Genetic Variants Associated with Biological Treatment Response in Inflammatory Bowel Disease: A Systematic Review.

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the digestive tract usually characterized by diarrhea, rectal bleeding, and abdominal pain. IBD includes Crohn's disease and ulcerative colitis as the main entities. IBD is a debilitating condition that can lead to life-threatening complications, involving possible malignancy and surgery. The available therapies aim to achieve long-term remission and prevent disease progression. Biologics are bioengineered therapeutic drugs that mainly target proteins. Although they have revolutionized the treatment of IBD, their potential therapeutic benefits are limited due to large interindividual variability in clinical response in terms of efficacy and toxicity, resulting in high rates of long-term therapeutic failure. It is therefore important to find biomarkers that provide tailor-made treatment strategies that allow for patient stratification to maximize treatment benefits and minimize adverse events. Pharmacogenetics has the potential to optimize biologics selection in IBD by identifying genetic variants, specifically single nucleotide polymorphisms (SNPs), which are the underlying factors associated with an individual's drug response. This review analyzes the current knowledge of genetic variants associated with biological agent response (infliximab, adalimumab, ustekinumab, and vedolizumab) in IBD. An online literature search in various databases was conducted. After applying the inclusion and exclusion criteria, 28 reports from the 1685 results were employed for the review. The most significant SNPs potentially useful as predictive biomarkers of treatment response are linked to immunity, cytokine production, and immunorecognition.

Nail fixation of unstable trochanteric fractures with or without cement augmentation: A cost-utility analysis in the United States: Cost-utility of cement augmentation.

OBJECTIVES: Recent clinical studies have shown favorable outcomes for cement augmentation for fixation of trochanteric fracture. We assessed the cost-utility of cement augmentation for fixation of closed unstable trochanteric fractures from the US payer's perspective. METHODS: The cost-utility model comprised a decision tree to simulate clinical events over 1 year after the index fixation surgery, and a Markov model to extrapolate clinical events over patients' lifetime, using a cohort of 1,000 patients with demographic and clinical characteristics similar to that of a published randomized controlled trial (age ≥75 years, 83 % female). Model outputs were discounted costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) over a lifetime. Deterministic and probabilistic sensitivity analyses were performed to assess the impact of parameter uncertainty on results. RESULTS: Fixation with augmentation reduced per-patient costs by $754.8 and had similar per-patient QALYs, compared to fixation without augmentation, resulting in an ICER of -$130,765/QALY. The ICER was most sensitive to the utility of revision surgery, mortality risk ratio after the second revision surgery, mortality risk ratio after successful index surgery, and mortality rate in the decision tree model. The probability that fixation with augmentation was cost-effective compared with no augmentation was 63.4 %, 58.2 %, and 56.4 %, given a maximum acceptable ceiling ratio of $50,000, $100,000, and $150,000 per QALY gained, respectively. CONCLUSION: Fixation with cement augmentation was the dominant strategy, driven mainly by reduced costs. These results may support surgeons in evidence-based clinical decision making and may be informative for policy makers regarding coverage and reimbursement.

Healthcare resource use and costs related to surgical infections of tibial fractures in a Spanish cohort.

Surgical site infection constitutes a serious complication in the healing process of bone fractures and has been associated with increases in medical resource use and healthcare costs. This study evaluates the economic impact of surgical site infection in tibial fractures in a Spanish cohort. It is a retrospective, single-centre, comparative cohort study of patients with tibial fractures with longitudinal follow-up for up to 18 months post-surgery. Included patients (n = 325) were adults, with tibial fracture, either isolated or polyfracture, or polytrauma with an Injury Severity Score >15. Patients had been surgically treated within 30 days of the tibial fracture by external or internal fixation, or external followed by internal fixation. Most patients (84.9%) had an American Society of Anaesthesiology score of 1-2. 20% of the patients had one open tibial fracture, 12.3% had polytrauma, and 20% had multiple fractures. Most patients were treated with a nail (41.8%) or a plate (33.8%). 56 patients (17.2%) developed surgical site infection. Patients with infection had significantly higher hospital length of stay (34.9 vs 12.0 days; p<0.001; +191%), readmissions (1.21 vs 0.25; p<0.001; +380%) and mean operating theatre time (499 vs 219 min; p<0.001; +128%) than patients without infection. Mean length of stay in intensive care did not significantly increase with infection (2.8 vs 1.7 days; p = 0.25). Total in-hospital costs for patients with infection increased from €7,607 to €17,538 (p<0.001; +131%). Overall, infections were associated with significantly increased healthcare resource use and costs. Preventive strategies to avoid infections could lead to substantial cost savings.

Cost-Effectiveness of Cement Augmentation Versus No Augmentation for the Fixation of Unstable Trochanteric Fractures.

BACKGROUND: A previous randomized controlled trial (RCT) demonstrated a trend toward a reduced risk of implant-related revision surgery following fixation with use of a Proximal Femoral Nail Antirotation (PFNA) with TRAUMACEM V+ Injectable Bone Cement augmentation versus no augmentation in patients with unstable trochanteric fractures. To determine whether this reduced risk may result in long-term cost savings, the present study assessed the cost-effectiveness of TRAUMACEM V+ cement augmentation versus no augmentation for the fixation of unstable trochanteric fractures from the German health-care payer's perspective. METHODS: The cost-effectiveness model comprised 2 stages: a decision tree simulating clinical events, costs, and utilities during the first year after the index procedure and a Markov model extrapolating clinical events, costs, and utilities over the patient's lifetime. Sources of model parameters included the previous RCT, current literature, and administrative claims data. Outcome measures were incremental costs (in 2020 Euros), incremental quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). Model uncertainty was assessed with deterministic and probabilistic sensitivity analyses. RESULTS: The base-case analysis showed that fixation with cement augmentation was the dominant strategy as it was associated with cost savings (€50.3/patient) and QALY gains (0.01 QALY/patient). Major influential parameters for the ICER were the utility of revision, rates of revision surgery within the first year after fixation surgery, and the costs of augmentation and revision surgery. Probabilistic sensitivity analyses demonstrated that estimates of cost savings were more robust than those of increased QALYs (66.4% versus 52.7% of the simulations). For a range of willingness-to-pay thresholds from €0 to €50,000, the probability of fixation with cement augmentation being cost-effective versus no augmentation remained above 50%. CONCLUSIONS: Fixation with use of cement augmentation dominated fixation with no augmentation for unstable trochanteric fractures, resulting in cost savings and QALY gains. Given the input parameter uncertainties, future analyses are warranted when long-term costs and effectiveness data for cement augmentation are available. LEVEL OF EVIDENCE: Economic and Decision Analysis Level II . See Instructions for Authors for a complete description of levels of evidence.

[Translated article] Spanish Asthma Management Guidelines (GEMA) v.5.1. Highlights and Controversies.

In this fifth phase of development, the contents of the Spanish Asthma Management Guidelines (GEMA), which include versions 5.0 and 5.1, have undergone a thorough review. The aim here is to set the main changes in context. These could be summarized as follows: DIAGNOSIS: new FENO cut-off and severity classification based on treatment needed to maintain control; INTERMITTENT ASTHMA: a more restrictive concept and treatment extended to include a glucocorticoid/adrenergic combination as needed; MILD ASTHMA: glucocorticoid/adrenergic therapy as needed as an alternative in case of low therapeutic adherence to conventional fixed-dose steroids; SEVERE ASTHMA: readjustment of phenotypes, incorporation of triple therapy in a single inhaler, and criteria for selection of a biologic in severe uncontrolled asthma; OTHERS: specific scoring in childhood asthma, incorporation of certain organizational aspects (care circuits, asthma units, telemedicine), new sections on COVID-19 and nasal polyposis.

Surgical treatment, complications, reoperations, and healthcare costs among patients with clavicle fracture in England.

INTRODUCTION: The clinical and economic burden of clavicle fractures in England is not well documented. This study evaluated rates of surgical treatment, post-surgical complications, reoperations and costs in patients with clavicle fractures using the Clinical Practice Research Datalink (CPRD) database. METHODS: CPRD data were linked to National Health Service Hospital Episode Statistics data. Patients with a diagnosis of clavicle fracture between 2010-2018 were selected in CPRD (date of fracture = index date). Of those, patients with surgical intervention within 180 days from index fracture were identified. Rates of post-surgical complications (i.e., infection, non-union, and mal-union), reoperations (for device removal or for postoperative complications), post-operative costs and median time to reoperations were evaluated up to 2 years after surgery. RESULTS: 21,340 patients with clavicle fractures were identified (mean age 35.0 years(standard deviation (SD): 26.5), 66.7% male). Surgery was performed on 672 patients (3.2% of total cohort) at an average 17.1 (SD: 25.2) days post-fracture. Complications (i.e., infection, non-union, or malunion) affected 8.1% of surgically treated clavicle fracture patients; the rate of infection was 3.5% (95% CI, 1.7%- 5.2%), non-union 4.4% (95% CI, 2.4%-6.5%), and mal-union 0.3% (95% CI, 0%-0.7%). Adjusting for age, gender, comorbidities and time to surgery, the all-cause reoperation rate was 20.2% (13.2%-30.0%) and the adjusted rate of reoperation for implant removal was 17.0% (10.7%-25.9%)-84% of all-cause reoperations were thus performed for implant removal. Median time to implant removal was 254 days. The mean cost of reoperations for all causes was £5,000. The most expensive reoperations were for cases that involved infection (mean £6,156). CONCLUSIONS: Complication rates following surgical clavicle fracture care averaged 8.1%. However, reoperation rates exceed 20%, the vast majority of reoperations being performed for device removal. Technologies to alleviate secondary device removal surgeries would address a significant clinical unmet need.

Spanish Asthma Management Guidelines (GEMA) VERSION 5.1. Highlights and Controversies. / Guía española para el manejo del asma (GEMA) versión 5.1. Aspectos destacados y controversias.

In this fifth phase of development, the contents of the Spanish Asthma Management Guidelines (GEMA), which include versions 5.0 and 5.1, have undergone a thorough review. The aim here is to set the main changes in context. These could be summarized as follows: DIAGNOSIS: new FENO cut-off and severity classification based on treatment needed to maintain control; INTERMITTENT ASTHMA: a more restrictive concept and treatment extended to include a glucocorticoid/adrenergic combination as needed; MILD ASTHMA: glucocorticoid/adrenergic therapy as needed as an alternative in case of low therapeutic adherence to conventional fixed-dose steroids; SEVERE ASTHMA: readjustment of phenotypes, incorporation of triple therapy in a single inhaler, and criteria for selection of a biologic in severe uncontrolled asthma; OTHERS: specific scoring in childhood asthma, incorporation of certain organizational aspects (care circuits, asthma units, telemedicine), new sections on COVID-19 and nasal polyposis.

Substance use, mental health and dual disorders on pregnancy: Results of prevalence and treatment rates in a developed country. / Salud mental, abuso de sustancias y trastornos duales en el embarazo: Tasas de prevalencia y tratamiento en un país desarrollado.

Smoking and substance use during pregnancy are major preventable causes of mortality and morbidity, having a bidirectional and deleterious relationship with the mental health of the mother and child. As part of the WOMAP (Woman Mental Health and Addictions on Pregnancy) initiative, our study aimed to describe the prevalence of co-occurring mental illness and substance use problems, diagnoses and severity of those considered at risk and rates of treatment.A screening of 2,014 pregnant women was done using the AC-OK scale and they were asked about their smoking habits and services use for mental health/substance abuse. Of these, 170 women were considered at risk of co-occurring mental illness and substance use problems (≥ 2 positive responses to the AC-OK-Mental Health subscale, ≥ 1 positive response to the AC-OK-Substance Abuse subscale and/or smoking more than once a month and no use of specialized services) and were assessed with a more extensive battery of measures (Patient Health Questionnaire [PHQ-9], General Anxiety Disorder [GAD-7], Posttraumatic stress disorder [PTSD] Checklist for DSM-5 [PCL-5], Alcohol Use Disorders Identification Test [AUDIT], Drug Abuse Screening Test [DAST] and Fagerström).In the last year, 614 women (30.5%) smoked tobacco (42.5% daily) and 9.8% were positive for both substance use and mental illness per the AC-OK. Only 11.1% of them received specific treatment in the previous three months while another 13.6% were scheduled to attend services in the following month. From the subsample assessed in depth, 62(36.5%) endorsed at least moderate depression, 35(20.6%) endorsed at least moderate anxiety, 32(18.8%) endorsed PTSD on the PCL, and 37 out of 88 alcohol users scored above the threshold in AUDIT (≥ 3). In conclusion, high prevalence and low treatment rates suggest that effective detection mechanisms should be integrated into usual care, allowing for early interventions.

El tabaquismo y el consumo de sustancias durante el embarazo son importantes causas prevenibles de morbimortalidad, teniendo una relación bidireccional y deletérea con la salud mental de la madre y el niño. Como parte de la iniciativa WOMAP (Woman Mental Health and Addictions on Pregnancy), se estudiaron 2.014 embarazadas buscando describir la prevalencia de trastornos mentales y por uso de sustancias concurrentes, las tasas de tratamiento y los diagnósticos y la gravedad. Las participantes fueron evaluadas con la escala AC-OK y se les preguntó sobre sus hábitos tabáquicos y uso de servicios de salud mental/sustancias. De las participantes, 170 mujeres resultaron positivas para un trastorno mental y por uso de sustancias concurrentes (≥ 2 positivos a la subescala AC-OK-Salud Mental, ≥ 1 positivos a la subescala AC-OK-Sustancias y/o fumar más de una vez al mes y no estar en tratamiento) y fueron evaluadas en profundidad mediante una batería de escalas (Patient Health Questionnaire [PHQ-9], General Anxiety Disorder [GAD-7], Post-traumatic stress disorder Checklist [PCL-5], Alcohol Use Disorders Identification Test [AUDIT], Drug Abuse Screening Test [DAST] y Fagerström).En el último año, 614 mujeres (30,5%) fumaron tabaco (42,5% diariamente) y el 9,8% fueron positivas para problemas por uso de sustancias y salud mental según la AC-OK. Solo el 11,1% había recibido tratamiento en los tres meses previos y solo un 13,6% tenía una cita en el siguiente mes. De las 170 pacientes evaluadas secundariamente, 62(36,5%) presentaron al menos depresión moderada, 35(20,6%) al menos ansiedad moderada, 32(18,8%) fueron positivas a la PCL-5, y 37 de las 88 que reconocieron uso de alcohol puntuaron por encima del umbral en AUDIT (≥ 3). En conclusión, la combinación de una prevalencia significativa junto con bajas tasas de tratamiento, remarcan la necesidad de mecanismos de detección efectivos en la atención habitual, permitiendo una intervención temprana.