Pharmacological Prevention Research Articles

Study of special adaptation mechanisms and morphological regularities of broiler chickens against the background of pharmacological prevention combined pre-slaughter, heat and transport stress in industrial poultry farming

The study was conducted to investigate the adaptation mechanisms of broiler chickens against the background of pharmacological prevention which includes combined pre-slaughter, heat and transport stress in industrial poultry farming. In summer, from clinically healthy Ross 308 chickens three groups of 95648 ± 931 chickens were formed on the principle of analogy. The first group was a control group and it was fed with complete feed. The second group was the first experimental group and it was fed with complete feed which included the anti-stress supplementary feed PIK-antistress at a dose of 1270 g per 1 ton of feed 5 days before slaughter. The third group was the second experimental group and it was fed with the anti-stress supplementary feed PIK-antistress which included L-carnitine at a dose of 1700 g per 1 ton of feed 5 days before slaughter. 38 days later broiler chickens were slaughtered. 3 main periods were commonly studied: the period after fasting, the period after transporting the chickens to the slaughter site and the period just before slaughter. Adaptation processes were developing during the slaughter of broiler chickens in summer. The processes are characterized by increasing the level of the ratio of heterophils to blood lymphocytes on average 2.8 times. The use of the complex food additive PIK-antistress and PIK-antistress in combination with L-carnitine can reduce the activity of stress-implementing mechanisms and increase the survivability of chickens by 3.20 and 4.58 %, respectively and the European productivity index by 32 and 45 units. All the data obtained are consistent with the morphometric studies of the adrenal glands while against the background of the use of anti-stress prophylaxis an increase of core area was noted by 43.0 % and 36.0 % and respectively against the background of a decrease of the area of the cytoplasm of the cortical cords by 11.2 % and 22.8 %, respectively, which indicates stabilization of metabolic processes in the cell.

Prevention and Management of Restenosis After Coronary Interventional Therapy

Percutaneous coronary intervention (PCI) is one of the key methods for treating coronary heart disease, yet post-procedural restenosis remains a significant clinical challenge. Restenosis refers to the re-narrowing of the coronary artery after PCI due to factors such as neointimal hyperplasia and smooth muscle cell proliferation, which adversely affects blood flow restoration and patient prognosis. To address this issue, this study systematically explores strategies for the prevention and management of restenosis. Effective preventive measures are discussed in terms of pharmacological prevention, stent selection, optimization of procedural techniques, and lifestyle interventions. Additionally, the article analyzes pharmacological treatment options and re-intervention strategies for patients experiencing restenosis. The findings indicate that personalized treatment plans, optimized stent selection, rigorous postoperative management, and long-term monitoring are key to reducing the incidence of restenosis. Future research should further investigate the application of genetic testing and smart healthcare technologies in the management of restenosis.

Pharmacological Prevention of Postoperative Delirium in Adults: A Review of Recent Literature.

Postoperative delirium (POD) is a common complication that has important implications for surgical patients, often leading to both short- and long-term cognitive deficits, worse outcomes, and increased healthcare costs. Given these implications, there may be a benefit in reducing the incidence of POD. Pharmacologic interventions may have the potential to reduce the risk of a patient developing POD. Recently studied therapies include dexmedetomidine, propofol, haloperidol, ketamine, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, acetaminophen, melatonin/ramelteon, corticosteroids, midazolam, physostigmine, and neostigmine. In addition, the implementation of regional anesthesia and reduction of overall anesthetic depth have been examined. Of these therapies, dexmedetomidine has been studied the most and has the most supporting evidence for prevention of POD, but current studies lack clarity on optimal dosing and timing of dexmedetomidine administration. Acetaminophen, corticosteroids, and melatonin/ramelteon are other plausible medications that have potential for reducing POD incidence, but they all require further investigation. Reduction of anesthetic depth and regional anesthetics are options for anesthetic management that show promise but still lack enough supporting evidence in recent literature to receive a strong recommendation. Future research should focus on identifying optimal strategies for the implementation of the pharmacological options listed, including doses and timing of administration. Attention should be given to dexmedetomidine given its promise demonstrated by recent literature.

Development and validation of an in vitro model to study thrombin generation on the surface of catheters in platelet-poor and platelet-rich plasma

IntroductionCoagulation activation on medical devices remains a significant problem as it can lead to dramatic thromboembolic complications. Understanding its poorly described mechanisms and finding optimal pharmacological prevention means is crucial to improve patient safety. MethodsWe developed an in vitro model to study thrombin generation (TG) initiated by the contact of plasma with the surface of catheters. Interventional cardiology catheters were cut into segments and inserted in the bottom of multi-well plates; TG was then measured with the calibrated automated thrombogram (CAT). Model performance (analytical, intra- and inter-individual variability) was investigated and compared with activation of thrombin generation by tissue factor (TF) or contact pathway activator (ellagic acid), in the presence (PRP) and absence (PPP) of platelets. Model response to unfractionated heparin (UFH) was also assessed. ResultsTG was greater when measured in presence of catheter segments, compared to conditions without activators. The analytical variability of the model was good (CV ≤ 5 %), both with PPP and PRP. Intra-individual variability was between 15 and 30 % with PPP and between 10 and 15 % with PRP. Inter-individual variability was between 15 and 30 % with both kinds of plasma samples. The analytical performance of the catheter-initiated TG model was equivalent to that observed when TG was initiated with TF or ellagic acid. Catheter-initiated TG was measurable until 0.1 IU/mL UFH with PPP and until 1.0 IU/mL UFH with PRP, highlighting the crucial requirement of platelets. ConclusionOur model is suitable for studying TG initiated with catheters. Inhibition of TG by UFH is overestimated in the absence of platelets.

Early High-Dose Erythropoietin and Cognitive Functions of School-Aged Children Born Very Preterm

Children born very preterm are at risk for long-term neurodevelopmental sequelae. Prophylactic high-dose recombinant human erythropoietin (rhEpo) shortly after birth has not been shown to improve cognitive, motor, and behavioral development at 2 and 5 years. To investigate whether early high-dose rhEpo is associated with better executive functions and processing speed-late-maturing cognitive functions-in school-aged children born very preterm. This single-center cohort study was a prospective, observational follow-up study of a multicenter neonatal clinical trial; 365 children born very preterm (mean gestational age, 29.3 weeks [range, 26.0-31.9 weeks]) who had been enrolled in the Swiss EPO Neuroprotection Trial at birth between 2005 and 2012, and who were included in the primary outcome analyses at 2 years, were eligible to be recruited for the EpoKids study between 2017 and 2021 when they were at school age. Term-born children were additionally recruited and included in a control group. Data were analyzed between May and September 2022. Administration of rhEpo (3000 IU/kg) or placebo (saline, 0.9%) intravenously 3 times within the first 2 days of life as part of the Swiss EPO Neuroprotection Trial. A comprehensive neuropsychological test battery assessed executive functions and processing speed, and parents reported on their child's executive functions in everyday life to test the hypothesis that early high-dose rhEpo administration is associated with better cognitive outcomes at school age. In the EpoKids study, 214 children born very preterm (58.6% of 365 children in eligible cohort) were assessed at a mean age of 10.4 years (range, 6.9-13.4 years); 117 (54.7%) were boys. There was no evidence that the 117 children who had received rhEpo differed from the 97 children who had received placebo in any of the 15 executive function and processing speed tests, nor in parent-rated executive functions (estimates ranged from -0.138 to 0.084, all 95% CIs included 0). Irrespective of rhEpo or placebo allocation, children born very preterm scored lower on 11 of 15 executive function and processing speed tests than term-born peers (estimates ranged from 0.112 to 0.255, 95% CIs did not include 0). This study found no evidence for a positive association between prophylactic early high-dose rhEpo administration and long-term neurodevelopmental outcomes after very preterm birth. These results suggest that a comprehensive approach, including pharmacological and nonpharmacological prevention and intervention strategies, is needed to support these children's neurodevelopmental outcome.

Routine beta-blocker therapy after acute coronary syndromes: The end of an era?

Beta-blocker therapy, a treatment burdened by side effects including fatigue, erectile dysfunction and depression, was shown to reduce mortality and cardiovascular events after acute coronary syndromes (ACS) in the pre-coronary reperfusion era. Potential mechanisms include protection from ventricular arrhythmias, increased ischaemia threshold and prevention of left ventricular (LV) adverse remodelling. With the advent of early mechanical reperfusion and contemporary pharmacologic secondary prevention, the benefit of beta-blockers after ACS in the absence of LV dysfunction has been challenged. The present narrative review discusses the contemporary evidence based on searching the PubMed database and references in identified articles. Recently, the REDUCE-AMI trial-the first adequately powered randomized trial in the reperfusion era to test beta-blocker therapy after myocardial infarction with preserved left ventricular ejection fraction (LVEF)-showed no benefit on the composite of all-cause death or myocardial infarction over a median 3.5-year follow-up. While the benefit of beta-blockers in patients with reduced LVEF remains undisputed, their value in post-ACS patients with mildly reduced systolic function (LVEF 41%-49%) has not been studied in contemporary randomized trials; in this setting, observational studies have suggested a reduction in cardiovascular events with these agents. The adequate duration of beta-blocker therapy remains unknown, but observational data suggests that any mortality benefit may be lost beyond 1-12 months after ACS in patients with LVEF >40%. We believe that there is sufficient evidence to abandon routine beta-blocker prescription in post-ACS patients with preserved LV systolic function.

Pediatric Chronic Intestinal Failure: Something Moving?

Pediatric chronic intestinal failure (PIF) is a rare and heterogeneous condition characterized by the inability of the patient's intestine to adequately absorb the required fluids and/or nutrients for growth and homeostasis. As a result, patients will become dependent on home parenteral nutrition (HPN). A MEDLINE search was performed in May 2024 with keywords "intestinal failure", "parenteral nutrition" and "pediatric". Different underlying conditions which may result in PIF include short bowel syndrome, intestinal neuromuscular motility disorders and congenital enteropathies. Most common complications associated with HPN are catheter-related bloodstream infections, catheter-related thrombosis, intestinal failure-associated liver disease, small intestinal bacterial overgrowth, metabolic bone disease and renal impairment. Treatment for children with PIF has markedly improved with a great reduction in morbidity and mortality. Centralization of care in specialist centers and international collaboration between centers is paramount to further improve care for this vulnerable patient group. A recently promising medical therapy has become available for children with short bowel syndrome which includes glucagon-like peptide 2, a naturally occurring hormone which is known to delay gastric emptying and induce epithelial proliferation. Despite advances in curative and supportive treatment, further research is necessary to improve nutritional, pharmacological and surgical care and prevention of complications associated with parenteral nutrition use.

First year report of the IMSS Multicenter Hip Fracture Registry.

Hip fracture registries provide a means to compare care and establish improvement processes. The Mexican population has aged; thus, there is a greater risk of osteoporosis, and its main consequence is hip fracture due to fragility. Its incidence is high, and it is expected to increase due to aging in our country. International guidelines provide standardized recommendations for the care of people with hip fractures, while hip fracture registries provide a means to compare care with local, national, and international clinical standards and establish improvement processes. Describe the standards of care for hip fractures in various hospital centers of the Mexican Social Security Institute. This was an observational, multicenter, longitudinal, and descriptive study. It included 24 hospital centers in Mexico. Informed consent was obtained. Data were recorded during the hospital stay, epidemiological data, and management, and follow-up was carried out 30 and 120days after discharge. The information was analyzed using SPSS version 22.0. A total of 1042 subjects aged 79.5 ± 7.6years participated, mostly women (n = 739; 70.9%) from the community (n = 1,021; 98.0%) and with functional independence (Barthel 80.9 ± 22.2). The transfer time to the emergency room was 4.6 ± 14.6days. Pertrochanteric hip fracture was the most common (n = 570, 54.7%). The most common type of procedure was dynamic hip screw (DHS) (n = 399; 40.1%). Documented thromboprophylaxis was granted in 91.5% (n = 953) and antibiotic prophylaxis in 53.0% (n = 552) of the patients. The goal of 36h for the surgical procedure was achieved in 7.6% of the subjects (n = 76), with the most frequent cause being a delay in scheduling (n = 673, 67.6%). The mean time from emergency room to surgery was 7.8 ± 7.0days. The acute mortality rate was 4.3%. Secondary pharmacologic prevention upon discharge occurred in 64.2% of patients. At 30days, 370 subjects (37.1%) were lost to follow-up, with a mortality of 3%, while at 120days, 166 subjects (27.8%) were lost, with a mortality of 2.8%. In the hospital centers where the study was carried out, there are still no standards of care for hip fractures, which makes it necessary to rethink the care for this population group through a strategy focused on meeting those standards.

Osteogenic-Like Microenvironment of Renal Interstitium Induced by Osteomodulin Contributes to Randall's Plaque Formation.

Calcium oxalate (CaOx) kidney stones are common and recurrent, lacking pharmacological prevention. Randall's plaques (RPs), calcium deposits in renal papillae, serve as niduses for some CaOx stones. This study exploresthe role of osteogenic-like cells in RP formation resembling ossification. CaP crystals deposit around renal tubules, interstitium, and blood vessels in RP tissues. Human renal interstitial fibroblasts (hRIFs) exhibit the highest osteogenic-like differentiation potential compared to chloride voltage-gated channel Ka positive tubular epithelial cells, aquaporin 2 positive collecting duct cells, and vascular endothelial cells, echoing the upregulated osteogenic markers primarily in hRIFs within RP tissues. Utilizing RNA-seq, osteomodulin (OMD) is found to be upregulated in hRIFs within RP tissues and hRIFs following osteogenic induction. Furthermore, OMD colocalizes with CaP crystals and calcium vesicles within RP tissues. OMD can enhance osteogenic-like differentiation of hRIFs in vitro and in vivo. Additionally, crystal deposits are attenuated in mice with Omd deletion in renal interstitial fibroblasts following CaOx nephrocalcinosis induction. Mechanically, a positive feedback loop of OMD/BMP2/BMPR1A/RUNX2/OMD drives hRIFs to adopt osteogenic-like fates, by which OMD induces osteogenic-like microenvironment of renal interstitium to participate in RP formation. Weidentify OMD upregulation as a pathological feature of RP, paving the way for preventing CaOx stones.

The clinical value of nonpharmacological interventions for preventing postoperative delirium: a narrative review.

Postoperative delirium (POD) is a prevalent perioperative complication among elderly individuals and is a cause of significant detrimental consequences for both individuals and society. Pharmacological and nonpharmacological prevention methods/therapies have been proposed to mitigate the risk of POD. Nevertheless, the efficacy of pharmacological interventions is controversial, and some of them cause side effects. Therefore, numerous studies have explored the effectiveness of nonpharmacological interventions in mitigating POD and have recommended the use of nonpharmacological multicomponent interventions by an interdisciplinary team as primary interventions. However, dedicated units aimed at promoting comanagement are rare and are only present in academic hospitals. Therefore, there is increasing interest in nonpharmacological mono-component interventions for preventing POD, which offer advantages such as easy application, cost-effectiveness, patient acceptability and noninvasiveness. These interventions are divided into cognitive training and noncognitive interventions. The former is aimed at increasing cognitive reserve, thus decreasing the incidence rate of POD. Noncognitive interventions, including sensory stimuli (music therapy, odor enrichment), improving sleep disturbances, physical activity, acupuncture and transcranial magnetic/direct current stimulation, are aimed at decreasing the risk factors for POD. This review provides a comprehensive overview of recently reported nonpharmacological mono-component interventions for preventing POD and briefly describes their clinical value.

Animal Models of Intracranial Aneurysms: History, Advances, and Future Perspectives.

Intracranial aneurysms (IA) are a disease process with potentially devastating outcomes, particularly when rupture occurs leading to subarachnoid hemorrhage. While some candidates exist, there is currently no established pharmacological prevention of growth and rupture. The development of prophylactic treatments is a critical area of research, and preclinical models using animals play a pivotal role. These models, which utilize various species and induction methods, each possess unique characteristics that can be leveraged depending on the specific aim of the study. A comprehensive understanding of these models, including their historical development, is crucial for appreciating the advantages and limitations of aneurysm research in animal models.We summarize the significant roles of animal models in IA research, with a particular focus on rats, mice, and large animals. We discuss the pros and cons of each model, providing insights into their unique characteristics and contributions to our understanding of IA. These models have been instrumental in elucidating the pathophysiology of IA and in the development of potential therapeutic strategies.A deep understanding of these models is essential for advancing research on preventive treatments for IA. By leveraging the unique strengths of each model and acknowledging their limitations, researchers can conduct more effective and targeted studies. This, in turn, can accelerate the development of novel therapeutic strategies, bringing us closer to the goal of establishing an effective prophylactic treatment for IA. This review aims to provide a comprehensive view of the current state of animal models in IA research.

Essential New Complexity-Based Themes for Patient-Centered Diagnosis and Treatment of Dementia and Predementia in Older People: Multimorbidity and Multilevel Phenomenology.

Dementia is a highly prevalent condition with devastating clinical and socioeconomic sequela. It is expected to triple in prevalence by 2050. No treatment is currently known to be effective. Symptomatic late-onset dementia and predementia (SLODP) affects 95% of patients with the syndrome. In contrast to trials of pharmacological prevention, no treatment is suggested to remediate or cure these symptomatic patients. SLODP but not young onset dementia is intensely associated with multimorbidity (MUM), including brain-perturbating conditions (BPCs). Recent studies showed that MUM/BPCs have a major role in the pathogenesis of SLODP. Fortunately, most MUM/BPCs are medically treatable, and thus, their treatment may modify and improve SLODP, relieving suffering and reducing its clinical and socioeconomic threats. Regrettably, the complex system features of SLODP impede the diagnosis and treatment of the potentially remediable conditions (PRCs) associated with them, mainly due to failure of pattern recognition and a flawed diagnostic workup. We suggest incorporating two SLODP-specific conceptual themes into the diagnostic workup: MUM/BPC and multilevel phenomenological themes. By doing so, we were able to improve the diagnostic accuracy of SLODP components and optimize detecting and favorably treating PRCs. These revolutionary concepts and their implications for remediability and other parameters are discussed in the paper.

Pharmacological and non-pharmacological prevention and management of delirium in critically ill and palliative patients in the inpatient setting: a review.

This review explores delirium in critically ill patients in the inpatient setting, focusing on its prevention and management. It evaluates the efficacy of both current pharmacological and non-pharmacological interventions, aiming to provide a comprehensive overview. A systematic literature search was conducted to identify relevant studies investigating the prevention and management of delirium resulting in a final sample of 26 articles for analysis. Of the 26 articles analyzed for this review (N = 8,831 participants) of controlled trials, 16 studies examined the prevention of delirium, 9 explored the treatment of delirium, and 1 investigated both prevention and treatment of delirium. Among the reviewed studies, there is evidence that non-pharmacologic methods are effective in the prevention of delirium. Evidence regarding pharmacological interventions for delirium prevention is varied and inconclusive, with some indication that atypical antipsychotics like aripiprazole and quetiapine may reduce the incidence of delirium. Regarding the treatment of delirium, there is limited evidence supporting the use of pharmacological agents. Additional double-blinded, randomized, placebo-controlled clinical trials are needed to investigate the efficacy of pharmacologic agents for diverse hospitalized populations.

Intermittend pneumatic venous thrombembolism (VTE) prophylaxis during neurosurgical procedures

BackgroundThe management of perioperative venous thrombembolism (VTE) prophylaxis is highly variable between neurosurgical departments and general guidelines are missing. The main issue in debate are the dose and initiation time of pharmacologic VTE prevention to balance the risk of VTE-based morbidity and potentially life-threatening bleeding. Mechanical VTE prophylaxis with intermittend pneumatic compression (IPC), however, is established in only a few neurosurgical hospitals, and its efficacy has not yet been demonstrated. The objective of the present study was to analyze the risk of VTE before and after the implementation of IPC devices during elective neurosurgical procedures.MethodsAll elective surgeries performed at our neurosurgical department between 01/2018–08/2022 were investigated regarding the occurrence of VTE. The VTE risk and associated mortality were compared between groups: (1) only chemoprophylaxis (CHEMO; surgeries 01/2018–04/2020) and (2) IPC and chemoprophylaxis (IPC; surgeries 04/2020–08/2022). Furthermore, general patient and disease characteristics as well as duration of hospitalization were evaluated and compared to the VTE risk.ResultsVTE occurred after 38 elective procedures among > 12.000 surgeries. The number of VTEs significantly differed between groups with an incidence of 31/6663 (0.47%) in the CHEMO group and 7/6688 (0.1%) events in the IPC group. In both groups, patients with malignant brain tumors represented the largest proportion of patients, while VTEs in benign tumors occurred only in the CHEMO group.ConclusionThe use of combined mechanical and pharmacologic VTE prophylaxis can significantly reduce the risk of postoperative thromboembolism after neurosurgical procedures and, therefore, reduce mortality and morbidity.

Recommendations for prescribing pharmacologic prevention during emergency department treatment of epileptic seizures

Recommendations for prescribing pharmacologic prevention during emergency department treatment of epileptic seizures

Patient knowledge about risk factors, achievement of target values, and guideline-adherent secondary prevention therapies 12 months after acute myocardial infarction.

The prospective GULLIVE-R study aimed to evaluate adherence to guideline-recommended secondary prevention, physicians' and patients' estimation of cardiac risk, and patients' knowledge about target values of risk factors after acute myocardial infarction (AMI). We performed a prospective study enrolling patients 9-12 months after AMI. Guideline-recommended secondary prevention therapies and physicians as well as patients' estimation about their risk and patients' knowledge about target values were prospectively collected. Between July 2019 and June 2021, a total of 2509 outpatients were enrolled in 150 German centres 10 months after AMI. The mean age was 66 years, 26.4% were women, 45.3% had ST elevation myocardial infarction, 54.7% had non-ST elevation myocardial infarction, and 93.6% had revascularization (84.0% percutaneous coronary intervention, 7.4% coronary artery bypass graft, 1.8% both). Guideline-recommended secondary drug therapies were prescribed in over 80% of patients, while only about 50% received all five recommended drugs (aspirin, P2Y12 inhibitors, statins, beta-blockers, renin-angiotensin-aldosterone system inhibitors), and regular exercise was performed by only one-third. About 90% of patients felt well informed about secondary prevention, but the correct target value for blood pressure was known in only 37.9% and for LDL-cholesterol in only 8.2%. Both physicians and patients underestimated the objective risk of future AMIs as determined by the thormbolysis in myocardial infarction (TIMI) risk score for secondary prevention. There is still room for improvement in patient education and implementation of guideline-recommended non-pharmacological and pharmacological secondary prevention therapies in patients in the chronic phase after AMI.

QIP on VTE prevention in stroke patients within 24 hours

This abstract focuses on the initial problem of suboptimal venous thromboembolism(VTE) prevention among stroke patients in our hospital’sstroke unit. The relevance to acute medicine and the subsequent analysis,intervention, and results are discussed. Lessons learned, additionalchanges, and the authors’ plans for sustainable practice change are alsoaddressed.The QIP revealed inadequate adherence to VTE prevention guidelinesin stroke patients, posing a significant risk. The relevance to acute medicinelies in the vulnerability of stroke patients to VTE due to immobilityand altered coagulation profiles.The analysis found that only 60% of eligible stroke patients receivedappropriate VTE prophylaxis, necessitating an intervention to improveadherence. A multidisciplinary team developed a protocol for risk assessment,pharmacological prevention, early mobilisation, and patienteducation.The intervention significantly improved adherence to VTE preventionmeasures, with 85% of eligible stroke patients receiving appropriate prophylaxis.Lessons learned emphasised collaboration, standardised protocols,and ongoing education. Regular audits and feedback facilitatedsustained improvements.Further changes were made to enhance sustainability, including integratingthe protocol into electronic medical records, educating new staff,and appointing a VTE prevention champion.In conclusion, this study successfully implemented an intervention forVTE prevention in stroke patients, resulting in improved adherence toguidelines and reduced VTE events. The findings underscore the importanceof proactive measures and interdisciplinary collaboration in acutemedicine, ultimately enhancing patient outcomes and safety.

Transgender people in clinical trials of drugs and biologics: An analysis of ClinicalTrials.gov from 2007 to 2023.

Transgender people have unmet health needs related to chronic conditions such as dementia, osteoporosis and hypertension. Community-driven advocacy increased transgender representation in phase III trials for pharmacological prevention of HIV, but the extent to which drug trials for other conditions have included transgender people is unknown. We investigated the extent to which trials of drugs and biologics represented transgender people across therapeutic areas on ClinicalTrials.gov. Cross-sectional analysis of trials of drugs and biologics registered on ClinicalTrials.gov from 2007-2023. We included efficacy and effectiveness trials (phase II-IV) with transgender-related terms (e.g. 'transgend*'). We labelled trials as Inclusive or Exclusive of transgender people using the trial eligibility criteria. We compared trials (therapeutic area, trial design, enrolment), summarized trials registered from 2008 onward and characterized participant enrolment for Inclusive trials with primary trial publications. We summarized continuous data using median (range), categorical data using frequencies and percentages and compared trial characteristics using Fisher's exact test. Ninety-seven trials represented transgender people. Characteristics were similar between 85 Inclusive and 12 Exclusive trials. Among Inclusive trials, 58% focused on infectious diseases (e.g. treatment or prevention of HIV and COVID-19), 15% on mental health (e.g. post-traumatic stress disorder, substance use-related disorders), and the remainder focused on endocrine (9%), pain (5%), digestive system disorders (1%) and neoplasms (1%). Twenty (of 25) trials reported enrolment of transgender participants in primary trial publications or reported results. Transgender-inclusive trials have increased since 2008. Most trials focused on infectious diseases and mental health. Investigators should increase opportunities to include of transgender people in trials of drugs and biologics for chronic diseases.

Pharmacological prevention of bone loss and fractures following solid organ transplantations: Protocol for a systematic review and network meta-analysis.

Solid organ transplant (SOT) recipients can experience bone loss caused by underlying conditions and the use of immunosuppressants. As a result, SOT recipients are at risk for decreased bone mineral density (BMD) and increased fracture incidences. We propose a network meta-analysis (NMA) that incorporates all available randomized control trial (RCT) data to provide the most comprehensive ranking of anti-osteoporotic interventions according to their ability to decrease fracture incidences and increase BMD in SOT recipients. We will search MEDLINE, EMBASE, Web of Science, CINAHL, CENTRAL and CNKI for relevant RCTs that enrolled adult SOT recipients, assessed anti-osteoporotic therapies, and reported relevant outcomes. Title and full-text screening as well as data extraction will be performed in-duplicate. We will report changes in BMD as weighted or standardized mean differences, and fracture incidences as risk ratios. SUCRA scores will be used to provide rankings of interventions, and quality of evidence will be examined using RoB2 and CINeMA. To our knowledge, this systematic review and NMA will be the most comprehensive quantitative analysis regarding the management of bone loss and fractures in SOT recipients. Our analysis should be able to provide physicians and patients with an up-to-date recommendation for pharmacotherapies in reducing incidences of bone loss and fractures associated with SOT. The findings of the NMA will be disseminated in a peer-reviewed journal.

Somatostatin Versus Octreotide for Prevention of Postoperative Pancreatic Fistula: The PREFIPS Randomized Clinical Trial: A FRENCH 007-ACHBT Study.

Pharmacological prevention of postoperative pancreatic fistula (POPF) after pancreatectomy is open to debate. The present study compares clinically significant POPF rates in patients randomized between somatostatin versus octreotide as prophylactic treatment. Multicentric randomized controlled open study in patient's candidate for pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) comparing somatostatin continuous intravenous infusion for 7 days versus octreotid 100 μg, every 8 hours subcutaneous injection for 7 days, stratified by procedure (PD vs DP) and size of the main pancreatic duct (>4 mm) on grade B/C POPF rates at 90 days based on an intention-to-treat analysis. Of 763 eligible patients, 651 were randomized: 327 in the octreotide arm and 324 in the somatostatin arm, with comparable the stratification criteria - type of surgery and main pancreatic duct dilatation. Most patients had PD (n=480; 73.8%), on soft/normal pancreas (n=367; 63.2%) with a nondilated main pancreatic duct (n=472; 72.5%), most often for pancreatic adenocarcinoma (n=311; 47.8%). Almost all patients had abdominal drainage (n=621; 96.1%) and 121 (19.5%) left the hospital with the drain in place (median length of stay=16 days). A total of 153 patients (23.5%) developed a grade B/C POPF with no difference between both groups: 24.1%: somatostatin arm and 22.9%: octreotide arm (χ 2 test, P =0.73, ITT analysis). Absence of statistically significant difference persisted after adjustment for stratification variables and in per-protocol analysis. Continuous intravenous somatostatin is not statistically different from subcutaneous octreotide in the prevention of grade B/C POPF after pancreatectomy. In the PREFIPS Randomized Clinical Trial including 651 patients, a total of 153 patients (23.5%) developed a grade B/C POPF with no significant difference between both groups: 24.1%: somatostatin arm and 22.9%: octreotide arm (χ 2 test, P =0.73, ITT analysis). Absence of statistically significant difference persisted after adjustment for stratification variables and in per-protocol analysis.