Significant Relative Reduction Research Articles

Employment Nondiscrimination Protection and Mental Health Among Sexual Minority Adults

In the 2020 Bostock v Clayton County decision, the US Supreme Court extended employment nondiscrimination protection to sexual minority adults. The health impacts of this ruling and similar policies related to sexual orientation-based discrimination are not currently known. To estimate changes in mental health following the Bostock decision among sexual minority adults in states that gained employment nondiscrimination protection (intervention states) compared with those in states with protections already in place (control states). This cross-sectional study used 2018-2022 data from the Behavioral Risk Factor Surveillance System and a difference-in-differences approach to evaluate changes in mental health after the Bostock decision by comparing sexual minority adults (aged ≥18 years and identifying as lesbian, gay, or bisexual) in 12 intervention states with those residing in 9 control states. Models were estimated for all participants and separately for employed participants. Data were analyzed between February and September 2024. Residing in a state that gained employment nondiscrimination protection after the Bostock decision. The primary outcome was number of poor mental health days during the past 30 days, and the secondary outcome was severe mental distress (defined as 14 or more past-month poor mental health days). Of 597 462 participants (306 365 in intervention states [77.7% aged 18-64 years and 22.3% aged ≥65 years; 51.7% female] and 291 097 in control states [77.5% aged 18-64 years and 22.5% aged ≥65 years; 50.6% female]), 5.1% in intervention states and 6.0% in control states self-identified as sexual minority adults. The mean (SE) number of past-month poor mental health days was unchanged after the Bostock decision among sexual minority adults in both intervention (from 8.70 [0.27] to 9.59 [0.24] days; adjusted difference, 0.57 [95% CI, -1.02 to 2.16] days) and control (from 8.53 [0.21] to 10.15 [0.20] days; adjusted difference, 1.17 [95% CI, -0.46 to 2.79] days) states, resulting in no differential change between the 2 groups (difference-in-differences, -0.60 days; 95% CI, -1.25 to 0.06 days). Among the subset of employed sexual minority adults, the mean (SE) number of poor mental health days did not change in intervention states (from 7.99 [0.38] to 8.83 [0.30] days; adjusted difference, 0.87 [95% CI, -0.49 to 2.22] days) but increased in control states (from 7.75 [0.27] to 9.75 [0.26] days; adjusted difference, 1.84 [95% CI, 0.44-3.24] days). These findings corresponded to a significant relative reduction in poor mental health days among employed sexual minority adults in intervention vs control states (difference-in-differences, -0.97 days; 95% CI, -1.74 to -0.21 days). Mean (SE) rates of severe mental distress increased less among employed sexual minority adults in intervention (from 26.35% [1.59%] to 29.92% [1.46%]; adjusted difference, 6.81% [95% CI, 2.20%-11.42%]) vs control (from 26.53% [1.27%] to 34.26% [1.16%]; adjusted difference, 10.30% [95% CI, 5.99%-14.61%) states, also corresponding to a significant relative reduction among employed sexual minority adults (difference-in-differences, -3.49%; 95% CI, -6.71% to -0.27%). These findings show significant relative reductions in past-month poor mental health days and severe mental distress among employed sexual minority adults after the implementation of a federal ban on employment discrimination based on sexual orientation. Larger and more consistent mental health benefits observed among sexual minority adults in the workforce underscore the importance of broadening protections to other social domains.

Cone Beam Computed Tomography-Based Online Adaptive Radiation Therapy of Esophageal Cancer: First Clinical Experience and Dosimetric Benefits

Radiation therapy (RT) plays a key role in the management of esophageal cancer (EC). However, toxicities caused by proximity of organs at risk (OAR) and daily target coverage caused by interfractional anatomic changes are of concern. Daily online adaptive RT (oART) addresses these concerns and has the potential to increase OAR sparing and improve target coverage. We present the first clinical experience and dosimetric investigations of cone beam CT-based oART in EC using the ETHOS platform. Treatment fractions of the first 10 EC patients undergoing cone beam CT-based oART at our institution were retrospectively analyzed. The prescription dose was 50.4 Gy in 28 fractions. The same clinical target volume (CTV) and planning target volume (PTV) margins as for nonadaptive treatments were used. For all sessions, the timestamp of each oART workflow step, PTV size, target volume doses, mean heart dose, and lung V20Gy of both the scheduled and the adapted treatment plan were analyzed. Following automatic propagation, the CTV was adapted by the physician in 164 (59%) fractions. The adapted treatment plan was selected in 276 (99%) sessions. The median time needed for an oART session was 28 minutes (range, 14.8-43.3). Compared to the scheduled plans, a significant relative reduction of 9.5% in mean heart dose (absolute, 1.6 Gy; P = .006) and 16.9% reduction in mean lung V20Gy (absolute, 2.3%; P < .001) was achieved with the adapted treatment plans. Simultaneously, we observed a significant relative improvement in D99%PTV and D99%CTV by 15.3% (P < .001) and 5.0% (P = .008), respectively, along with a significant increase in D95%PTV by 5.1% (P = .003). Although being resource-intensive, oART for EC is feasible in a reasonable timeframe and results in increased OAR sparing and improved target coverage, even without a reduction of margins. Further studies are planned to evaluate the potential clinical benefits.

Impact of rosuvastatin on metabolic syndrome patients with moderate to severe metabolic associated fatty liver disease without overt diabetes: A randomized clinical trial

ObjectiveThis investigation aimed to evaluate the efficacy and safety of rosuvastatin in treating moderate to severe metabolic associated fatty liver disease (MAFLD). MethodsThis prospective, open-label, randomized study included non-diabetic participants with metabolic syndrome and intrahepatocellular lipid (IHCL) levels >10 %, as determined by proton magnetic resonance spectroscopy (1H-MRS). The primary objective was the effect of a 52-week rosuvastatin treatment (10 mg/day) on IHCL content. Secondary objectives included the association between IHCL reduction and lipid metabolism parameters, along with safety indices such as glycemic control and hepatic and renal function. ResultsThirty-two participants completed the study. Rosuvastatin resulted in a significant absolute (△IHCL: 7.61 ± 4.51 vs. 1.54 ± 5.33, p = 0.002) and relative reduction in IHCL (△IHCL%: −42.28 ± 24.90 % vs. −8.91 ± 31.93 %, p = 0.003) compared to the control. Reduction in IHCL correlated significantly with decreases in low-density lipoprotein cholesterol (LDL-C) (r = 0.574, p < 0.01), apolipoprotein B (ApoB) (r = 0.660, p < 0.001), and free fatty acids (FFA) (r = 0.563, p = 0.005). No significant safety differences were observed between groups. ConclusionsRosuvastatin significantly reduced hepatic steatosis in individuals with moderate to severe MAFLD and metabolic syndrome over 52 weeks, while maintaining a favorable safety profile.

Investigation of Lithium-Ion Battery Performance Utilizing Magnetic Controllable Superionic Conductor Li3(V1-x Fe x )2(PO4)3/C (x = 0.05 and 0.10).

Lithium-ion batteries with Li3V2(PO4)3/C as the cathode have been a popular research topic in recent years; however, studies of the effects of external magnetic fields on them are less common. This study investigates the effects of an external magnetic field applied parallel to the direction of the anode and cathode on the ion transport through iron-doped Li3(V1-x Fe x )2(PO4)3, the outer carbon coating, the film/electrolyte/separator, and up to the lithium metal electrode on a microscopic level. The results reveal that for the x = 0.05 sample with lower doping, the magnetostriction expansion of Li3(V1-x Fe x )2(PO4)3 and the magnetostrictive contraction effect of the outer ordered carbon layer cancel each other out, resulting in no significant enhancement of the battery's energy and power density due to the external magnetic field. In contrast, the x = 0.1 sample, lacking magnetostrictive contraction in the outer ordered carbon layer, shows that its energy and power density can be influenced by the magnetic field. Under zero magnetic field, the cyclic performance exhibits superior average capacity performance in the x = 0.05 sample, while the x = 0.1 sample shows a lower decay rate. Both samples are affected by the magnetic field; however, the x = 0.1 sample performs better under magnetic conditions. In particular, in the C-rate tests under a magnetic field, the sample with x = 0.1 showed a significant relative reduction in capacity decay rate by 20.18% compared to the sample with x = 0.05.

Spread and persistence of antimicrobial resistance genes in wastewater from human and animal sources in São Paulo, Brazil.

The spread of antimicrobial resistance (AMR) through multiple reservoirs is a global concern. Wastewater is a critical AMR dissemination source, so this study aimed to assess the persistence of resistance genetic markers in wastewater using a culture-independent approach. Raw and treated wastewater samples (n = 121) from a wastewater treatment plant (WWTP), a human hospital, a veterinary hospital, and a pig farm were monthly collected and concentrated by filtration. DNA was extracted directly from filter membranes, and PCR was used in the qualitative search of 32 antimicrobial resistance genes (ARGs). Selected genes (blaCTX-M, blaKPC, qnrB, and mcr-1) were enumerated by quantitative real-time PCR (qPCR). Twenty-six ARGs were detected in the qualitative ARGs search, while quantitative data showed a low variation of the ARG's relative abundance (RA) throughout the months, especially at the human hospital and the WWTP. At the WWTP, despite significantly reducing the absolute number of gene copies/L after each treatment stage (p < 0.05), slight increases (p > 0.05) in the RAs of genes blaCTX-M, qnrB, and mcr-1 were observed in reused water (tertiary treatment) when compared with secondary effluent. Although the increase is not statistically significant, it is worth noting that there was some level of ARGs concentration after the disinfection process. No significant absolute or relative after-treatment quantification reductions were observed for any ARGs at the veterinary hospital or the pig farm. The spread of ARGs through sewage needs to be continuously addressed, because their release into natural environments may pose potential risks of exposure to resistant bacteria and impact local ecosystems.

Intradermal and Subcutaneous Lignocaine for Arterial Blood Gas Sampling: A Randomized Controlled Trial

Introduction: The use of local anesthesia (LA) prior to arterial blood gas sampling is recommended but is not widely used. We tested the hypothesis that intradermal administration of local anesthesia would be as effective as subcutaneous administration in reducing pain from arterial blood gas sampling. Aims: The primary aim of this study was to evaluate the effect of intradermal and subcutaneous lignocaine on patient-perceived pain during arterial blood gas sampling. The secondary aims were to evaluate if different routes of LA administration had an impact on the difficulty and complications of ABG sampling. Methods: We undertook a randomized, single-blind, placebo-controlled trial in New Zealand. We enrolled patients attending a nurse-led outpatient oxygen clinic who were 18 to 90 years of age and who had an oxygen saturation of 93% or less at rest. Patients were randomly assigned to receive intradermal 1% lignocaine, subcutaneous 1% lignocaine, or subcutaneous normal saline. Patients and nurse assessors were blinded to the treatment allocation. The primary endpoint was a patient-assessed pain score using a graphic rating scale (0-10). Results: 135 patients were randomized (54 patients in the intradermal lignocaine group, 54 patients in the subcutaneous lignocaine group, and 27 in the subcutaneous saline group). The mean patient-assessed pain score for the intradermal lignocaine group was 1.8 (+/- 1.1), which was a relative reduction of 47% (95% C.I. 31%-59%, p &lt; 0.0001) from the mean patient-assessed pain score of 3.4 (+/- 1.1) for the subcutaneous saline group. The mean patient-assessed pain score for the subcutaneous lignocaine group was 2.1 (+/- 1.1), which was also a significant relative reduction of 36% (95% C.I. 17%-51%, p = 0.0001) compared to the subcutaneous saline group. Intradermal lignocaine reduced pain more than subcutaneous lignocaine, with a relative pain reduction difference of 20% (95% CI -4%-49%, p = 0.05). Bruising was more frequent in the subcutaneous lignocaine group (9.3%) than in the intradermal (0%) and saline groups (0%). Conclusion: Intradermal lignocaine is at least as effective as subcutaneous lignocaine for reducing patient-perceived pain from arterial blood gas sampling and results in less bruising.

Cationic Vitamin E-TPGS Mixed Micelles of Berberine to Neutralize Doxorubicin-Induced Cardiotoxicity via Amelioration of Mitochondrial Dysfunction and Impeding Apoptosis.

Anthracycline antibiotics, namely, doxorubicin (DOX) and daunorubicin, are among the most widely used anticancer therapies, yet are notoriously associated with severe myocardial damage due to oxidative stress and mitochondrial damage. Studies have indicated the strong pharmacological properties of Berberine (Brb) alkaloid, predominantly mediated via mitochondrial functions and nuclear networks. Despite the recent emphasis on Brb in clinical cardioprotective studies, pharmaceutical limitations hamper its clinical use. A nanoformulation for Brb was developed (mMic), incorporating a cationic lipid, oleylamine (OA), into the TPGS-mixed corona of PEGylated-phosphatidylethanolamine (PEG-PE) micelles. Cationic TPGS/PEG-PE mMic with superior Brb loading and stability markedly enhanced both intracellular and mitochondria-tropic Brb activities in cardiovascular muscle cells. Sub-lethal doses of Brb via cationic OA/TPGS mMic, as a DOX co-treatment, resulted in significant mitochondrial apoptosis suppression. In combination with an intense DOX challenge (up to ~50 µM), mitochondria-protective Brb-OA/TPGS mMic showed a significant 24 h recovery of cell viability (p ≤ 0.05-0.01). Mechanistically, the significant relative reduction in apoptotic caspase-9 and elevation of antiapoptotic Bcl-2 seem to mediate the cardioprotective role of Brb-OA/TPGS mMic against DOX. Our report aims to demonstrate the great potential of cationic OA/TPGS-mMic to selectively enhance the protective mitohormetic effect of Brb to mitigate DOX cardiotoxicity.

Nirmatrelvir-Ritonavir and COVID-19 Mortality and Hospitalization Among Patients With Vulnerability to COVID-19 Complications

Postmarket analysis of individuals who receive nirmatrelvir and ritonavir (Paxlovid [Pfizer]) is essential because they differ substantially from individuals included in published clinical trials. To examine the association of nirmatrelvir and ritonavir with prevention of death or admission to hospital in individuals with different risks of complications from COVID-19 infection. This is a cohort study of adult patients in British Columbia, Canada, between February 1, 2022, and February 3, 2023. Patients were eligible if they belonged to 1 of 4 higher-risk groups of individuals who received priority for COVID-19 vaccination. Two groups included clinically extremely vulnerable (CEV) people who were severely (CEV1) or moderately immunocompromised (CEV2). CEV3 individuals were not immunocompromised but had medical conditions associated with a high risk for complications from COVID-19. A fourth expanded eligibility (EXEL) group was added to allow wider access to nirmatrelvir and ritonavir for certain other higher-risk individuals who were not in a CEV group, such as those older than 70 years who were unvaccinated. Patients with COVID-19 who received nirmatrelvir and ritonavir were matched to patients in the same vulnerability group; who were of the same sex, age, and propensity score for nirmatrelvir and ritonavir treatment; and who were also infected within 1 month of the individual treated with nirmatrelvir and ritonavir. The primary outcome was death from any cause or emergency hospitalization with COVID-19 within 28 days. There were 6866 individuals included in the study, of whom 3888 (56.6%) were female and whose median (IQR) age was 70 (57-80) years. Compared with unexposed controls, treatment with nirmatrelvir and ritonavir was associated with statistically significant relative reductions in the primary outcome in the CEV1 group (560 patients; risk difference [RD], -2.5%, 95% CI, -4.8% to -0.2%) and the CEV2 group (2628 patients; RD, -1.7%; 95% CI, -2.9% to -0.5%). In the CEV3 group, the RD was -1.3%, but the findings were not statistically significant (2100 patients; 95% CI, -2.8% to 0.1%). In the EXEL group, treatment was associated with higher risk of the outcome (RD, 1.0%), but the findings were not statistically significant (1578 patients; 95% CI, -0.9% to 2.9%). In this cohort study of 6866 individuals in British Columbia, nirmatrelvir and ritonavir treatment was associated with reduced risk of COVID-19 hospitalization or death in CEV individuals, with the greatest benefit observed in severely immunocompromised individuals. No reduction in the primary outcome was observed in lower-risk individuals, including those aged 70 years or older without serious comorbidities.

Treatment of Rat Lymphedema by Propeller Lymphatic Tissue Flap Combined with Nanofibrillar Collagen Scaffolds.

The aim of our study was to evaluate a new propeller vascularized lymphatic tissue flap (pVLNT) combined with aligned nanofibrillar collagen scaffolds (CS) (BioBridge) in reducing lymphedema in the rat lymphedema model. Unilateral left hindlimb lymphedema was created in 15 female Sprague-Dawley rats following inguinal and popliteal lymph nodes (LN) resection and radiation. An inguinal pVLNT was elevated from the contralateral groin and transferred through a skin tunnel to the affected groin. Four collagen threads were attached to the flap and inserted in the hindlimb at the subcutaneous level in a fan shape. The three study groups consisted of group A (control), group B (pVLNT), and group C (pVLNT + CS). Volumetric analysis of both hindlimbs was performed using micro-computed tomography imaging before the surgery (at initial time point) and then at 1 and 4 months, postoperatively, and the relative volume difference (excess volume) was measured for each animal. Lymphatic drainage was assessed by indocyanine green (ICG) fluoroscopy for number and morphology of new collectors and the time required for ICG to move from injection point to the midline. Four months after the induction of lymphedema, an increased relative volume difference remained in group A (5.32 ± 4.74%), while there was a significant relative volume reduction in group B (-13.39 ± 8.55%) and an even greater reduction in group C (-14.56 ± 5.04%). ICG fluoroscopy proved the functional restoration of lymphatic vessels and viability of pVLNT in both B and C groups. Notably, only group C demonstrated statistically significant improvements in lymphatic pattern/morphology and in the number of lymphatic collectors as compared with the control group A. The pedicle lymphatic tissue flap combined with SC is an effective procedure for the treatment of lymphedema in rats. It can be easily translated into treatment of humans' lower and upper limb lymphedema and further clinical studies are warranted.

Diuresis inducida frente a hidratación combinada en pacientes sometidos a procedimientos cardiovasculares percutáneos: metanálisis de ensayos clínicos aleatorizados

Introduction and objectivesContrast-associated acute kidney injury (CA-AKI) is a potential complication of procedures requiring administration of iodinated contrast medium. RenalGuard, which provides real-time matching of intravenous hydration with furosemide-induced diuresis, is an alternative to standard periprocedural hydration strategies. The evidence on RenalGuard in patients undergoing percutaneous cardiovascular procedures is sparse. We used a Bayesian framework to perform a meta-analysis of RenalGuard as a CA-AKI preventive strategy. MethodsWe searched Medline, Cochrane Library and Web of Science for randomized trials of RenalGuard vs standard periprocedural hydration strategies. The primary outcome was CA-AKI. Secondary outcomes were all-cause death, cardiogenic shock, acute pulmonary edema, and renal failure requiring renal replacement therapy. A Bayesian random-effect risk ratio (RR) with corresponding 95% credibility interval (95%CrI) was calculated for each outcome. PROSPERO database number CRD42022378489. ResultsSix studies were included. RenalGuard was associated with a significant relative reduction in CA-AKI (median RR, 0.54; 95%CrI, 0.31-0.86) and acute pulmonary edema (median RR, 0.35; 95%CrI, 0.12-0.87). No significant differences were observed for the other secondary endpoints [all-cause death (RR, 0.49; 95%CrI, 0.13-1.08), cardiogenic shock (RR, 0.06; 95%CrI, 0.00-1.91), and renal replacement therapy (RR, 0.52; 95%CrI, 0.18-1.18)]. The Bayesian analysis also showed that RenalGuard had a high probability of ranking first for all the secondary outcomes. These results were consistent in multiple sensitivity analyses. ConclusionsIn patients undergoing percutaneous cardiovascular procedures, RenalGuard was associated with a reduced risk of CA-AKI and acute pulmonary edema compared with standard periprocedural hydration strategies.

Migration and Rural Sustainability: Relative Poverty Alleviation by Geographical Mobility in China

Migration is an important way for rural labourers to break the uneven distribution of resources, earn more income and seek their own sustainable development. However, existing studies have focused more on rural–urban migration and less on geographical migration. Our study further enriches the existing research on poverty reduction and provides a theoretical reference for policy decisions to promote a balanced regional development. Using data from the China Family Panel Studies (CFPS) 2012–2020, we conduct benchmark estimates through linear probability models and estimate the impact of migration on the relative poverty of the rural labourer through binary probit models. The results show that migration could significantly reduce the likelihood of a relatively poor state of rural labourers by around 4%; the greater the distance of migration, the greater the effects; and migration of rural labourers in the central region has the largest and most significant relative poverty reduction effect. Furthermore, migration could also compensate for the disadvantages of rural labourers who are unemployed, less educated and in poor health, making them less likely to be relatively poor. We also use multiple linear models to examine whether migration has a significant income-boosting effect on the rural people and found a positive result in which the effect reaches its highest in the central region at 22.95%. Therefore, it is necessary to further break down the barriers to geographical migration of rural labourers, strengthen the public transportation system and pay greater attention to Central China in order to better promote balanced development among regions.

Study protocol of a randomised, double-blind, placebo-controlled, two-arm parallel-group, multi-centre phase 3 pivotal trial to investigate the efficacy and safety of recombinant human alkaline phosphatase for treatment of patients with sepsis-associated acute kidney injury

IntroductionSepsis, the leading cause of acute kidney injury (AKI), is associated with a high morbidity and mortality. Alkaline phosphatase (ALP) is an endogenous detoxifying enzyme. A recombinant human ALP compound,...

Heat treatment effect on tocopherols, total phenolics and fatty acids in table olives (Olea europaea L.)

The olive fruits are rich source of oil, vitamins, minerals, organic acids and pigments. The fruits contain high level of bioactive compounds. The aim of this study was to examine the effect of heat treatment on tocopherols, total phenolics and antioxidant activity in green and black olives, as well as their fatty acid composition. The instrumental methods used in this experiment were high performance liquid chromatography (HPLC), gas chromatography with flame ionization detection (GC/FID) and spectrophotometric methods. The results revealed that the β+γ-tocopherols content after the heat treatment had the biggest reduction, which was 68.4% for green and 80.2% for black olives. Also, a significant loss of total phenolic content was observed after heat treatment in green and black olives by 18.6% and 18.4%, respectively, as well as antioxidant activity (decrease up to 28.1%). The most abundant fatty acids in green and black olives were oleic (C18:1), palmitic (C16:0) and linoleic acid (C18:2). The changes in fatty acids composition during the heat treatment occurred mostly at the level of polyunsaturated fatty acids, especially linolenic acid (C18:3) in black olives had the significant reduction (by 57.4%) in relation to the initial quantity.

Diuresis-matched versus standard hydration in patients undergoing percutaneous cardiovascular procedures: meta-analysis of randomized clinical trials

Introduction and objectivesContrast-associated acute kidney injury (CA-AKI) is a potential complication of procedures requiring administration of iodinated contrast medium. RenalGuard, which provides real-time matching of intravenous hydration with furosemide-induced diuresis, is an alternative to standard periprocedural hydration strategies. The evidence on RenalGuard in patients undergoing percutaneous cardiovascular procedures is sparse. We used a Bayesian framework to perform a meta-analysis of RenalGuard as a CA-AKI preventive strategy. MethodsWe searched Medline, Cochrane Library and Web of Science for randomized trials of RenalGuard vs standard periprocedural hydration strategies. The primary outcome was CA-AKI. Secondary outcomes were all-cause death, cardiogenic shock, acute pulmonary edema, and renal failure requiring renal replacement therapy. A Bayesian random-effect risk ratio (RR) with corresponding 95% credibility interval (95%CrI) was calculated for each outcome. PROSPERO database number CRD42022378489. ResultsSix studies were included. RenalGuard was associated with a significant relative reduction in CA-AKI (median RR, 0.54; 95%CrI, 0.31-0.86) and acute pulmonary edema (median RR, 0.35; 95%CrI, 0.12-0.87). No significant differences were observed for the other secondary endpoints [all-cause death (RR, 0.49; 95%CrI, 0.13-1.08), cardiogenic shock (RR, 0.06; 95%CrI, 0.00-1.91), and renal replacement therapy (RR, 0.52; 95%CrI, 0.18-1.18)]. The Bayesian analysis also showed that RenalGuard had a high probability of ranking first for all the secondary outcomes. These results were consistent in multiple sensitivity analyses. ConclusionsIn patients undergoing percutaneous cardiovascular procedures, RenalGuard was associated with a reduced risk of CA-AKI and acute pulmonary edema compared with standard periprocedural hydration strategies.

Bedside check of medication appropriateness (BED-CMA) as a risk-based tool for bedside clinical pharmacy services: A proof-of-concept study at the trauma surgery ward

BackgroundBedside clinical pharmacy prevents drug-related problems, but is not feasible in many countries due to limited resources. Hence, clinical rules using structural information in the electronic health record can help identifying potentially inappropriate prescriptions (PIPs). We aimed to develop and implement a risk-based clinical pharmacy service and evaluate its impact on prescribing at the trauma surgery ward. MethodsThe proportion of residual PIPs per day, i.e. the number of PIPs that persisted up to 24 h after pharmacist intervention divided by the number of PIPs at T0, was evaluated before and after implementation of the intervention in an interrupted time series analysis. The pre-intervention cohort received usual pharmacy services, i.e. a 0.3 FTE clinical pharmacist trainee. Fifteen clinical rules, targeting antimicrobial, anticoagulant and analgesic therapy were implemented in the post-intervention period. The pre-intervention period was compared to two post-intervention scenarios: A) clinical rule alerts reviewed by a 0.3 FTE clinical pharmacist trainee; and B) clinical rule alerts reviewed daily for approximately 1 h by a clinical pharmacist trainee. ResultsPre-intervention, a median proportion of 67% (range 0%−100%) residual PIPs per day was observed. Scenario A showed an immediate relative reduction of 14% (p = 0.72) and scenario B a significant immediate relative reduction of 85% (p = 0.0015) in residual PIPs per day. In scenario A, recommendations were provided for 19% of clinical rule alerts, of which 67% was accepted by the surgeon within 24 h. In scenario B, recommendations were given for 56% of alerts, of which 84% was accepted. ConclusionsUsing clinical rules is an effective approach to organize bedside clinical pharmacy services and improves prescribing at the trauma surgery ward. Advanced training and daily follow-up of the clinical rules are two requirements to be considered.

Safety, pharmacokinetics, and pharmacodynamics of pegozafermin in patients with non-alcoholic steatohepatitis: a randomised, double-blind, placebo-controlled, phase 1b/2a multiple-ascending-dose study

Management strategies for non-alcoholic steatohepatitis (NASH) are based predominantly on lifestyle modification, with no approved disease-modifying drugs yet available. We aimed to evaluate the safety, pharmacokinetics, and pharmacodynamics of pegozafermin (BIO89-100), a glycoPEGylated FGF21 analogue, in participants with NASH. This randomised, double-blind, placebo-controlled, phase 1b/2a multiple-ascending-dose study enrolled adults (aged 21-75 years) who had NASH with stage F1-F3 fibrosis, or non-alcoholic fatty liver disease and a high risk of NASH (referred to in this study as phenotypic NASH) due to central obesity with type 2 diabetes, or central obesity with increased alanine aminotransferase (ALT) or a Fibroscan score of 7 kPa or greater, across 12 specialist centres and clinics in the USA. Patients were centrally randomised by use of an interactive web response system to receive subcutaneously administered pegozafermin (3, 9, 18, or 27 mg once weekly; 18 or 36 mg once every 2 weeks) or placebo for 12 weeks. The primary endpoints were the safety, tolerability, and pharmacokinetics of pegozafermin. This trial is registered with ClinicalTrials.gov (NCT04048135). Between July 29, 2019, and Aug 3, 2020, 275 participants were screened and 81 (15 [19%] with biopsy-confirmed NASH) were randomly assigned: 62 to pegozafermin (six to 3 mg once weekly, 12 to 9 mg once weekly, 11 to 18 mg once weekly, ten to 27 mg once weekly, 14 to 18 mg once every 2 weeks, and nine to 36 mg once every 2 weeks) and 19 to placebo; 63 received pegozafermin and 18 received placebo, as one participant in the placebo group inadvertently received 3 mg pegozafermin once weekly. Adverse events were reported in eight (44%) of 18 participants in the pooled placebo group, six (86%) of seven in the 3 mg once weekly pegozafermin group, four (33%) of 12 in the 9 mg once weekly group, seven (64%) of 11 in the 18 mg once weekly group, seven (70%) of ten in the 27 mg once weekly group, eight (57%) of 14 in the 18 mg once every 2 weeks group, and eight (89%) of nine in the 36 mg once every 2 weeks group. The most common treatment-related adverse event was mild increased appetite (in ten [16%] of 63 participants in the pooled pegozafermin group vs none of 18 in the pooled placebo group), which was not associated with bodyweight gain. Two patients discontinued treatment due to an adverse event (one each in the 27 mg once weekly and 18 mg once every 2 weeks groups). No treatment-related serious adverse events or deaths occurred. Dose-proportional pharmacokinetics were observed. Anti-drug antibodies were detected in 41 (65%) of 63 participants treated with pegozafermin. By week 13, pegozafermin significantly reduced the least squares mean (LSM) absolute differences in hepatic fat fraction versus pooled placebo (-8·9% [95% CI -14·8 to -3·1; p=0·0032] for 3 mg once weekly, -11·5% [-16·1 to -6·9; p<0·0001] for 9 mg once weekly, -8·9% [-13·7 to -4·2; p=0·0004] for 18 mg once weekly, -14·9% [-20·1 to -9·7; p<0·0001] for 27 mg once weekly, -10·4% [-14·7 to -6·1; p<0·0001] for 18 mg once every 2 weeks, and -11·1% [-16·2 to -6·0; p<0·0001] for 36 mg once every 2 weeks). At week 13, significant LSM relative reductions versus pooled placebo in ALT were observed for pegozafermin 9 mg once weekly, 18 mg once weekly, 27 mg once weekly, and 36 mg once every 2 weeks. At week 13, significant LSM relative reductions versus pooled placebo in aspartate aminotransferase were observed for pegozafermin 3 mg once weekly, 27 mg once weekly, and 36 mg once every 2 weeks. Significant improvements were also observed with pegozafermin treatment for triglycerides (9 mg once weekly, 27 mg once weekly, and 18 mg once every 2 weeks), LDL-C (9 mg once weekly and 27 mg once weekly), HDL-C (3 mg once weekly and 18 mg once every 2 weeks), non-HDL-C (9 mg once weekly and 27 mg once weekly), adiponectin (all doses except for 36 mg once every 2 weeks), PRO-C3 (27 mg once weekly), and bodyweight (27 mg once weekly). Changes in insulin resistance and HbA1c were not significant. Pegozafermin was generally well tolerated and associated with clinically meaningful reductions in liver fat, measures of liver function, and circulating lipids. Further evaluation of pegozafermin in individuals with NASH is warranted. 89bio.

Effect of Abandoned Housing Interventions on Gun Violence, Perceptions of Safety, and Substance Use in Black Neighborhoods

Structural racism has resulted in long-standing disinvestment and dilapidated environmental conditions in Black neighborhoods. Abandoned houses signal neglect and foster stress and fear for residents, weakening social ties and potentially contributing to poor health and safety. To determine whether abandoned house remediation reduces gun violence and substance-related outcomes and increases perceptions of safety and use of outdoor space. This cluster randomized trial was conducted from January 2017 to August 2020, with interventions occurring between August 2018 and March 2019. The study included abandoned houses across Philadelphia, Pennsylvania, and surveys completed by participants living nearby preintervention and postintervention. Data analysis was performed from March 2021 to September 2022. The study consisted of 3 arms: (1) full remediation (installing working windows and doors, cleaning trash, weeding); (2) trash cleanup and weeding only; and (3) a no-intervention control. Difference-in-differences mixed-effects regression models were used to estimate the effect of the interventions on multiple primary outcomes: gun violence (weapons violations, gun assaults, and shootings), illegal substance trafficking and use, public drunkenness, and perceptions of safety and time outside for nearby residents. A master list of 3265 abandoned houses was randomly sorted. From the top of this randomly sorted list, a total of 63 clusters containing 258 abandoned houses were formed and then randomly allocated to 3 study arms. Of the 301 participants interviewed during the preintervention period, 172 (57.1%) were interviewed during the postintervention period and were included in this analysis; participants were predominantly Black, and most were employed. Study neighborhoods were predominantly Black with high percentages of low-income households. Gun violence outcomes increased in all study arms, but increased the least in the full remediation arm. The full housing remediation arm, compared with the control condition, showed reduced weapons violations by -8.43% (95% CI, -14.68% to -1.19%), reduced gun assaults by -13.12% (95% CI, -21.32% to -3.01%), and reduced shootings by a nonsignificant -6.96% (95% CI, -15.32% to 3.03%). The trash cleanup arm was not associated with a significant differential change in any gun violence outcome. Instances of illegal substance trafficking and use and public drunkenness outcomes were not significantly affected by the housing remediation or trash cleanup treatment. Perceptions of neighborhood safety and time spent outside were unaffected by the intervention. The study arms did differ in a baseline characteristic and some preintervention trends, which raises questions regarding other potential nonmeasured differences between study arms that could have influenced estimates. No evidence of displacement of gun violence outcomes was found. In this cluster randomized controlled trial among low-income, predominantly Black neighborhoods, inexpensive, straightforward abandoned housing remediation was directly linked to significant relative reductions in weapons violations and gun assaults, and suggestive reductions in shootings. isrctn.org Identifier: ISRCTN14973997.

Impact of Mepolizumab on Exacerbations in the US Medicare Population

Asthma is a common chronic respiratory disorder associated with significant disease and economic burden. Mepolizumab is an anti-IL-5 mAb approved for use as an add-on treatment in patients with severe eosinophilic asthma. To assess the impact of mepolizumab initiation on asthma exacerbation frequency, oral corticosteroid (OCS) use, and asthma exacerbation-related costs in a US Medicare population. This was a retrospective cohort study of mepolizumab claims from patients with asthma in the Centers for Medicare and Medicaid Services Medicare database carried out between January 2016 and December 2018. The index date (first claim for mepolizumab) was required to occur between January and December 2017. The baseline and follow-up periods were the 12 months before and 12 months after the index, respectively. Outcomes included changes in the proportion of patients experiencing exacerbations (primary), OCS use (secondary), and asthma exacerbation-related costs during the baseline and follow-up periods. The study identified 1,278 patients (mean age, 67.9 years; 65% female) with one or more prescription or administration claim for mepolizumab who were eligible for study inclusion. There was a significant relative reduction in the proportion of patients with an asthma exacerbation (27%; P < .0001) in the follow-up versus baseline period. Similarly, a lower proportion of patients received OCS for asthma (16% relative reduction; P < .0001), fewer patients were chronic OCS users (5 mg/day or more; 48% relative reduction; P < .0001), and there was a significant decrease in asthma exacerbation-related costs (total reduction, $888; P= .0002) during the follow-up versus the baseline period. Mepolizumab reduced exacerbations, OCS use, and exacerbation-related healthcare costs in a US Medicare population, confirming its benefits in this specific population with severe asthma.

A novel technology for disinfecting surfaces infested with Candida auris: the UVC chip

Abstract Background The fungal pathogen Candida Auris is increasingly associated with multidrug-resistant infections that are highly expensive for the Health Care System. The spreading of this pathogen can occur, among others, through contact with infected surfaces or medical instruments. This study evaluated the efficacy of a novel UVC chip, novel alternative to UVC LEDs and lamps, in inactivating Candida auris strain. Methods This experimental study was carried out between July and September 2020 at the University of Siena. Candida auris (ATCC 12372) at two known concentrations (1.5X107 and 1.5x106 CFU/ml) at a fixed distance (7,5 cm) from the chip (5.1mW radiant power) was tested, in triplicates, with three exposure times (5, 10 and 15 minutes). Potato Dextrose Agar (PDA) plates without the plate lid and containing Candida auris were exposed to UVC light. Subsequently, the plates were incubated at 36 °C for 48 h. Log reduction between treated and positive control (not exposed to UVC light) samples was calculated. Results At 15 minutes, we had the highest inactivation result, mean 4.43 log10, starting from a 1.5x106 CFU/mL concentration. At a higher concentration, 1.5X107 CFU/mL, the reduction had a mean of 3.51 log10. Conclusions The results of the experiments showed a significant microbial reduction in relation to the exposure time. The highest level of reduction was reached after 15 minutes of exposure. UVC chip had a relevant biocidal effect on Candida auris and may represent a valuable tool in the prevention of infections caused by this pathogen, which is becoming increasingly prevalent and persistent globally. Key messages • The use of UVC Chip decreases surface contamination. • New technology against healthcare-associated infections.

Assessment of efficacy and safety of volanesorsen for treatment of metabolic complications in patients with familial partial lipodystrophy: Results of the BROADEN study: Volanesorsen in FPLD; The BROADEN Study

BackgroundVolanesorsen, an antisense oligonucleotide, is designed to inhibit hepatic apolipoprotein C-III synthesis and reduce plasma apolipoprotein C-III and triglyceride concentrations. ObjectiveThe present study assessed efficacy and safety of volanesorsen in patients with familial partial lipodystrophy (FPLD) and concomitant hypertriglyceridemia and diabetes. MethodsBROADEN was a randomized, placebo-controlled, phase 2/3, 52-week study with open-label extension and post-treatment follow-up periods. Patients received weekly subcutaneous volanesorsen 300 mg or placebo. The primary endpoint was percent change from baseline in fasting triglycerides at 3 months. Secondary endpoints included relative percent change in hepatic fat fraction (HFF), visceral adiposity, and glycated hemoglobin levels. ResultsForty patients (11 men, 29 women) were enrolled, majority of whom were aged <65 years (mean, 47 years) and White. Least squares mean (LSM) percent change in triglycerides from baseline to 3 months was −88% (95% CI, −134 to −43) in the volanesorsen group versus –22% (95% CI, −61 to 18) in the placebo group, with a difference in LSM of −67% (95% CI, –104 to –30; P=0.0009). Volanesorsen induced a significant LSM relative reduction in HFF of 53% at month 12 versus placebo (observed mean [SD]: 9.7 [7.65] vs. 18.0 [8.89]; P=0.0039). No statistically significant changes were noted in body volume measurements (fat, liver, spleen, visceral/subcutaneous adipose tissue) or glycated hemoglobin. Serious adverse events in patients assigned to volanesorsen included 1 case each of sarcoidosis, anaphylactic reaction, and systemic inflammatory response syndrome. ConclusionIn BROADEN, volanesorsen significantly reduced serum triglyceride levels and hepatic steatosis in patients with FPLD.