Initial Treatment Research Articles

Endovascular management of acute superior mesenteric vein thrombosis: a retrospective study on thrombolysis outcomes.

Acute superior mesenteric vein thrombosis (ASMVT) is a rare but life-threatening condition associated with high morbidity and mortality. While anticoagulation remains the standard treatment, endovascular therapies such as thrombolysis, thrombectomy, and angioplasty are increasingly utilized in selected cases. However, evidence on their outcomes remains limited. This study retrospectively reports the clinical outcomes of ASMVT patients treated with endovascular combination therapies. Between August 2019 and May 2024, 12 patients (males = 9; mean age, 52.33 ± 12.51years) were diagnosed with ASMVT. The study collected comprehensive data on demographic details, presenting symptoms, etiology, treatment modalities, response to treatment, and follow-up outcomes. Computed Tomography (CT) was available from diagnosis, and an average of 6.3 CT scans with a median follow-up of 3months (IQR: 2-20months). The average time from symptom onset to angiographic treatment initiation was 8.0 ± 4.71days, preceded by anticoagulation with heparin from the time of diagnosis. Patients were treated with combination therapy involving endovascular thrombolysis, rheolytic thrombectomy, and balloon angioplasty via transjugular (n = 9, 75%) or percutaneous (n = 3, 25%) approaches. Thrombolysis was performed with an average recombinant tissue plasminogen activator (rt-PA) infusion duration of 2.75 ± 1.14days and a total dose of 61.25 ± 18.48mg rt-PA. Superior mesenteric vein (SMV) flow was initially restored almost completely in 58.3% and partially in 41.7% of patients. Complications observed were hepatic artery bleeding (n = 2, 16.7%), hepatic arteriovenous fistula (n = 1, 8.3%), hepatic parenchymal bleeding (n = 1, 8.3%), melena (n = 1, 8.3%), and nostril bleeding (n = 1, 8.3%). Two patients experienced worsening symptoms of post-intervention, leading to bowel resection revealing intestinal necrosis. SMV patency was almost complete in 25%, and partially in 25% of patients at follow-up. Endovascular combination therapy with long-term thrombolysis and thrombectomy in patients with ASMVT demonstrated promising technical outcomes. In view of complications, individual indication for intervention needs to be confirmed in a multidisciplinary team.

Developing the MyCancerGene Digital Health Portal to Improve Patients' Understanding of Germline Cancer Genetic Test Results: Development, User, and Usability Testing Study.

The use of multigene panels has significantly increased the likelihood that genetic testing will leave patients with uncertainties regarding test interpretation, implications, and recommendations, which will change over time. Effective longitudinal care models are needed to provide patients with updated information and to obtain patient and family history updates. To bridge this gap, we aimed to develop a patient- and genetic provider-informed digital genetic health portal (GHP), MyCancerGene, to improve longitudinal patient understanding of and responses to genetic testing. We used a 5-step process to develop MyCancerGene. To better understand their interest in and willingness to use a digital GHP, we surveyed 307 patients who completed genetic testing (step 1). We completed qualitative interviews with 10 patients and a focus group with 17 genetic providers to inform the content and function of MyCancerGene (step 2). Next, we developed initial intervention content (step 3) and completed user testing of intervention content with 25 providers and 28 patients (step 4). After developing the prototype intervention, we completed usability testing with 8 patients for their feedback on the final content, functions, and ease of use (step 5). In surveys conducted in step 1, 90% of patients with positive results reported interest in a digital GHP, and over 75% of participants with variants of uncertain significance or uninformative negative results reported similar interest. The most frequently reported advantages among patients were increasing accessibility, convenience, and efficiency (103/224, 46%); keeping genetic information organized (54/224, 24.1%); and increasing or maintaining patient understanding of the information (38/224, 17%). In qualitative interviews (step 2), both patients and genetic providers endorsed the benefit of the tool for updating personal and family history and for providers to share new risk information, test interpretation, or other medical changes. Patient and provider input informed eight key components of the tool: (1) Landing Page, (2) Summary of Care page, (3) My Genetic Test Results page, (4) My Family History page, (5) Provide an Update page, (6) Review an Update page, (7) Resources page, and (8) the Screenings Tracker. They also recommended key functions, including the ability to download and print materials and the inclusion of reminders and engagement functions. Potential challenges identified by patients included privacy and security concerns (67/206, 32.5%) and the potential for electronic information to generate distress (20/206, 9.7%). While patients were comfortable with updates (ie, even variant reclassification upgrades or clinically significant results), 44% (11/25) of genetic providers were uncomfortable sharing variant reclassification upgrades through MyCancerGene. MyCancerGene, a patient-centered digital GHP, was developed with extensive patient and genetic provider feedback and designed to enhance longitudinal patient understanding of and affective and behavioral responses to genetic testing, particularly in the era of evolving evidence and risk information.

Cost-effectiveness of opportunistic osteoporosis screening using chest radiographs with deep learning in Germany

BackgroundOsteoporosis is often underdiagnosed due to limitations in traditional screening methods, leading to missed early intervention opportunities. AI-driven screening using chest radiographs could improve early detection, reduce fracture risk, and improve public health outcomes.AimsTo assess the cost-effectiveness of deep learning models (hereafter referred to as AI-driven) applied to chest radiographs for opportunistic osteoporosis screening in German women aged 50 and older.MethodsA decision tree and microsimulation Markov model were used to calculate the cost per quality-adjusted life year (QALY) gained (€2024) for screening with AI-driven chest radiographs followed by treatment, compared to no screening and treatment. Patient pathways were based on AI model accuracy and German osteoporosis guidelines. Women with a fracture risk below 5% received no treatment, those with 5–10% risk received alendronate, and women 65 + with a risk above 10% received sequential treatment starting with romosozumab. Data was validated by a German clinical expert, incorporating real-world treatment persistence, DXA follow-up rates, and treatment initiation. Sensitivity analyses assessed parameter uncertainty.ResultsThe cost per QALY gained from screening was €13,340, far below the typical cost-effectiveness threshold of €60,000. Optimizing follow-up, treatment initiation, and medication adherence further improved cost-effectiveness, with dominance achievable by halving medication non-persistence, and in women aged 50–64.ConclusionAI-driven chest radiographs for opportunistic osteoporosis screening is a cost-effective strategy for German women aged 50+, with the potential to significantly improve public health outcomes, reduce fracture burdens and address healthcare disparities. Policymakers and clinicians should consider implementing this scalable and cost-effective screening strategy.

Late gestational nutrient restriction decreases placental size and calf birth weight without altering uterine blood flow in primiparous beef females.

To investigate impacts of late gestational nutrient restriction in first-parity beef females on prenatal nutrient availability to calves, fall-calving heifers [body weight (BW): 472 ± 33 (SD) kg; body condition score (BCS): 5.4 ± 0.5] were individually-fed 100% (control; CON; n = 13) or 70% (nutrient restricted; NR; n = 13) of metabolizable energy and metabolizable protein requirements for maintenance, pregnancy, and growth from day 160 of gestation to calving. Maternal measures were determined every 21 d (BW and metabolites) or 42 d (BCS, backfat, and longissimus muscle area) during gestation and post-calving. Doppler ultrasonography of both uterine arteries was conducted every 21 d until day 244 of gestation. At birth, calf BW and size were measured, and expelled placentas were dissected and dried. Targeted messenger ribonucleic acid (mRNA) expression was determined for cotyledons. Data were analyzed with nutritional plane, treatment initiation date, heifer's sire, and calf sex (when P < 0.25) as fixed effects. Metabolites and uterine blood flow included day and nutritional plane × day as repeated measures. Circulating glucose was less (P = 0.05) for NR dams than CON. Circulating urea N and triglycerides were less (P ≤ 0.05), but non-esterified fatty acids were greater (P ≤ 0.05), for NR at most timepoints after treatment initiation. Post-calving, NR dams were 62.1kg and 2.1 BCS less (P < 0.01) than CON. Moreover, NR had less (P < 0.01) backfat and longissimus muscle area, but similar (P = 0.72) shoulder height compared with CON. Heart rate was less (P < 0.01) for NR dams than CON after treatment initiation. Nutritional plane did not affect (P ≥ 0.15) ipsilateral, contralateral, or total uterine artery blood flow. Number of cotyledons was greater (P = 0.03), average cotyledon weight was less (P = 0.04), and total placental weight tended to be less (P = 0.10) for NR than CON. Cotyledonary relative mRNA expression of GLUT1 was greater (P = 0.04) and SNAT2 tended to be greater (P = 0.07) for NR, but other nutrient transporters, angiogenic factors, and PAG2 were not affected (P ≥ 0.13). Calves born to NR dams weighed 14.4% (P = 0.03) less at birth and had smaller (P ≤ 0.03) heart girth and volume than CON. Despite catabolizing maternal tissue stores, beef heifers experiencing late gestational nutrient restriction had altered circulating metabolites and smaller placentas, independent of a reduction in uterine blood flow, which compromised fetal growth.

A Rare Case of Cervical Subcutaneous Emphysema Following Swimming.

Subcutaneous cervical emphysema refers to the presence of air or gas trapped beneath the skin in the neck or cervical region. It typically occurs when air is introduced into the tissues due to trauma, infection, or medical procedures that disrupt the respiratory tract. Diagnosis is based on clinical presentation in addition to chest and neck radiographic examinations. Subcutaneous cervical emphysema resulting from swimming is extremely rare, and patients may be asymptomatic or present with crepitus, neck swelling, and dysphonia. In severe cases, life-threatening complications can occur, such as airway compromise or tension pneumothorax. The authors of this manuscript report a rare case of a 9-year-old female, previously healthy, who presented with subcutaneous cervical emphysema following a swimming training session. This patient was followed up for 1 month with conservative management and experienced self-resolution of her symptoms. Early diagnosis, monitoring, and initiation of treatment are highly recommended to prevent any long-term or life-threatening complications.

Effect of Cumulative Exposure on the Efficacy of Paroxetine: A Population Pharmacokinetic-Pharmacodynamic and Machine Learning Analyses.

Selective serotonin reuptake inhibitors (SSRIs) are widely used in depression treatment. However, the relationship between treatment efficacy and plasma concentrations remains unclear. We assessed whether the anti-depressive response can be predicted based on the pharmacokinetic (PK) data of paroxetine, a frequently used SSRI. During treatment, we measured the plasma paroxetine concentrations in 179 paroxetine-treated patients with major depressive disorder. Of these patients, 50 patients had received a pre-treatment personality assessment using the Temperament and Character Inventory at baseline, and their depression severity was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) at baseline and 1, 2, 4, and 6 weeks after treatment initiation. We conducted population PK modeling followed by a population PK-pharmacodynamic (popPK/PD) model to analyze the enhancement in depression severity until 6 weeks of paroxetine treatment using nonlinear mixed-effects modeling. Additionally, we developed machine learning models to predict the likelihood of remission after 6 weeks. The contribution of each feature to the prediction was explained using SHapley Additive exPlanations (SHAP) values. The area under the plasma paroxetine concentration-time curve during the first week (AUC0-1week) and MADRS score after 1 week of treatment (MADRSW1) were incorporated into the popPK/PD model. The SHAP values indicated that the AUC0-1week and MADRSW1 were the significant predictors of remission. Our results indicate that therapeutic responsiveness to paroxetine can be anticipated from its cumulative exposure, highlighting the clinical relevance of assessing SSRI blood concentrations.

Study assessing the effectiveness of overdose prevention centers through research (SAFER): an overview of the study protocol

More than one million people have died from drug overdose in the United States in the past 20 years. The overdose crisis started in the late 1990s with the proliferation of overdoses involving prescription opioids, transitioned to heroin-involved overdoses in 2010, and is currently driven by illegally manufactured synthetic opioids such as fentanyl. In response to this crisis, New York City implemented two publicly recognized overdose prevention centers (OPCs) in the nation in November 2021. Rhode Island became the first US state to authorize OPCs through state legislation and will open a site in Fall 2024. We are conducting a rigorous, multi-site, multi-component evaluation of OPCs in New York City and Rhode Island. At the individual level, we assess whether a cohort of 500 persons utilizing OPCs experience lower rates of overdose, other health problems (e.g., hepatitis C, skin infections), and emergency department use, and a higher rate of substance use treatment initiation, compared to a cohort of 500 persons who use drugs but do not utilize OPCs. At the community level, we examine whether neighborhoods surrounding the OPCs experience a greater change in overdose, measures of drug-related public disorder, and acute economic conditions following the opening of OPCs, compared to neighborhoods with no OPCs. Third, we delve into the role that the operational context, including neighborhood location, program models, and operating procedures, plays in shaping the effectiveness of OPCs using qualitative and ethnographic approaches. Fourth, we estimate the costs and cost savings associated with starting up and operating OPCs. In this paper, we: (1) present the study design and harm reduction framework which is used to evaluate the impact of OPCs in New York City and Rhode Island; (2) share the types of assessment instruments and data sources used to measure changes at the individual and community level; and (3) discuss the strengths and limitations associated with the planned approach to evaluate the health and community effects of OPCs.

Rechallenge of an alternative CDK 4/6 inhibitor after hepatotoxicity in the treatment of hormone-positive metastatic breast cancer.

IntroductionCyclin Dependent Kinase (CDK) 4/6 inhibitors are changing the landscape of breast cancer treatment. These medications are generally well-tolerated, but incidences of hepatotoxicity have been reported in the literature.Case ReportIn this case, we present a 36-year-old Caucasian female who was diagnosed with hormone-receptor (HR) positive, human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer who initiated first line treatment with an aromatase inhibitor and a cyclin-dependent kinase (CDK) 4/6 inhibitor, ribociclib. Following treatment initiation, she experienced grade 4 hepatoxicity.Management and OutcomeRibociclib was discontinued due to probable cause of hepatotoxicity based on a Naranjo score of 7. Once her liver enzymes resolved to grade 1 toxicity, she was transitioned to another CDK 4/6 inhibitor, palbociclib. The patient has remained on palbociclib for 1 year of treatment with normalization of her liver function enzymes and stable disease.DiscussionThis case presents a successful rechallenge of an alternative CDK 4/6 inhibitor after grade 4 ribociclib-induced hepatotoxicity and reviews similar cases of ribociclib-induced hepatoxicity and management strategies.

Revisiting the Open Vein Hypothesis to Reduce the Postthrombotic Syndrome: Implications for Multidisciplinary Care and Research: A Scientific Statement From the American Heart Association.

The "open vein hypothesis" postulates that early thrombus clearance and restoration of venous blood flow may prevent postthrombotic syndrome after proximal deep vein thrombosis. Since its proposal several decades ago, new insights from basic and clinical studies have motivated a re-evaluation and refinement of this hypothesis. According to data from these studies, susceptibility to postthrombotic syndrome occurs as a result of differences in genetic composition, thrombophilic conditions, predilection to inflammation and fibrosis, endogenous fibrinolytic capability, timing of s ymptom presentation and treatment initiation, and efficacy of antithrombotic therapy. Although initial restoration of an open vein appears to be beneficial for selected patient groups, freedom from postthrombotic syndrome is more likely in the setting of long-term venous patency, reduced recurrent thrombotic episodes, and reduced perithrombotic (eg, vein wall and valve) inflammation. These underlying biological mechanisms need further elucidation, with a long-term goal of personalizing treatment by mapping the individuals' clinical presentation with their underlying risk factors and assessing time-dependent biological processes that occur as a clinical venous thrombosis resolves. This scientific statement (1) highlights historical fundamentals of the open vein hypothesis and then showcases new research insights into the pathophysiological factors driving postthrombotic syndrome; (2) discusses advantages and disadvantages of imaging modalities for deep vein thrombosis used in clinical practice, including the potential to depict thrombus chronicity and status of vein wall injury; (3) proposes measures to develop integrated multidisciplinary care for deep vein thrombosis focused on the reduction of postthrombotic syndrome; and (4) identifies priority areas and questions for further research.

Adaptive Servo-ventilation for Treatment-emergent Central Sleep Apnea: The READ-ASV Registry.

Treatment-emergent central sleep apnea (TE-CSA) is the most common indication for adaptive servo-ventilation (ASV). Evidence on the effects of TE-CSA treatment on quality of life (QoL) is limited. To test the hypotheses that patients with TE-CSA who have cardiovascular disease (CVD) would be less symptomatic than those with CVD, and that the beneficial effects of ASV on QoL/sleepiness might be smaller in individuals with versus without CVD. ASV-naïve adults with TE-CSA and an ASV prescription were included in this analysis of the Registry on the Treatment of Central and Complex Sleep-Disordered Breathing with ASV (READ-ASV). QoL (Functional Outcomes of Sleep Questionnaire [FOSQ] and daytime sleepiness (Epworth Sleepiness Scale [ESS]) were assessed at baseline and 12-month follow-up. Of 452 TE-CSA patients, 81% had CVD. Before treatment initiation FOSQ and ESS scores were better in those with versus without CVD. On ASV, in the CVD and no CVD subgroups, median [interquartile range] FOSQ score significantly increased (+0.72 [-0.20; +1.98], p<0.001 and +0.90 [-0.12; +2.29], p<0.001, respectively) and the ESS score significantly decreased (-2.00 [-5.00; 0.00], p<0.001 and -3.00 [-6.75; 0.00], p<0.001); improvement magnitude was similar in both subgroups (p=0.454 and p=0.120). The majority of individuals with TE-CSA and an ASV therapy prescription had CVD. Although those with TE-CSA and CVD were less symptomatic than those without CVD, ASV had a positive effect on QoL and sleepiness in these individuals, as well as those without CVD.

Pearls & Oy-sters: Late-Onset Presumed SUNA in a 91-Year-Old Woman With Headache.

Short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) is a rare form of headache classified under trigeminal autonomic cephalalgias. It typically occurs in middle adulthood, most commonly between ages 30 and 60 years; however, a case of an 88-year-old patient has been reported. Here, we present a 91-year-old woman with a 2-month history of headaches with features suggestive of SUNA. However, the criterion of experiencing a second bout 3 months apart was not satisfied, rendering the diagnosis presumptive. Comprehensive investigations, including MRI and MRA of the brain, ruled out secondary causes such as vascular or structural abnormalities. The patient was successfully treated with pregabalin, achieving full remission of attacks within 2 weeks of treatment initiation. Recognizing SUNA in the older population is crucial because this headache disorder can present later in life. Key diagnostic features include cranial autonomic symptoms, brief attack duration, high attack frequency, and stabbing pain quality, enabling prompt diagnosis and treatment to improve patients' quality of life.

Fathoming the scientific paradox of intangibles: protocol reappraisal for optimizing cognitive outcomes in faciocraniosynostosis-an institutional experience.

The critical nature of normal intracranial pressure (ICP) and proper airway function in early brain development, particularly in the first 5years, are well established. These elements are compromised in faciocraniosynostoses and potentially affect neurological growth. The impact of variations in ICP and airway on cognitive development remains underappreciated and challenging to quantify. The primary aim of this study was to assess the efficacy and safety of a comprehensive early surgical intervention institutional protocol in children (0-5years) with syndromic faciocraniosynostosis. We retrospectively analyzed our comprehensive surgical protocol in children who consecutively underwent cranial vault and midface procedures for syndromic craniosynostosis between July 2015 and January 2024, focusing on those who underwent both calvarial and midface surgeries before the age of 5years. Our treatment algorithm prioritized posterior calvarial distraction (PCVD) as the initial intervention for children with faciocraniosynostoses. Frontal orbital advancement and remodeling (FOAR) is preferred to address aesthetic concerns and ICP in older children. Midface distraction was performed for clinically significant airway compromise. The cohort included 31 children with a mean age of 18.8months at the initial surgery. The primary procedures included PCVD (n = 16), robotic-assisted frontofacial advancement (RAFFA) (n = 5), robotic-assisted midface distraction (RAMD) (n = 6), and FOAR (n = 4). The second procedure (n = 25) included RAFFA (n = 5), RAMD (n = 13), and FOAR (n = 7). The third procedure (n = 11) included RAMD (n = 1), FOAR (n = 9), and repeat PCVD (n = 1). The mean age of the patients at the final surgery was 57.5months. This comprehensive strategy addresses both cranial and midface issues and the challenge of optimizing cognitive development within the critical developmental window.

Oral Anticoagulation and Risk of Adverse Clinical Outcomes in Venous Thromboembolism.

Over the past decade, there has been a considerable shift in the use of pharmacologic agents for venous thromboembolism (VTE), with direct oral anticoagulants replacing warfarin as the drugs of choice for VTE recurrence prevention; however, evidence from head-to-head comparison studies remains limited. To compare the effectiveness and safety of 3 common oral anticoagulants (apixaban, rivaroxaban, and warfarin) in patients with VTE. This population-based cohort study used Medicare and 2 commercial insurance databases from 2016 up to 2024 to identify patients 18 years and older who initiated an oral anticoagulant following VTE and had at least 1 year of continuous insurance enrollment before the index date. Initiation of apixaban, rivaroxaban, or warfarin within 30 days after VTE discharge. The primary effectiveness outcome was hospitalization for recurrent VTE. The primary safety outcome was major bleeding. Patients were followed up from treatment initiation until outcome occurrence, treatment discontinuation/switch, disenrollment, death, or end of available data. Propensity score-matching weights were used to adjust for confounding. Weighted Cox proportional hazard models estimated weighted hazard ratios (HRs) and 95% CIs. Among 163 593 eligible individuals (mean [SD] age, 71.4 [13.5] years; 56.7% female), 58.5% initiated apixaban, 25.7% initiated rivaroxaban, and 15.8% initiated warfarin. Overall, 3270 hospitalizations for recurrent VTE and 4229 hospitalizations for bleeding events occurred. Compared with warfarin, patients taking apixaban (HR, 0.67; 95% CI, 0.61-0.75) and rivaroxaban (HR, 0.77; 95% CI, 0.69-0.87) had a lower risk of recurrent VTE. Apixaban showed a further decrease in risk compared with rivaroxaban (HR, 0.87; 95% CI, 0.78-0.96). Patients taking apixaban also had a lower risk of major bleeding compared with warfarin (HR, 0.70; 95% CI, 0.64-0.76) and rivaroxaban (HR, 0.69; 95% CI, 0.63-0.75). No difference in bleeding risk was observed between rivaroxaban and warfarin (HR, 1.02; 95% CI, 0.92-1.12). These findings were consistent across subgroups defined by age, sex, cancer, chronic kidney disease, bleeding history, and frailty. In this cohort study of patients with VTE who initiated an oral anticoagulant, apixaban was associated with a lower risk of VTE recurrence and major bleeding compared with rivaroxaban and warfarin. These results provide evidence to guide the selection of appropriate initial oral anticoagulant regimens for adult patients with VTE.

High-Deductible Health Plans and Out-of-Pocket Health Care Costs Among Younger Patients With Multiple Myeloma.

This study aimed to determine if high-deductible health plan (HDHP) enrollment contributes to financial burden and hinders access to care for patients with multiple myeloma (MM). Patients diagnosed with MM from 2010 to 2020 were identified in Merative MarketScan, an employer-based health insurance database. Primary outcomes were total health care and out-of-pocket (OOP) costs in the year after diagnosis. Secondary outcomes included time to treatment initiation and stem-cell transplant receipt. Multivariable analyses using linear, logistic, and Cox regression were performed, as appropriate. Covariates included age, sex, year diagnosed, comorbidities, data provider, and stem-cell transplant receipt. The cohort included 4,029 patients; 17.6% were enrolled on HDHPs. HDHP enrollees were younger (mean age, 54.9 v 55.5 years; P = .036). Over the first year, mean total and OOP costs were $406,401 in US dollars (USD) and $9,220 USD for HDHP enrollees, respectively, versus $386,802 USD (P = .027) and $7,021 USD (P < .001) for the standard plan enrollees. There was no statistically significant difference in total cost (β = 11; P = .999) but mean OOP costs were $2,544 USD (β = 2,544; P < .001) higher for HDHP enrollees after adjusting for covariates. The additional OOP costs incurred in the first 2 months, presumably because of deductibles, and after the deductible reset. Contrary to our hypothesis, HDHPs enrollees had shorter time to treatment initiation (median, 20 v 22 days; hazard ratio, 1.18; P < .001) and were more likely to receive a stem-cell transplant (55.1% v 47.6%; odds ratio, 1.25; P = .010), after adjusting for covariates. Compared with standard plan enrollees, OOP costs were higher for HDHP enrollees in the year after diagnosis, but HDHP enrollment was not associated with delays in treatment initiation or reduced access to stem-cell transplant.

Pharmacological treatment of ADHD in children and adults

Medication is an essential component of the comprehensive treatment of ADHD in both children and adults. This review finds that both stimulant (first-line drugs) and non-stimulant medications have shown strong evidence in managing the core symptoms of ADHD. The initiation of pharmacological treatment should be conducted by a physician or specialist familiar with ADHD. Follow-up care may be managed by the primary care physician, and the Danish Health Authority recommends biannual check-ups. Pharmacological treatment for ADHD should always be combined with psychosocial interventions.

Diabetic ketoacidosis and cerebral edema: a rare case of infarct-like MRI findings in a pediatric patient

Introduction and importance: Diabetic ketoacidosis (DKA) is a serious and potentially life-threatening complication of type 1 diabetes mellitus, particularly in pediatric patients. Cerebral edema (CE) is a rare but devastating consequence of DKA. Although neuroimaging findings in CE are typically nonspecific, infarct-like changes are exceedingly rare and may complicate clinical management. Case presentation: We report the case of an 11-year-old boy with a history of type 1 diabetes mellitus who presented with epigastric pain, vomiting, polydipsia, and polyuria. Despite timely initiation of standard treatment for DKA, the patient developed acute neurological deterioration consistent with CE. Brain MRI revealed restricted diffusion in the basal ganglia, corpus callosum, and internal capsule – findings suggestive of infarction rather than typical vasogenic edema. Clinical discussion: This case highlights the diagnostic and therapeutic challenges posed by DKA-associated CE with atypical imaging findings. The observed infarct-like MRI pattern is rarely reported and may reflect underlying cytotoxic edema or ischemic injury. Understanding the multifactorial pathophysiology – including osmotic shifts, inflammatory processes, and impaired cerebral autoregulation – is critical for effective management. Conclusion: Early recognition of atypical cerebral involvement in pediatric DKA is essential. Advanced neuroimaging can aid in diagnosis and guide appropriate intervention. Clinicians should remain vigilant for neurological complications even during early phases of treatment and consider infarct-like patterns in differential diagnosis.

Associations between immune checkpoint inhibitor response, immune-related adverse events, and steroid use in RADIOHEAD: a prospective pan-tumor cohort study.

Immune checkpoint inhibitors (ICIs) have led to enduring responses in subsets of patients with cancer. However, these responses carry the risk of immune-related adverse events (irAEs), which can diminish the overall benefit of ICI treatment. While associations between irAE development and overall survival have been increasingly documented, there is a need for further understanding of these connections in large prospective real-world cohorts. The Resistance Drivers for Immuno-Oncology Patients Interrogated by Harmonized Molecular Datasets (RADIOHEAD) study, a pan-tumor, prospective cohort of 1,070 individuals undergoing standard of care first-line ICI treatment, aims to identify factors driving irAEs and clinical response. Clinical data and longitudinal blood samples were collected prospectively at multiple time points from 49 community-based oncology clinics across the USA. Structured, harmonized clinical data underwent unbiased statistical analysis to uncover predictors of real-world overall survival (rwOS) and risk factors for irAEs. Across 1,070 participants' treatment courses, RADIOHEAD accumulated over 4,500 clinical data points. Patients experiencing any irAE (25.4%, n=272) exhibited significantly improved rwOS in the pan-tumor cohort (n=1,028, HR=0.41, 95% CI=(0.31, 0.55)). This association persisted when adjusting for age and metastatic disease in multivariate time-dependent Cox proportional hazard analysis, and was consistent across major tumor subtypes, including lung cancer and melanoma. Skin and endocrine irAEs of any grade were strongly associated with improved rwOS (Cox proportional hazard analysis, skin, p=2.03e-05; endocrine, p=0.0006). In this real-world cohort, the irAE rate appeared lower than those reported in clinical trials. Patients receiving corticosteroids prior to initiation of ICI treatment had significantly worse survival outcomes than non-users (HR 1.37, p=0.0054), with a stronger association with systemic steroid use (HR 1.75, p=0.0022). The risk of irAE was increased by exposure to combination immunotherapy relative to monotherapy (OR 4.17, p=2.8e-7), zoster vaccine (OR 2.4, p=5.2e-05), and decreased by prior chemotherapy (OR 1.69, p=0.0005). The RADIOHEAD cohort is a well-powered, real-world cohort that clearly demonstrates the association between irAE development with improved response and baseline steroid use with worse response to ICI treatment after adjustment for survival bias.

Prevention and control of multidrug-resistance tuberculosis in Ethiopia: Patients' perspectives from the Oromia region.

Multi-drug-resistant tuberculosis (MDR-TB) is one of the biggest challenges worldwide to end tuberculosis. It is vital to understand the challenges and opportunities of patients during MDR-TB treatment to enhance prevention and control efforts. The gap in research on the challenges and opportunities of patients during the screening, diagnosis, referral, and follow-up of MDR-TB prompted this study. The purpose of the study was to assess the challenges and opportunities for patients with MDR-TB during the diagnosis and treatment of MDR-TB in the Oromia region of Ethiopia. A qualitative approach was applied. The data were collected from 30 MDR-TB patients from 1 to 30 April 2022 using semi-structured interviews after written informed consent was signed by each participant to understand the challenges and opportunities of MDR-TB treatment. Data was analysed by thematic analysis using ATLAS.ti software. This article identifies challenges that include delays in diagnosis and treatment initiation due to inadequate diagnostic services, physical inaccessibility, and financial problems faced by patients to pay for transport, food, diagnosis, and accommodation. Other challenges included lack of psychosocial support, shortage of healthcare providers, poor communication, drug side effects, and interruption of food and housing support. In addition, participants mentioned opportunities, which include the availability of free diagnosis, treatment, and admission; availability of transport; food and housing allowance; and use of an ambulance for referral. This study filled a research gap in Ethiopia by identifying challenges and opportunities during the MDR-TB treatment program. The MDR-TB treatment program should focus on improving inadequate screening and resources, shortage of healthcare providers, delays in the referral process, and non-compliance of patients.

Delayed emergence after general anesthesia: working through the differential diagnosis

Introduction and importance: Delayed emergence (DE) following general anesthesia is a critical postoperative complication characterized by the patient’s inability to regain an appropriate level of consciousness 30–60 minutes after surgery. Rapid identification and management of potential causes, including metabolic disturbances and pharmacologic effects, are essential to prevent adverse outcomes. Case presentation: We present the case of a 67-year-old female with multiple comorbidities, including chronic obstructive pulmonary disease, hemochromatosis, and hypothyroidism, who underwent emergent exploratory laparoscopy for a pelvic abscess. Despite uneventful hemodynamic stability and appropriate anesthetic management, the patient experienced delayed emergence. Initial interventions included reversal agents for neuromuscular blockade and opioids; however, the patient’s mental status continued to fluctuate. Arterial blood gas analysis revealed hypercapnic respiratory metabolic acidosis, prompting ventilatory support and subsequent reintubation. Neurovascular events were ruled out with unremarkable imaging findings. Clinical discussion: Delayed emergence can result from a variety of etiologies, including residual anesthetic effects, metabolic imbalances, and neurologic events. This case highlights the importance of prompt identification of hypercapnic respiratory metabolic acidosis as a reversible cause of DE. Management included ventilatory support with bilevel positive airway pressure and subsequent intubation, which resolved the acidosis and restored consciousness. Conclusion: This case underscores the need for a systematic approach in the differential diagnosis of delayed emergence. Timely recognition and management of hypercapnic respiratory metabolic acidosis through ventilatory support were crucial in preventing further complications.

Weight loss maintenance among truck drivers in the SHIFT randomised controlled trial, USA.

To evaluate weight loss maintenance among truck drivers following an effective initial intervention and to test a priori hypotheses that social support and stress factors would moderate long-term success. Commercial truck drivers enrolled in the Safety & Health Involvement For Truckers cluster-randomised controlled trial (22 terminal clusters; n=452) completed measurements at baseline, postintervention (6 months) and 1 year postintervention (18 months) in the USA in 2012-2015. The mobile health intervention was a group-based competition involving self-monitoring, feedback, incentives, online training and motivational interviewing. In an intent-to-treat analysis, the difference between groups at 18 months post-baseline in mean body weight was -0.92 kg (p=0.328; intervention=0.00, control=+0.92). Moderation analyses revealed a significant between-group intervention effect on body weight at 18 months for drivers with supervisors who engaged in higher levels of family supportive supervisor behaviours (p=0.033; group difference=-2.74 kg). Intervention effects on several diet and exercise outcomes at 18 months were also significantly moderated by social support and stress factors. Within the intervention group, high initial programme participation was associated with significantly greater 18-month weight loss than lower participation (p<0.001; -3.43 kg vs +2.17 kg). The intervention produced significant long-term weight loss for truck drivers with a supportive supervisor, providing further evidence for the broad health benefits of this workplace relationship. Additional findings highlight the value of initial programme participation and may inform future replications and extensions of similar health programmes for truck drivers. NCT02105571.