Real-world Practice Research Articles

Referring wisely: knowing when and how to make subspecialty consultations in hospital medicine.

Subspecialty consultations are becoming highly prevalent in hospital medicine, due to an ageing population with multimorbid conditions and increasingly complex care needs, as well as medicolegal fears that lead to widespread defensive medical practices. Although timely subspecialty consultations in the appropriate clinical context have been found to improve clinical outcomes, there remains a significant proportion of specialty referrals in hospital medicine which are inappropriate, excessive, or do not add value to patient care. In this article, we sought to provide an overview of the common problems pertaining to excessive quantity and suboptimal quality of inpatient subspecialty consultations made in real-world practice and highlight their implications for healthcare financing and patient care. In addition, we discuss the underlying contributing factors that predispose to inappropriate use of the specialist referral system. Finally, we offer a practical, multitiered approach to help rationalize subspecialty consultations, through (i) a systematic model ('WISE' template) for individual referral-making, (ii) development of standardized healthcare institutional referral guidelines with routine clinical audits for quality control, (iii) adopting an integrated generalist care model, and (iv) incorporating training on effective referral-making in medical education.

Effectiveness of Vortioxetine Treatment on Depression and Cognitive Functions in Patients with Alzheimer's Disease: A 12-Month, Retrospective, Observational Study.

This study aimed to assess the effectiveness of vortioxetine for improving depressive symptoms, cognitive performance, daily and global functioning in patients with Alzheimer's disease (AD) and major depressive disorder (MDD) in real-world clinical practice. We retrospectively identified 46 AD patients who had received treatment for 12 months with vortioxetine. Drug effects were evaluated at baseline, 4, 8, and 12 months. The primary endpoint was change from baseline in the Hamilton Depression Rating Scale (HDRS) and in the Cornell Scale for Depression in Dementia (CSDD) to month 12. Cognitive and daily and global functioning changes were also evaluated. Significant baseline-to-endpoint improvement in depressive symptom severity was observed (p < 0.0001). At month 12, the least-square mean (standard error) change score from baseline was -10.48 (±0.42) on the HDRS and -9.04 (±0.62) on the CSDD. Significant improvements in cognitive performance were observed for the Rey Auditory Verbal Learning Test, the Symbol Digit Modalities Test, the Letter Fluency Test, the Category Fluency Test, and the Trail Making Test-A. Patients also experienced significant improvements in daily and global functioning. Vortioxetine was safe and well tolerated. Patients with AD and MDD receiving vortioxetine showed meaningful improvements in depressive symptoms, cognitive performance, and daily and global functioning over the 12-month treatment period.

Real-World Retention Rate, Effectiveness, and Safety of Netakimab in the Treatment of Patients with Ankylosing Spondylitis: First Year Results of the LIBRA Post-Registration Safety Study.

: To evaluate retention rates and safety of netakimab in patients with AS in real-world clinical practice. Additionally, the efficacy of netakimab was evaluated at 1-year follow-up. : Patients were recruited for the study from August 2020 to December 2021 at 23 centers in the Russian Federation. The study included patients who were prescribed netakimab therapy before enrollment, so clinical and medical history data for the first visit were entered retrospectively, and following visits at 12, 24, and 52 weeks of therapy were collected within the study. Drug survival rate was calculated according to Kaplan-Meier analysis. : The study included 137 (93 men and 44 women) patients with AS. The average age of patients was 42.3 (11.9) years, 34.3% of patients had previously received therapy with bDMARD, mainly TNF inhibitors. At the end of the analyzed period (52 weeks of therapy), 90.4% (95% CI, 85.4-95.7) of patients continued treatment with netakimab. The BASDAI and ASDAS-CRP showed statistically significant decreases in scores from baseline at all time points. Netakimab was well tolerated by patients; AEs, related to therapy according to the investigator's opinion, were reported in 7 (5.1%) patients. Two patients stopped taking netakimab due to AEs (terminal ileitis and chronic colitis). : In real-world clinical practice, netakimab demonstrated high retention rates, a favorable safety profile, and sustained efficacy throughout the first year of therapy.

Sexual side effects of antipsychotic drugs in schizophrenia: Protocol for a systematic review with single-arm, pairwise and network meta-analysis of randomized controlled trials and non-randomized studies

Introduction Sexual dysfunctions are common yet underreported side effects of antipsychotics for schizophrenia, affecting 30-80% of treated individuals. These side effects can severely impact social interactions and treatment adherence for individuals with schizophrenia, but comprehensive comparative evidence assessing the risk profiles of different antipsychotics is lacking. This study aims to address this gap using network meta-analysis that integrates data from both randomized-controlled trials (RCTs) and non-randomized studies (NRS). Protocol This systematic review will include both RCTs and NRS focusing on participants with schizophrenia or schizophrenia-like psychoses, without restrictions on symptoms, gender, ethnicity, age, or setting. For interventions, all second-generation antipsychotics will be included. The primary outcome will be the occurrence of at least one sexual adverse event of any kind. Secondary outcomes will be the occurrence of any sexual adverse event evaluated in men and women separately, and any adverse event related to the three phases of sexual response cycle separately: desire (e.g. libido, sexual thoughts), arousal (e.g. erection, lubrication) and orgasm (e.g. ejaculation, anorgasmia), and any adverse effect related to breast dysfunction and menstruation irregularities. Study selection and data extraction will be performed independently by two reviewers. The Cochrane Risk of Bias tool 1 and ROBINS-I will be employed to evaluate the risk of bias for RCTs and NRS, respectively. Single-arm meta-analysis of proportions will synthesize the average frequency of sexual adverse events in treated participants. Pairwise and network meta-analysis of RCTs and NRS will be used to evaluate comparative tolerability. Subgroup and sensitivity analyses will explore possible heterogeneity in results and validate the findings’ robustness. The quality of the evidence will be evaluated using GRADE. Discussion This study will provide vital insights into the sexual side effects of antipsychotics by combining evidence from clinical trials and real-world practice, facilitating better decision-making in choosing the optimal antipsychotic for individuals.

Efficient capture of dry eye data from the real world: The Save Sight Dry Eye Registry

PurposeTo describe a web-based, high-quality data collection tool able to track the clinical data of patients with dry eye disease (DED) in routine clinical practice. DesignRetrospective analysis of core system web data from a prospectively designed, observational, routine clinical practice registry, the Save Sight Dry Eye Registry (SSDER). MethodsPatients with DED, from 11-Nov-2020 to 04-Mar-2024 were analysed. Ocular Surface Disease Index (OSDI) and Ocular Comfort Index (OCI) questionnaires collected patient-reported DED symptoms, and the Patient Health Questionnaire-4 (PHQ-4) screened for anxiety and depression. Outcome data include index visit demography, DED symptoms and signs. ResultsFifteen clinicians (ophthalmologists and optometrists) from nine practices across Australia, France, Germany, Nepal, Spain and the United Kingdom contributed data, comprising index visits of 958 eyes from 479 patients (mean±SD age 56±17 years; 78.7% female). Up to 89.9% of the patients had either evaporative or mixed DED based on clinician's judgement. Mean OSDI symptom score at index visit was 35.7 ± 19.4 (n = 366), and the mean sores for frequency and intensity of discomfort with the OCI was 31.9 ± 6.1 and 31.4 ± 6.8 (n = 202) respectively. Forty-one percent of patients had mild to severe symptoms of anxiety and depression. Median tear breakup time and tear meniscus height were 5 (IQR 2–8) seconds and 0.3 (IQR 0.2–0.4) mm, respectively. Ocular surface staining was graded as none (37.6%), minimal (31.7%), mild (19.8%), moderate (8.8%) and severe (2.1%). ConclusionThe SSDER facilitated the collection of data from patients with DED from real-world clinical practice. Presenting patients had moderate DED, which was mostly evaporative in nature. Symptoms of anxiety and depression were reported by more than one-third of the cohort.

Real-World Practices of Pentosan Polysulfate Maculopathy Screening in Various Clinical Settings and Practice-Associated Factors.

Objectives: This study investigated the practice patterns of pentosan polysulfate (PPS) maculopathy screening in various clinical settings and demographic and clinical characteristics associated with these screening practices using a health claims database. Methods: In this nationwide population-based study, data from the Health Insurance Review and Assessment database in South Korea were analyzed to identify patients who underwent PPS. The participants were categorized based on whether they had undergone a baseline examination (the first ophthalmic examination since PPS prescription) within one year of PPS use, subsequent monitoring within one year of the baseline examination, or recent monitoring within a 1-year period before the study end date. Demographic and clinical factors were compared between the groups, and factors associated with screening practices were identified using logistic regression analyses. Results: Significant differences in screening practices were observed based on sex, age, residence, the medical specialty of the prescribing physician, indications for PPS use, and hospital type of prescription. Older patients who received PPS prescriptions from urologists were more likely to undergo baseline and monitoring examinations. Logistic regression analyses revealed that older age, female sex, and a longer duration of PPS use were significantly associated with baseline screening. Subsequent and recent monitoring was significantly associated with age, duration of PPS use, and treatment at primary hospitals. Conclusions: This study underscores the variability in screening practices for PPS users based on demographic and clinical factors, emphasizing the need for standardized guidelines. Enhanced awareness and timely referral for maculopathy screening, particularly among non-urological specialties, are essential.

Treatment outcome of bridge mechanical thrombectomy with different IV-tPA dosages in the standard and extended time window in real-world practice.

Differences of treatment outcome between full or reduced dose of tissue plasminogen activator (tPA) for bridge mechanical thrombectomy (MT) in the extended time window have not been clearly established. We aimed to present real-world results of bridge MT with different tPA dosages in the standard and extended windows. Patients with anterior circulation stroke treated with MT between 2017 and 2021 at two stroke referral centers were retrospectively reviewed. Bridge MT with tPA were categorized as full (0.9mg/kg) or reduced (<0.9mg/kg) dose. Standard window (SW) cohort was defined as MT performed within 6h of acute ischemic stroke onset, while those beyond 6h as the extended window (EW) cohort. 90days Modified Rankin Scale (mRS) score, technical treatment success, in-hospital mortality, and post-treatment hemorrhage were analyzed. A total of 423 patients met the inclusion criteria, 218 of which treated in the SW, while 205 treated in the EW. Within the SW cohort, the full-dose tPA group demonstrated a higher proportion of good functional outcome (GFO) at 90days (mRS0-3) versus reduced (49% vs 21%, p = 0.0358). The overall GFO of SW was higher than that of the EW cohort (33% vs 20%, p = 0.0480). Within the EW cohort, GFO was similar between full and reduced dose groups. Successful reperfusion rate was lower in SW versus EW cohorts (39% vs 58%, p = 0.0199). In real-world practice, the GFO of bridge MT is better than MT alone. The tPA dosage is not a determining factor of GFO in EW MT.

Acute procedural safety of the latest radiofrequency ablation catheters in atrial fibrillation ablation: Data from a large prospective ablation registry.

Safety data of the latest radiofrequency (RF) technologies during atrial fibrillation (AF) ablation in real-world clinical practice are limited. We sought to evaluate the acute procedural safety of the four latest ablation catheters commonly used for AF ablation. A total of 3957 AF ablation procedures performed between January 2022 and December 2023 at 20 centers with either the THERMOCOOL SMARTTOUCH SF (STSF), TactiCath (TC), QDOT Micro (QDM), or TactiFlex (TF) were retrospectively analyzed. In total, QDM, STSF, TF, and TC were used in 343 (8.7%), 1793 (45.3%), 1121 (28.4%), and 700(17.7%) procedures. Among 2406 index procedures, electrical pulmonary vein isolations were successfully achieved in 99.5%. Despite similar total procedure times in the four groups, the total fluoroscopic time was significantly shorter for QDM/STSF with CARTO than TF/TC with EnSite (18.7 ± 14 vs. 27.6 ± 20.6 min, p < .001) and longest in the TF group. The incidence of cardiac tamponade was 0.7% (0.5% and 0.9% during index and redo procedures, 0.8% and 0.3% for paroxysmal and non-paroxysmal AF) and was significantly lower for QDM/STSF than TF/TC (0.2% vs. 1.1%, p = .008) and highest in the TF group. The incidence of cardiac tamponade was higher for TF than TC and STSF than QDM. In the multivariate analysis, TF/TC with EnSite was a significant independent predictor of cardiac tamponade during both the index (odds ratio [OR] = 4.8, 95% confidence interval [CI] = 1.3-17.5, p = .02) and all procedures (OR = 3.0, 95% CI = 1.3-7.2, p = .01). The incidence of cardiac tamponade and the fluoroscopic time during AF ablation significantly differed among the latest RF catheters and mapping systems in real-world clinical practice.

One hundred cases of Rezum water vapor thermal therapy for benign prostatic hyperplasia: Real-world data at a single institution in Japan.

The objective of our study was to assess the efficacy of Rezum, a minimally invasive surgical treatment, for patients with lower urinary tract symptoms related to benign prostatic hyperplasia (BPH) in real-world clinical practice at a single institution in Japan. We conducted a prospective study involving 100 patients who underwent the Rezum procedure between October 2022 and February 2024. We analyzed patient backgrounds that are compliant with Japanese regulations and assessed descriptive outcomes such as symptom scores, peak flow in uroflowmetry, post-void residual (PVR) volume, and prostate volume (PVol). These data were collected at 1 and/or 3 months postoperatively. On average, 4.7 water vapor injections were administered during the Rezum procedures, with a mean operative time of 6.3 min. Patients experienced significant relief in symptoms, with reductions of 55% in International Prostate Symptom Score, 53% in quality of life score, and 30% in Overactive Bladder Symptom Score. There was also a significant decrease in mean PVR volume (50% reduction) and PVol (27% reduction). Among the subgroup of 23 pre-interventional catheter-dependent patients, 91% achieved catheter independence. Our single-center analysis demonstrates that Rezum is an effective and safe minimally invasive therapeutic option for patients with BPH. This promising novel technique can be particularly beneficial for patients at an augmented risk of bleeding or those considered high risk for anesthesia.

Factors encouraging participation in social activities after hospital discharge in people with severe mental illness who received occupational therapy.

Occupational therapy (OT), a vital part of psychiatric rehabilitation, encourages participation in social activities, which is critical for the recovery of people with severe mental illnesses (SMI). However, the effects of OT on the subsequent social activities of patients with SMI have not been fully clarified. We aimed to identify the factors that encourage post-discharge social activity participation among patients with SMI who received OT. Patients who underwent OT at the Kyorin University Hospital between April 2016 and March 2020 were retrospectively examined for baseline data during hospitalization and social activity status 1 year after discharge. Occupational support, group adaptation, artistic activities, and exercise programs were considered. Activities requiring social interaction were defined as social activities, including employment, schooling, sheltered work, and volunteer work. Multiple logistic regression analyses using demographic and medical data, prehospitalization social activity status, and OT participation rates as independent variables were used to examine the factors encouraging social activity participation after discharge. Decision tree analysis was conducted to identify patients who specifically needed to increase OT participation. Of 524 eligible patients, 247 were included in the study. The number of patients who were socially active at admission and after discharge was 116 and 188, respectively. Multiple logistic regression analyses revealed that the following factors were likely to encourage social activity participation after discharge: higher rates of OT participation to facilitate group adaptation (OR = 1.015, 95% CI 1.003-1.027), being socially active at admission (OR = 4.557, 95% CI 2.155-9.637), and no marital history (OR = 0.293, 95% CI 0.130-0.661). Decision tree analysis showed that for patients who were socially inactive at admission and had a history of marriage, increasing OT participation to 52.6% or higher may ensure social activity participation after discharge. This study identified patients whose social participation after discharge could be boosted by OT that facilitates group adaptation. Our findings would facilitate the development of individualized add-on rehabilitation based on the effects of real-world OT practices.

Efficacy and safety of tegoprazan- and rabeprazole-based concomitant therapies for Helicobacter pylori infection: Real-world evidence.

Tegoprazan, a novel potassium-competitive acid blocker, has been approved for Helicobacter pylori eradication in Korea. We compared the efficacy and safety of tegoprazan- and rabeprazole-based concomitant therapies for H.pylori eradication in real-world clinical practice. We retrospectively analyzed data from patients with H.pylori infection treated with tegoprazan- or rabeprazole-based concomitant therapies. The primary endpoint was H.pylori eradication rate. The secondary endpoint was adverse events. Among the 1474 included patients, 620 and 854 received tegoprazan- and rabeprazole-based concomitant therapies, respectively. Intention-to-treat analysis showed no significant difference in the eradication rates between the tegoprazan- and rabeprazole-based concomitant therapy groups (74.7% [95% confidence interval [CI], 71.1-78.0%] vs 72.7% [95% CI, 69.7-75.6%], P=0.400). Per-protocol analysis also demonstrated similar eradication rates for the groups (tegoprazan vs rabeprazole: 88.0% [95% CI, 85.0-90.6%] vs 85.9% [95% CI, 83.2-88.3%], P=0.288). Although the overall adverse event rate did not differ between groups (tegoprazan vs rabeprazole, 39.2% vs 40.6%, P=0.578), abdominal discomfort was less frequent in the tegoprazan group than in the rabeprazole group (1.3 vs 4.8%, P=0.001). Tegoprazan- and rabeprazole-based concomitant therapies for H.pylori eradication showed comparable efficacy and overall safety. The effect of tegoprazan on dose increases or other regimens, such as bismuth-containing quadruple therapy, should be further evaluated, because the efficacy of tegoprazan-based concomitant therapy may be suboptimal in regions where the clarithromycin resistance rate is high.

The status of MRI databases across the world focused on psychiatric and neurological disorders.

Neuroimaging databases for neuro-psychiatric disorders enable researchers to implement data-driven research approaches by providing access to rich data that can be used to study disease, build and validate machine learning models, and even redefine disease spectra. The importance of sharing large, multi-center, multi-disorder databases has gradually been recognized in order to truly translate brain imaging knowledge into real-world clinical practice. Here, we review MRI databases that share data globally to serve multiple psychiatric or neurological disorders. We found 42 datasets consisting of 23,293 samples from patients with psychiatry and neurological disorders and healthy controls; 1245 samples from mood disorders (major depressive disorder and bipolar disorder), 2015 samples from developmental disorders (autism spectrum disorder, attention-deficit hyperactivity disorder), 675 samples from schizophrenia, 1194 samples from Parkinson's disease, 5865 samples from dementia (including Alzheimer's disease), We recognize that large, multi-center databases should include governance processes that allow data to be shared across national boundaries. Addressing technical and regulatory issues of existing databases can lead to better design and implementation and improve data access for the research community. The current trend toward the development of shareable MRI databases will contribute to a better understanding of the pathophysiology, diagnosis and assessment, and development of early interventions for neuropsychiatric disorders.

Remote Symptom Alerts and Patient-Reported Outcomes (PROS) in Real-World Breast Cancer Practice: Innovative Data to Derive Symptom Burden and Quality of Life.

Treatment for breast cancer (BC) can lead to debilitating symptoms that can reduce outcomes and quality of life (QoL). Symptom surveillance using a remote symptom monitoring (RSM) platform enables the capture and reporting of patient-reported outcomes (PROs) from home. Women with BC used an RSM platform to complete weekly surveys and report any symptoms experienced during treatment. Symptoms reported as moderate/severe generated alerts to the clinical team. Clinical actions in response to the alert were captured. Results highlighted the value of data generated from a PRO-generated alert system to characterize longitudinal symptom burden and QoL in real-world BC practice, particularly in patients with poor functional status. The most prevalent symptoms that resulted in alerts were pain, nausea/vomiting, neuropathy, fatigue, and constipation. Most women reported one or more moderate/severe symptoms that generated an alert with an average of two alerts per week. Patients with frail status had more alerts, worse QoL and higher treatment bother, indicating that frail patients may benefit from continuous monitoring of symptoms, function, and QoL over time. A case study of patients without pre-existing peripheral neuropathy showed the rapid trajectory from the first report of mild neuropathy until alerts were generated, making a case for early intervention.

Genicular nerve radiofrequency ablation practice patterns: A survey study of the International Pain and Spine Interventional Society

IntroductionChronic knee pain often results from degenerative conditions such as knee osteoarthritis (OA) and can worsen after surgical interventions like total knee arthroplasty (TKA). Knee OA affects approximately 86 million individuals globally, leading to decreased function, mobility limitations, and disability. While TKA is a common surgical treatment for refractory knee OA, though up to 20 % of patients experience chronic post-operative knee pain worse than their pre-operative pain. Genicular nerve radiofrequency ablation (GnRFA) has emerged as a promising intervention for knee OA pain unresponsive to conservative management and for chronic post-TKA pain. GnRFA is an evidence-based technique supported by multiple prospective cohort studies and randomized controlled trials (RCTs). However, practice patterns and GnRFA techniques vary, and no peer-reviewed publication has yet quantified these variations in real-world clinical practice. ObjectiveThis study aims to understand the practice patterns of interventional pain physicians regarding patient selection, use of prognostic blocks, imaging, nerve targets, GnRFA types, and GnRFA techniques in treating knee pain secondary to OA or persistent post-TKA pain. MethodsAn anonymous 29-question survey was distributed via electronic mail to members of the International Pain and Spine Intervention Society (IPSIS) from January 16, 2024, to February 29, 2024. The survey assessed practice patterns related to patient selection, prognostic block use, and GnRFA techniques. Data were collected and stored using REDCap software, with descriptive statistics calculated. ResultsA total of 150 completed surveys were analyzed, representing a completion rate of 2.0 % of surveys sent, 3.5 % of emails opened, and 56.8 % of those who clicked on the survey link. Respondents generally use common selection protocols regarding OA grade (Kelgren-Lawrence 3 and 4), duration of failed conservative care (3–6 months), a single anesthetic block paradigm, and use of fluoroscopic guidance for the GnRFA procedure. More variability was reported between respondents regarding the volume of anesthetic used during prognostic blocks, the threshold to consider a prognostic block “positive,” the technology used, and nerves targeted during the GnRFA procedure. ConclusionThe study provides valuable insights into the current practice patterns of GnRFA among interventional pain physicians. While there is consensus on some aspects of patient selection and procedural techniques, significant variability exists in prognostic block protocols and nerve targets for GnRFA. These findings highlight the need for further research to explore the long-term efficacy and safety of GnRFA and to standardize techniques and protocols across different practice settings, ultimately improving patient outcomes and quality of life. The low response rate may limit generalizability, and the survey did not include data on active tip sizes used for ablation or whether other procedures should be exhausted before resorting to GnRFA. Additionally, a survey to IPSIS membership only may not fully represent a diverse cohort of pain management specialists, potentially introducing sampling bias. Future studies should include members from a broader range of professional organizations to enhance representativeness.

Stage IC grade 1 endometrioid adenocarcinoma of the ovary: assessment of post-operative chemotherapy de-escalation

ObjectiveGiven limited real-world practice data evaluating the National Comprehensive Cancer Network clinical practice guidelines for possible post-operative chemotherapy omission as a treatment option for patients with stage IC grade 1...

Caveats of Covariate Adjustment in Disproportionality Analysis for Best Practices.

Spontaneous reporting systems (SRS) provide valuable data for detecting unidentified adverse events not observed in clinical trials and for conducting safety assessments that accurately reflect real-world clinical practice. With the increasing number of publications using the SRS for disproportionality analysis (DA), there is an increasing demand for a comprehensive understanding of the research limitations associated with the SRS. However, there is a lack of understanding of the caveats associated with adjusting covariates in DA of the SRS. Herein, we summarized the use of covariate adjustment and its caveats in DA. The Council for International Organizations of Medical Sciences VIII suggests considering adjustments such as stratification when they can enhance the sensitivity and/or specificity of statistical analysis. However, several database-specific and statistical caveats have been identified when adjusting for covariates derived from the SRS. Disproportionality analysis may be affected not only by reporting bias at the time of enrollment but also by sparse-data bias due to variations in the number of enrollment reports. Statistical evidence is needed to determine in which cases and to what extent sensitivity and/or specificity are affected. Nevertheless, it is important for researchers to acknowledge that certain limitations discussed in this context may be inherent and cannot be rectified. Based on this understanding, they can then make an informed decision on whether to perform a covariate adjustment.

A community development approach for regenerative tourism in the Nordics: lifestyle entrepreneurs towards a placed-based research agenda

PurposeThe purpose of this conceptual paper is to explore the potential of regenerative tourism practices and their influence on destinations and their stakeholders from a community development approach focusing on Nordic lifestyle entrepreneurs. We focus on small and micro-sized enterprises (SMiEs) that conform to the realities of tourism systems in Nordic regions.Design/methodology/approachWe explore how community development can be used as an approach for regenerative tourism and vice versa. Our conceptual paper builds from recent work of the Nordic Regenerative Tourism project, which aims to develop place-based practices for SMiEs that contribute to the regeneration of natural and cultural resources.FindingsRegenerative tourism research should focus on developing tools that aid in capacity sharing and equitable partnerships through a community development approach. However, there is a lack of understanding of the processes of how to implement this in real world practice. More research is needed in developing tools to mobilize Nordic communities, particularly within the countryside to help transform tourism towards a regenerative model. It was found that much of these efforts comes from MSMEs. Therefore, more case studies are needed to understand how and why lifestyle entrepreneurs play in community revitalization efforts and the potential linkages with regenerative tourism management and marketing.Originality/valueThis conceptual paper contributes to the discussion of regenerative tourism and focus on smaller countryside communities within the Nordics. We argue that community development is linked with the concept of regenerative tourism through lifestyle entrepreneurs.

Exploring the Clinical Utility of Targeted MECP2 Testing in Real-World Practice

BackgroundThis study aimed to explore the clinical utility of targeted MECP2 testing in a large cohort of females with neurodevelopmental delays. Our aim was to identify suitable candidates for testing based on prevailing diagnostic criteria. MethodsEligible participants with global developmental delay/arrest or regression before age 36 months underwent MECP2 testing. MECP2-positive patients were further categorized based on Rett syndrome (RTT) diagnostic criteria, including typical, atypical, possible, and unclassified, to assess disease typicality and progression with respect to age. ResultsOf the 683 patients, 162 (23.7%) were diagnosed with MECP2-related RTT. Global developmental delay was the predominant initial symptom in approximately 75% of the cohort with developmental arrest/regression at testing. Symptoms emerged before age six months in 14 patients (8.6%). The average age at the time of MECP2 testing was 3.7 years, with 31.5% of the patients tested under two years. Of those under two years, 15 were initially categorized into the unclassified group; however, 12 were later reclassified into the typical/atypical RTT groups based on follow-up evaluation. Among the 119 patients monitored beyond age five years, 80% displayed typical RTT symptoms, 10 remained unclassified, and 9.8% had exonic deletions, posing challenges for detection using next-generation sequencing. ConclusionsTargeted MECP2 testing has emerged as a clinically valuable tool with a high diagnostic yield, including the identification of small deletions. Given that younger patients may not always meet the classic RTT criteria, this study recommends targeted MECP2 testing in younger patients without typical RTT features.

Design for excellence (DfX) for high-rise modular buildings: from DfX considerations to module design guidelines using the case of Hong Kong

ABSTRACT Design for excellence (DfX) presents a significant opportunity for early design to ensure the efficiency and buildability of high-rise modular buildings and realize their multidimensional benefits. Previous DfX contributions have primarily concentrated on its conception, offering various considerations from downstream construction stakeholders. Little research has integrated and transformed them into more practical, ready-to-use guidelines for upstream design professionals. This research, therefore, aims to incorporate prevailing piecemeal DfX considerations and establish module design guidelines. The guidelines were initially developed based on prior literature and case study, and their alignment with existing practices was subsequently tested. They recommend 1) a simplified rectangular module shape, 2) suggested module size, 3) standardized space across projects, and 4) dimensional coordination among modules and spaces. By utilizing them to analyze 39 high-rise module designs in Hong Kong, the results reveal some similarities between the proposed guidelines and real-world practices, affirming their concurrent validity and creating warrant assertions. This research bridges the knowledge gap between upstream and downstream practitioners, offers transformed DfX knowledge to systematically guide future implementations, and finally explains changes in architectural design. Future studies are advised to fine-tune the guidelines and incorporate findings with computational technologies to enhance generative DfX.

The effectiveness of 0.5 mg and 1mg of semaglutide in patients with type two diabetes and predictors of response: a retrospective cohort study.

Semaglutide is a glucagon-like peptide-1 receptor agonists (GLP-1-RAs) approved for the treatment of type 2 diabetes mellitus (T2DM) at doses up to 1 mg. The results from randomized control trials and real-world studies revealed that weekly semaglutide was associated with significant improvements in HbA1c and body weight. To our knowledge, no study assessed the effectiveness of using semaglutide for patients with T2DM in the Saudi population. We aim to assess the effectiveness of once weekly SC 0.5 and 1 mg of semaglutide on HbA1c and weight reduction in patients with T2DM in the Saudi population within 12 months of use, evaluate the predictors of response, and compare the effect of the two doses. This is a retrospective cohort study conducted at Security Force Hospital in Riyadh, Saudi Arabia. Using electronic medical records of patients with type two diabetes who received semaglutide 0.5 or 1 mg for a total duration of at least 12 months of use. Within the study period of semaglutide use, HbA1c significantly decreased from baseline by -2.1% (-2.3 to -1.91, 95% CI) (P <0.001). While the mean change in weight was -6.19kg (-6.66 to -5.72, 95% CI) (P<0.001). Moreover, BMI, FBG, total cholesterol, LDL, and TG all decreased significantly from baseline (p<0.001). When comparing the sub-groups of 0.5 and 1 mg doses, although results were numerically favorable of 1 mg, there were no statistically significant differences in HbA1c % (-2.1 ± 1.8 vs. -2.1 ± 1.9, p-value= 0.934, respectively), and weight (-6.1 ± 5 vs. -6.2 ± 4.4kg, p-value=0.837, respectively). Significant predictors of HbA1c reduction were the duration of DM, baseline HbA1c, and insulin therapy. While the significant predictor for weight reduction was insulin therapy. This study is document the effectiveness of once-weekly SC semaglutide on glycemic control and weight loss in real-world practice. We recommend a starting goal dose of 0.5 mg and gradual increase of dose based individual patient response. further studies are needed to assess the effectiveness and tolerability of various semagltude doses.