Electrolyte imbalances as poor prognostic markers in COVID-19: a systemic review and meta-analysis.

PURPOSE: Serum electrolyte imbalances are highly prevalent in COVID-19 patients. However, their associations with COVID-19 outcomes are inconsistent, and of unknown prognostic value. We aim to systematically clarify the associations and prognostic accuracy of electrolyte imbalances (sodium, calcium, potassium, magnesium, chloride and phosphate) in predicting poor COVID-19 clinical outcome. METHODS: PubMed, Embase and Cochrane Library were searched. Odds of poor clinical outcome (a composite of mortality, intensive-care unit (ICU) admission, need for respiratory support and acute respiratory distress syndrome) were pooled using mixed-effects models. The associated prognostic sensitivity, positive and negative likelihood ratios (LR + , LR-) and predictive values (PPV, NPV; assuming 25% pre-test probability), and area under the curve (AUC) were computed. RESULTS: We included 28 observational studies from 953 records with low to moderate risk-of-bias. Hyponatremia (OR = 2.08, 95% CI = 1.48-2.94, I2 = 93%, N = 8), hypernatremia (OR = 4.32, 95% CI = 3.17-5.88, I2 = 45%, N = 7) and hypocalcemia (OR = 3.31, 95% CI = 2.24-4.88, I2 = 25%, N = 6) were associated with poor COVID-19 outcome. These associations remained significant on adjustment for covariates such as demographics and comorbidities. Hypernatremia was 97% specific in predicting poor outcome (LR + 4.0, PPV = 55%, AUC = 0.80) despite no differences in CRP and IL-6 levels between hypernatremic and normonatremic patients. Hypocalcemia was 76% sensitive in predicting poor outcome (LR- 0.44, NPV = 87%, AUC = 0.71). Overall quality of evidence ranged from very low to moderate. CONCLUSION: Hyponatremia, hypernatremia and hypocalcemia are associated with poor COVID-19 clinical outcome. Hypernatremia is 97% specific for a poor outcome, and the association is independent of inflammatory marker levels. Further studies should evaluate if correcting these imbalances help improve clinical outcome.

Adherence to Iron Chelation Therapy Among Children with Beta Thalassemia Major: A Multicenter Cross-Sectional Study.

BACKGROUND: Adherence to iron chelation therapy (ICT) remains an issue among thalassemia patients. This study aimed to determine the prevalence of non-adherence to ICT among children with beta thalassemia major in Malaysia and the factors associated with it. METHODS: This was a cross-sectional study conducted between November 2019 and November 2021 at seven tertiary hospitals in Malaysia. Participants registered with Malaysian Thalassemia Registry were recruited by convenience sampling. Adherence was measured via pill count and self-reported adherence. Knowledge about thalassemia and ICT was measured using a questionnaire from Modul Thalassemia by Ministry of Health of Malaysia. A decision tree was used to identify predictors of non-adherence. RESULTS: A total of 135 patients were recruited. The prevalence of non-adherence to ICT in those who took subcutaneous ± oral medications was 47.5% (95% CI: 31.5%, 63.9%) and the prevalence of non-adherence to ICT in those who took oral medications only was 21.1% (95% CI: 13.4%, 30.6%). The median knowledge score was 67.5% (IQR 15%). A decision tree has identified two factors associated with non-adherence. They were ICT's route of administration and knowledge score. Out of 100 patients who were on oral medications only, 79 were expected to adhere. Out of 100 patients who were on subcutaneous ± oral medications and scored less than 56.25% in knowledge questionnaire, 86 were expected to non-adhere. Based on the logistic regression, the odds of non-adherence in patients who took oral medications only was 71% lower than the odds of non-adherence in patients who took subcutaneous ± oral medications (OR = 0.29; 95% CI = 0.13, 0.65; p = .002). CONCLUSION: The prevalence of non-adherence to ICT among children with beta thalassemia major in Malaysia was 20/95 (21.1%) in those who took oral medications only and the prevalence of non-adherence was 19/40 (47.5%) in those who took subcutaneous ± oral medications. The factors associated with non-adherence were ICT's route of administration and knowledge score.

FATIGUE IN PATIENTS WITH LONG COVID.

Purpose of the study - to characterize the metabolomic profile in patients with fatigue developing within the Long COVID, during dynamic observation. 24 patients diagnosed with U09.9 "Condition after COVID-19 unspecified" were included in a prospective study. Patients were recommended to engage in physical activity, which included moderate aerobic activity such as walking for 45 minutes a day, three days a week. Clinical assessment by scales (Modified Medical Research Council dyspnea scale; 6-minute walk test; Multidimensional fatigue inventory scale; Barthel index), and determination of metabolomic parameters were performed on days 1 and 14-18 of the study. During the observation period, lactate, fumaric acid, symmetrical dimethylarginine, asymmetric dimethylarginine remained above the reference values. The level of adipic acid returns to normal values. As a result of performing physical activity, such as walking, results on the Modified Medical Research Council scale dyspnea scale, Multidimensional fatigue inventory scale, 6 Minutes Walking Test and Barthel Index improve (p<0,001). Metabolic profile of patients with Long COVID demonstrates the complex of abnormalities at 60 days after the onset of the disease. These metabolic changes are point to possible therapeutic targets for specific pathogenetic pharmacotherapy.

Investing in scholarship for health professions education: Learning from the past to move into the future.

There have been recent discourses of what scholarship means for health professions education (HPE) and how it may need a rethink during the pandemic. One key take home message from these discourses is the role of institutions in nurturing and investing in scholarship. Given the current challenges faced by both higher education and healthcare, there is a risk that activities and resources for scholarship in HPE may be neglected. How do institutions make a case for continuous investment in HPE scholarship? Despite being a relatively new and small private university with no public funding, IMU has made fairly significant progress in delivering a unique model of HPE programmes with HPE scholarly output. This commentary discusses the importance of investing in scholarship for HPE with the International Medical University (IMU) in Kuala Lumpur, Malaysia as a case study. Examples of institutional initiatives that support and enhance scholarship are presented based on the recent AMEE guide (142) on redefining scholarship.

Transfer of knowledge, skills and confidence from a faculty development programme for health professions educators into practice.

BACKGROUND: Faculty development programmes should incorporate the transfer of knowledge, skills, and confidence from the training to educational practice. However, there is a risk that transfer may fail due to inadequate integration of knowledge, skills, and confidence. The study evaluated transfer levels, guided by learned principles from a faculty development programme. METHOD: The submitted self-reports on a pedagogical intervention of 92 out of 190 health professions educators who participated in a mandatory teaching and learning training programme, were analysed by a mixed-method approach guided by a structured conceptual framework. RESULTS: Overall 93.4% reported the successful transfer of learning. Participants incorporated sustainable changed practice (level A, 57.6%), showed reflection on the impact of changed practice (level B, 21.7%), and performed effect analysis (level C, 14.1%). The rest planned application of learning (level D, 4.4%) and identified gaps in current practice or developed an idea for educational intervention but did not implement (level E, 2.2%). CONCLUSION: The majority of participants transferred their learning. Faculty development programmes must ensure successful transfer of knowledge, skills, and confidence from the training to educational practice to ensure sustainable development of teaching and learning practices.

[Change in the expression of gene transcription negative regulator SOCS1 in the patients with bronchial asthma and metabolic disorders].

AIM: Comprehensive study of the negative regulation components of cell signaling in the bronchial asthma (BA) patients with metabolic disorders. MATERIALS AND METHODS: 113 people were examined: 63 patients with allergic BA (ABA), 50 patients with a non-allergic variant of the disease (NABA). SOCS1 mRNA expression was evaluated by reverse transcription PCR (RT-PCR). SOCS1 protein expression was investigated by immunoblotting. The determination of cytokine levels was carried out according to the standard protocol on a Bio-Plex flow fluorimeter. RESULTS: A significant and multidirectional change in the expression of SOCS1 mRNA was found at a body mass index 25 (greater than normal) in ABA and NABA. The positive correlations between SOCS1 mRNA expression and body mass index indicate the regulatory role of SOCS1 in leptin signaling. The spectra of correlations in ABA and NABA are different, it indicates the probable existence of specificity in the pathogenesis of these variants of the diseases. CONCLUSION: The obtained data allow us to consider the complexity of regulation disorders occurring at different levels of cell signaling. The multifunctionality of the SOCS1 regulator provides complex control of cytokine signaling simultaneously in different signaling pathways in the BA with metabolic disorders.

[Role of negative regulators of SOCS1, SOCS3, and SOCS5 gene transcription in the negative cell signaling regulation system in asthma]. / Rol' negativnykh regulyatorov transkriptsii genov SOCS1, SOCS3 i SOCS5 v sisteme negativnoi regulyatsii kletochnoi signalizatsii pri bronkhial'noi astme.

AIM: To conduct a comprehensive study of the components of negative cell signaling regulation in different types of asthma. SUBJECTS AND METHODS: A total of 171 people, including 80 patients with allergic asthma (AA), 60 patients with non-allergic asthma (NAA), and 31 apparently healthy individuals, were examined. SOCS5 mRNA expression was assessed by reverse-transcription polymerase chain reaction. The expression of SOCS1 and SOCS3 proteins was investigated by immunoblotting. The concentration of total serum IgE was determined by enzyme immunoassay; the level of cytokines was measured according to the standard protocol using a Bio-Plex fluorometer. RESULTS: The findings show that the patients with AA generally display more marked changes in the expression of all three investigated SOCSes (SOCS1, SOCS3, and SOCS5) at baseline and when interleukin 4 (IL-4) acts. In NAA, there are pronounced changes in the expression of SOCS3 only and, to a lesser extent, SOCS5. The results of investigating the concentrations of IL-4 in the examined groups demonstrate its significant decrease in the AA group, whereas in the NAA group, it is similar to those in healthy individuals. On the contrary, IL-10 concentrations in AA tend towards those in the control group, but much exceed in NAA. CONCLUSION: The findings allow one to consider the complexity of regulatory disorders arising at various levels of cell signaling in the context of the multifunctional nature of the molecules from the family of negative regulators of transcription of the SOCS1, SOCS3, and SOCS5 genes, which provide the comprehensive control of cytokine signaling simultaneously in different signal pathways.

Laser and light therapy for facial warts: a systematic review.

Facial verruca plana, or flat warts, are benign skin papillomas caused by human papillomavirus infections. A large portion of cases are refractory to treatment and can cause psychosocial distress in patients. Laser and light modalities offer an alternative therapeutic approach that has not been extensively explored. We systematically reviewed PubMed for studies describing treatment of facial verruca plana using lasers, photodynamic therapy and infrared coagulation. Final inclusion and review of eighteen studies suggests laser and light therapies to have considerable potential in the treatment of this recalcitrant condition. In particular, yttrium aluminium garnet lasers, infrared coagulation and photodynamic therapies have been reported to demonstrate efficacy. Further studies with larger power are required to determine which method should be established as the alternative treatment of choice for recalcitrant facial verrucae.

Measures of acute physiology, comorbidity and functional status to differentiate illness severity and length of stay among acute general medical admissions: a prospective cohort study.

BACKGROUND: Simple measures of acute physiologic compromise, functional status and comorbidity may help clinicians to make decisions relating to clinical care and resource utilisation. AIMS: To explore the usefulness of common assessment tools in predicting outcomes of (i) death or intensive care unit (ICU) admission and (ii) length of hospital stay at a busy tertiary hospital in Singapore. METHODS: Three hundred and ninety-eight consecutive admissions to two general medicine teams were prospectively assessed during 2 months in 2011. Patients were followed until discharge or transfer to ICU/high dependency unit (HDU). Data collected included routine demographic data, final diagnosis, comorbid conditions including a weighted prognostic comorbidity index (the updated Charlson index) and the modified Early Warning Score (MEWS) at presentation to the emergency department. The admission modified Barthel Index was recorded for patients aged 65 and over. Death and total length of hospital stay were recorded in all cases. RESULTS: Of 398 patients, 16 (4 %) died or were transferred to ICU and 99 (25%) stayed for more than 7 days. Medical early warning (MEW) scores of ≥5 were significantly associated with death or ICU admission (hazard ratio 5.50, 95% confidence interval 1.77-17.07, P = 0.003). There was no independent association between this outcome and the Charlson score or admission Barthel Index. Excess length of stay was associated with a modified Barthel Index ≤17 and altered mental status at presentation. CONCLUSION: Among unselected general medical patients, MEW scores of ≥5 were significantly associated with death or ICU admissions and only functional status and altered mental status were independent predictors of excess length of stay.

Effects of reversible inhibition of cholinesterase and nicotine on mouse mortality and blood levels of proinflammatory cytokines during the early phase of sepsis.

Experiments on outbred albino mice have shown that proserine (reversible cholinesterase inhibitor) and nicotine (nicotinic receptor agonist) in a equivalent dose of 0.2 DL(50)injected 2 h before sepsis induction significantly reduced animal mortality from experimental infection due to reduction of blood concentrations of proinflammatory cytokines TNF-α, IL-1ß, and IL-6.

Role of nicotinic and muscarinic cholinoreceptors in the realization of the cholinergic anti-inflammatory pathway during the early phase of sepsis.

Stimulation of nicotinic and muscarinic cholinoreceptors (nAChR, mAChR) in outbred albino mice with nicotine and aceclidine, respectively, in single equilethal doses 0.5 DL(50)6 h before sepsis induction significantly reduced animal mortality due to a decrease in blood concentrations of proinflammatory cytokines IL-1ß, IL-6, and MIP-2. Stimulation of mAChR (injection of aceclidine) stimulated the neutrophilic phagocytic and metabolic activity. Realization of the cholinergic anti-inflammatory pathway (stimulation of the peripheral nicotinic cholinoreceptors (α7nAChR) and central muscarinic cholinoreceptors (mAChR) was modulated by stimulation of the muscarinic cholinoreceptors of the phagocytic monocytic system cells.

[Disturbances of immune status and cytokine profile caused by chronic intoxication with organophosphorus compounds and their correction by administration of imunofan].

Experiments on noninbred rats showed that the chronic intoxication with organophosphorus compounds sarin and methylparathion (30 days; total dose, 0.9 LD50; single daily dose, 0.03 mg/kg,) significantly decreases the immune responses and reduces the concentrations of blood cytokines IFN-gamma, IL-2, IL-4, IL-6, and IL-10. The damage is more pronounced in Th1 cells than in Th2 lymphocytes. The administration of imunofan (single daily dose, 20 microg/kg) for 5 days partly recovers the immune status and the content of cytokines in the blood.

Acceptability of atraumatic restorative treatment and Hall Technique among children, parents, and general dental practitioners: a systematic review and meta-analysis.

OBJECTIVE: This systematic review aimed to evaluate the acceptance level of atraumatic restorative treatment (ART) and Hall Technique (HT) among children, parents, and general dental practitioners. METHOD AND MATERIALS: The study was registered in the PROSPERO database. Articles published between January 1960 and January 2021 were searched in 11 online databases and six textbooks according to PRISMA guidelines. Fifteen studies were chosen for qualitative and quantitative analyses. Among them, five studies focused on ART, seven studies on HT, and the remaining three studies compared both ART and HT. The children, parents, and general dental practitioners' acceptance were estimated using the DerSimonian-Laird random--effects method based on both single-arm and two-arm approaches. The risks of bias were evaluated using Cochrane RoB 2, ROBINS-1, NOS, and JBI assessment tools, while evidence levels were determined using OCEBM. Subgroup analysis and meta-regression were conducted to assess the effect of different evaluation methods on the acceptance rates of ART and HT among children and parents. RESULTS: The acceptance rates of ART among children, parents and general dental practitioners were 90.1%, 95.7%, and 67.7%, respectively, whilst the acceptance rates of HT were 88.3%, 85.7%, and 81.8%, respectively. Two-arm meta-analysis revealed no significant difference (P > .05) between the acceptance of HT and ART among children and parents, respectively. Subgroup analysis showed that using questionnaire-based evaluation had a higher (P < .05) acceptance value than using face scale-based evaluation. CONCLUSION: Both ART and HT are considered well--accepted among children, parents, and general dental practitioners, although general dental practitioners showed a slightly lower level of acceptance. A standardized evaluation tool for assessing acceptance level should be established for better comparison among published articles. Future well-designed studies are warranted to verify the validity of the present review.

Mechanisms of immune status disorders in chronic ethanol intoxication.

Experiments of outbred albino rats showed that chronic ethanol intoxication (20 days, summary dose 5 LD(50)) inhibited immune reactions mainly mediated by Th1-cells, increased blood corticosterone concentration, reduced T-lymphocyte acetylcholinesterase activity, blood concentrations of IFN-γ, IL-2, IL-4, IL-10, and increased IL-6 level.

Leptospirosis: a re-emerging infection.

Leptospirosis is a re-emerging zoonotic infection. In developing countries large outbreaks have occurred in urban slums and following floods. Individuals from developed nations are also now more frequently exposed to the infection as a result of international travel and greater participation in certain outdoor recreational activities. Leptospirosis remains a diagnostic challenge since it often presents as a non-specific febrile event and laboratory diagnosis is still currently inadequate. Rapid tests may not be sufficiently sensitive in early disease and culture facilities are not widely available. A severe pulmonary haemorrhagic form of the infection is increasingly being encountered in many countries including Malaysia. The control of leptospirosis is largely dependent on general hygienic measures and rodent control. An effective human vaccine is still not available. There remains much that is unknown about this disease and there is scope and opportunity for good quality research.

Multicentre phase I/II study of PI-88, a heparanase inhibitor in combination with docetaxel in patients with metastatic castrate-resistant prostate cancer.

BACKGROUND: Docetaxel (Taxotere) improve survival and prostate-specific antigen (PSA) response rates in patients with metastatic castrate-resistant prostate cancer (CRPC). We studied the combination of PI-88, an inhibitor of angiogenesis and heparanase activity, and docetaxel in chemotherapy-naive CRPC. PATIENTS AND METHODS: We conducted a multicentre open-label phase I/II trial of PI-88 in combination with docetaxel. The primary end point was PSA response. Secondary end points included toxicity, radiologic response and overall survival. Doses of PI-88 were escalated to the maximum tolerated dose; whereas docetaxel was given at a fixed 75 mg/m(2) dose every three weeks RESULTS: Twenty-one patients were enrolled in the dose-escalation component. A further 35 patients were randomly allocated to the study to evaluate the two schedules in phase II trial. The trial was stopped early by the Safety Data Review Board due to a higher-than-expected febrile neutropenia of 27%. In the pooled population, the PSA response (50% reduction) was 70%, median survival was 61 weeks (6-99 weeks) and 1-year survival was 71%. CONCLUSIONS: The regimen of docetaxel and PI-88 is active in CRPC but associated with significant haematologic toxicity. Further evaluation of different scheduling and dosing of PI-88 and docetaxel may be warranted to optimise efficacy with a more manageable safety profile.

[Pharmacological correction of Th1 and Th2 lymphocyte activity and cytokine profile in ethanol intoxicated rats].

It was established in experiments on noninbred rats that their ethanol intoxication (13 days; total dose, 2.6 LD50) significantly reduces the concentration of blood cytokines IFNgamma, IL-2, IL-4, IL-10, increases the concentration of IL-6, suppresses the immune responses, and reduces the interrelation IFNgamma/IL-4 in comparison to the control, which testifies to the greater damage of Th1 cells in comparison to Th2 lymphocytes. The immunomodulator polyoxidonium administered for four days at a daily dose of 700 microg/kg fully restores the cellular and humoral immune responses and the synthesis of cytokines IFNgamma, IL-2, and IL-4 and partly restores the production of IL-10.

[Complex rehabilitation of a patient with marked motor and cognitive impairments after a brain injury]. / Kompleksnaya reabilitatsiya patsienta posle tyazheloi zakrytoi cherepno-mozgovoi travmy s vyrazhennymi dvigatel'nymi i kognitivnymi narusheniyami.

In the presented case report, the complex approach of rehabilitation in the remote period of traumatic brain injury (TBI) allowed the achievement of the significant clinical effect. The authors analyzed the experience of reflex therapy in the treatment of TBI. The effectiveness and potential of acupuncture, objectification of the results are topical issues that require further research.

The educational environment and self-perceived clinical competence of senior medical students in a Malaysian medical school.

INTRODUCTION: The educational environment is widely considered to be a major factor affecting students' motivation and learning outcomes. Although students' perceptions of their educational environment are often reported, we are unaware of any published reports that relate this information to students' clinical competence, either self-perceived or objectively measured. OBJECTIVES: We aimed to correlate students' perceptions of their learning environment and their self-perceived competence in clinical, practical and personal skills, using validated scales. METHODS: Subjects included a cohort of 71 final-year medical students who were posted to a peripheral campus affiliated with a district hospital. Two questionnaires were administered concurrently: a modified DREEM (50 items) to assess the learning environment and an abbreviated IMU Student Competency Survey (29 items) to examine self-perceived competence across a wide range of skills and work-readiness. We correlated the major domains in both surveys using Spearman's Correlation. FINDINGS: Fifty-nine students (83%) completed the questionnaires. Comparing correlations of the five major domains of the modified DREEM questionnaire ("Perception of learning", "Perception of teachers", "Academic self-perception", "Perception of atmosphere" and "Social self-perception") with all subscales in the abbreviated IMU Student Competency Survey (clinical, practical, personal skills and overall work-readiness), we found that academic self-perception domain had the strongest correlations (r:0.405 to 0.579, p:0.002 to < 0.001) and perception of teachers bears the weakest correlations (r:0.171 to 0.284, p:0.254 to 0.031). Self-perceived competence in practical skills in the IMU Student Competency Survey correlated the weakest with all domains of the modified DREEM (r:0.206 to 0.405, p:0.124 to 0.002). DISCUSSION AND CONCLUSION: The overall weak-to-moderate correlations between perceptions of learning environment and self-perceived clinical competence suggest that other factors might interact with the learning environment to determine students' confidence and achievements.

Role of cholinergic and cytokine regulation of T cell function in stimulation and inhibition of immune reactions in intoxication by organophosphorus compounds in different doses.

Experiments on outbred albino rats showed that administration of acetylcholine and aceclidine in a dose of 0.1 LD50 for 3 days and of dimethyl dichlorovinyl phosphate (organophosphorus compound) in a single dose of 0.05 LD50 stimulated the function of Th1 and Th2 lymphocytes and cytokine production by these cells. Dimethyl dichlorovinyl phosphate in a single dose of 0.5 LD50 produced an opposite effect. Acetylcholine and aceclidine stimulated activity of acetylcholinesterase in T cells, while dimethyl dichlorovinyl phosphate in a single dose of 0.5 LD50 inhibited it. During acute intoxication, the organophosphorus compound, depending on the dose, can stimulate (acetylcholine effect) and inhibit the immune reactions (acetylcholinesterase inhibition of T cells).