Preloaded combination nicotine replacement therapy for smoking cessation in Kazakhstan: A randomized controlled trial study protocol.

BACKGROUND: Tobacco use is a major cause of premature death and disease in Kazakhstan, with over 22,500 deaths per year. Although efforts have been made to control tobacco use, smoking-related deaths have continued to increase. One strategy to help smokers quit is to use nicotine replacement therapy (NRT), with combination NRT resulting in higher long-term quit rates than a single form of NRT. A study aims to determine the effectiveness of preloaded combination NRT on smoking cessation, the change in health-related quality of life due to smoking cessation, and explore treatment adherence perceptions. METHODS AND ANALYSIS: The study will be conducted as a randomized, single-blind superiority trial, with 100 participants in each arm. The trial will be carried out at the National Research Cardiac Surgery Center, Astana, Kazakhstan, and will recruit current smokers aged 18 years and above with a motivation to quit. Participants will be randomly allocated to either the intervention group or the control group. The former will receive preloaded combination NRT, while the latter will receive fast-acting NRT alone. The primary outcome measure will be sustained abstinence from smoking after six months. Secondary outcome measures will include health-related quality of life and adherence to the treatment. DISCUSSION: The study may gather further evidence that a combination NRT is more efficient than a fast-acting NRT alone. The findings of this study may help to improve tobacco cessation strategies in Kazakhstan and other countries with high smoking prevalence rates. TRIAL REGISTRATION NUMBER: NCT05484505.

NTRK1 gene-related congenital insensitivity to pain with anhidrosis: a nationwide multicenter retrospective study.

Congenital insensitivity to pain with anhidrosis (CIPA) is a rare autosomal recessive disease resulting from mutations in the NTRK1 gene encoding the neurotrophic tyrosine kinase-1 receptor. In this multicenter observational retrospective study, we investigated CIPA patients identified from French laboratories sequencing the NTRK1 gene, and seven patients were identified. Patients originated from France (2), Suriname (2), Mali (1), Kazakhstan (1), and Algeria (1). Mean age of patients was 9.8 years (4-20), four patients were female (57%), infant developmental milestones were delayed in four cases (57%), and four patients had a family history of consanguinity (57%). Mean age at diagnosis was 4.8 months (3-6), and all patients presented with pain insensitivity, anhidrosis, intellectual disability, self-mutilation, febrile episodes, impaired temperature perception, and autonomous nervous system impairment. Patients also showed an assortment of associated findings, including hyperactivity (86%), emotional lability (86%), joint deformities (71%), bone fractures (57%), abnormal sense of touch, vibration and position (50%), skin, hair and nails abnormalities (28%), and hypothermia episodes (28%). Two patients died at age 9 and 12 years from infection. In three cases, nerve conduction studies showed absent lower limbs sensory nerve action potentials. In one case, sensory nerve biopsy showed complete absence of unmyelinated fibers. Nine NTRK1 pathogenic variants were found, including three newly described mutations. This nationwide study confirms that NTRK1 gene-related CIPA is an extremely rare disorder and expands the genotypic spectrum of NTRK1 mutations.

Changes in Prehospital Stroke Care and Stroke Mimic Patterns during the COVID-19 Lockdown.

The impact of COVID-19 lockdown on prehospital stroke care is largely unknown. We aimed to compare stroke care patterns before and during a state-wide lockdown. Thus, we analysed prospective data of stroke alerts referred to our stroke centre between 1 December 2019 and 16 June 2020, and compared them between two periods-15 weeks before and 13 weeks during the state-wide lockdown declared in Lithuania on 16 March 2020. Among 719 referrals for suspected stroke, there was a decrease in stroke alerts (rate ratio 0.61, 95% CI (0.52-0.71)), stroke admissions (0.63, 95% CI (0.52-0.76)), and decrease in prehospital stroke triage quality (positive predictive value 72.1% vs. 79.9%, p = 0.042) during the lockdown. The onset-to-door time was longer (153.0 vs. 120.5 min, p = 0.049) and seizures and intracranial tumours were more common among stroke mimics (16.9% vs. 6.7%, p = 0.012 and 9.6% vs. 3.0%, p = 0.037, respectively). We conclude that there was a decline in prehospital stroke triage quality during the lockdown despite low COVID-19 incidence in the country. Moreover, we observed an increase in hospital arrival delays and severe conditions presenting as stroke mimics. Our findings suggest that improved strategies are required to maintain optimal neurological care during public health emergencies.