Health-related quality of life in patients with generalized pustular psoriasis: A systematic literature review.

Generalized pustular psoriasis (GPP) is a rare, chronic, neutrophilic inflammatory skin disease characterized by episodes of widespread eruption of sterile, macroscopic pustules that can be accompanied by systemic inflammation and symptoms. A systematic literature review and narrative synthesis were conducted to determine the impact of GPP on patients' health-related quality of life (HRQoL) and patient-reported severity of symptoms and to compare its impact to patients with plaque psoriasis (plaque PsO). Searches were undertaken in Embase, MEDLINE and the Cochrane Library from 1 January 2002 to 15 September 2022. Screening was carried out by two reviewers independently. Outcome measures included generic (e.g. EQ-5D, SF-36) and dermatology-specific (e.g. DLQI) clinical outcome assessments, and other relevant patient-reported outcome measures (PROMs) (e.g. severity of pain measured by a numerical rating scale). Overall, 20 studies were found to be eligible for inclusion, of which seven also had data for plaque PsO. The DLQI was the most frequently reported outcome measure (16 out of 20 studies). When reported, mean DLQI (SD) scores varied from 5.7 (1.2) to 15.8 (9.6) across the studies, indicating a moderate to very large effect on HRQoL; the wide range of scores and large SDs were explained by the small population sizes (n ≤ 12 for all studies except two). Similar ranges and large SDs were also observed for other measures within individual studies. However, in general, people with GPP reported a greater impact of their skin condition on HRQoL, when compared to people with plaque PsO (i.e. higher DLQI scores) and higher severity for itch, pain and fatigue. This systematic review highlighted the need for studies with a larger population size, a better understanding of the impact of cutaneous and extracutaneous symptoms and comorbidities on HRQoL during and between GPP flares, and outcome measures specifically tailored to the unique symptoms and the natural course/history of GPP.

The 1st year of the COVID-19 epidemic in Estonia: a population-based nationwide sequential/consecutive cross-sectional study.

OBJECTIVES: The objective of this study was to assess the population prevalence of SARS-CoV-2 and changes in the prevalence in the adult general population in Estonia during the 1st year of COVID-19 epidemic. STUDY DESIGN: This was a population-based nationwide sequential/consecutive cross-sectional study. METHODS: Using standardised methodology (population-based, random stratified sampling), 11 cross-sectional studies were conducted from April 2020 to February 2021. Data from nasopharyngeal testing and questionnaires were used to estimate the SARS-CoV-2 RNA prevalence and factors associated with test positivity. RESULTS: Between April 23, 2020, and February 2, 2021, results were available from 34,915 individuals and 27,870 samples from 11 consecutive studies. The percentage of people testing positive for SARS-CoV-2 decreased from 0.27% (95% confidence interval [CI] = 0.10%-0.59%) in April to 0.04% (95% CI = 0.00%-0.22%) by the end of May and remained very low (0.01%, 95% CI = 0.00%-0.17%) until the end of August, followed by an increase since November (0.37%, 95% CI = 0.18%-0.68%) that escalated to 2.69% (95% CI = 2.08%-2.69%) in January 2021. In addition to substantial change in time, an increasing number of household members (for one additional odds ratio [OR] = 1.15, 95% CI = 1.02-1.29), reporting current symptoms of COVID-19 (OR = 2.21, 95% CI = 1.59-3.09) and completing questionnaire in the Russian language (OR 1.85, 95% CI 1.15-2.99) were associated with increased odds for SARS-CoV-2 RNA positivity. CONCLUSIONS: SARS-CoV-2 population prevalence needs to be carefully monitored as vaccine programmes are rolled out to inform containment decisions.

Analysis of Omega-3 Fatty Acid Content in Fish Oil Products.

BACKGROUND: Omega-3 fatty acids eicosapentaenoic acid (EPA) and docosehexaenoic acid (DHA), often found in fish oil supplements, have been linked to cardiovascular benefits in proper doses. OBJECTIVES: Quantify serving sizes and EPA and DHA content of fish oil products and determine which products contain appropriate amounts of EPA and DHA per serving to lower cholesterol. METHODS: Products were identified through the National Institutes of Health's Dietary Supplement Label Database using the search term "fish oil." Product labels were reviewed for EPA and DHA content. The number of units, such as capsules, gummies, or milliliters, necessary to obtain a total of at least 2,000 mg of EPA and DHA was also evaluated. Descriptive statistics were used to report findings. RESULTS: Of 493 products identified, 231 products were analyzed. Two (0.9%) products, both of which were liquid formulations, contained at least 2,000 mg of EPA and DHA in the standard serving size listed on the labeling. The total amount of EPA and DHA per serving ranged from 60.2 mg to 2684 mg with an average of 697 mg. The number of servings necessary to achieve 2,000 mg of EPA and DHA ranged from 1 to 34 servings with an average of 5 servings. CONCLUSIONS: Serving sizes of fish oil products rarely result in adequate EPA and DHA intake to provide cholesterol-lowering benefit. Instruction by a trained healthcare professional, such as a pharmacist, is important to ensure patients are taking an appropriate serving of fish oil to obtain cardiovascular benefit.

Predictors of voter support for the legalization of recreational cannabis use and supply via a national referendum.

BACKGROUND: A national referendum to legalise recreational cannabis use and supply in New Zealand via the Cannabis Legalisation and Control Bill (CLCB) was recently narrowly defeated. Understanding the underlying factors for this result can inform the cannabis legalisation debate in other countries. AIMS: To investigate predictors of voter support for and opposition to the CLCB. METHOD: A representative population panel of 1,022 people completed an online survey of intended voting on the CLCB referendum, which included questions on demographics, drug use history, medicinal cannabis, perceptions of the health risk and moral views of cannabis use, political affiliation, religiosity, community size and reading of the CLCB. Regression models were developed to predict support for the CLCB, with additional predictor variables added over successive iterations. RESULTS: The most robust predictors of support for the CLCB were use of and policy support for medicinal cannabis use, voting for a left-wing political party, having a positive moral view of cannabis use, living in a small town and having read the CLCB. Predictors of opposing the CLCB were voting for right-wing parties, considering "frequent" cannabis use to be a high health risk, and lifetime use of other drugs. Age, ethnicity, education, employment status, religiosity and lifetime cannabis use were not significant predictors after controlling for other variables. CONCLUSIONS: Support for cannabis legalization was not based on broad demographics, but rather specific views concerning the medicinal benefit, morality of cannabis use, health risk of frequent cannabis use, political party affiliation, and knowledge of the proposed regulatory controls of the CLCB. The influence of moral views of cannabis use on voting behaviour suggest the need to debate the right to use cannabis. The importance of knowledge of the proposed regulatory controls of the CLCB on voting underlines the need to raise awareness of proposed regulatory controls during debate.

In silico evaluation of limited sampling strategies for individualized dosing of extended half-life factor IX concentrates in hemophilia B patients.

PURPOSE: Hemophilia B is a bleeding disorder, caused by a factor IX (FIX) deficiency. Recently, FIX concentrates with extended half-life (EHL) have become available. Prophylactic dosing of EHL-FIX concentrates can be optimized by assessment of individual pharmacokinetic (PK) parameters. To determine these parameters, limited sampling strategies (LSSs) may be applied. The study aims to establish adequate LSSs for estimating individual PK parameters of EHL-FIX concentrates using in silico evaluation. METHODS: Monte Carlo simulations were performed to obtain FIX activity versus time profiles using published population PK models for N9-GP (Refixia), rFIXFc (Alprolix), and rIX-FP (Idelvion). Fourteen LSSs, containing three or four samples taken within 8 days after administration, were formulated. Bayesian analysis was applied to obtain estimates for clearance (CL), half-life (t1/2), time to 1% (Time1%), and calculated weekly dose (Dose1%). Bias and precision of these estimates were assessed to determine which LSS was adequate. RESULTS: For all PK parameters of N9-GP, rFIXFc and rIX-FP bias was generally acceptable (range: -5% to 5%). For N9-GP, precision of all parameters for all LSSs was acceptable (< 25%). For rFIXFc, precision was acceptable for CL and Time1%, except for t1/2 (range: 27.1% to 44.7%) and Dose1% (range: 12% to 29.4%). For rIX-FP, all LSSs showed acceptable bias and precision, except for Dose1% using LSS with the last sample taken on day 3 (LSS 6 and 10). CONCLUSION: Best performing LSSs were LSS with samples taken at days 1, 5, 7, and 8 (N9-GP and rFIXFc) and at days 1, 4, 6, and 8 (rIX-FP), respectively.

Scabies itch: an update on neuroimmune interactions and novel targets.

Frequently described as 'the worst itch' one can ever experience scabies itch is the hallmark of Sarcoptes scabiei mite infestation. Notably, the itchiness often persists for weeks despite scabicides therapy. The mechanism of scabies itch is not yet fully understood, and effective treatment modalities are still missing which can severely affect the quality of life. The aim of this review is to provide an overview of the scope of itch in scabies and highlight candidate mechanisms underlying this itch. We herein discuss scabies itch, with a focus on the nature, candidate underlying mechanisms and treatment options. We also synthesize this information with current understanding of the mechanisms contributing to non-histaminergic itch in other conditions. Itch is a major problem in scabies and can lead to grave consequences. We provide the latest insights on host-mite interaction, secondary microbial infection and neural sensitization with special emphasis on keratinocytes and mast cells to better understand the mechanism of itch in scabies. Also, the most relevant current modalities remaining under investigation that possess promising perspectives for scabies itch (i.e. protease-activated receptor-2 (PAR-2) inhibitor, Mas-related G protein-coupled receptor X2 (MRGPRX2) antagonist) are discussed. Greater understanding of these diverse mechanisms may provide a rational basis for the development of improved and targeted approaches to control itch in individuals with scabies.

Richter transformation in chronic lymphocytic leukemia (CLL)-a pooled analysis of German CLL Study Group (GCLLSG) front line treatment trials.

Richter transformation (RT) is defined as development of aggressive lymphoma in patients (pts) with CLL. The incidence rates of RT among pts with CLL range from 2 to 10%. The aim of this analysis is to report the frequency, characteristics and outcomes of pts with RT enrolled in trials of the GCLLSG. A total of 2975 pts with advanced CLL were reviewed for incidence of RT. Clinical, laboratory, and genetic data were pooled. Time-to-event data, starting from time of CLL diagnosis, of first-line therapy or of RT diagnosis, were analyzed by Kaplan-Meier methodology. One hundred and three pts developed RT (3%): 95 pts diffuse large B-cell lymphoma (92%) and eight pts Hodgkin lymphoma (8%). Median observation time was 53 months (interquartile range 38.1-69.5). Median OS from initial CLL diagnosis for pts without RT was 167 months vs 71 months for pts with RT (HR 2.64, CI 2.09-3.33). Median OS after diagnosis of RT was 9 months. Forty-seven pts (46%) received CHOP-like regimens for RT treatment. Three pts subsequently underwent allogeneic and two pts autologous stem cell transplantation. Our findings show that within a large cohort of GCLLSG trial participants, 3% of the pts developed RT after receiving first-line chemo- or chemoimmunotherapy. This dataset confirms the ongoing poor prognosis and high mortality associated with RT.

A feasibility study on two tailored interventions to improve adherence in adults with haemophilia.

INTRODUCTION: Haemophilia is a congenital bleeding disorder mainly affecting males. To prevent bleeding, patients need to perform regular intravenous injections (prophylaxis) throughout life. Non-adherence often occurs. Problems with acceptance or self-management appear to be the main reasons for non-adherence in haemophilia. The aim of this study was to test the feasibility and effects of two interventions focussed on acceptance (face-to-face) and self-management (online). METHODS: Patients with severe haemophilia and acceptance or self-management problems were eligible. The face-to-face group intervention was based on Acceptance and Commitment Therapy (ACT) (8 sessions/6 months, target N = 8 participants). The online intervention was based on a successful online programme in rheumatoid arthritis (5-8 modules/2 months, target N = 8). Both interventions were designed according to the MRC framework in collaboration with the patient society and experts. We compared adherence (VERITAS-Pro, optimum 0), quality of life (SF-36, optimum 100) and illness perception (BIPQ, optimum 0) before start (T0) and after 2 months (T2). Feasibility criteria were as follows: completion of training by > 50% of participants and ability to collect at least 80% of outcome parameters. RESULTS: The face-to-face intervention was feasible (89% enrolment and recruitment, 100% retention). One hundred percent of the outcome parameters was collected. Results were promising: although adherence (VERITAS-Pro) was stable (from 64 to 62 points), quality of life (SF-36) showed a clinically relevant improvement (> 5 points) in five of eight domains. Illness perception (BIPQ) showed a clinically relevant increase from 47 to 39 points. Patient evaluation was positive. The online intervention, however, was infeasible: enrolment was only 20% (6/30). Only three patients signed informed consent (recruitment 10%), and none completed more than one module (retention 0%). Consequently, the online intervention was terminated. CONCLUSION: The face-to-face acceptance intervention was considered feasible with promising results. Unfortunately, the online intervention was infeasible and therefore terminated. These findings suggest that adapting effective interventions to other settings does not guarantee success, despite the use of established methodology and patient participation. Population differences (only male participants, congenital disease) could be an explanation for failure of the online intervention in haemophilia despite success in rheumatoid arthritis. TRIAL REGISTRATION: NL55883.041.16.

The Perspectives of Adolescents and Young Adults on Adherence to Prophylaxis in Hemophilia: A Qualitative Study.

PURPOSE: Adolescents and young adults (AYAs) with severe hemophilia use prophylaxis that requires a high level of adherence. The present study aimed to explore the underlying reason for adherence and non-adherence to prophylaxis in hemophilia from the perspective of AYAs. PATIENTS AND METHODS: A qualitative study in Dutch AYAs with hemophilia (14-25 years) using prophylaxis was executed. Focus group interviews and individual interviews were recorded, transcribed, coded and analyzed using an iterative process. Member checking in three respondents was used to validate the potential model. RESULTS: A total of 21 interviews were performed. Parental support decreased when AYAs gained more treatment responsibilities, which resulted in a higher risk for non-adherence. AYAs were weighing their potential bleeding risk per activity based on the wish to do what they prefer while also wanting to simultaneously feel safe. When bleeding with low impact on their daily life occurred, or when bleeding remained absent, AYAs felt safe and the perceived need for prophylaxis decreased. CONCLUSION: The level of treatment responsibility per AYA and estimated risks per activity were the two main underlying reasons for (non-)adherence. CLINICAL IMPLICATIONS: We suggest using a conversation technique to discuss adherence, especially during bleeding assessment visits.

[Differential diagnosis of acute back pain and demarcation to other specialist fields]. / Differenzialdiagnose akuter Rückenschmerz und Abgrenzung zu anderen Fachgebieten.

The treatment of patients with acute back pain is becoming increasingly more important due to the high incidence; however, acute clinical pictures from other disciplines can also primarily be symptomatic with back pain and falsely lead to a consultation with an orthopedist. In order to assure an adequate treatment of potentially critical patients, it is absolutely necessary to exclude life-threatening differential diagnoses by a structured study of the patient history, investigations and diagnostics. Depending on the suspected diagnosis, necessary first aid measures and emergency referral to the appropriate specialist department should be initiated. This article gives an overview of selected clinical pictures and tries to look beyond the field of orthopedics.

[Geriatric patients in orthopedics]. / Der geriatrische Patient in der Orthopädie.

The treatment of geriatric patients in orthopedics is increasing in importance due to the demographic changes. In order to ensure an adequate treatment it is absolutely necessary to address age-specific risk factors. The decision between conservative and surgical treatment has to be made with the patient and the relatives together, taking all comorbidities into consideration and with the objective of preserving the quality of life. This decision also includes the fact that not only the immediate perioperative course but also hospital morbidity and long-term outcome are substantially influenced by typical age-related risk factors. Due to the advancement of interdisciplinary cooperation and an increase in quality and quantity of publications in this field, there are increasingly more unified treatment recommendations for geriatric patients in orthopedics.

Timeline of functional recovery after hip fracture in seniors aged 65 and older: a prospective observational analysis.

We investigated the timeline of functional recovery after hip fracture over 12 months in adults age ≥ 65 years using objective lower extremity function tests and subjective physical functioning. Objective functional recovery was largely complete in the first 6 months, whereas subjective recovery improved up to 9 months after hip fracture. INTRODUCTION: Hip fractures are a major cause of loss of function among seniors. We assessed the timeline of objective and subjective functional recovery after hip fracture. METHODS: We conducted a prospective observational secondary analysis of a 1-year clinical trial on vitamin D and home exercise treatment and complications after hip fracture among 173 patients age ≥ 65 years (mean age 84 years; 79.2% women; 77.4% community-dwelling) conducted from January 2005 through December 2007. Lower extremity function (Timed Up and Go test (TUG), knee extensor and flexor strength) and grip strength was assessed at baseline and at 6 and 12 months follow-up. Subjective physical functioning was assessed using the SF-36 questionnaire also at 3 and 9 months follow-up. Multivariable-adjusted repeated-measures models were used to assess the timeline of functional recovery in the total population and in subgroups of patients. RESULTS: Lower extremity function including TUG (- 61.1%), knee extensor (+ 17.6%), and knee flexor (+ 11.6%) strength improved significantly in the first 6 months (P < 0.001). However, between 6 and 12 months, there was no further significant improvement for any of the functional tests. Grip strength decreased from baseline to 6 months (- 7.9%; P < 0.001) and from 6 to 12 months (- 10.8%; P < 0.001). Subjective physical functioning improved from 3 to 9 months (+ 15.2%, P < 0.001), but no longer thereafter. CONCLUSIONS: Functional recovery after hip fracture may be largely complete in the first 6 months for objective functional tests, whereas may extend up to 9 months for subjective recovery, with oldest-old, female, institutionalized, and cognitively impaired patients recovering most poorly. CLINICAL TRIALS REGISTRY (ORIGINAL TRIAL): NCT00133640.

Effects of a simple home exercise program and vitamin D supplementation on health-related quality of life after a hip fracture: a randomized controlled trial.

PURPOSE: To test the effects of vitamin D intervention and a simple home exercise program (HE) on health-related quality of life (HRQL) in the first 12 months after hip fracture. METHODS: HRQL was reported in 173 acute hip fracture patients (mean age 84 years, 79% females, 77% community dwelling) who were enrolled in the 12-month 2 × 2 factorial Zurich Hip Fracture Trial. Pre-fracture HRQL was assessed at baseline (4.2 ± 2.2 days post-surgery) and then again at 6 and 12 months after hip fracture surgery by the EuroQol EQ-5D-3L index value (EQ-5D-3L questionnaire). The effects of vitamin D intervention (2000 vs. 800 IU vitamin D3) and exercise (HE vs. no HE) or of the combined interventions on HRQL were assessed using multivariable-adjusted repeated-measures linear mixed-effects regression models. RESULTS: The EQ-5D-3L index value significantly worsened from 0.71 pre-fracture to 0.57 over 12 months, but the degree of worsening did not differ between individual or combined interventions. However, regarding only the late recovery between 6 and 12 months, the group receiving neither intervention (800 IU/day and no HE) experienced a significant further decline in the EQ-5D-3L index value (adjusted mean change = 0.08 [95% CI 0.009, 0.15], p = 0.03) while all other groups remained stable. CONCLUSION: Hip fractures have a long-lasting negative effect on HRQL up to 12 months after hip fracture. However, HE and/or 2000 IU vitamin D per day may help prevent a further decline in HRQL after the first 6 months following the acute hip fracture event.

[Urinary marker-old wine in new bottles?] / Urinmarker ­ alter Wein in neuen Schläuchen?

Some urine-based molecular markers can be used effectively in certain clinical situations, but so far none of them have made it into the daily routine. For this purpose, clinical validation in large multicentre prospective studies with defined endpoints is lacking, whereby the cost effectiveness should also be a criterion of the evaluation. This also applies to the many promising "research parameters", which were usually only examined in small groups of patients. The uniform standardization of molecular biological methods is the first step that makes a comparison possible. Current impediments to conducting such studies include elaborate analytics and their still high costs. In summary, the development that has occurred-from the uroscopy to the information that a drop of urine is able to provide today-gives an optimistic outlook on the future: the old idea (of comprehensive urine diagnostics) in new bottles (with new analysis methods?) maybe yet be realized.

BAY 94-9027, a PEGylated recombinant factor VIII, exhibits a prolonged half-life and higher area under the curve in patients with severe haemophilia A: Comprehensive pharmacokinetic assessment from clinical studies.

INTRODUCTION: Recombinant factor VIII (rFVIII) products with extended half-lives, such as BAY 94-9027, can potentially maintain higher FVIII levels for longer periods of time, thus providing improved bleeding protection vs standard-acting FVIII products. AIM: To characterize the pharmacokinetic (PK) profile of BAY 94-9027 from phase 1, phase 2/3 (PROTECT VIII) and phase 3 (PROTECT VIII Kids) clinical trials in adults, adolescents and children with severe haemophilia A METHODS: Patients with severe haemophilia A (FVIII <1%) with >50 FVIII exposure days (EDs) and no history of inhibitors were included in the phase 1 (18-65 years, ≥150 EDs), PROTECT VIII (12-65 years, ≥150 EDs) and PROTECT VIII Kids (<12 years, >50 EDs) trials. PK parameters were assessed following a 25-IU/kg or 60-IU/kg BAY 94-9027 dose in the phase 1 study after the first and repeated infusion, in PROTECT VIII after the first and repeated 60-IU/kg infusion and in PROTECT VIII Kids after a single 60-IU/kg infusion. The chromogenic assay was used to assess FVIII activity. RESULTS: Compared with sucrose-formulated rFVIII, BAY 94-9027 had reduced clearance that resulted in a ~1.4-fold increase in half-life and dose-normalized area under the curve (AUC). The BAY 94-9027 PK profile was comparable after single- and repeated-dose administrations. Dose-proportional increases were observed between 25- and 60-IU/kg administrations. BAY 94-9027 PK characteristics were age dependent, consistent with other FVIII products. CONCLUSIONS: BAY 94-9027 shows an extended half-life and increased AUC vs standard-acting FVIII products. These PK characteristics will result in higher FVIII levels for longer duration.