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.

Actovegin in the management of patients after ischemic stroke: A systematic review.

BACKGROUND: Actovegin is a hemodialysate of calf's blood and has been used for several decades in the countries of Central Asia, East Asia, Russia and some European countries. It has been used to treat patients with various neurological conditions, vascular disorders, and ischemic stroke. OBJECTIVES: To perform a systematic review to evaluate the effect of Actovegin in patients who have suffered an ischemic stroke. METHODS: A search of MEDLINE, PubMed, Cochrane and Embase was carried out from inception to October 10, 2021 for clinical trials and observational studies with a control group, published in English or Russian. RESULTS: Of 220 identified unique records, 84 full-text articles were screened, and 5 studies were selected that met the inclusion criteria. This included 4 observational studies with control groups and one randomized, placebo-controlled clinical trial. These studies enrolled a total of 3879 patients of which 720 patients received Actovegin administered intravenously and/or orally for a duration ranging from 10 to 180 days. Because of study heterogeneity, meta-analysis was not performed. No consistent evidence on improved survival, quality of life, neurologic symptoms, activities of daily living or disability was identified. One study showed statistically significant improvements in the Alzheimer's Disease Assessment Scale, cognitive subscale, extended version (ADAS-cog+) for Actovegin compared with placebo at 6 months but the clinical relevance of this change is uncertain. One study reported a higher incidence of recurrent ischemic stroke, transient ischemic attack or intracerebral hemorrhage in patients taking Actovegin compared to placebo. CONCLUSIONS: The benefits of Actovegin are uncertain and that there is potential risk of harm in patients with stroke. More evidence is needed from rigorously designed clinical trials to justify the role of Actovegin in patients with ischemic stroke.

Repurposing potential of posaconazole and grazoprevir as inhibitors of SARS-CoV-2 helicase.

As the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) pandemic engulfs millions worldwide, the quest for vaccines or drugs against the virus continues. The helicase protein of SARS-CoV-2 represents an attractive target for drug discovery since inhibition of helicase activity can suppress viral replication. Using in silico approaches, we have identified drugs that interact with SARS-CoV-2 helicase based on the presence of amino acid arrangements matching binding sites of drugs in previously annotated protein structures. The drugs exhibiting an RMSD of ≤ 3.0 Å were further analyzed using molecular docking, molecular dynamics (MD) simulation, and post-MD analyses. Using these approaches, we found 12 drugs that showed strong interactions with SARS-CoV-2 helicase amino acids. The analyses were performed using the recently available SARS-CoV-2 helicase structure (PDB ID: 5RL6). Based on the MM-GBSA approach, out of the 12 drugs, two drugs, namely posaconazole and grazoprevir, showed the most favorable binding energy, - 54.8 and - 49.1 kcal/mol, respectively. Furthermore, of the amino acids found conserved among all human coronaviruses, 10/11 and 10/12 were targeted by, respectively, grazoprevir and posaconazole. These residues are part of the crucial DEAD-like helicase C and DEXXQc_Upf1-like/ DEAD-like helicase domains. Strong interactions of posaconazole and grazoprevir with conserved amino acids indicate that the drugs can be potent against SARS-CoV-2. Since the amino acids are conserved among the human coronaviruses, the virus is unlikely to develop resistance mutations against these drugs. Since these drugs are already in use, they may be immediately repurposed for SARS-CoV-2 therapy.

Successful heart transplantation after 17 h ex vivo time using the Organ Care System-3 years follow-up.

Cold storage preservation is the standard approach for heart transplantation but is a time-limited method of care. Ex vivo heart perfusion expands the donor pool due by mitigating time and distance barriers and allows the possibility to improve graft function. We report long term follow up of a successful heart transplantation following an ex vivo time of 17 h using the Organ Care System in a patient with a left ventricular assist device.

Contemporary Fertility-Sparing Management Options of Early Stage Endometrioid Endometrial Cancer in Young Nulliparous Patients.

Incidence of endometrial cancer (EC) has been increasing in recent years, especially in high-income countries. The disease commonly affects peri- and postmenopausal women; however, about 5% of women are diagnosed with EC in their reproductive age. Due to both the increasing incidence of EC among reproductive age women and trends to delayed childbearing, fertility-sparing treatment for young patients with EC has become extremely important for researchers and practitioners. Because the classic treatment with total hysterectomy and bilateral saplingo-oophorectomy is not an appropriate approach for young women demanding fertility preservation, several fertility-sparing options have been developed and summarized in this review. Utilization of different medications and their combination (progestagens, gonadotropin releasing hormones analogues, and metformin in different formulations) are tested and found as efficient for fertility-sparing treatment. New minimally invasive surgical techniques, combined with progestagens, are also confirmed as valuable. There are many novel conservative and surgical treatment approaches under investigation. Assuming that molecular biomarkers can be both diagnostic and prognostic to assist in prediction of response to a certain therapy, prognostic risk groups' stratification along with specific biomarkers' identification will ensure low recurrence and decrease mortality rates in young women with EC.

[Ropivacaine withdrawal syndrome: a case report]. / Síndrome de abstinência de ropivacaína: relato de caso.

INTRODUCTION AND OBJECTIVES: Ropivacaine is a long-acting local anesthetic that causes prolonged anesthesia and is beneficial for a wide variety of surgeries. Systemic toxicity has been reported after usage of high dose ropivacaine or inadvertent intravascular administration. We report a case of ropivacaine withdrawal, which to our knowledge has not been previously described in the literature. CASE REPORT: The patient presented to our department with uncontrolled belt-like upper-abdominal pain, self-rated as a 9/10 on the numeric rating scale. We decided to use continuous epidural analgesia with ropivacaine through a multi-port epidural catheter. Pain was well controlled for one month without significant adverse effects. However, ropivacaine unexpectedly ran out and two hours later the patient developed agitation, generalized tremor, tachycardia, and tachypnea. These symptoms resolved 30 minutes after reinitiating epidural ropivacaine. DISCUSSION: Our hypothesis of ropivacaine withdrawal was related to the timing of symptoms in relation to drug administration over two episodes. The possible mechanism of the observed withdrawal syndrome is upregulation of voltage-gated sodium channels after prolonged inhibition, resulting in increase in sodium influx and genetic variation.

Ropivacaine withdrawal syndrome: a case report / Síndrome de abstinência de ropivacaína: relato de caso

Abstract Introduction and objectives: Ropivacaine is a long-acting local anesthetic that causes prolonged anesthesia and is beneficial for a wide variety of surgeries. Systemic toxicity has been reported after usage of high dose ropivacaine or inadvertent intravascular administration. We report a case of ropivacaine withdrawal, which to our knowledge has not been previously described in the literature. Case report: The patient presented to our department with uncontrolled belt-like upper-abdominal pain, self-rated as a 9/10 on the numeric rating scale. We decided to use continuous epidural analgesia with ropivacaine through a multi-port epidural catheter. Pain was well controlled for one month without significant adverse effects. However, ropivacaine unexpectedly ran out and two hours later the patient developed agitation, generalized tremor, tachycardia, and tachypnea. These symptoms resolved 30 minutes after reinitiating epidural ropivacaine. Discussion: Our hypothesis of ropivacaine withdrawal was related to the timing of symptoms in relation to drug administration over two episodes. The possible mechanism of the observed withdrawal syndrome is upregulation of voltage-gated sodium channels after prolonged inhibition, resulting in increase in sodium influx and genetic variation.

Resumo Justificativa e objetivos: A ropivacaína é um anestésico local de ação prolongada indicado em uma ampla variedade de cirurgias. Toxicidade sistêmica tem sido relatada após o uso de dose alta de ropivacaína ou administração intravascular inadvertida. Relatamos um caso de crise de abstinência de ropivacaína que, até onde sabemos, não foi descrita anteriormente na literatura. Relato do caso: O paciente procurou nosso departamento com dor não controlada abdominal do tipo em cinta, avaliada pelo paciente como sendo 9/10 no escala de avaliação numérica. Decidimos usar analgesia peridural contínua com ropivacaína através de cateter peridural multiperfurado. A dor foi bem controlada por um mês sem efeitos adversos significativos. No entanto, a ropivacaína inesperadamente se esgotou e, duas horas depois, o paciente desenvolveu agitação, tremor generalizado, taquicardia e taquipneia. Esses sintomas regrediram completamente 30 minutos após o reinício da ropivacaína por via peridural. Discussão: Nossa hipótese de abstinência de ropivacaína foi relacionada à cronologia dos sintomas em relação à administração da droga ao longo de dois episódios. O possível mecanismo da síndrome de abstinência observada é a regulação positiva dos canais de sódio dependentes de voltagem após inibição prolongada, resultando em aumento do influxo de sódio e variação genética.

Outcome Predictors of Stroke Mortality in the Neurocritical Care Unit.

Background: Risk factors for medium to long-term mortality after stroke are well-established but predictors of in-hospital stroke mortality are less clearly characterized. Kazakhstan has the highest age-standardized mortality rate from ischemic stroke in the world. Methods: We performed a retrospective analysis of patients with stroke who were admitted over a 3.5-years period to the neurocritical care unit of a tertiary care hospital in Nur-Sultan, Kazakhstan. Results: In total, 148 critically ill patients were included in the analysis (84 ischemic stroke, 64 hemorrhagic stroke). The mean age was 63 years, 45% were male and the mean Glasgow Coma Score (±SD) at baseline was 10.3 (±3.4). The in-hospital mortality rate was similar in patients with ischemic (36%) and hemorrhagic (39%) stroke (HR 0.88, 95%CI 0.48-1.60). Median survival was 38 days (range: 1-89 days) in patients with ischemic stroke and 39 days (range: 1-63 days) in patients with hemorrhagic stroke. Univariable analysis found that patients who had a lower Glasgow Coma Scale, were in coma and who had cerebral edema were more likely to die in-hospital (P = 0.04, 0.02, <0.01, respectively). Conclusions: Our analysis showed that mortality risk in critically ill patients with hemorrhagic stroke was closer to mortality risk in patients with ischemic stroke than has been reported in other analyses. Hypertension, chronic heart failure, ischemic heart disease and atrial fibrillation were the most frequent comorbidities in patients who developed severe (life-threatening) stroke. Coma and cerebral edema on admission appear to be associated with poor outcome. This is the first publication of in-hospital stroke mortality from a Central Asian population and could form the basis for future research including development of risk scores and identifying modifiable risk factors.

Left Ventricular Assist Device Outflow Graft Pseudoaneurysm Treated with Covered Balloon Expandable Stent.

Left ventricular assist device (LVAD) outflow graft injury is a very rare complication after LVAD implantation and is usually treated surgically. This is a case report of successful stenting of the damaged outflow graft 2.5 years after LVAD implantation, followed by successful heart transplantation.

Comparison of Custodiol vs warm blood cardioplegia and conditioning of donor hearts during transportation with the organ care system.

OBJECTIVES: Cold crystalloid cardioplegia for donor heart harvesting and cold ischemic storage conditions during the transportation is the standard of care during heart transplantation procedure. Organ care system (OCS) was introduced for more prolonged and reliable ex vivo organ management. This study evaluated the two different techniques used for myocardial preservation during the procurement and transportation of the heart using the OCS. METHODS: We performed prospective analysis of 43 patients with heart failure undergoing heart transplantation and using the OCS for donor organ transport. Donor hearts were arrested using blood cardioplegia and conditioning (n = 30) or standard Custodiol (SC) solution ( n = 13). Perfusion and cardiac function parameters were continuously monitored while the donor hearts were perfused in the OCS. Impact of preservation techniques on biochemical parameters and clinical outcomes were evaluated. RESULTS: All donor hearts had stable perfusion and lactate characteristics in the OCS, with similar measures between the two groups at the beginning of the ex vivo perfusion. Ex vivo heart perfusion mean ending concentration of Interleukin (IL)-6 and IL-8 was significantly lower in the blood cardioplegia group compared to the standard care group. Clinical outcomes were comparable between the two groups of patients. CONCLUSIONS: The use of blood cardioplegia and conditioning could be a safe method for myocardial protection in distant procurement and preservation of donor hearts in the OCS.

Hemofiltration for neuroprotection in acute ischemic stroke: A prospective, pilot study.

BACKGROUND: Hemofiltration reduces blood levels of cytokines, glutamate, and other substances that increase the risk of stroke-associated neurodegeneration. This study aimed to assess the safety and efficacy of hemofiltration in acute ischemic stroke patients. METHODS: A total of 37 patients (mean age 56 ± 16 years) who had an ischemic stroke within the previous 12 hours were randomized to receive hemofiltration for 36 hours (n = 19) or standard treatment (n = 18). The primary outcome of interest was the occurrence of adverse events during the 28-day period following the stroke symptom onset. The secondary outcome was to assess the efficacy of hemofiltration in acute ischemic stroke. RESULTS: Eighteen patients who received hemofiltration and 17 patients who received standard care completed the study. There were no cases of sepsis or infection at the hemofiltration cannula site, nor other hemofiltration-related complications. There was one case of fatal hemorrhagic transformation in each of the two groups. We failed to find any favorable effects on NIHSS scores at 7 days. However, we observed 17 patients (94%) with systemic inflammatory response syndrome in the control group and only 13 (68%) in the hemofiltration group. CONCLUSION: Hemofiltration appears to be safe in acute ischemic stroke patients, but we were unable to demonstrate its efficacy. However, for a definite conclusion on efficacy, a larger study with longer follow-up is required.

Mentoring a health technology assessment initiative in Kazakhstan.

OBJECTIVES: The aim of this study was to assist in the development of a health technology assessment (HTA) program for the Ministry of Health (MOH) of the Republic of Kazakhstan METHODS: Mentoring of an initial HTA program in Kazakhstan was provided by the Canadian Society for International Health (CSIH) by means of a partnership with the Kazakhstan MOH. HTA materials, courses, and one-on-one support for the preparation of a series of initial HTA reports by MOH HTA staff were provided by a seven-member CSIH team over a 2.5-year project. RESULTS: Guidance documents on HTA and institutional strengthening were prepared in response to an extensive set of deliverables developed by the MOH and the World Bank. Introductory and train-the-trainer workshops in HTA and economic evaluation were provided for MOH staff members, experts from Kazakhstan research institutes and physicians. Five short HTA reports were successfully developed by staff in the Ministry's HTA Unit with assistance from the CSIH team. Challenges that may be relevant to other emerging HTA programs included lack of familiarity with some essential underlying concepts, organization culture, and limited time for MOH staff to do HTA work. CONCLUSIONS: The project helped to define the need for HTA and mentored MOH staff in taking the first steps to establish a program to support health policy decision making in Kazakhstan. This experience offers practical lessons for other emerging HTA programs, although these should be tailored to the specific context.