An experimental study of countermeasures against threats: real-world effects meet treatment effects.
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ABSTRACT: Supplementary information
The online version contains supplementary material available at 10.1007/s11135-022-01354-4.
SUBMITTER: Chytilek R
PROVIDER: S-EPMC8861618 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe use of growth-promoters in beef cattle, despite the EU ban, remains a frequent practice. The use of transcriptomic markers has already proposed to identify indirect evidence of anabolic hormone treatment. So far, such approach has been tested in experimentally treated animals. Here, for the first time commercial samples were analyzed.ResultsQuantitative determination of Dexamethasone (DEX) residues in the urine collected at the slaughterhouse was performed by Liquid Chromatography-Mass Spectrometry (LC-MS). DNA-microarray technology was used to obtain transcriptomic profiles of skeletal muscle in commercial samples and negative controls. LC-MS confirmed the presence of low level of DEX residues in the urine of the commercial samples suspect for histological classification. Principal Component Analysis (PCA) on microarray data identified two clusters of samples. One cluster included negative controls and a subset of commercial samples, while a second cluster included part of the specimens collected at the slaughterhouse together with positives for corticosteroid treatment based on thymus histology and LC-MS. Functional analysis of the differentially expressed genes (3961) between the two groups provided further evidence that animals clustering with positive samples might have been treated with corticosteroids. These suspect samples could be reliably classified with a specific classification tool (Prediction Analysis of Microarray) using just two genes.ConclusionsDespite broad variation observed in gene expression profiles, the present study showed that DNA-microarrays can be used to find transcriptomic signatures of putative anabolic treatments and that gene expression markers could represent a useful screening tool.
| S-EPMC3541986 | biostudies-literature
Project description:Regulatory agencies typically evaluate the efficacy and safety of new interventions and grant commercial approval based on randomized controlled trials (RCTs). Other major healthcare stakeholders, such as insurance companies and health technology assessment agencies, while basing initial access and reimbursement decisions on RCT results, are also keenly interested in whether results observed in idealized trial settings will translate into comparable outcomes in real world settings-that is, into so-called "real world" effectiveness. Unfortunately, evidence of real world effectiveness for new interventions is not available at the time of initial approval. To bridge this gap, statistical methods are available to extend the estimated treatment effect observed in a RCT to a target population. The generalization is done by weighting the subjects who participated in a RCT so that the weighted trial population resembles a target population. We evaluate a variety of alternative estimation and weight construction procedures using both simulations and a real world data example using two clinical trials of an investigational intervention for Alzheimer's disease. Our results suggest an optimal approach to estimation depends on the characteristics of source and target populations, including degree of selection bias and treatment effect heterogeneity.
| S-EPMC8359356 | biostudies-literature
Project description:Talaromycosis is a leading cause of AIDS-associated opportunistic infections and death in Southeast Asia. We have recently shown in the Itraconazole versus Amphotericin for Talaromycosis (IVAP) trial that induction therapy with amphotericin B reduced mortality over 24 weeks, but not during the first 2 weeks. Antifungal treatment effects in real-world settings have not been rigorously evaluated. Using data obtained from patient records at the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam from 2004 to 2009, we first developed a prognostic model using Bayesian logistic regression to identify predictors of death. Second, we developed a causal model using propensity score matching to assess the treatment effects of amphotericin B and itraconazole. Our prognostic model identified intravenous drug use (odds ratio [OR] = 2.01), higher respiratory rate (OR = 1.12), higher absolute lymphocyte count (OR = 1.62), a concurrent respiratory infection (OR = 1.67) or central nervous system infection (OR = 2.66) as independent predictors of death. Fever (OR = 0.56) was a protective factor. Our prognostic model exhibits good in-sample performance and out-of-sample validation, with a discrimination power of 0.85 and 0.91, respectively. Our causal model showed no significant difference in treatment outcomes between amphotericin B and itraconazole over the first 2 weeks (95% credible interval: 0.62, 2.50). Our prognostic model provides a simple tool based on routinely collected clinical data to predict individual patient outcome. Our causal model shows similar results to the IVAP trial at 2 weeks, demonstrating an agreement between real-world data and clinical trial data.
| S-EPMC8023982 | biostudies-literature
Project description:IntroductionDespite considerable advances in the last decade, major adverse events remain a concern after transcatheter aortic valve implantation (TAVI). The aim of this study was to provide a detailed overview of their underlying causes and contributing factors in order to identify key domains for quality improvement.MethodsThis observational, prospective registry included all patients undergoing TAVI between 31 December 2015 and 1 January 2020 at the St. Antonius Hospital in Nieuwegein and the University Medical Centre in Utrecht. Outcomes of interest were all-cause mortality, stroke, major bleeding, life-threatening or disabling bleeding, major vascular complications, myocardial infarction, severe acute kidney injury and conduction disturbances requiring permanent pacemaker implantation within 30 days after TAVI, according to the Valve Academic Research Consortium‑2 criteria.ResultsOf the 1250 patients who underwent TAVI in the evaluated period, 146 (11.7%) developed a major complication. In 54 (4.3%) patients a thromboembolic event occurred, leading to stroke in 36 (2.9%), myocardial infarction in 13 (1.0%) and lower limb ischaemia in 11 (0.9%). Major bleeding occurred in 65 (5.2%) patients, most frequently consisting of acute cardiac tamponade (n = 25; 2.0%) and major access-site bleeding (n = 21; 1.7%). Most complications occurred within 1 day of the procedure. Within 30 days a total of 54 (4.3%) patients died, the cause being directly TAVI-related in 30 (2.4%). Of the patients who died from causes that were not directly TAVI-related, 14 (1.1%) had multiple hospital-acquired complications.ConclusionA variety of underlying mechanisms and causes form a wide spectrum of major threats affecting early safety in 11.7% of patients undergoing TAVI in a contemporary cohort of real-world patients.
| S-EPMC8630308 | biostudies-literature
Project description:ObjectivesThe efficacy of app-based treatment for stress urinary incontinence (SUI) has been demonstrated in a randomised controlled trial (RCT). In this study, we investigate the user characteristics and the effectiveness of the same app when freely available, and compare these results with the RCT.DesignProspective cohort study.ParticipantsDuring a 17-month period, 24?602 non-pregnant, non-postpartum women older than 18 years downloaded the app and responded anonymously to a questionnaire. Of these, 2672 (11%) responded to the 3-month follow-up.InterventionThree months' use of the app Tät, containing information, a pelvic floor muscle training programme and lifestyle advice.Main outcome measuresChange in symptom severity (International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF)) and subjective improvement (Patient Global Impression of Improvement (PGI-I)).ResultsOf the respondents, 88% lived in Sweden and 75% (18 384/24 602) were incontinent with a mean age of 45.5 (SD 14.1) years. The UI types, based on symptoms, were SUI (53%), urgency UI (12%), mixed UI (31%) and undefined (4%). The mean ICIQ-UI SF score was 8.2 (SD 4.0) at baseline. The mean ICIQ-UI SF score reduction at follow-up was 1.31 (95% CI: 1.19 to 1.44) with a larger reduction in those with more severe incontinence at baseline (severe/very severe 3.23 (95% CI: 2.85 to 3.61), moderate 1.41 (95% CI: 1.24 to 1.59) and slight 0.24 (95% CI 0.06 to 0.42). When the results were weighted to match the distribution of severity in the RCT, the ICIQ-UI SF score reduction was 2.2 compared with 3.9 in the RCT. Regarding PGI-I, 65% experienced improvement compared with 92% in the RCT.ConclusionsThe app Tät was effective for self-management of UI even in the real world. Although the reduction in incontinence symptoms was less than in the RCT, two-thirds of the users improved. App-based treatment reaches many women without requiring resources from ordinary healthcare services.
| S-EPMC7783523 | biostudies-literature
Project description:AimsTo analyse real-world treatment patterns of sacubitril/valsartan (sac/val) using data from a pharmacy database in Germany.Methods and resultsA retrospective cohort study of 26 191 adult patients (aged ≥ 18 years) in the IMS® longitudinal prescriptions database in Germany who were dispensed sac/val from January 2016 to June 2017 was conducted. The analysis included sac/val dose titration assessed in the 6 months from first sac/val prescription; prescriptions of concomitant cardiovascular medications in the 6 months pre- and post-index and compliance and persistence during 12 months post-index. Two-thirds of patients were prescribed the lowest sac/val dose of 50 mg twice daily (b.i.d.) at index and up-titration during the first 6 months was attempted in 41% of these patients. Ten percent of patients prescribed 200 mg b.i.d. at index had to be stably down-titrated; among patients prescribed 50 or 100 mg b.i.d. at index that were up-titrated, > 80% remained on the higher dose. Overall, the mean daily diuretic dose decreased by 25% after initiation of sac/val. High compliance and persistence rates were observed across sac/val doses, increasing with higher sac/val dose at index. Prior dose of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker had only minor impact on first sac/val dose, compliance and persistence.ConclusionsMost patients prescribed sac/val are not initiated on the recommended dose nor up-titrated as recommended by the EU Summary of Product Characteristics. Initiation of sac/val was associated with high persistence and compliance and a dose reduction of diuretics. Barriers to up-titration must be explored.
| S-EPMC6607491 | biostudies-literature
Project description:Hypertension requires strict treatment because it causes diseases that can lead to death. Although various classes of antihypertensive drugs are available, the actual status of antihypertensive drug selection and the transition in prescription patterns over time have not been fully examined. Therefore, we conducted a claims-based study using two claims databases (2008-16) to determine this status in Japan. We examined the prescription rate for each class of antihypertensive drugs in hypertensive patients and compared the patients' ages and the sizes of the medical institutions treating these patients. Among the 1 560 865 and 302 433 hypertensive patients in each database, calcium channel blockers (CCBs) (>60%) and angiotensin II receptor blockers (ARBs) (>55%) were the most frequently prescribed classes. The prescription rate of CCBs increased and ARBs decreased with the patients' ages. Although the Japanese guidelines for management of hypertension in 2014 changed the recommendation and indicated that β-blockers should not be used as first-line drugs, their prescription status did not change during this study period up to 2016. Use of CCBs and ARBs as first-line drugs differed by the types of patient comorbidities. Although ARBs or angiotensin-converting enzyme inhibitors were recommended for patients with some comorbidities, CCBs were used relatively frequently. In conclusion, the patients' ages and comorbidities and the sizes of the medical institutions affect the selection of antihypertensive drugs. Selection and use of drugs may not always follow the guidelines.
| S-EPMC8075880 | biostudies-literature
Project description:Background and Purpose- Recent landmark trials provided overwhelming evidence for effectiveness of endovascular stroke therapy (EST). Yet, the impact of these trials on clinical practice and effectiveness of EST among lower volume centers remains poorly characterized. Here, we determine population-level patterns in EST performance in US hospitals and compare EST outcomes from higher versus lower volume centers. Methods- Using validated diagnosis codes from data on all discharges from hospitals and Emergency Rooms in Florida (2006-2016) and the National Inpatient Sample (2012-2016) we identified patients with acute ischemic stroke treated with EST. The primary end point was good discharge outcome defined as discharge to home or acute rehabilitation facility. Multivariate regressions adjusted for medical comorbidities, intravenous tPA (tissue-type plasminogen activator) usage and annual hospital stroke volume were used to evaluate the likelihood of good outcome over time and by annual hospital EST volume. Results- A total of 3890 patients (median age, 73 [61-82] years, 51% female) with EST were identified in the Florida cohort and 42?505 (median age, 69 [58-79], 50% female) in the National Inpatient Sample. In both Florida and the National Inpatient Sample, the number of hospitals performing EST increased continuously. Increasing numbers of EST procedures were performed at lower annual EST volume hospitals over the studied time period. In adjusted multivariate regression, there was a continuous increase in the likelihood of good outcomes among patients treated in hospitals with increasing annual EST procedures per year (odds ratio, 1.1; 95% CI, 1.1-1.2 in Florida and odds ratio, 1.3; 95% CI, 1.2-1.4 in National Inpatient Sample). Conclusions- Analysis of population-level datasets of patients treated with EST from 2006 to 2016 demonstrated an increase in the number of centers performing EST, resulting in a greater number of procedures performed at lower volume centers. There was a positive association between EST volume and favorable discharge outcomes in EST-performing hospitals.
| S-EPMC6407696 | biostudies-literature
Project description:Despite the availability of various osteoporosis treatments, adherence remains suboptimal. One contributing factor may be patient experience with therapy. This US, multicenter, combined retrospective chart review and patient questionnaire study included postmenopausal women at high risk for fracture and is the first study to describe real-world patient experience with abaloparatide (ABL) injection. Eight geographically diverse secondary care sites in the United States participated (n = 193). Mean ± SD age was 67.4 ±8.62 years. Most patients (86%) were satisfied with the ABL regimen, especially with ease of preparation (82%), ease of storage (87%), and storage convenience (89%), an attribute 83% of the patients thought was important. The majority of patients reported complete satisfaction with the ABL regimen allowing for their ability to conduct daily activities (85%) and convenience to fit into their daily schedule (84%). All reported taking ABL as directed, by injection in the lower abdomen, and 83% of patients reported medium or high adherence. Patients were satisfied with the needle size (76% completely satisfied), and 93% reported never deliberately missing a dose. Although injecting medication (18%) and higher out-of-pocket costs (17%) were deemed the most bothersome attributes, the majority (69%) noted their healthcare team understands how osteoporosis impacts their lives. In multivariable analyses, ease of preparation (OR = 2.62; 95% CI, 1.01-6.81; p = 0.048) and fracture history (OR = 1.72; 95% CI, 1.03-2.86; p = 0.037) were significantly associated with overall satisfaction. Ease of preparation was a predictor of higher satisfaction with treatment convenience (coefficient = 13.60; 95% CI, 8.08-19.12; p = 0.00). Remembering to take the medication was a significant predictor of self-reported adherence (OR = 16.66; 95% CI, 3.30-84.24; p = 0.001). In conclusion, the majority of patients were satisfied with ABL and found it convenient/easy to prepare and store. High self-reported adherence may be associated with positive patient experience including ease of use and adequate support from healthcare providers. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.
| S-EPMC7990148 | biostudies-literature
Project description:Objective: Pegloticase is used in severe refractory gout or in cases of intolerance to other urate-lowering therapies. We sought to evaluate the patterns of pegloticase use in the USA and the incidence of safety outcomes.Methods: We conducted a retrospective descriptive study using data from two US commercial insurance claims databases (2010-2018). We identified new initiators of pegloticase with ?1 gout diagnosis code in the 365-day baseline period prior to pegloticase initiation. We measured the number and duration of pegloticase infusions. We assessed the risk of anaphylaxis or anaphylactoid reactions, cardiovascular events, including myocardial infarction or stroke, and hospitalisation for heart failure (new onset or exacerbations) while undergoing pegloticase therapy.Results: Among 2.9 million patients with ?1 diagnosis of gout, we identified only 483 (179 in Optum and 304 in MarketScan) pegloticase initiators. The mean age and % female was 55.6 years, 10.9% for MarketScan and 60.6 years and 17.3% for Optum. Hypertension was present in up to 85%, diabetes mellitus in 38%, chronic kidney disease in 46% and heart failure in 21% of the patients. The median number of infusions was four and the duration of therapy was 3 months. During the mean 0.5-year follow-up time on pegloticase, there were 3 (0.6%) anaphylaxis, 7 (1.4%) composite cardiovascular, 31 (6.4%) heart failure hospitalisations and 3 (0.6%) deaths.Conclusion: Pegloticase is rarely used in gout, and the median duration of pegloticase therapy was 3 months. There were few anaphylaxis events captured in this claims-based study, while heart failure hospitalisations were common.
| S-EPMC7722814 | biostudies-literature