Conectar
Thanks to the introduction of recent national guidelines for treating herpes simplex virus (HSV) encephalitis, health outcomes have improved. This paper evaluates the health system costs and the health-related quality of life implications of these guidelines.
A sub-analysis of data from a prospective, multi-centre, observational cohort ENCEPH-UK study conducted across 29 hospitals in the UK from 2012 to 2015.
Data for patients aged ≥16 years with a confirmed HSV encephalitis diagnosis admitted for treatment with aciclovir were collected at discharge, 3 and 12 months.
Patient health outcomes were measured by the Glasgow outcome score (GOS), modified ranking score (mRS) and the EuroQoL; healthcare costs were estimated per patient at discharge from hospital and at 12 months follow-up. In addition, Quality Adjusted Life Years (QALYs) were calculated from the EQ-5D utility scores. Cost–utility analysis was performed using the NHS and Social Care perspective.
A total of 49 patients were included; 35 were treated within 48 hours, ‘early’ (median (IQR) 8.25 [3.7–20.5]) and 14 were treated after 48 hours ‘delayed’ (median (IQR) 93.9 [66.7–100.1]). At discharge, 30 (86%) in the early treatment group had a good mRS outcome score (0–3) compared with 4 (29%) in the delayed group. According to GOS, 10 (29%) had a good recovery in the early treatment group, but only 1 (7%) in the delayed group. EQ-5D-3L utility value at discharge was significantly higher for early treatment (0.609 vs 0.221, p
This study suggests that early treatment may be associated with better health outcomes and reduced patient healthcare costs, with a potential for savings to the NHS with faster treatment.
To evaluate an innovative approach to recruit 40 hospitals to a cluster randomised controlled trial (RCT) to improve discharge antibiotic prescribing.
This study describes the design, implementation and impact of a theory-informed recruitment approach for hospitals participating in the Reducing Overuse of Antibiotics at Discharge (ROAD) Home trial.
An inperson meeting of a quality improvement collaborative of acute care hospitals in the state of Michigan.
Representatives from acute care hospitals that are part of the Michigan Hospital Medicine Safety Consortium.
Small group recruitment sessions that combined deliberative participation and credible messengers to recruit hospitals to participate in a cluster RCT on a single date (1 November 2023).
The primary outcome was the number of hospitals which agreed to participate in the trial. We also assessed participant feedback, effectiveness of recruitment methods and resources required for implementation of this approach.
We recruited 51 (74%) of 69 eligible hospitals. Survey participants reported: sessions made clear the purpose of the trial (94%, 64/68) and time commitment required (87%, 59/68); agreed deliberative participation was helpful (82%, 56/68) and were ‘very satisfied’ with the session (82%, 56/68). Investigators largely reported credible messengers were a positive influence, though this varied across sessions. Hospital recruitment was time intensive, taking 179.5 total person hours. The recruitment process involved 3 months of preparation for the sessions and 2 months of follow-up prior to closing recruitment.
We demonstrated the feasibility and impact of a novel approach to recruit hospitals from an existing collaborative to a cluster RCT using the principles of deliberative participation and credible messengers. While the approach was time-consuming, we achieved success at over-recruiting hospitals in a relatively short period of time. Strategies presented here may assist future trial organisers in implementing hospital-based cluster RCTs.
The ROAD Home trial is registered on Clinical.Trials.gov (NCT06106204).
by Cheyenne R. Wagi, Renee McDowell, Anyssa Wright, Kathleen L. Egan, Christina S. Meade, April M. Young, Madison N. Enderle, Angela T. Estadt, Kathryn E. Lancaster
BackgroundHepatitis C virus (HCV) and injection drug use among young women are dramatically rising in the rural United States. From 2004 to 2017, heroin use among non-pregnant women increased 22.4% biennially, mirroring increases in HCV cases, especially among younger populations. Young women who inject drugs (YWID, ages 18–35) face elevated HCV risk due to biological, behavioral, and socio-cultural factors. Barriers to HCV testing and treatment services further delay diagnoses, fuel transmission, and limit access to harm reduction services. This study applies the Theoretical Domains Framework (TDF) to identify factors influencing HCV testing and treatment among YWID in rural Appalachia Ohio.
MethodsWe conducted in-depth interviews with YWID (n = 30) in 2023 to understand their HCV testing and treatment experiences in rural Appalachia Ohio. Interviews were transcribed, inductively coded, and analyzed using grounded theory. Identified themes were mapped onto the TDF domains.
ResultsKey TDF domains influencing HCV care included knowledge, beliefs about consequences, and intentions. While YWID knew where to get tested, they expressed uncertainty about treatment value and access while actively using drugs. Social influences, stigma, and mistreatment by healthcare providers created barriers to treatment. Environmental context and resources, such as transportation, also influenced access to care.
ConclusionsYWID in rural Appalachia face barriers to HCV care, such as gaps in knowledge about HCV treatment, which is compounded by gendered stigma, and logistical challenges. Rapidly changing treatment restrictions led to misinformation about treatment access. These gaps highlight the need for interventions specifically designed to address YWID lived experiences.
Head and neck cancer (HNC) accounts for over 4% of global cancer incidence, yet the oncological treatment induces several sequelae such as oral dysfunction, cervical and shoulder impairments or pain that are not well addressed. Thus, survivors of HNC (sHNC) perceive a decrease in their quality of life (QoL). This study protocol aims to investigate the effects of manual therapy (MT) to determine the effectiveness and safety on oral opening, swallow function and upper quarter mobility, cervical muscle strength, pain, functionality and QoL of sHNC.
A randomised controlled trial will include 70 sHNC over 18 years of age and will be divided into two groups. Intervention will last for 6 weeks with a total of 18 sessions, including MT targeting mastication and head and neck muscles. The control group will receive motor control exercises. The main outcomes will be oral opening and swallow function. An intention-to-treat analysis will be performed to evaluate the effectiveness of the intervention, which will be further determined with the calculation of effect sizes expressed in Cohen’s d.
The study was approved by the Ethics Committee of the Universidad de La Frontera (File 001_24) according to the Helsinki Declaration for Biomedical Research. All participants will provide informed consent. Study results will be published in open access peer-reviewed journals and may be shared at relevant meetings and research meetings.
This trial was registered with ClinicalTrials.gov on 28 November 2023 (code: NCT06148077).
Pharmacist prescribing has evolved to meet healthcare system needs, but the effectiveness, mechanisms and contextual factors influencing education programmes remain poorly understood. Realist approaches are fairly novel in pharmacy practice research. This realist synthesis aims to answer the question: to what extent do pharmacy prescribing education programs work (or not), for whom and under what circumstances, and why?
A realist methodology (realist synthesis) will be used to review the outcomes of programmes. Pawson’s key stages will be followed: (1) clarifying the scope; (2) determining the search strategy; (3) study selection; (4) extracting and analysing data; and (5) synthesising findings and drawing conclusions. The synthesis will follow Realist And Meta-narrative Evidence Syntheses–Evolving Standards publication guidelines. Data extracted will include the study characteristics, alongside the contexts, mechanisms and outcomes of varied pharmacy prescribing education programmes. The search strategy will include searching PubMed, Scopus, Web of Science and CINAHL Complete. An initial programme theory will use selected grey literature. Context-mechanism-outcome configurations will be identified, and recurring patterns will be synthesised to refine the initial programme theory.
Ethics approval is not required. Dissemination will be sought via peer-reviewed academic conferences and journals.
CRD420251056576.
by Kanyanee Promsawan, Chalurmpon Srichomthong, Monnat Pongpanich, Vorasuk Shotelersuk
DNA methylation, a key epigenetic modification, regulates gene expression and diverse cellular functions. Bisulfite sequencing (BS) remains the gold standard for methylation detection, while PacBio HiFi sequencing enables direct detection without chemical conversion. Although both technologies are increasingly used, few studies have directly compared their concordance, particularly in clinically relevant settings such as Down syndrome (DS). We performed a comparative analysis of DNA methylation profiles using whole-genome bisulfite sequencing (WGBS) and PacBio high-fidelity (HiFi) whole-genome sequencing (WGS) in a pair of monozygotic twins with DS. WGBS data were processed with two pipelines, wg-blimp and Bismark, while HiFi WGS data were analyzed using pb-CpG-tools. Our analysis focused on four key aspects: CpG site detection, genomic distribution of methylated CpGs (mCs), average methylation levels, and inter-platform concordance. HiFi WGS detected a greater number of mCs—particularly in repetitive elements and regions with low WGBS coverage—while WGBS reported higher average methylation levels than HiFi WGS. Both platforms exhibited methylation patterns consistent with known biological principles, such as low methylation in CpG islands, and the relative methylation patterns across genomic features were largely concordant. Pearson correlation coefficients indicated strong agreement between platforms (r ≈ 0.8), with higher concordance in GC-rich regions and at increased sequencing depths. Depth-matched comparisons and site-level down-sampling revealed that methylation concordance improves with increasing coverage, with stronger agreement observed beyond 20 × . Our findings support the reliability of HiFi WGS for methylation detection and highlight its advantages in regions that are challenging for bisulfite-based methods. This study demonstrates that HiFi WGS can serve as a robust alternative for genome-wide methylation profiling.Acute intracerebral haemorrhage (ICH) is devastating with a 1 month mortality rate of ~40%. Cerebral oedema can complicate acute ICH and is associated with poor outcome. In patients with large ICH, the accompanying swelling increases mass effect and causes brain herniation. Mannitol, an osmotic diuretic, is used to treat cerebral oedema after traumatic brain injury, but its safety and efficacy in ICH is unclear. We aim to assess the feasibility of a phase II randomised, controlled trial of mannitol in patients with ICH with, or at risk of, cerebral oedema to inform a definitive trial.
The mannitol for cerebral oedema after acute intracerebral haemorrhage trial (MACE-ICH) aims to include 45 ICH participants from 10 UK sites with estimated largest diameter of haematoma volume >2 cm, presenting within 72 hours of onset with, or at risk of, cerebral oedema (limited Glasgow Coma Scale (GCS)8) with or without mass effect. Participants will be randomised (1:1:1) to 1 g/kg 10% single-dose intravenous mannitol, 1 g/kg 10% mannitol followed by a second dose at 24 hours, or standard care alone. Outcome assessors will be masked to treatment allocation. Feasibility outcomes include proportion of patients approached being randomised, participants receiving allocated treatment, recruitment rate, treatment adherence and follow-up. Secondary outcomes include serum electrolytes and osmolality at days 1–2; change in ICH and oedema volume at day 5; number of participants who developed urinary tract infection, GCS and National Institutes of Health Stroke Scale at day 5±2; length of hospital stay, discharge destination and death up to day 28; death and death or dependency by day 180 and disability (Barthel Index), quality of life (EuroQol, 5-D) and cognition (telephone mini-mental state examination) at day 180.
MACE-ICH received ethics approval from the East Midlands-Leicester Central research ethics committee (22/EM/0242). The trial is funded by a National Institute for Health and Care Research RfPB grant (203080). The results will be published in an academic journal and disseminated through academic conferences and patient support groups. Reporting will be in line with Consolidated Standards of Reporting Trials recommendations.
ISRCTN15383301; EUDRACT 2022-000283-22.
by Chayanee Noosak, Pavarish Jantorn, Suvimol Surassmo, Sittichat Chukaew, Jirut Meesane, Dennapa Saeloh Sotthibandhu
Chronic osteomyelitis, often accompanied by bone loss, requires an adequate angiogenic response for bone regeneration. Loading growth factors into a drug vehicle to promote angiogenesis can address this challenge. In a previous study, we demonstrated the potential of sericin/polyvinyl alcohol (PVA) hydrogel as a functional biomaterial carrier for osteomyelitis treatment. In this study, we optimized sericin/PVA hydrogel for enhanced angiogenesis by supplementing sericin nanoparticles as vascular endothelial growth factor (VEGF) nanocarriers. Sericin nanoparticles, 284.20 ± 13.20 nm in size, exhibited a spherical morphology with 86% VEGF encapsulation efficiency. After integrating VEGF-loaded sericin nanoparticles, the hydrogel was coated with 0.1% and 1% gelatin, and its physical and mechanical properties were assessed. Coating the hydrogel with gelatin enhanced its swelling properties, providing an appropriate degradation rate to support bone regeneration and angiogenesis, and improve mechanical properties. The uncoated hydrogel and hydrogels coated with 0.1% and 1% gelatin exhibited burst release rates of 70%, 60%, and 45% with cumulative release rates on day 14 measured at 76%, 67%, and 57%, respectively. The hydrogels were biocompatible with MC3T3-E1 osteoblastic cell lines and human umbilical vein endothelial cells (HUVEC). The gelatin-coated hydrogels also promoted cell attachment of HUVEC cells. Gelatin-coated hydrogels containing VEGF-loaded sericin nanoparticles were evaluated for their bioactivity on HUVEC cell proliferation. After a 14-day treatment, cell proliferation in 0.1% gelatin-coated hydrogel was significantly higher than in 1% gelatin-coated hydrogel, with over a 160% increase. The expression levels of genes related to angiogenesis were quantitatively examined and results suggested that the hydrogels affected the eNOS pathway to promote angiogenesis. Despite optimization efforts, the sericin/PVA hydrogel maintained effective antibacterial activity against Gram-positive and Gram-negative bacteria. The enhanced sericin/PVA hydrogel showed promise as a novel implant biomaterial for treating chronic osteomyelitis, particularly by promoting angiogenesis.by Iyarath Putchong, Thaweesak Songserm, Sittinee Kulprasertsri, Shintaro Kobayashi, Preeda Lertwatcharasarakul, Wallaya Phongphaew
Duck Tembusu virus (DTMUV) belongs to the family Flaviviridae and genus Orthoflavivirus. It causes disease in ducks, affecting the nervous system and significantly reducing egg production. The first outbreak of DTMUV in Thailand was reported in 2013, with widespread cases across various regions. However, serological diagnosis of DTMUV is challenging due to antibody cross-reactivity with other flaviviruses. To address this issue, we developed an ELISA based on subviral particles. The cassette encoding the membrane precursor and envelope genes of DTMUV (strain KPS54A61) were cloned into a pCAGGS vector with an OSF-tag and transfected into HEK-293T cells to generate subviral particles. The subviral particles were detected in the supernatant of the transfected cell via immunoblotting using anti-DTMUV E protein and anti-Strep-tag antibodies, which revealed a protein band of approximately 59 kDa. An electron microscopy confirmed the presence of particles approximately 35 nm in diameter. To optimize the SP-based ELISA, checkerboard titration identified the optimal antigen concentration as 70 µg/mL and the optimal serum dilution as 1:100,000. A cut-off value was established for the assay, and testing 300 duck serum samples using the SP-based ELISA identified 41 positive samples (14%) and 259 negative samples (86%). The SP-based ELISA exhibited 100% sensitivity and specificity, achieving a perfect agreement score of 1.0 in comparison with the serum neutralization test. Additionally, specificity testing using antibodies specific to Japanese Encephalitis virus (JEV) revealed no cross-reactivity in the ELISA test. Therefore, the developed SP-based ELISA is highly effective for screening and monitoring DTMUV outbreaks in duck farms, significantly reducing the risk of viral spread and enabling the timely implementation of disease control measures.Hypernatraemia, defined as a plasma sodium concentration >145 mmol/L, is a frequent complication in critically ill patients treated in the intensive care unit (ICU) (= ICU-acquired hypernatraemia), with reported prevalence ranging from 4% to 26%. Hypernatraemia adversely affects various physiological functions and is associated with delirium, prolonged length of stay and increased ICU and post-discharge mortality. The sodium load from intravenous drug diluents significantly contributes to ICU-acquired hypernatraemia, with drug infusions comprising about 30% of the daily fluid volume of an average ICU patient. This study aims to investigate if using glucose 5% solution as the default drug diluent, instead of sodium chloride 0.9%, can reduce the prevalence of ICU-acquired hypernatraemia and improve patient outcomes.
To test the effectiveness of glucose 5% solution as the default drug diluent, we will conduct a multicentre, pragmatic, embedded, open-label, stepped-wedge, cluster-randomised trial. The study will include twelve clusters (ICUs and one intermediate care unit) across six hospitals in Germany, with a projected total sample size of 4485 patients. In line with the stepped-wedge cluster-randomised design, one ICU will transition every 4 weeks, in a randomised sequence, from using sodium chloride 0.9% as the default drug diluent to glucose 5%.
The primary endpoint is the prevalence of hypernatraemia >150 mmol/L through day 28. The number of days alive and free of the ICU through day 28 will be tested hierarchically as a key secondary endpoint. Other exploratory endpoints include ICU mortality, ICU-free days, hospital-free days and other clinical outcomes. The primary endpoint will be analysed using a logistic mixed-effects model.
The trial was approved by the Charité—Universitätsmedizin Berlin Ethics Board and by the ethics board of each enrolled hospital. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.
The trial protocol was registered with the German Clinical Trials Register on 21 June 2024 prior to initiation of patient enrolment (DRKS00033397).
Deep brain stimulation (DBS) is a proven effective treatment for Parkinson’s disease (PD). However, titrating DBS stimulation parameters is a labourious process and requires frequent hospital visits. Additionally, its current application uses continuous high-frequency stimulation at a constant intensity, which may reduce efficacy and cause side effects. The objective of the AI-DBS study is to identify patient-specific patterns of neuronal activity that are associated with the severity of motor symptoms of PD. This information is essential for the development of advanced responsive stimulation algorithms, which may improve the efficacy of DBS.
This longitudinal prospective observational cohort study will enrol 100 patients with PD who are bilaterally implanted with a sensing-enabled DBS system (Percept PC, Medtronic) in the subthalamic nucleus as part of standard clinical care. Local neuronal activity, specifically local field potential (LFP) signals, will be recorded during the first 6 months after DBS implantation. Correlations will be tested between spectral features of LFP data and symptom severity, which will be assessed using (1) inertial sensor data from a wearable smartwatch, (2) clinical rating scales and (3) patient diaries and analysed using conventional descriptive statistics and artificial intelligence algorithms. The primary objective is to identify patient-specific profiles of neuronal activity that are associated with the presence and severity of motor symptoms, forming a ‘neuronal fingerprint’.
Ethical approval was granted by the local ethics committee of the Amsterdam UMC (registration number 2022.0368). Study findings will be disseminated through scientific journals and presented at national and international conferences.
by Wiriya Mahikul, Wisut Lamlertthon, Kanchana Ngaosuwan, Pawaree Nonthasaen, Napat Srisermphoak, Wares Chancharoen, Saimai Chatree, Arpaporn Arnamwong, Pisinee Narayam, Chatchamon Wandeecharassri, Pakin Wongpanawiroj
BackgroundDepression has a growing trend in the population worldwide. In this cross-sectional study, we investigated the prevalence and associated factors of depression among individuals residing in rural (Ban Luang district, Nan Province) and urban (Lak Si, Bangkok) areas of Thailand. Understanding the differences in depression between these two settings can provide insights for specific targeted interventions and mental health policies.
MethodsThe multistage stratified random sampling was applied to select the study participants. We recruited participants from rural and urban communities in Thailand using a structured survey questionnaire through either face-to-face interviews or in paper or electronic form. We collected data on depression using the Patient Health Questionnaire-9 (PHQ-9) tool and sociodemographic characteristics and conducted descriptive statistics and logistic regression analysis.
ResultsOf 867 survey participants, 420 were from rural areas (Nan) and 447 were from urban areas (Bangkok). Participants’ mean age was 55.9±9.5 years in rural areas and 56.0±12.0 years in urban areas. Most participants in urban areas were women, married, and had lower education levels (71.1%, 50.3%, 58.8%, respectively). The overall prevalence of depression across both settings was 18.6%. We found a higher prevalence of depression in the urban (31.8%) than the rural (4.5%) setting. In multiple logistic regression analysis, urban residence was significantly associated with higher rates of depression compared with rural residence (adjusted odds ratio [AOR] 9.43, 95% confidence interval [CI] 5.08–17.52). Nuclear family and using social media were associated with lower levels of depression in urban areas (AOR 0.50 and 0.43, 95% CI 0.27–0.93 and 0.22–0.84, respectively). Higher education level was significantly associated with higher levels of depression in rural areas (AOR 3.84, 95% CI 1.19–12.42).
ConclusionThis study emphasized the difference in depression and related factors between rural and urban areas of Thailand, highlighting a greater prevalence in urban areas. To help prevent depression, it is important to address specific challenges in each setting, such as those faced by highly educated individuals living in rural areas with high depression rates, exploring social media use patterns in urban populations, and understanding dynamics of the nuclear family. Our findings can inform the development of public health policies aimed at effectively mitigating the burden of depression and improving overall mental well-being in specific settings.
FreshRSS 