Diagnostic outcome and safety of plugged liver biopsy in high-risk patients: a systematic review and meta-analysis.

Antihypertensive prescribing and risk of adverse events in a female medicaid population

<h3>Introduction</h3> Liver biopsy (LB) can be associated with adverse outcomes including technical failures, complications and inadequate tissue for histological analysis. The indication for a chosen route of LB is variable between physicians and the impact of the chosen route of LB is often unclear. <h3>Method</h3> Retrospective review of all LB performed at a UK transplant centre over a 12 month period focussing on indication and route of LB, complications, histological adequacy and variability in operator specialty and experience. <h3>Results</h3> Over the 12 month period 570 LB were performed, of which 330 were transjugular liver biopsies (TJLB) and 240 were percutaneous liver biopsies (PCLB). A LB was categorised as being histologically adequate if a histological diagnosis could be made, or if the sample met the histological standard in the literature (a 15 mm sample, with 6 or more complete portal tracts). Overall, 94% of LB were adequate based on the histological standard, and 98% allowed histological diagnosis. There were no significant differences in adequacy when comparing TJLB vs. PCLB route; however, a consultant radiologist was more likely to provide an adequate sample than a radiology registrar (p = 0.02). The overall complication rate for a liver biopsy was 5.6%. This included 8 major complications (1.4%) and 24 minor complications (4.2%). Neither the route of LB (TJLB vs. PCLB) or operator (consultant radiologist vs. radiology registrar vs. hepatologist) was significantly associated with the development of a complication. The technical failure rate of a TJLB was 4%; these included failure to puncture internal jugular vein, failure to cannulate the hepatic vein, or an unstable sheath position. There were no technical failures in the PCLB group. Screening time for a TJLB was significantly longer if the procedure was done by a radiology registrar when compared to both a hepatologist (p = 0.01) or consultant radiologist (p = 0.003). Apart from the standard indications for a TJLB we found a patient was significantly more likely to undergo a TJLB if they were post-transplant compared to pre-transplant (p = 0.001) and if the biopsy was deemed an emergency compared to an elective procedure (p = 0.001). In our cohort we identified 130 patients who had a TJLB with no indication for this procedure. <h3>Conclusion</h3> We have demonstarted that TJLB and PCLB have no significant differences in complication rates or adequacy of histological sample. Technical failure is more common in TJLB compared to PCLB. A TJLB is our preferred method in emergency cases and post-transplant patients. Further information regarding cost and patient experience is needed to identify if a change in practice is indicated. <h3>Disclosure of interest</h3> None Declared.

Objective To compare the survival and risk of serious adverse events in older patients with stages II-IIIA non-small cell lung cancer treated with or without postoperative platinum based chemotherapy.Design Observational...

Previous works investigating rates of adverse events (AEs) in spine surgery have been retrospective, with data collection from administrative databases, and often from single centers. To date, there have been no prospective reports capturing AEs in spine surgery on a national level, with comparison among centers. The Spine Adverse Events Severity system was used to define the incidence and severity of AEs after spine surgery by using data from the Canadian Spine Outcomes and Research Network (CSORN) prospective registry. Patient data were collected prospectively and during hospital admission for those undergoing elective spine surgery for degenerative conditions. The Spine Adverse Events Severity system defined minor and major AEs as grades 1-2 and 3-6, respectively. There were 3533 patients enrolled in this cohort. There were 85 (2.4%) individual patients with at least one major AE and 680 (19.2%) individual patients with at least one minor AE. There were 25 individual patients with 28 major intraoperative AEs and 260 patients with 275 minor intraoperative AEs. Postoperatively there were 61 patients with a total of 80 major AEs. Of the 487 patients with minor AEs postoperatively there were 698 total AEs. The average enrollment was 321 patients (range 47-1237 patients) per site. The rate of major AEs was consistent among sites (mean 2.9% ± 2.4%, range 0%-9.1%). However, the rate of minor AEs varied widely among sites-from 7.9% to 42.5%, with a mean of 18.8% ± 9.7%. The rate of minor AEs varied depending on how they were reported, with surgeon reporting associated with the lowest rates (p < 0.01). The rate of major AEs after lumbar spine surgery is consistent among different sites but the rate of minor AEs appears to vary substantially. The method by which AEs are reported impacts the rate of minor AEs. These data have implications for the detection and reporting of AEs and the design of strategies aimed at mitigating complications.

There is currently no consensus on the optimal treatment for Dupuytren contracture. Prior meta-analyses have been limited by suboptimal data synthesis methodologies. The authors conducted an updated evidence review comparing the effectiveness and safety of percutaneous needle fasciotomy (PNF), collagenase clostridium histolyticum (CCH), and limited fasciectomy (LF) using the Grading of Recommendations Assessment, Development and Evaluation approach. CENTRAL, MEDLINE, and Embase were searched for randomized controlled trials comparing outcomes following PNF, CCH, and LF for Dupuytren contracture treatment. Outcomes of interest included residual contracture, recurrence rate, hand function, pain, global satisfaction, and adverse events. Time points included 3 months, 1 year, and 2 to 3 years. Seventeen publications (1010 patients) were included. High- to moderate-certainty evidence showed no clinically important difference in long-term contracture reduction (PNF versus LF: mean difference [MD], 7.6 degrees; 95% CI, 1.8 to 13.4 degrees. CCH versus LF: MD, 4.8 degrees; 95% CI, -1.3 to 10.9 degrees). Moderate-certainty evidence indicated that LF provides the lowest risk of long-term recurrence (PNF versus LF: relative risk [RR], 12.3; 95% CI, 1.6 to 92.4. CCH versus LF: RR, 9.5; 95% CI, 1.2 to 73.4), LF has a higher risk of serious adverse events than PNF (RR, 0.5; 95% CI, 0.3 to 0.9), and CCH has a higher risk of overall adverse events than PNF (RR, 4.8; 95% CI, 2.9 to 7.0). CCH, PNF, and LF are equally effective in long-term contracture reduction. However, LF yields more durable results at a higher risk of rare but serious adverse events. Current evidence suggests the use of PNF over CCH. However, ultimate treatment decisions should be tailored to individual patient preferences. Therapeutic, II.

ObjectiveTo evaluate the relative risk (RR) of serious and non-serious adverse events in patients treated with exercise therapy compared with those in a non-exercising control group.DesignSystematic review and meta-analysis.Data sourcesPrimary...

ObjectiveTo evaluate the prognostic impact of collateral circulation on outcomes of direct thrombectomy (DT) versus bridging thrombectomy (BT) for acute ischemic stroke (AIS) patients with anterior circulation large vessel occlusion (LVO).MethodThis retrospective study included 460 AIS patients with anterior circulation LVO who underwent either DT (n = 220) or BT (n = 240). Collateral status was assessed using multiphase computed tomographic angiography. The primary outcome was functional prognosis at 3 months, measured by the modified Rankin Scale (mRS). Prognostic factors for good prognosis (90-day mRS ≤ 2) and adverse events were identified through multivariate logistic regression and receiver operating characteristic (ROC) analyses.ResultsThe BT group had significantly higher rates of intracerebral hemorrhage and hemorrhagic transformation compared to the DT group (p < 0.05). Good collateral circulation was independently associated with good prognosis and lower risk of serious adverse events (p < 0.001). Lower NIHSS scores, shorter OTR, absence of atrial fibrillation, and lower serum BNP levels were also significantly associated with favorable outcomes in AIS patients (all p < 0.01). Elevated serum BNP levels increased the risk of serious adverse events in both DT and BT groups (p < 0.001). ROC analysis showed that a combined model including NIHSS, BNP, collateral circulation, onset-to-reperfusion time, and atrial fibrillation achieved high predictive performance for good prognosis (AUC = 0.907, 95% CI: 0.881–0.934, p < 0.001).ConclusionCollateral circulation is a strong predictor of both functional recovery and risk of adverse events in AIS patients undergoing thrombectomy, regardless of treatment strategy. While serum BNP may offer additional prognostic value, its moderate performance and overlap with cardiovascular conditions suggest that it should be interpreted cautiously. Pre-intervention collateral assessment remains a valuable tool for guiding individualized treatment decisions.

Safety of diphtheria, tetanus, acellular pertussis and inactivated poliovirus (DTaP–IPV) vaccine

Case reports and pharmacokinetic studies have suggested that concomitant use of low-dose methotrexate and nonsteroidal anti-inflammatory drugs (NSAIDs) may be associated with increased risk of methotrexate toxicity. This study aimed to investigate the risk of serious adverse events associated with concomitant use of low-dose methotrexate and NSAIDs, compared with use of methotrexate alone, among patients with rheumatoid arthritis. The study was conducted as a register-based cohort study in Denmark, 2004 to 2015, including episodes of concomitant use of methotrexate and NSAIDs (n=21536) and control episodes of use of methotrexate alone (n=21725). The primary outcome was the composite end point any serious adverse event, including liver toxicity, acute renal failure, and cytopenia. Secondary outcomes were the individual outcome components. Analyses were conducted using proportional-hazards regression, with adjustment using inverse-probability-of-treatment weighting based on propensity scores. During follow-up, 110 cases of the primary outcome occurred during concomitant use of methotrexate and NSAIDs (unadjusted incidence rate 12.1 per 1000 person-years) and 129 during control episodes (11.0 per 1000 person-years). Concomitant use of methotrexate and NSAIDs was associated with a significantly increased risk of any serious adverse event (weighted hazard ratio 1.40; 95% CI, 1.07-1.82). In secondary analyses, concomitant use of methotrexate and NSAIDs was associated with a significantly increased risk of acute renal failure and cytopenia. Concomitant use of low-dose methotrexate and NSAIDs was associated with a significantly increased risk of serious adverse events, expanding on the evidence base for current regulatory recommendations that advocate caution when low-dose methotrexate and NSAID are coprescribed.

Risk of Serious Adverse Events, Infection and Sepsis in Patients with Relapsed and Refractory Chronic Lymphocytic Leukemia/ Small Lymphocytic Lymphoma Treated with Idelalisib

Low-dose methotrexate is used to treat rheumatoid arthritis and psoriasis. Due to its kidney elimination, better evidence is needed to inform its safety in adults with chronic kidney disease (CKD). To compare the 90-day risk of serious adverse events among adults with CKD who started low-dose methotrexate vs those who started hydroxychloroquine and to compare the risk of serious adverse events among adults with CKD starting 2 distinct doses of methotrexate vs those starting hydroxychloroquine. This retrospective, population-based, new-user cohort study was conducted in Ontario, Canada (2008-2021) using linked administrative health care data. Adults aged 66 years or older with CKD (defined as an estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2 but not receiving dialysis) who started low-dose methotrexate (n = 2309) were matched 1:1 with those who started hydroxychloroquine. Low-dose methotrexate (5-35 mg/wk) vs hydroxychloroquine (200-400 mg/d). The primary outcome was a composite of serious adverse events: a hospital visit with myelosuppression, sepsis, pneumotoxic effects, or hepatotoxic effects within 90 days of starting the study drug. Prespecified subgroup analyses were conducted by eGFR category. Propensity score matching was used to balance comparison groups on indicators of baseline health. Risk ratios (RRs) were obtained using modified Poisson regression, and risk differences (RDs) using binomial regression. In a propensity score-matched cohort of 4618 adults with CKD (3192 [69%] women; median [IQR] age, 76 [71-82] years), the primary outcome was higher in patients who started low-dose methotrexate vs those who started hydroxychloroquine (82 of 2309 [3.55%] vs 40 of 2309 [1.73%]; RR, 2.05 (95% CI, 1.42-2.96); RD, 1.82% [95% CI, 0.91%-2.73%]). In subgroup analysis, the risks increased progressively at lower eGFR (eg, eGFR <45 mL/min/1.73 m2: RR, 2.79 [95% CI, 1.51-5.13]). In the secondary comparison with hydroxychloroquine, methotrexate users at 15 to 35 mg/wk had a higher risk of the primary outcome. In this cohort of 4618 older patients with CKD, the 90-day risk of serious adverse events was higher among those who started low-dose methotrexate than those who started hydroxychloroquine. If verified, these risks should be balanced against the benefits of low-dose methotrexate use.

<i>Circulation</i> : Clinical Summaries

A meta-analysis was performed to compare the risk of serious adverse events associated with the use of all formulations of isradipine, when used as monotherapy in hypertension, to active drug or placebo controls. Eligible studies totalled 65 published and unpublished randomised controlled trials involving 9903 subjects and 10,675 treatment exposures: 4492 to isradipine, 1473 to isradipine sustained release, 2768 to other active drugs, and 1942 to placebo. Mortality, cardiovascular outcomes, other serious incident illnesses, such as cancer, and withdrawals were sought. Seventy-five per cent of the isradipine exposures were to standard-release formulations and 25% were to sustained-release formulations. Overall, isradipine therapy shows no difference in risk of major adverse events or withdrawals compared to other active controls or placebo (odds ratios [OR] 0.9; 95% CI 0.7-1.46 and 0.5; 95% CI 0.2-1.3). These major adverse events included angina, fatal and non-fatal myocardial infarction, stroke and overall mortality. Isradipine sustained release could be compared only to placebo, based on available data, and shows a lower risk of withdrawals (OR 0.5; 95% CI 0.3-0.9), and a similar trend was observed for major adverse events, (OR 0.8; 95% CI 0.3-2.5). Published and unpublished randomised controlled trials were analysed in separate meta-analyses and later combined when this sensitivity analysis of risk showed no differences between the groups. In conclusion, we find no evidence for increased risk of serious adverse events in patients receiving isradipine as monotherapy for hypertension.

ObjectiveIncreased risk of serious adverse events (AEs) was reported for tofacitinib relative to tumour necrosis factor inhibitor therapy in patients with rheumatoid arthritis (RA) aged ≥50 years enriched for cardiovascular...

Background Alirocumab and evolocumab, as protein convertase subtilisin kexin type 9 (PCSK9) inhibitors, have been reported to reduce cardiovascular risk. This meta-analysis is aimed at updating the safety data of PCSK9 inhibitors. Methods We assessed the relative risk for all treatment-related adverse events, serious adverse events, diabetes-related adverse events, and neurocognitive and neurologic adverse events with PCSK9 inhibitors compared to controls (placebo or ezetimibe). In addition, we conducted a meta-analysis to quantitatively integrate and estimate the adverse event rates in long-term studies. Results There were no significant differences between PCSK9 inhibitors and controls in the relative risk analysis. In a subgroup analysis of each PCSK9 inhibitor, alirocumab treatment significantly reduced the risk of serious adverse events compared to control treatment (risk ratio (RR) = 0.937; 95% confidence interval (CI), 0.896–0.980), but no significant difference was observed with evolocumab treatment (RR = 1.003; 95% CI, 0.963–1.054). Moreover, alirocumab treatment afforded a significant reduction in the risk of diabetes-related adverse events compared to control treatment (RR = 0.9137; 95% CI, 0.845–0.987). The overall incidence (event rate) of long-term adverse events was 75.1% (95% CI, 71.2%–78.7%), and the incidence of serious long-term event rate was 16.2% (95% CI, 11.6%–22.3%). Conclusions We suggest that alirocumab and evolocumab are generally safe and well tolerated and that their addition to background lipid-lowering therapy is not associated with an increased risk of adverse events or toxicity.