complete cessation of any other pharmacological pain treatments.

CONCLUSION: Add-on treatment with DRO in patients with refractory CP was well tolerated and associated with a significant improvement.

PMID:35104881 | DOI:10.1093/pm/pnac010

J Ethnopharmacol. 2022 Jan 29:115053. doi: 10.1016/j.jep.2022.115053. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Houttuynia cordata Thunb., a plant belonging to the family of Saururaceae, has been used as a traditional Chinese medicine for more than 1500 years. Because of its various pharmacological activities, it was widely used as antipyretic, detoxification, anti-inflammatory drugs. Houttuynia cordata (HC) injection was prepared using contemporary methods to extract effective components from H. cordata Thunb. However, the adverse event reports of HC injection are accumulating remarkably with the HC injection clinical applications increased. Previous studies demonstrated that the major side effects of HC injection were anaphylactoid reactions. Our work might shed the light on the role of Mas-related G-protein coupled receptor-X2 (MRGPRX2) in modulating drug-induced anaphylactoid reactions.

AIM OF THE STUDY: We aimed to investigate the role of the mouse Mas-related G-protein coupled receptor B2 (Mrgprb2) (the orthologous gene of human MRGPRX2) in anaphylactoid reactions induced by HC injection.

MATERIALS AND METHODS: Mrgprb2 related anaphylactoid reactions induced by HC injection were investigated by histamine/β-hexosaminidase releasing, mast cell degranulation, and hind paw swelling assays by using a Mrgprb2 knockout mouse model. Furthermore, the transcriptomic profiles of the anaphylactoid reaction induced by HC injection was analyzed by RNA sequencing.

RESULTS: Mice without Mrgprb2 exhibited significantly decreasing in mast cell degranulation, serum histamine release, and hind paw swelling degrees. The RNA sequencing results indicated that Mrgprb2 could play a pivotal role in HC injection induced anaphylactoid reaction mediated by mTOR/AMPK pathway. Intriguingly, our results showed that Mrgprb2 might involve in Compound 48/80 induced anaphylactoid reactions mediated by Reelin/E-cadherin axis, which suggested different roles of Mrgprb2 in anaphylactoid reactions induced by HC injection and C48/80.

CONCLUSION: Our studies reported effects and underlying mechanisms of Mrgprb2 in the anaphylactoid reaction induced by HC injection.

PMID:35104575 | DOI:10.1016/j.jep.2022.115053

Drug Ther Bull. 2022 Jan 31:dtb-2022-000002. doi: 10.1136/dtb.2022.000002. Online ahead of print.

ABSTRACT

Overview of: Jayk Bernal A, Gomes da Silva MM, Musungaie DB, et al Molnupiravir for oral treatment of COVID-19 in nonhospitalized patients. NEJM 2021;doi:10.1056/NEJMoa2116044 [Epub ahead of print 16 Dec 2021].

PMID:35101888 | DOI:10.1136/dtb.2022.000002

PLoS One. 2022 Jan 31;17(1):e0263117. doi: 10.1371/journal.pone.0263117. eCollection 2022.

ABSTRACT

Drug-induced QT prolongation is one of the most common side effects of drug use and can cause fatal outcomes such as sudden cardiac arrest. This study adopts the data-driven approach to assess the QT prolongation risk of all the frequently used drugs in a tertiary teaching hospital using both standard 12-lead ECGs and intensive care unit (ICU) continuous ECGs. We used the standard 12-lead ECG results (n = 1,040,752) measured in the hospital during 1994-2019 and the continuous ECG results (n = 4,835) extracted from the ICU's patient-monitoring devices during 2016-2019. Based on the drug prescription frequency, 167 drugs were analyzed using 12-lead ECG data under the case-control study design and 60 using continuous ECG data under the retrospective cohort study design. Whereas the case-control study yielded the odds ratio, the cohort study generated the hazard ratio for each candidate drug. Further, we observed the possibility of inducing QT prolongation in 38 drugs in the 12-lead ECG analysis and 7 drugs in the continuous ECG analysis. The seven drugs (vasopressin, vecuronium, midazolam, levetiracetam, ipratropium bromide, nifedipine, and chlorpheniramine) that showed a significantly higher risk of QT prolongation in the continuous ECG analysis were also identified in the 12-lead ECG data analysis. The use of two different ECG sources enabled us to confidently assess drug-induced QT prolongation risk in clinical practice. In this study, seven drugs showed QT prolongation risk in both study designs.

PMID:35100302 | DOI:10.1371/journal.pone.0263117

Anticancer Res. 2022 Feb;42(2):1031-1041. doi: 10.21873/anticanres.15564.

ABSTRACT

BACKGROUND/AIM: This study aimed to provide real-world safety and effectiveness data of everolimus (EVE) plus exemestane (EXE) in estrogen receptor positive/human epidermal growth factor receptor 2 negative (ER+/HER2-) advanced breast cancer (aBC).

PATIENTS AND METHODS: This prospective observational study was conducted by 19 hospital-based oncologists in Greece. Eligible patients were treated with EVE+EXE in the first-line setting; EVE was initiated according to the approved label.

RESULTS: Overall, 75 eligible patients (mean age: 66.9 years; visceral metastases: 49.3%; bone-only metastases: 37.3%) were included in the effectiveness analyses. Over a median (interquartile range) of 12.1 months (range=4.2-20.5 months) of EVE treatment, the median progression-free survival was 18.0 months and the overall response rate was 22.7%. Among patients that received ≥1 EVE dose (n=80), the incidence of EVE-related adverse events was 72.5% (serious: 55.0%); stomatitis (22.5%), fatigue (22.5%), pneumonitis (18.8%); and cough (18.8%) were the most common.

CONCLUSION: In the routine care in Greece, EVE demonstrates clinical benefit and a predictable safety profile.

PMID:35093904 | DOI:10.21873/anticanres.15564

Asian Pac J Cancer Prev. 2022 Jan 1;23(1):93-100. doi: 10.31557/APJCP.2022.23.1.93.

ABSTRACT

OBJECTIVE: To investigate the prevalence of chemotherapy-induced adverse events and the associated risk factors in pediatric patients with osteosarcoma.

METHODS: This retrospective cross-sectional study enrolled 90 pediatric osteosarcoma patients (with 1,017 chemotherapy cycles) treated at Srinagarind Medical Center, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand, between January 1, 2008 and December 31, 2018. The prevalence of major adverse events and a correlation between baseline characteristics and adverse events were analyzed using a generalized estimating equation model.

RESULT: The prevalence of adverse events in 90 pediatric osteosarcoma patients (with 1,017 chemotherapy cycles) was determined as chemotherapy-induced nausea and vomiting (29.2%; n=296), hepatotoxicity (21.2%; n=215), anemia (70.69%; n=719), neutropenia (26.65%; n=271), and thrombocytopenia (13.65%; n=139). Factors associated with chemotherapy-induced hepatotoxicity included methotrexate dose ≥ 12 g/m2 (odds ratio [OR] 1.30; 95% confidence interval [CI] 1.22-1.39; P<0.001), plasma concentration of methotrexate at 72 hours >0.1 μM (OR 1.22; 95% CI 1.19-1.25; P<0.001), and pre-hydration rate ≤ 125 mL/m2/h (OR 1.10; 95% CI 1.07-1.12; P<0.001).

CONCLUSION: Major adverse events are becoming more common in pediatric osteosarcoma patients, and risk factors include larger chemotherapy doses, higher plasma methotrexate concentrations, and a slower pre-hydration rate. The outcomes of the study could aid in the better treatment of toxicity in children with osteosarcoma.

PMID:35092376 | DOI:10.31557/APJCP.2022.23.1.93

Colloids Surf B Biointerfaces. 2022 Jan 20;212:112351. doi: 10.1016/j.colsurfb.2022.112351. Online ahead of print.

ABSTRACT

Fluorometholone (FMT) is a frequently prescribed drug for the alleviation of dry eye. However, due to low aqueous solubility, it has been routinely used as an ophthalmic suspension, which is characterized by low bioavailability, inconvenience of administration, and difficulty in delivering accurate dose. Furthermore, the opaque appearance of the ophthalmic suspension is not desirable for optical purpose. In the present study, a transparent FMT nanoformulation (FMT-CD NPs) was fabricated by the cyclodextrin (CD) nanoparticle technology without organic solvents. It was demonstrated that FMT was encapsulated in an amorphous form, which was associated with increased release rate and enhanced corneal penetration efficiency. The biocompatibility of FMT-CD NPs was confirmed by the Live/Dead assay, CCK-8 assay and the wound healing assay. Most importantly, FMT-CD NPs alleviated dry eye signs more efficiently than the commercial eye drop, with one-fifth the dosage of FMT in the latter. Collectively, our study provides a promising FMT formulation for improved management of dry eye while reducing drug related side effects.

PMID:35091382 | DOI:10.1016/j.colsurfb.2022.112351

Acta Derm Venereol. 2022 Feb 11;102:adv00648. doi: 10.2340/actadv.v102.175.

ABSTRACT

Genetic defects in interleukin-12/23/17 immunity are associated with an increased risk of Staphylococcus aureus and herpesvirus skin infections. This study analysed spontaneous safety reports from the WHO Pharmacovigilance Center of bacterial skin or herpesvirus infections associated with secukinumab, ustekinumab and tumour necrosis factor-α inhibitors. Associations found in disproportionality analyses were expressed as reporting odds ratios (ROR). For bacterial skin infections, ustekinumab showed the strongest association (ROR 6.09; 95% confidence interval (95% CI) 5.44-6.81), and, among the tumour necrosis factor-α inhibitors, infliximab showed the strongest association (ROR 4.18; 95% CI 3.97-4.40). Risk was comparable between infliximab and secukinumab (ROR 3.51; 95% CI 3.00-4.09). Secukinumab showed the strongest association with herpes simplex infection (ROR 4.80; 95% CI 3.78-6.10). All biologics were equally associated with herpes zoster. Infliximab was the only biologic associated with cytomegalovirus infection (ROR 5.66; 95% CI 5.08-6.31) and had the strongest association with Epstein-Barr virus infection (ROR 6.90; 95% CI 6.03-7.90). All biologics evaluated were positively associated with bacterial skin infections, herpes simplex, and herpes zoster, compared with all other drugs in the WHO database for which individual case safety reports were collected. The possibility of under-reporting, reporting bias and difference in causality assessment between countries and reporters must be taken into account when interpreting the results of disproportionality analyses.

PMID:35088874 | DOI:10.2340/actadv.v102.175

Drug Ther Bull. 2022 Jan 27:dtb-2022-000001. doi: 10.1136/dtb.2022.000001. Online ahead of print.

ABSTRACT

Overview of: Leitch S, Dovey SM, Cunningham WK, et al Medication-related harm in New Zealand general practice: a retrospective records review. Br J Gen Pract 2021;71:e626-e633.

PMID:35086808 | DOI:10.1136/dtb.2022.000001

Eur J Hosp Pharm. 2022 Jan 27:ejhpharm-2021-003124. doi: 10.1136/ejhpharm-2021-003124. Online ahead of print.

ABSTRACT

Dl-3-n-butylphthalide (DL-NBP) has good neuroprotective function and is safe for use in patients with acute ischaemic stroke. DL-NBP induced anaphylactic shock is rarely reported. Here we describe the case of a 75-year-old woman who received an injection of DL-NBP (25 mg/100 mL intravenously guttae, twice daily) for acute ischaemic stroke. Approximately 5 min after the DL-NBP injection was administered, the patient developed a decrease in blood pressure and an increase in heart rate along with skin pruritus, mottlement of the lower limbs, discomfort, and the desire to defecate, following which DL-NBP was discontinued immediately. The patient recovered with antiallergic therapy and could tolerate further treatment. We emphasise that the increased use of DL-NBP in recent year raises the importance of attention to potential allergies in clinical use, especially in patients with a history of allergies to multiple drugs.

PMID:35086804 | DOI:10.1136/ejhpharm-2021-003124

J Subst Abuse Treat. 2022 Jan 22:108720. doi: 10.1016/j.jsat.2022.108720. Online ahead of print.

ABSTRACT

INTRODUCTION: This paper explores the impact of the COVID-19 pandemic on health care professionals who support clients experiencing addiction. During the pandemic, addiction support became more challenging, as existing health care models had changed or been completely abolished. Clients continued to engage with social, justice, and health services in limited capacities, connecting with general practitioners, key workers, homelessness support workers, and other service providers. This marginalized population was among the most high-risk groups for adverse health outcomes during the pandemic and understanding the associated implications for practitioner well-being is crucial.

METHODS: Fifteen health care professionals who work with active addiction in homelessness, public health, addiction, emergency medicine, and other areas participated in individual semi-structured interviews. Data analyses utilized reflexive thematic analysis.

RESULTS: Four core themes emerged from the analysis: (i) Shift in Priority, (ii) Being Left Behind, (iii) Managing a Death, and (iv) Anxious Environment. Within each core theme, associated subthemes provide further context. The COVID-19 pandemic had a significant impact on the well-being of clinicians who work with people who use drugs, fostering a more anxious environment and compounding what can already be a high-stress occupation. Participants exhibited high levels of concern for the well-being of clients, and uncertainty permeated throughout conversations. Furthermore, staff expressed concern for their own well-being in the long term due to the inability to process adverse events, such as a service user's death, due to the chaotic nature of the pandemic.

CONCLUSIONS: This paper highlights some areas of concern to address for future service delivery and presents opportunities to future-proof services as the world moves toward hybrid models of working. The inflexibility of service provision during the pandemic and the digital divide due to public health measures pushed marginalized groups further into the margins, with significant implications for practitioner occupational well-being due to feelings of anxiety, powerlessness, and concern for mortality of clients. This study collects a broad scope of experiences across disciplines in health care and demonstrates how professionals navigated unprecedented circumstances.

PMID:35086760 | DOI:10.1016/j.jsat.2022.108720