-
PloS One 2024The global rise in diabetes, particularly in India, poses a significant public health challenge, with factors such as limited awareness, financial strain, and cultural...
BACKGROUND
The global rise in diabetes, particularly in India, poses a significant public health challenge, with factors such as limited awareness, financial strain, and cultural considerations hindering its effective management. Although lifestyle changes have shown promising results, their consistent implementation and maintenance continue to pose challenges. Most studies have focused primarily on dietary modifications, overlooking other essential aspects of lifestyle intervention. The DiRemI study aims to address these gaps by evaluating the efficacy of a comprehensive one-year program that combines diet, exercise, psychological support, and medical management to achieve weight loss, diabetes remission, and improved glycemic control among patients with type 2 diabetes (T2D) in India, while also considering the unique needs of the Indian population.
METHODS
The DiRemI study is a prospective, open-label, matched-group trial aimed at assessing the impact of a one-year online integrated intensive lifestyle intervention (ILI) comprising dietary modifications, physical activity, psychological support, and medical management on weight loss and remission in adult T2D patients (aged 30-70 years), with a body mass index (BMI) between 25 and 35 kg/m2, and disease duration of <15 years. ILI will be compared with routine medical care (RMC). Participants will be recruited from three clinics: one providing ILI and two others providing RMC. The co-primary outcome will be weight loss and remission at 12 months, with a follow-up at 18 months. The proposed sample size is 360 participants (180 each in intervention and control group).
DISCUSSION
The DiRemI study represents the first large-scale remission study in India to show the effectiveness of an integrated approach in the remission and management of T2D and its complications. The findings of this study hold the potential to report evidence-based strategies for managing T2D both in India and globally, thus alleviating the substantial burden of diabetes on public health systems.
TRIAL REGISTRATION
Clinical Trials Registry, India (Registered Number: CTRI/2023/06/053885).
Topics: Humans; Diabetes Mellitus, Type 2; India; Prospective Studies; Middle Aged; Adult; Female; Male; Aged; Weight Loss; Exercise; Life Style; Remission Induction; Body Mass Index
PubMed: 38941311
DOI: 10.1371/journal.pone.0306394 -
JACC. Advances May 2024The prognostic impact of catheter ablation (CA) of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients has not yet been satisfactorily elucidated.
BACKGROUND
The prognostic impact of catheter ablation (CA) of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients has not yet been satisfactorily elucidated.
OBJECTIVES
The aim of the study was to assess the impact of CA of AF on clinical outcomes in a large cohort of HCM patients.
METHODS
In this retrospective multicenter study, 555 HCM patients with AF were enrolled, 140 undergoing CA and 415 receiving medical therapy. 1:1 propensity score matching led to the inclusion of 226 patients (113 medical group, 113 intervention group) in the final analysis. The primary outcome was a composite of all-cause mortality, heart transplant and acute heart failure exacerbations. Secondary outcomes included AF recurrence and transition to permanent AF. Additionally, an inverse probability weighted (IPW) model was examined.
RESULTS
At propensity score matching analysis, after a median follow-up of 58.1 months, the primary endpoint occurred in 29 (25.7%) patients in intervention group vs 42 (37.2%) in medical group ( = 0.9). Thromboembolic strokes and major arrhythmic events in intervention vs medical group were 9.7% vs 7.1% ( = 0.144) and 4.4 vs 8.0% ( = 0.779), respectively. Fewer patients in intervention vs medical group experienced AF recurrences (63.7% vs 84.1%, = 0.001) and transition to permanent AF pattern (20.4% vs 33.6%, = 0.026). IPW analysis showed consistent results. Severe complications related to CA were uncommon (0.7%).
CONCLUSIONS
After 5 years of follow-up, CA did not improve major adverse cardiac outcomes in a large cohort of patients with HCM and AF. Nevertheless, CA seems to facilitate the maintenance of sinus rhythm and slow the progression to permanent AF, without significant safety concerns.
PubMed: 38939638
DOI: 10.1016/j.jacadv.2024.100899 -
Cureus May 2024A case of a 43-year-old male with a history of Graves' disease treated with propylthiouracil was investigated for vasculitis and lymphoproliferative disease. However,...
Diagnostic Dilemma of a Complex Case of Cerebral Vasculitis: A Rare Probable Drug-Induced Antineutrophil Cytoplasmic Antibody-Associated Vasculitis With Large Vessel Involvement.
A case of a 43-year-old male with a history of Graves' disease treated with propylthiouracil was investigated for vasculitis and lymphoproliferative disease. However, his clinical picture was complicated by recurrent episodes of neurological symptoms resembling stroke syndrome, which widened the breadth of the diagnostic workup. Extensive investigations, including imaging and biopsies, excluded other possibilities. The patient was treated as probable cerebral vasculitis after identifying new narrowing in the left middle cerebral artery and was treated with pulsed intravenous methylprednisolone, followed by high-dose oral prednisolone and cyclophosphamide. Repeated brain imaging showed further narrowing of the large vessels, which reaffirmed the likelihood of vasculitis necessitating continuation of induction therapy with further maintenance treatment, which led to stabilization of neurological burden and symptom recovery. This case elucidates complexities in reaching the diagnosis of drug-induced antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, which can present heterogeneously and mimic other clinical entities such as stroke.
PubMed: 38939237
DOI: 10.7759/cureus.61254 -
Health Care Science Jun 2023The COVID-19 pandemic has created challenges with respect to HIV care services. Remote online services might provide an effective method for health service delivery to...
BACKGROUND
The COVID-19 pandemic has created challenges with respect to HIV care services. Remote online services might provide an effective method for health service delivery to people living with HIV (PLHIV). Few studies have focused on the efficacy of telemedical services for PLHIV and the effect of antiretroviral treatment via online services in China.
METHODS
We developed a platform called the "No. 8 Health" for online antiretroviral drug collection and delivery services in Beijing from January 21 to June 30, 2022. We evaluated the online treatment service according to viral load suppression rates and compared differences in social characteristics between PLHIV who received antiretroviral drugs through online or offline treatment services.
RESULTS
By June 2022, 9528 PLHIV had received outpatient treatment services, among which 44.6% (4031/9528) used the online treatment and drug delivery services for a total of 5590 person-times. The satisfaction rate was 100%. Rates of viral load suppression among PLHIV who initiated antiretroviral therapy (ART) in 2020 and 2021 were 96.4% and 93.1%, respectively. Results showed that the viral load suppression rate was 97.9%. Regarding HIV rapid self-testing, 4513 men who have sex with men used the online HIV rapid testing service. The number of users was approximately the same as in 2021, but both were slightly lower than those in 2020.
CONCLUSION
This study was the first to evaluate the effect of online drug collection and delivery services and virologic outcomes among PLHIV in China. The online service helped with maintenance of ART services, but the COVID-19 pandemic still had some impacts on viral load suppression.
PubMed: 38939113
DOI: 10.1002/hcs2.54 -
Frontiers in Sleep 2024Identifying intervention methods that target sleep characteristics involved in memory processing is a priority for the field of cognitive aging. Older adults with...
INTRODUCTION
Identifying intervention methods that target sleep characteristics involved in memory processing is a priority for the field of cognitive aging. Older adults with greater sleep efficiency and non-rapid eye movement slow-wave activity (SWA) (0.5-4 Hz electroencephalographic activity) tend to exhibit better memory and cognitive abilities. Paradoxically, long total sleep times are consistently associated with poorer cognition in older adults. Thus, maximizing sleep efficiency and SWA may be a priority relative to increasing mere total sleep time. As clinical behavioral sleep treatments do not consistently enhance SWA, and propensity for SWA increases with time spent awake, we examined with a proof-of concept pilot intervention whether a greater dose of time-in-bed (TiB) restriction (75% of habitual TiB) would increase both sleep efficiency and SWA in older adults with difficulties staying asleep without impairing memory performance.
METHODS
Participants were adults ages 55-80 with diary-reported sleep efficiency <90% and wake after sleep onset (WASO) >20 min. Sleep diary, actigraphy, polysomnography (PSG), and paired associate memory acquisition and retention were assessed before and after a week-long TiB restriction intervention ( = 30). TiB was restricted to 75% of diary-reported habitual TiB. A comparison group of = 5 participants repeated assessments while following their usual sleep schedule to obtain preliminary estimates of effect sizes associated with repeated testing.
RESULTS
Subjective and objective sleep measures robustly improved in the TiB restriction group for sleep quality, sleep depth, sleep efficiency and WASO, at the expense of TiB and time spent in N1 and N2 sleep. As hypothesized, SWA increased robustly with TiB restriction across the 0.5-4 Hz range, as well as subjective sleep depth, subjective and objective WASO. Despite increases in sleepiness ratings, no impairments were found in memory acquisition or retention.
CONCLUSION
A TiB restriction dose equivalent to 75% of habitual TiB robustly increased sleep continuity and SWA in older adults with sleep maintenance difficulties, without impairing memory performance. These findings may inform long-term behavioral SWA enhancement interventions aimed at improving memory performance and risk for cognitive impairments.
PubMed: 38938690
DOI: 10.3389/frsle.2023.1265006 -
NPJ Primary Care Respiratory Medicine Jun 2024The British Thoracic Society (BTS) and Scottish Intercollege Guidelines Network (SIGN), as well as National Institute for Health and Care Excellence (NICE), have... (Review)
Review
The British Thoracic Society (BTS) and Scottish Intercollege Guidelines Network (SIGN), as well as National Institute for Health and Care Excellence (NICE), have previously produced separate asthma guidance differing in some key aspects in diagnosis and management leading to confusion, potentially hampering guideline dissemination and uptake. While there are inherent challenges, the upcoming release of new joint BTS/SIGN/NICE asthma guidance presents an opportunity to assess guideline adoption and its impact on clinical practice. The use of prescription data via databases such as OpenPrescribing can be used as a surrogate for guideline adoption and potentially linked to clinical outcomes such as hospital episode statistics (HES). The potential recommendation for anti-inflammatory reliever therapy (AIR) and maintenance and reliever therapy (MART) with inhaled corticosteroid/formoterol combination therapy in the next iteration of UK asthma guidance will require the accurate coding for the respective therapeutic approaches on prescribing platforms in order to assess their impact in real-life clinical practice. This could then direct targeted measures to improve wider guidance adoption leading to better clinical care in asthma based on up to date evidence.
Topics: Humans; Asthma; Practice Guidelines as Topic; United Kingdom; Anti-Asthmatic Agents; Guideline Adherence; Adrenal Cortex Hormones
PubMed: 38937520
DOI: 10.1038/s41533-024-00379-6 -
Global Health, Science and Practice Jun 2024Barriers to achieving and sustaining access to water, sanitation, hygiene, cleaning, and waste management (WASH) in health care facilities include a lack of supportive...
Barriers to achieving and sustaining access to water, sanitation, hygiene, cleaning, and waste management (WASH) in health care facilities include a lack of supportive policy environment and adequate funding. While guidelines exist for assessing needs and making initial infrastructure improvements, there is little guidance on how to develop budgets and policies to sustain WASH services. We conducted costing and advocacy activities in Thakurbaba municipality, Nepal, to develop a budget and operations and maintenance policy for WASH in health care facilities in partnership with the municipal government. Our objectives for this study were to (1) describe the process and methods used for costing and advocacy, (2) report the costs to achieve and maintain basic WASH services in the 8 health care facilities of Thakurbaba municipality, and (3) report the outcomes of advocacy activities and policy development. We applied bottom-up costing to enumerate the resources necessary to achieve and maintain basic WASH services and their costs. The annual costs to achieve, operate, and maintain basic access to WASH services ranged from US$4881-US$9695 per facility. Cost findings were used to prepare annual budgets recommended to achieve, operate, and maintain basic services, which were presented to the municipal government and incorporated into an operations and maintenance policy. To date, the municipality has adopted the policy and established a recovery fund of US$3831 for repair and maintenance of infrastructure and an additional US$153 per facility for discretionary WASH spending, which were to be replenished as they were spent. Advocacy at the national level for WASH in health care facilities is currently being championed by the municipality, and findings from this project have informed the development of a nationally costed plan for universal access. This study is intended to provide a roadmap for how cost data can be collected and applied to inform policy.
Topics: Nepal; Sanitation; Humans; Hygiene; Health Facilities; Budgets; Water Supply; Waste Management
PubMed: 38936959
DOI: 10.9745/GHSP-D-23-00491 -
Tumour Virus Research Jun 2024HPV + oropharyngeal squamous cell carcinoma (OPC) incidence recently surpassed cervical cancer and is the most common HPV-related cancer in the developed world. HPV16...
HPV + oropharyngeal squamous cell carcinoma (OPC) incidence recently surpassed cervical cancer and is the most common HPV-related cancer in the developed world. HPV16 is in ∼90 % of HPV + OPCs, with episomal genomes in the majority of cases. Most existing HPV16+ cancer cell lines derive from outside the oropharynx and harbor integrated HPV genomes. Thus, there is need for OPC preclinical models to evaluate standard and experimental therapeutics in the presence of episomal HPV16 oncogenic drivers. Here we characterize HPV genome structures in eight HPV16+ OPC patient-derived xenografts (PDXs), and evaluate their responses to standard chemotherapy. HPV genome state was investigated by combining Southern blot, T5 exonuclease assay, whole genome sequencing, and RNAseq data. This analysis revealed complexity and variation in integrated vs. episomal HPV forms across PDXs and demonstrated that four PDXs predominantly contain episomal HPV16. Episomal status did not ensure favorable in vivo responses to cisplatin therapy, despite the more favorable prognosis previously attributed to episomal HPV + tumors; this could be due to the small number present in the dataset. Our analysis establishes PDX models as test platforms for novel therapies designed to target maintenance of the episomal forms of HPV16 that commonly appear in OPC.
PubMed: 38936774
DOI: 10.1016/j.tvr.2024.200285 -
The Lancet. Oncology Jul 2024Neuroblastoma is the most common extracranial solid tumour in children. Relapsed or refractory neuroblastoma is associated with a poor outcome. We assessed the... (Randomized Controlled Trial)
Randomized Controlled Trial
Irinotecan and temozolomide in combination with dasatinib and rapamycin versus irinotecan and temozolomide for patients with relapsed or refractory neuroblastoma (RIST-rNB-2011): a multicentre, open-label, randomised, controlled, phase 2 trial.
BACKGROUND
Neuroblastoma is the most common extracranial solid tumour in children. Relapsed or refractory neuroblastoma is associated with a poor outcome. We assessed the combination of irinotecan-temozolomide and dasatinib-rapamycin (RIST) in patients with relapsed or refractory neuroblastoma.
METHODS
The multicentre, open-label, randomised, controlled, phase 2, RIST-rNB-2011 trial recruited from 40 paediatric oncology centres in Germany and Austria. Patients aged 1-25 years with high-risk relapsed (defined as recurrence of all stage IV and MYCN amplification stages, after response to treatment) or refractory (progressive disease during primary treatment) neuroblastoma, with Lansky and Karnofsky performance status at least 50%, were assigned (1:1) to RIST (RIST group) or irinotecan-temozolomide (control group) by block randomisation, stratified by MYCN status. We compared RIST (oral rapamycin [loading 3 mg/m on day 1, maintenance 1 mg/m on days 2-4] and oral dasatinib [2 mg/kg per day] for 4 days with 3 days off, followed by intravenous irinotecan [50 mg/m per day] and oral temozolomide [150 mg/m per day] for 5 days with 2 days off; one course each of rapamycin-dasatinib and irinotecan-temozolomide for four cycles over 8 weeks, then two courses of rapamycin-dasatinib followed by one course of irinotecan-temozolomide for 12 weeks) with irinotecan-temozolomide alone (with identical dosing as experimental group). The primary endpoint of progression-free survival was analysed in all eligible patients who received at least one course of therapy. The safety population consisted of all patients who received at least one course of therapy and had at least one post-baseline safety assessment. This trial is registered at ClinicalTrials.gov, NCT01467986, and is closed to accrual.
FINDINGS
Between Aug 26, 2013, and Sept 21, 2020, 129 patients were randomly assigned to the RIST group (n=63) or control group (n=66). Median age was 5·4 years (IQR 3·7-8·1). 124 patients (78 [63%] male and 46 [37%] female) were included in the efficacy analysis. At a median follow-up of 72 months (IQR 31-88), the median progression-free survival was 11 months (95% CI 7-17) in the RIST group and 5 months (2-8) in the control group (hazard ratio 0·62, one-sided 90% CI 0·81; p=0·019). Median progression-free survival in patients with amplified MYCN (n=48) was 6 months (95% CI 4-24) in the RIST group versus 2 months (2-5) in the control group (HR 0·45 [95% CI 0·24-0·84], p=0·012); median progression-free survival in patients without amplified MYCN (n=76) was 14 months (95% CI 9-7) in the RIST group versus 8 months (4-15) in the control group (HR 0·84 [95% CI 0·51-1·38], p=0·49). The most common grade 3 or worse adverse events were neutropenia (54 [81%] of 67 patients given RIST vs 49 [82%] of 60 patients given control), thrombocytopenia (45 [67%] vs 41 [68%]), and anaemia (39 [58%] vs 38 [63%]). Nine serious treatment-related adverse events were reported (five patients given control and four patients given RIST). There were no treatment-related deaths in the control group and one in the RIST group (multiorgan failure).
INTERPRETATION
RIST-rNB-2011 demonstrated that targeting of MYCN-amplified relapsed or refractory neuroblastoma with a pathway-directed metronomic combination of a multkinase inhibitor and an mTOR inhibitor can improve progression-free survival and overall survival. This exclusive efficacy in MYCN-amplified, relapsed neuroblastoma warrants further investigation in the first-line setting.
FUNDING
Deutsche Krebshilfe.
Topics: Humans; Temozolomide; Irinotecan; Antineoplastic Combined Chemotherapy Protocols; Male; Female; Neuroblastoma; Child, Preschool; Child; Dasatinib; Adolescent; Neoplasm Recurrence, Local; Infant; Adult; Sirolimus; Young Adult; Germany; Drug Resistance, Neoplasm; Progression-Free Survival
PubMed: 38936379
DOI: 10.1016/S1470-2045(24)00202-X -
Clinical Neurology and Neurosurgery May 2024The use of endovascular therapy (EVT) has become a widespread strategy for the clinical management of acute ischemic stroke (AIS). However, the combination of arterial... (Review)
Review
OBJECT
The use of endovascular therapy (EVT) has become a widespread strategy for the clinical management of acute ischemic stroke (AIS). However, the combination of arterial injection of tirofiban with EVT for AIS continues to be a subject of controversy. This meta-analysis was conducted to assess the safety and efficacy of this treatment approach.
METHODS
Relevant studies were identified through a systematic literature search in Pubmed, EMBASE, Web of Science, and Cochrane Library databases, covering articles published from January 2010 to January 2023. The efficacy outcomes included favorable functional outcomes, recanalization rates, and safety outcomes including mortality and symptomatic intracranial hemorrhage (sICH).
RESULTS
The meta-analysis consisted of data from 13 studies, which included 1 randomized controlled trial (RCT), 7 prospective cohort studies, and 5 retrospective cohort studies, encompassing a total of 3477 patients. The study results indicate that the intra-arterial (IA) tirofiban+EVT for AIS is associated with significant improvements in favorable functional outcomes (OR, 1.21; 95%CI, 1.05-1.40; P = 0.009) and recanalization rate (OR, 1.33; 95%CI, 1.06-1.65; P = 0.01), as well as significant reductions in mortality rates (OR, 0.65; 95%CI, 0.53-0.79; P = 0.0001). Subgroup analysis revealed that administering a maintenance dose of intravenous (IV) tirofiban post-EVT was significantly associated with improved functional outcomes and reduced mortality in patients. In addition, there was no increase in the incidence of sICH (OR, 0.92; 95%CI, 0.71-1.20; P = 0.54).
CONCLUSION
The administration of Intra-arterial tirofiban combined with EVT is an effective and safe treatment strategy for AIS, and postoperative maintenance doses of intravenous tirofiban may be more effective than IA only.
PubMed: 38936178
DOI: 10.1016/j.clineuro.2024.108330