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Cost-effectiveness of olaparib plus bevacizumab versus bevacizumab monotherapy in the maintenance of patients with homologous recombination deficiency-positive advanced ovarian cancer after response to first-line platinum-based chemotherapy

ObjectiveThe PAOLA-1 trial confirmed that adding olaparib to bevacizumab significantly increased clinical benefit following response to platinum-based chemotherapy in homologous recombination deficiency-positive ovarian cancer. The objective of this analysis was to determine the cost-effectiveness of olaparib plus bevacizumab compared with bevacizumab alone as maintenance treatment for patients with homologous recombination deficiency-positive advanced ovarian cancer from the Spanish National Health System perspective.MethodsA lifetime partitioned survival model with four health states (progression-free, post-progression 1, post-progression 2, and death) and monthly cycles was developed. Long-term survival, defined as 60 months, was included as a landmark to extrapolate progression-free survival from PAOLA-1. Weibull distribution was selected as the most accurate survival model for progression-free survival extrapolation. Time to second progression and overall survival were extrapolated using parametric survival models. Mortality was obtained from the overall survival and adjusted by Spanish women mortality rates. Health state utilities and utility decrements for adverse events were included. An expert panel validated data and assumptions. Direct costs (in 2021 euros (€)) were obtained from local sources and included drug acquisition and administration, subsequent therapies, monitoring costs, adverse events, and palliative care. A 3% annual discount rate was applied to costs and outcomes. The incremental cost-effectiveness ratio was calculated as cost per quality-adjusted life-years (QALYs) gained. Deterministic and probabilistic sensitivity analyses were performed.ResultsCompared with bevacizumab alone, olaparib plus bevacizumab increased QALYs and life-years by 2.39 and 2.77, respectively, at an incremental cost of €58 295.31, resulting in an incremental cost-effectiveness ratio of €24 371/QALY. Probabilistic sensitivity analysis demonstrated that olaparib plus bevacizumab had a 49.5% and 90.3% probability of being cost-effective versus bevacizumab alone at a willingness-to-pay threshold of €25 000 and €60 000 per QALY gained, respectively.ConclusionFor patients with homologous recombination deficiency-positive advanced ovarian cancer, olaparib plus bevacizumab is a cost-effective maintenance therapy compared with bevacizumab alone in Spain.

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Evolution of psychopathology, purpose in life, and moral courage in healthcare workers during the COVID-19 pandemic: a longitudinal study.

Almost 2 years and five infection waves after the COVID-19 pandemic started, healthcare workers continued dealing with the pandemic situation and facing the health consequences and the mental health disorders it caused. This study aimed to evaluate the onset and progression of psychopathology as well as the role of predictor variables such as purpose in life and moral courage among healthcare workers during this time. This was a longitudinal prospective study carried out with 45 Spanish healthcare workers who answered two questionnaires, the first questionnaire in April-May 2020 (T1) and the second questionnaire in September-October 2021 (T2). Although 29.5% of the sample considered that their mental health had improved over this time, almost half of them (47.7%) said it had not changed, while 22.7% reported a decline in their mental health from the first time they were asked. Specifically, 46.8% presented anxiety, 23.4% depression, and 42.6% acute stress at T1, and 38.3% had anxiety, 17% depression, and 27.7% post-traumatic stress disorder at T2. Despite this, there were no differences between T1 and T2 anxiety scores (p = 0.53), although there was a decrease in depression (p = 0.03) and acute stress (p = 0.02) scores. Predictor variable outcomes such as purpose in life (p = 0.88) and moral courage (p = 0.86; p = 0.38) did not change over time, but when modelling the data, purpose in life predicted psychopathology at T1, which in turn affected the psychopathology results at T2. This study showed that, although psychopathology decreased over the months, its prevalence remained high. Even though the purpose in life predicted psychopathology at T1, it seems that once the psychopathology is established (T2), the factors that would improve it would be different from the protective factors that prevented its establishment, which become secondary.

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Treatment of dissociative symptoms with opioid antagonists: a systematic review

ABSTRACT Background: The clinical guidelines for the treatment of dissociation focus primarily on psychotherapy. However, different psychoactive drugs are used in clinical practice. The use of opioid antagonists has been proposed as a therapeutic option based on the theory that dissociation might be a phenomenon mediated by dysregulation of the endogenous opioid system. Objective: To review and meta-analyse the available evidence on the efficacy of the opioid antagonists naltrexone, naloxone, and nalmefene as treatments for dissociative symptoms and disorders. Method: The PRISMA guidelines were followed, and this review was registered in Prospero with reference number CRD42021280976. The search was performed in the PubMed, Scopus, Web of Science, EMBASE, PsycINFO, and PubPsych databases. Results: 1,798 citations were obtained. After removing duplicates and applying inclusion and exclusion criteria, we included 5 comparative studies with 9 dissociation measures that had included a total of 154 participants, of whom 134 had been treated with an opioid antagonist. The results of the meta-analysis showed a treatment effect for dissociation when using opioid antagonists [pooled d = 1.46 (95% CI: 0.62–2.31)]. However, the studies we included were very heterogeneous [Q = 66.89 (p < .001)] and there may have been publication bias. Conclusions: Although more research is needed and the results must be interpreted with caution because of the limited amount of data and heterogeneity in the studies and their methodological qualities, opioid antagonists (particularly naltrexone) are promising candidates for the treatment of dissociative symptoms and showed a moderate – large effect size in reducing these symptoms.

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Pruritus and Pain Constitute the Main Negative Impact of Atopic Dermatitis From the Patient's Perspective: A Systematic Review.

Atopic dermatitis (AD) is an inflammatory skin disease characterized by intense itching and highly visible signs, representing a great burden to the patient. Despite its straightforward diagnosis, AD severity and burden can be underestimated in routine clinical practice. This review aims to determine the impact of AD on patients' lives, establish which domains of life are most affected, and identify symptom drivers of AD burden. A systematic literature review was conducted in Pubmed/Medline, Web of Science, and Scopus following Cochrane and PRISMA recommendations. Observational studies published in English or Spanish between January 1, 2018, and August 31, 2022, evaluating the impact of AD and its symptoms from the patient's perspective, were included. Reviewed studies were assessed for quality following the STrengthening the Reporting of OBservational studies in Epidemiology Checklist. A total of 28 observational studies evaluating the impact of AD and its symptoms from the patient's perspective were included in the review. All domains of the AD patient's life were found to be greatly affected, including health-related quality of life (HRQoL), emotional health, sleep disorders, work impairment, health care resource utilization, cognitive function, and development of comorbidities. The more severe the disease, the greater the impact, worsening in patients with moderate and severe AD. Pruritus and pain are reported to be the disease symptoms with the greatest impact. In conclusion, AD impacts several domains of patients' lives, especially HRQoL and mental health. Pruritus and pain are identified as the main drivers of AD impact, suggesting that optimal symptom control may reduce the burden and improve disease management.

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Acuerdo de riesgo compartido basado en resultados de salud para el tratamiento de psoriasis moderada-grave con certolizumab pegol

ObjectiveTo provide evidence of the effectiveness of certolizumab pegol (CZP) in real clinical practice in adult patients with moderate-to-severe plaque psoriasis (PsO) in the context of a risk-sharing agreement (RSA). MethodsRetrospective observational study based on variables collected in the RSA for treatment with CZP of adult patients with moderate-severe plaque PsO. Ten Spanish hospitals where the RSA was implemented participated. The percentage of patients who achieved the target clinical response of the RSA at the follow-up visit (week 16) was evaluated: absolute Psoriasis Area and Severity Index (PASI) value ≤3 for biologic naïve population, and ≤5 in case of previous failure to a single biologic drug. In addition, the improvement in the scores of other scales included in the study was analyzed: Body Surface Area (BSA), Dermatology Life Quality Index (DLQI), Physician's Global Assessment (PGA), and Nail Psoriasis Severity Index (NAPSI). A descriptive analysis was performed for the total population and by patient subgroups (naive vs. non-naive to biologic, male vs. female, and with vs. without discontinuation). ResultsSixty-six patients were included, 12 men and 54 women. 90.9% achieved the target clinical response, with a mean reduction of 8 (−78.4%) absolute PASI points. Improvement was observed in BSA, PGA, NAPSI and DLQI, with a reduction of 11.3 (−80.6%), 1.9 (−65.5%), 3.3 (−30.7%) and 9.0 (−66.4%) absolute value points, respectively. Despite not achieving the therapeutic target set in the RSA in six patients (9%) (the cost of the drug was assumed by the laboratory), only two (3%) discontinued treatment. ConclusionOur study shows that CZP is effective in real clinical practice in patients with moderate-severe plaque PsO, with an improvement in absolute PASI and DLQI, as well as other scales, both for the total population and in the subgroups analyzed. Nearly 91% of patients reached the therapeutic target fixed in the RSA. Implementing this type of agreement can provide a direct or indirect benefit for all the agents involved in the process, providing valuable information for decision-making.

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Impact of hand osteoarthritis in women on maximal forces in six different grasp types

This work aims to: (1) Provide maximal hand force data on six different grasp types for healthy subjects; (2) detect grasp types with maximal force significantly affected by hand osteoarthritis (HOA) in women; (3) look for predictors to detect HOA from the maximal forces using discriminant analyses. Thirty-three healthy subjects (37 ± 17 years, 17 women, 16 men) and 30 HOA patients (72 ± 9 years, all women) participated in the experiment. Participants were asked to exert their maximal force while performing six different grasp types 3 times. Two MANOVAs were conducted to detect if force depended on gender in healthy participants and if force significantly diminished in women with HOA. Finally, a linear discriminant analysis for detecting HOA was performed using forces of the grasp types that were significantly affected by HOA. Gender-disaggregated statistics are provided for healthy participants. Significant differences are obtained for all grasp types per gender. The women with HOA exerted significantly lower force values (p < 0.001) for all the grasp types than healthy ones. The discriminant analysis revealed that oblique grasp was the most significant one for detecting HOA. A discrimination equation was obtained with a specificity of 88.2% and a sensitivity of 83.3%. This work provides grip force data on six grasp types for healthy participants and for women with HOA. HOA women present reduced strength in all grasps due to pathology. Three of these grasps are a novelty. Oblique grasp strength may suffice to discriminate a patient with HOA, which might help non-invasive HOA detection.

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