Open Study Research Articles

Guidelines-based therapeutic strategies for controlling hypertension in non-controlled hypertensive patients followed by family physicians in primary health care in Portugal: the GPHT-PT study

Purpose In a prospective open study, with intervention, conducted in Primary Health Care Units by General Practitioners (GPs) in Portugal, the effectiveness of a single pill of candesartan/amlodipine (ARB/amlodipine), as the only anti-hypertension (anti-HTN) medication, in adult patients with uncontrolled HTN (BP > 140/or > 90 mm Hg), either previously being treated with anti-HTN monotherapies (Group I), or combinations with hydrochlorothiazide (HCTZ) (Group II), or not receiving medication at all (Group III), was evaluated across 12-weeks after implementation of the new therapeutic measure. Materials and methods A total of 118 GPs recruited patients with uncontrolled HTN who met inclusion/exclusion criteria. Participants were assigned, according to severity, one of 3 (morning) fixed combination candesartan/amlodipine dosage (8/5 or 16/5 or 16/10 mg/day) and longitudinally evaluated in 3 visits (v0, v6 and v12 weeks). Office blood pressure was measured in each visit, and control of HTN was defined per guidelines (BP< 140/90 mmHg). Results Of the 1234 patients approached, 752 (age 61 ± 10 years, 52% women) participated in the study and were assigned to groups according to previous treatment conditions. The 3 groups exhibited a statistically significant increased control of blood pressure after receiving the fixed combination candesartan/amlodipine dosage. The overall proportion of controlled HTN participants increased from 0,8% at v0 to 82% at v12. The mean arterial blood pressure values decreased from SBP= 159.0 (± 13.0) and DBP= 91.1 (± 9.6) at baseline to SBP= 132,1 (± 11.3) and DBP= 77,5 (± 8.8) at 12 weeks (p < 0.01). Results remained consistent when controlling for age and sex. Conclusion In patients with uncontrolled HTN, therapeutic measures in accordance with guidelines, with a fixed combination candesartan/amlodipine, allowed to overall achieve HTN control at 12 weeks in 82% of previously uncontrolled HTN patients, reinforcing the advantages of these strategies in primary clinical practice.

A meta-analysis investigating the efficacy and safety of allergen-specific immunotherapy in the management of respiratory allergies

Background This meta-analysis aimed to evaluate the effectiveness and adverse effects of specific immunotherapy (SIT) in the management of respiratory allergens, including allergic asthma, rhinitis, and related disorders, based on a review of current literature up to November 8, 2022. Methods We conducted a search of databases, including PubMed, Embase, Cochrane, and Web of Science, to identify relevant randomized controlled trials (RCTs) assessing respiratory allergy-specific immunotherapy. We employed the Consolidated Standards of Reporting Trials (CONSORT) Statement to select RCTs that adhered to rigorous reporting standards. Specifically, we focused on double-blind placebo-controlled (DBPC) trials and open studies involving both adults and children, considering factors such as dosage, inclusion criteria, allergens, and primary outcome measurements. Results A total of 25 meta-analyses were included in this study. Among them, 14 evaluated sublingual-specific allergen immunotherapy (SLIT), 4 assessed subcutaneous allergen immunotherapy (SCIT), 4 explored both sublingual and subcutaneous immunotherapy, and 3 investigated intralymphatic immunotherapy. The outcomes of these meta-analyses indicated a reduction in medication scores in 20 cases and a decrease in symptom scores in 23 cases. Additionally, six studies reported on changes in IgE levels, seven studies focused on IgG4, four studies examined FEV1 (forced expiratory volume in 1 s), and eight studies reported on symptom and medication scores. Furthermore, 11 studies reported on differences in adverse reactions. Conclusion The results of our meta-analysis suggest that specific immunotherapy, while associated with some adverse effects, effectively reduces the symptoms of asthma and rhinitis. Therefore, we recommend its use in the treatment of respiratory allergies.

Safety and Effectiveness of Percutaneous Ultrasound-Guided Galvanic Current in Tunnels of Patients with Hidradenitis Suppurativa: A Pilot Study.

The recurrent nature of hidradenitis suppurativa (HS), even under maintained systemic treatment, makes it necessary to have effective local treatments; however, the response to these therapies is variable (44-81%). The application of galvanic current (GC) has demonstrated its utility in humans in treating lesions structurally similar to those of HS. With this background, the main objective of this study was to evaluate the efficacy and safety of ultrasound-guided percutaneous GC in inflamed and/or draining tunnels of HS. This was an open study (one-way repeated measures design over time). Patients were evaluated at 4 and 12weeks after receiving GC. A combined clinical response at week12 (absence of suppuration/inflammation on examination and clinical interview) was considered the principal variable of efficacy. Adverse effects potentially associated with GC were reported by telephone and at each visit. Twenty-six patients were included, with a male/female ratio of 5:8. The mean age was 35.84 (13.14) years. At 12weeks after the administration of GC, a complete response was achieved in 77% (20/26) of the treated lesions. No serious adverse effects were observed, and the mean procedural pain assessed by the numeric rating scale was 0.03 (0.2). GC has proven to be effective and well tolerated in inflamed and draining tunnels of patients with HS.

Behavioral changes in patients with Prader-Willi syndrome receiving diazoxide choline extended-release tablets compared to the PATH for PWS natural history study

BackgroundPrader-Willi syndrome (PWS) is a rare neurobehavioral-metabolic disease caused by the lack of paternally expressed genes in the chromosome 15q11-q13 region, characterized by hypotonia, neurocognitive problems, behavioral difficulties, endocrinopathies, and hyperphagia resulting in severe obesity if energy intake is not controlled. Diazoxide choline extended-release (DCCR) tablets have previously been evaluated for their effects on hyperphagia and other behavioral complications of people with PWS in a Phase 3 placebo-controlled study of participants with PWS, age 4 and older with hyperphagia (C601) and in an open label extension study, C602.MethodsTo better understand the longer-term impact of DCCR, a cohort from PATH for PWS, a natural history study that enrolled participants with PWS age 5 and older, who met the C601 age, weight and baseline hyperphagia inclusion criteria and had 2 hyperphagia assessments ≥ 6 months apart, were compared to the C601/C602 cohort. Hyperphagia was measured using the Hyperphagia Questionnaire for Clinical Trials (HQ-CT, range 0–36). The primary analysis used observed values with no explicit imputation of missing data. A sensitivity analysis was conducted in which all missing HQ-CT assessments in the C601/C602 cohort were assigned the highest possible value (36), representing the worst-case scenario. Other behavioral changes were assessed using the Prader-Willi Syndrome Profile questionnaire (PWSP).ResultsRelative to the PATH for PWS natural history study cohort, the DCCR-treated C601/C602 cohort showed significant improvements in HQ-CT score at 26 weeks (LSmean [SE] -8.3 [0.75] vs. -2.5 [0.43], p < 0.001) and 52 weeks (LSmean [SE] -9.2 [0.77] vs. -3.4 [0.47], p < 0.001). The comparison between the cohorts remained significant in the worst-case imputation sensitivity analysis. There were also significant improvements in all domains of the PWSP at 26 weeks (all p < 0.001) and 52 weeks (all p ≤ 0.003) for C601/C602 participants compared to the PATH for PWS participants.ConclusionLong-term administration of DCCR to people with PWS resulted in changes in hyperphagia and other behavioral complications of PWS that are distinct from the natural history of the syndrome as exemplified by the cohort from PATH for PWS. The combined effects of administration of DCCR should reduce the burden of the syndrome on the patient, caregivers and their families, and thereby may benefit people with PWS and their families.Trial RegistrationClinical study C601 was originally registered on ClinicalTrials.gov on February 22, 2018 (NCT03440814). Clinical study C602 was originally registered on ClinicalTrials.gov on October 22, 2018 (NCT03714373). PATH for PWS was originally registered on ClinicalTrials.gov on October 24, 2018 (NCT03718416).

Dissipation, processing factors and dietary risk assessment of the bioinsecticide abamectin in herbal plants belonging to Lamiaceae family from open field to herbal tea infusion

Abamectin, the mixture of avermectin B1a and B1b, is widely used as a bioinsecticide and is an alternative to chemical pest control from insects. To our knowledge, its behaviour is not fully recognized, especially in herbs. Thus, the objective of this study was to investigate the environmental fate of abamectin in herbal plants belonging to the Lamiaceae family, its dissipation in open field studies laboratory processing treatments and dietary risk assessment. Three medicinally and culinary important species of herbs: Melissa officinalis L., Mentha × piperita L. and Salvia L. were treated with single and double dose than recommended on the label during their cultivation (BBCH 11–29). Residues were monitored using the QuEChERS method followed by the LC-MS/MS. The dissipation pattern of the sum of avermectin B1a and B1b and their persistence were observed 14 d after spraying. Abamectin decline was very rapid in plants and followed the first-order kinetics model. The half-life (t1/2) was in the range of 0.96–1.08 d (single dose) and 0.93–1.02 d (double dose). The pre-harvest intervals (decrease to the level of 0.01 mg kg−1) were 7.29–7.92 d at single and 7.99–8.64 d at double dose application. Herbal infusion preparation in previously washed and dried mint, lemon balm and sage leaves was the key processing step in the removal of abamectin residues. The reduction of initial deposits after single dose treatment was noted up to 65% (PF = 0.35–0.67) and up to 79% after double dose application (PF = 0.21–0.72) in herbal tea. Acute risk assessment of children and adults for the highest residues in EFSA PRIMo model at single and double dose expressed as hazard quotients (HQ) were <1, indicating no risk to humans via consumption of the herbal products. The data provide a better understanding of abamectin behaviour in herbal plants and can help assure herbs' safety for consumers.

Somatostatin Versus Octreotide for Prevention of Postoperative Pancreatic Fistula: The PREFIPS Randomized Clinical Trial: A FRENCH 007-ACHBT Study.

Pharmacological prevention of postoperative pancreatic fistula (POPF) after pancreatectomy is open to debate. The present study compares clinically significant POPF rates in patients randomized between somatostatin versus octreotide as prophylactic treatment. Multicentric randomized controlled open study in patient's candidate for pancreaticoduodenectomy (PD) or distal pancreatectomy (DP) comparing somatostatin continuous intravenous infusion for 7 days versus octreotid 100 μg, every 8 hours subcutaneous injection for 7 days, stratified by procedure (PD vs DP) and size of the main pancreatic duct (>4 mm) on grade B/C POPF rates at 90 days based on an intention-to-treat analysis. Of 763 eligible patients, 651 were randomized: 327 in the octreotide arm and 324 in the somatostatin arm, with comparable the stratification criteria - type of surgery and main pancreatic duct dilatation. Most patients had PD (n=480; 73.8%), on soft/normal pancreas (n=367; 63.2%) with a nondilated main pancreatic duct (n=472; 72.5%), most often for pancreatic adenocarcinoma (n=311; 47.8%). Almost all patients had abdominal drainage (n=621; 96.1%) and 121 (19.5%) left the hospital with the drain in place (median length of stay=16 days). A total of 153 patients (23.5%) developed a grade B/C POPF with no difference between both groups: 24.1%: somatostatin arm and 22.9%: octreotide arm (χ 2 test, P =0.73, ITT analysis). Absence of statistically significant difference persisted after adjustment for stratification variables and in per-protocol analysis. Continuous intravenous somatostatin is not statistically different from subcutaneous octreotide in the prevention of grade B/C POPF after pancreatectomy. In the PREFIPS Randomized Clinical Trial including 651 patients, a total of 153 patients (23.5%) developed a grade B/C POPF with no significant difference between both groups: 24.1%: somatostatin arm and 22.9%: octreotide arm (χ 2 test, P =0.73, ITT analysis). Absence of statistically significant difference persisted after adjustment for stratification variables and in per-protocol analysis.

Clinical evaluation of therapeutic efficacy of a Siddha herbo mineral formulation “Kumaara Veeriya Kaantha Chenduram’’ with “Nellikkai Legiyam” (internal) in the treatment of Iron Deficiency Anemia

Abstract: Background: Kumaara veeriya kaantha chenduram (KVKC) is a siddha herbomineral formulation indicated for paandunoi in Siddha literature (1).Paandu noi is a disease characterized by changes in the body's natural color andpallor found in the skin, nails and conjunctiva. Objectives: To determine the efficacy of the KVKC, the open labed clinical study was conducted in National Institute of Siddha OPD. Materials and Methods: The 30 patients with Iron deficiency anaemiawere selected and treated with KVKC orally with the dose of 260 milli gram twice in a day with Nellikailegiyam6 gram continuously for 45 days. Laboratory investigations for hemoglobin was done on 1st day and every 15 days once of the study. Results: Clinical assessment was done, based on the before and after treatment scores which was compared statistically and recorded.Regarding Hemoglobin level, 24(80%) patients showed increase of 1 to 3 grams from base level, 6(20%) patients showed increase of 0.1 to 0.9 grams from base level.Regarding Serum Ferritin, out of 30 patients, 9 (30%) patients showed 0.1-3.5 ng/ml increase from its base level, 21 (70%) patients showed 3.6-7.0 ng/ml increase from its base level.From the Statistical studies, the Mean ± Standard deviation for Haemoglobin before treatment was 9.7 ± 0.93 and after treatment was 11.18 ± 1.08 which was statistically highly significant (p&lt;0.0001).And Serum ferritin before treatment was 9.27 ± 3.31, after treatment was 13.5 ± 3.49 which was statistically significant (p&lt;0.0001).

The long-term impact of vaginal surgical mesh devices on pain clinic and psychological service referrals, anti-inflammatory testing and pelvic scans in UK primary care: A cohort study with the Clinical Practice Research Datalink.

To examine long-term complications in women with stress urinary incontinence (SUI) and pelvic organ prolapse (POP), with and without surgical mesh implants. Longitudinal open cohort study from 1 April 2006 (or 1 April 2012) to 30 November 2018. The Clinical Practice Research Datalink (CPRD) Gold database, which is linked to Hospital Episodes Statistics (HES) inpatient data, the HES Diagnostic Imaging Dataset (DID), Office for National Statistics mortality data and Index of Multiple Deprivation socio-economic status data. Women aged ≥18 years with a diagnostic SUI/POP Read code. Rates are estimated using negative binomial regression. Rates of referrals for: psychological and pain services; urinalysis, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) testing; and pelvic ultrasound, computed tomography (CT) and magnetic resonance imaging (MRI) scans. A cohort of 220 544 women were eligible for inclusion; 74% (n = 162 687) had SUI, 37% (n = 82 123) had POP and 11% (n = 24 266) had both. Rates of psychological referrals and CT scans were lower in women with SUI mesh surgery, but this was offset by higher rates of CRP testing in women with SUI or POP mesh, MRI scans in women with SUI mesh, and urinalysis testing and referrals to pain clinics for women with POP mesh. Our results suggest a higher burden of morbidity in women with SUI/POP mesh surgery, and that these women may require ongoing follow-up in the primary care setting.

Animal‐pollinated crops and cultivars—A quantitative assessment of pollinator dependence values and evaluation of methodological approaches

Abstract Crop pollinator dependence (PD) values are key when assessing a pollinator's contribution to agriculture, guiding management plans and policies for sustainable crop production. However, the available global compilations of crops PD are outdated and neglect variability between related crops and accessions (variety/cultivar), as well as pollen limitation (PL), that is the production lost due to inadequate pollen receipt. Here, we obtained quantitative PD values for animal‐pollinated crops and their accessions, using data from available pollination experiments worldwide. We also tested pollination methodologies to assess their impact on PD values and to define suitable methodological guidelines for future pollination studies. We provide a list of continuous PD values for 141 crops, including 317 accessions and 37 crops not listed in previous assessments. We found that, globally, 74% of animal‐pollinated crops are highly dependent on pollinators, and more than 40% of their production is associated with animal pollination. Pollen limitation was detected in 51% of the dataset entries, indicating that estimates calculated with open pollination studies underestimate crop pollinator dependence and, therefore, do not represent the true contribution of pollinators to food production. Synthesis and applications: Commonly applied methods for assessing PD values can lead to underestimations. Future studies evaluating pollinator dependence levels of crops and their accessions (i.e. potential pollinator contribution) should consider the possibility of pollen limitation in the study site, incorporating hand pollen supplementation (to open flower), open pollination, and pollinator exclusion treatments, preferably using the whole plant or branch as the unit of assessment. The PD values provided here, from studies that allow the incorporation of the concept of pollen limitation, enable more accurate quantifications of pollinator contribution to crop production. These PD values are an invaluable baseline and a requirement for future accurate evaluations of the value of pollinators for food security, supporting pollinator‐friendly practices in agroecosystems.

Mental health and burnout during medical school: Longitudinal evolution and covariates.

Medical students' rate of depression, suicidal ideation, anxiety, and burnout have been shown to be higher than those of the same-age general population. However, longitudinal studies spanning the whole course of medical school are scarce and present contradictory findings. This study aims to analyze the longitudinal evolution of mental health and burnout from the first to the last year of medical school using a wide range of indicators. Moreover, biopsychosocial covariates that can influence this evolution are explored. In an open cohort study design, 3066 annual questionnaires were filled in by 1595 different students from the first to the sixth year of the Lausanne Medical School (Switzerland). Depression symptoms, suicidal ideation, anxiety symptoms, stress, and burnout were measured along with biopsychosocial covariates. The longitudinal evolution of mental health and burnout and the impact of covariates were modelled with linear mixed models. Comparison to a same-aged general population sample shows that medical students reported significantly more depression symptoms and anxiety symptoms. Medical students' mental health improved during the course of the studies in terms of depression symptoms, suicidal ideation, and stress, although suicidal ideation increased again in the last year and anxiety symptoms remained stable. Conversely, the results regarding burnout globally showed a significant worsening from beginning to end of medical school. The covariates most strongly related to better mental health and less burnout were less emotion-focused coping, more social support, and more satisfaction with health. Both improvement of mental health and worsening of burnout were observed during the course of medical school. This underlines that the beginning and the end of medical school bring specific challenges with the first years' stressors negatively impacting mental health and the last year's difficulties negatively impacting burnout.

Multicomponent Co-Occurring Disorders Treatment and Wraparound Services for Individuals Experiencing Chronic Homelessness.

Individuals experiencing chronic homelessness have high rates of persistent co-occurring mental health and substance use disorders (COD), and they often have difficulty with service engagement and retention, resulting in symptom exacerbation and housing loss. This study pilot tested Maintaining Independence and Sobriety Through Systems Integration, Outreach and Networking (MISSION), a multicomponent wraparound treatment approach to improve COD symptoms and housing stability among individuals experiencing chronic homelessness and persistent COD. This open pilot study enrolled and assessed 109 individuals with a COD experiencing chronic homelessness and offered one year of MISSION. Statistically significant improvements were observed in behavioral health symptoms and functioning, days of illicit drug use, and housing stability. By treatment completion, 85% of participants were referred to social and behavioral supports. This pilot study demonstrates that MISSION helped to successfully engage participants in treatment, reduce substance use and mental health symptoms, and improve housing outcomes.

Patterns and trends of medicinal poisoning substances: a population-based cohort study of injuries in 0–11 year old children from 1998–2018

BackgroundThere have been sharp increases in antidepressant and opioid prescriptions over the last 10 years, as well as increased over-the-counter medicine availability. However, the impact on childhood medicinal poisonings rates, particularly by socioeconomic deprivation is unclear. This study reports population level medicinal poisoning substance patterns in England among children aged 0–11 years, helping inform safety advice and poisoning prevention interventions.MethodsAn open cohort study of 1,489,620 0–11 year olds was conducted from 1998 to 2018, using the Clinical Practice Research Datalink, to examine inpatient hospital admissions for poisoning. Incidence rates and adjusted incidence rate ratios (aIRR) were calculated for poisoning substance groups by age, sex, socio-economic deprivation and year.Results3,685 medicinal poisoning hospital admissions were identified. The most common substances were paracetamol (33.2%), dependence/withdrawal risk drugs (DWRD - antidepressants, opioids, gabapentinoids, benzodiazepines) (13.5%) and other over-the-counter (OTC) analgesics/anti-common cold drugs (13.0%). Over the study period DWRD poisonings decreased 33% (aIRR 0.67, 95%CI 0.50–0.90 comparing 2013/14-2017/18 to 1998/99-2002/03), while paracetamol poisonings increased 43% (aIRR 1.43, 95%CI 1.20–1.70 for the same periods), with no change in incidence rates for other OTC drugs (aIRR 0.82, 95% CI 0.60–1.12) or all medications combined (aIRR 0.97, 95%CI 0.88–1.07). A gradient in poisonings by area-level socioeconomic deprivation was shown for all medications (aIRR 1.32, 95%CI 1.18–1.47 for most deprived compared to least deprived quintile), and DWRDs (aIRR 2.03, 95%CI 1.42–2.88 for 4th most deprived quintile and aIRR 1.88, 95%CI 1.32–2.66 for 5th most deprived quintile, compared to least deprived quintile), but not for paracetamol or other OTC drug poisonings.ConclusionsPoisonings from DWRDs decreased by 33%, while paracetamol poisonings increased by 43% during the study period. There was a gradient by area-level socioeconomic deprivation in prescribed medication poisonings, including drugs with withdrawal/dependence risk, but not OTC medication poisonings. Households in more socioeconomically deprived areas have the potential to benefit most from measures to improve safe storage of medicines and are likely to require targeted interventions providing education and safety equipment. In addition, universal promotion of the safe storage of OTC and prescribed medicines must be provided by prescribers, community pharmacies and other outlets of such medication.

Potential of the domestic biosimile omalizumab in achievement of control in patients with severe asthma: short communication

BACKGROUND: Severe atopic asthma is a medical and social problem due to its prevalence, the tendency to exacerbations, the impact on the quality of life and on the work ability, and high treatment costs. The appearance biosimilar omalizumab among biologicals makes such therapy more accessible to patients. This article presents the results of an open prospective clinical study of the biosimilar omalizumab in patients with the severe atopic asthma.&#x0D; AIM: To evaluate the efficacy and tolerability of the domestically produced biosimilar omalizumab in the real clinical practice.&#x0D; MATERIALS AND METHODS: The study involved 15 adult patients (19–66 years) with a reliable history consistent with moderate to severe atopic asthma who hadn`t have asthma control at the time of inclusion in the study. All patients received the Genolar (omalizumab, Generic JSC, Russia) for 52 weeks at the dose calculated according to the instructions. The efficacy was evaluated taking into account changes in symptom severity, improved asthma control using the Asthma Control Questionnaire (ACQ-5), pulmonary function tests, peak flow measurements, assessment the asthma exacerbations number and the healthcare resources use.&#x0D; RESULTS: According to our study results, all patients demonstrated a decrease in the night and daytime attacks frequency and the shortness of breath severity due to omalizumab, which made it possible to reduce the basic therapy and refuse systemic glucocorticosteroids using in patients who previously received there. After 6 months we obtained an improvement in the asthma symptoms control: ΔACQ-5=-1.87 (p=0.0002) compared to baseline with a trend towards further improvement in indicators and reached ΔACQ-5=-2.18 (p=0.0001) to the 52nd week. We also obtained a statistically significant improvement in pulmonary function (after a year of treatment, the increase in forced expiratory volume in the first second was +19.85% compared to baseline, p=0.0001). No asthma exacerbation was registered during 12 months omalizumab treatment.&#x0D; CONCLUSION: Our study showed that the biosimilar treatment in patients with severe atopic asthma allowed to achieve asthma control, decrease the exacerbations number and reduce the basic therapy volume, including oral-corticosteroid elimination.

Istradefylline/L‐DOPA Parkinson's disease therapy and energy coupling

AbstractBackgroundBoth dopamine and adenosine are physiologically involved in cellular energy metabolism.AimNovel approaches targeting delaying progression strategies for Parkinson's disease (PD) examined the effects of long‐term use of A2AR antagonist/istradefylline (IST) adjunct to L‐DOPA (LD), nutshell IST‐LD, with an expected energy coupling (EC) to attenuate neuronal excitotoxicity.MethodsA single‐center prospective open cohort study was conducted at the Department of Neurology, Okinawa Islands, Japan. The cohort included incident and prevalent PD cases that were non‐randomly assigned to the IST‐LD (n = 90) and LD (n = 157) groups, followed by an open‐label treatment in clinical practice from October 2013 to September 2020. Patients were evaluated using physician‐rated MDS‐UPDRS I/III, and patient‐rated MDS‐NMS using the total score, body weight, and blood biomarkers of EC.ResultsAs the primary clinical outcome, MDS‐UPDRS part III scores showed less worsening in the IST‐LD than in the LD group (1.29 ± 6.0 vs. 5.0 ± 6.5, p &lt; 0.01) and off‐time Hoehn and Yahr stage (0.05 ± 0.49 vs. 0.26 ± 0.54, p &lt; 0.01). As the secondary clinical outcome, the detected mean body weight losses were similar between the two groups; however, the evident linkage of the daily dose of LD and variations in the blood markers of IGF‐I and HKII, which were inferred as LD‐mediated energy demand effects, were partially attenuated by IST.ConclusionIST‐LD plays an essential role in behavioral outputs for patients with PD and might contribute to the interplay of energy‐consuming demands of LD with the attenuation of weight loss and emerging type 2 diabetes mellitus.

A clinical study of Sidharthakadi Lepa in management of Yuvanpidika (Acne Vulgaris)

Introduction: Acne is a distressing condition that affects the majority of adolescents and harms beauty of the face so person may suffer with inferiority complex, anxiety, isolation etc. Due to wide spectrum of disease, much prevalence in the society and lack of effective medicine, this is the main cause of the global shift toward Ayurveda and Herbal skin care. The present study was conducted to evaluate the effect of Sidharthakadi Lepa in management of Yuvanpidika. Methodology: Single arm open randomized clinical study was conducted on 40 clinically diagnosed patients with Acne Vulgaris for Sidharthakadi Lepa in the Postgraduate Institute of Ayurveda, DSRRAU, Jodhpur. Study evaluates their role in management of Pidika (Prescence of Acne), Kandu (Itching), Vedana (Pain), Daha (Burning sensation) and Srava (Discharge) Results: Result of the study depicts that Lepa has significantly helps in reducing the Acne vulgaris. Conclusion: Out of 40 patients selected for the study, a greater number of young adults &amp; 11 patients were male and 29 were female. It showed the high rate of occurrence and consciousness of this condition in females. Sidharthakadi Lepa is more effective in Vata and Kapha Prakrithi individuals.

A central vein sign in the magnetic resonance diagnosing of multiple sclerosis

Background. Multiple sclerosis (MS) is a chronic autoimmune demyelinating disease, which is characterized by the inevitable disability of patients in the long term, which determines the relevance of this problem. Currently, active improvements are being made in the methods of diagnosing multiple sclerosis, which include the use of the central vein sign in magnetic resonance imaging (MRI) as a neuroimaging biomarker of MS with high sensitivity and specificity.Aim of study. Determination of the possibility of assessing the central vein sign (CVS) according to MRI data as a potential diagnostic biomarker of MS.Object and methods. An open single-center prospective study of brain MR data was conducted in 55 patients with a verified diagnosis of MS (EDSS 1.0-6.5) aged 19 to 72 years. MR-images were obtained on a tomograph with a magnetic field induction force of 3.0 T. Patients underwent MRI of the brain according to the standard protocol: T2-VI, FLAIR, T1-VI (before and after administration of contrast agent), SWI. A comprehensive statistical analysis and evaluation of the obtained MRI data was performed using the Statistica 12 program.Result. During the evaluation of MR-tomograms, all patients with a verified diagnosis in the foci of MS were found to have CVS. In 14.5 % of patients, CVS was detected in 10-30 % of foci, in 61.8 % of patients in 30-60 %, in 23.6 % of patients, from 60 to 95 % was detected. Accordingly, 52.7 % of patients overcame the threshold value of 45 % required for the differential diagnosis of MS from other conditions.Conclusion. The use of CVS in MRI helps to solve the problem of differential diagnosis of MS from other demyelinating diseases when using its threshold criterion – the percentage of foci containing central veins.

Search for predictors of complications of acute coronary syndrome with ST segment elevation – protocol of a prospective open cohort study PROMETHEUS

During the first year after myocardial infarction, coronary artery restenosis, fatal arrhythmias, hospitalization for heart failure or cardiac death may occur. It is necessary to search for biomarkers to predict complications of myocardial infarction. As such predictors, it seems promising to introduce the ABCDE-SE echocardiographic protocol, as well as study the metabolism of vitamin D and proteins of the fibrinolysis system. Cardiospecific microRNAs-21, -29, -143 can be used as pathogenetic factors in the development of complications; it is proposed to study the ongoing pharmacotherapy and patients’ compliance with it as controllable factors.Aim: To search for predictors of complications of myocardial infarction based on the assessment of echocardiographic parameters, vitamin D metabolism, components of the fibrinolysis system and cardiac-specific microRNAs.Material and Methods. The PROMETHEUS study is designed as a prospective, open-label, non-randomized cohort study. It is planned to include 300 patients newly admitted to the vascular center with a preliminary diagnosis of ST-segment elevation ACS. All patients will have their vitamin D concentrations determined; genetic variants of polymorphisms of the vitamin D receptor gene and vitamin D binding protein; concentrations of urokinase and soluble urokinase receptor; microRNA-21, -29, -143, as well as echocardiography using the ABCDE-SE protocol at 1, 3, 6 and 12 months from inclusion. Pharmacotherapy will be assessed at all stages.Expected results: Based on the results of the study, a comprehensive algorithm for optimizing the prediction and prevention of complications of myocardial infarction will be developed and introduced into practical healthcare.

Conception and implementation of an MRI-compatible device to elicit the bulbocavernosus reflex for an open spinal cord study.

Functional MRI (fMRI) can be employed to assess neuronal activity in the central nervous system. However, investigating the spinal cord using fMRI poses several technical difficulties. Enhancing the fMRI signal intensity in the spinal cord can improve the visualization and analysis of different neural pathways, particularly those involved in bladder function. The bulbocavernosus reflex (BCR) is an excellent method for evaluating the integrity of the sacral spinal cord. Instead of stimulating the glans penis or clitoris, the BCR can be simulated comfortably by tapping the suprapubic region. In this study, we explain the necessity and development of a device to elicit the simulated BCR (sBCR) via suprapubic tapping while conducting an fMRI scan. The device was successfully tested on a group of 20 healthy individuals. Two stimulation task block protocols were administered (empty vs. full bladder). Each block consisted of 40 s of suprapubic tapping followed by 40 s of rest, and the entire sequence was repeated four times. Our device can reliably and consistently elicit sBCR noninvasively as demonstrated by electromyographic recording of pelvic muscles and anal winking. Participants did note mild to moderate discomfort and urge to void during the full bladder task. Our device demonstrates an efficacious approach to elicit sBCR within an MRI bore to assess sacral spinal cord functional activity without generating any significant motion artifacts. This device can explore the mechanisms and processes controlling urinary, digestive, or sexual function within this region in humans.

Objectification of the method for glomerular filtration rate assessing in patients with diffuse large B-cell lymphoma during induction immunochemotherapy

Aim. To study the glomerular filtration rate (GFR) dynamics calculated by creatinine and cystatin C during induction immunochemotherapy in patients with newly diagnosed diffuse large B-cell lymphoma in order to objectify the method for estimation.Materials and methods. The open longitudinal study included 39 patients with newly diagnosed diffuse large B-cell lymphoma who received specialized treatment at the Oncohematology Department of National Medical Research Centre for Oncology (Rostov-on-Don) in 2021. Patients received induction immunochemotherapy according to the R-CHOP regimen (rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisolone) in combination with accompanying therapy (allopurinol 300 mg/day). Blood sampling was carried out at 0, 24, 48, 72, 120 hours and on 21st day of the 1st therapy cycle. Patients were divided into 2 groups depending on the GFR level, calculated by creatinine, before treatment: group A – 27 (69 %) patients with GFR &gt;90 ml/min/1.73 m2, group B – 12 (31 %) patients with GFR &lt;90 ml/min/1.73 m2.Results. During the immunochemotherapy in patients with initially reduced GFR, a further decrease was observed with the restoration of the initial level by day 21 of therapy. When calculating GFR by cystatin C, in contrast to the calculation by creatinine, it revealed the dependence of GFR level on pathological process stage: GFR in group A patients with stages I–II is 20.4 % lower than in patients with stages III–IV, in group B – by 30.5 %. The use of the fisher test at GFR thresholds of 90 and 60 ml/min/1.73 m2 revealed a greater advantage in establishing absolute GFR levels, especially in the range of 60 to 90 ml/min/1.73 m2.Conclusion. The data obtained confirm that the determination of GFR by cystatin C in patients with diffuse large B-cell lymphoma is a more sensitive method that objectively reflects the functional state of the kidneys, especially when values are within the “gray area” – from 90 to 60 ml/min/1.73 m2.

The effects of radiofrequency electromagnetic fields exposure on human self-reported symptoms: A systematic review of human experimental studies

BackgroundThe technological applications of radiofrequency electromagnetic fields (RF-EMF) have been steadily increasing since the 1950s exposing large proportions of the population. The World Health Organization (WHO) is assessing the potential health effects of exposure to RF-EMF. ObjectivesTo systematically assess the effects of exposure to RF-EMF on self-reported non-specific symptoms in human subjects and to assess the accuracy of perceptions of presence or absence of RF-EMF exposure. MethodsEligibility criteria: experimental studies carried out in the general population and in individuals with idiopathic environmental intolerance attributed to EMF (IEI-EMF), in any language.Information sources: Medline, Web of Science, PsycInfo, Cochrane Library, Epistemonikos, Embase and EMF portal, searched till April 2022.Risk of Bias (ROB): we used the RoB tool developed by OHAT adapted to the topic of this review.Synthesis of results: we synthesized studies using random effects meta-analysis and sensitivity analyses, where appropriate. ResultsIncluded studies: 41 studies were included, mostly cross over trials and from Europe, with a total of 2,874 participants.Synthesis of results: considering the primary outcomes, we carried out meta-analyses of 10 exposure-outcomes pairs. All evidence suggested no or small non-significant effects of exposure on symptoms with high (three comparisons), moderate (four comparisons), low (one comparison) and very low (two comparisons) certainty of evidence. The effects (standard mean difference, where positive values indicate presence of symptom being exposed) in the general population for head exposure were (95% confidence intervals) 0.08 (−0.07 to 0.22) for headache, −0.01 (−0.22 to 0.20) for sleeping disturbances and 0.13 (−0.51 to 0.76) for composite symptoms; and for whole-body exposure: 0.09 (−0.35 to 0.54), 0.00 (−0.15 to 0.15) for sleeping disturbances and −0.05 (−0.17 to 0.07) for composite symptoms. For IEI-EMF individuals SMD ranged from −0.19 to 0.11, all of them with confidence intervals crossing the value of zero.Further, the available evidence suggested that study volunteers could not perceive the EMF exposure status better than what is expected by chance and that IEI-EMF individuals could not determine EMF conditions better than the general population. DiscussionLimitations of evidence: experimental conditions are substantially different from real-life situations in the duration, frequency, distance and position of the exposure. Most studies were conducted in young, healthy volunteers, who might be more resilient to RF-EMF than the general population. The outcomes of interest in this systematic review were symptoms, which are self-reported. The available information did not allow to assess the potential effects of exposures beyond acute exposure and in elderly or in chronically ill people. It cannot be ruled out that a real EMF effect in IEI-EMF groups is masked by a mix with insensitive subjects. However, studies on symptoms reporting and/or field perceptions did not find any evidence that there were particularly vulnerable individuals in the IEI-EMF group, although in open provocation studies, when volunteers were informed about the presence or absence of EMF exposure, such differences were consistently observed.Interpretation: available evidence suggests that acute RF-EMF below regulatory limits does not cause symptoms and corresponding claims in the everyday life are related to perceived and not to real EMF exposure status.