Classic ketogenic diet versus further antiseizure medicine in infants with drug-resistant epilepsy (KIWE): a UK, multicentre, open-label, randomised clinical trial.

BACKGROUND: Many infancy-onset epilepsies have poor prognosis for seizure control and neurodevelopmental outcome. Ketogenic diets can improve seizures in children older than 2 years and adults who are unresponsive to antiseizure medicines. We aimed to establish the efficacy of a classic ketogenic diet at reducing seizure frequency compared with further antiseizure medicine in infants with drug-resistant epilepsy. METHODS: In this phase 4, open-label, multicentre, randomised clinical trial, infants aged 1-24 months with drug-resistant epilepsy (defined as four or more seizures per week and two or more previous antiseizure medications) were recruited from 19 hospitals in the UK. Following a 1-week or 2-week observation period, participants were randomly assigned using a computer-generated schedule, without stratification, to either a classic ketogenic diet or a further antiseizure medication for 8 weeks. Treatment allocation was masked from research nurses involved in patient care, but not from participants. The primary outcome was the median number of seizures per day, recorded during weeks 6-8. All analyses were by modified intention to treat, which included all participants with available data. Participants were followed for up to 12 months. All serious adverse events were recorded. The trial is registered with the European Union Drug Regulating Authorities Clinical Trials Database (2013-002195-40). The trial was terminated early before all participants had reached 12 months of follow-up because of slow recruitment and end of funding. FINDINGS: Between Jan 1, 2015, and Sept 30, 2021, 155 infants were assessed for eligibility, of whom 136 met inclusion criteria and were randomly assigned; 75 (55%) were male and 61 (45%) were female. 78 infants were assigned to a ketogenic diet and 58 to antiseizure medication, of whom 61 and 47, respectively, had available data and were included in the modifified intention-to-treat analysis at week 8. The median number of seizures per day during weeks 6-8, accounting for baseline rate and randomised group, was similar between the ketogenic diet group (5 [IQR 1-16]) and antiseizure medication group (3 [IQR 2-11]; IRR 1·33, 95% CI 0·84-2·11). A similar number of infants with at least one serious adverse event was reported in both groups (40 [51%] of 78 participants in the ketogenic diet group and 26 [45%] of 58 participants in the antiseizure medication group). The most common serious adverse events were seizures in both groups. Three infants died during the trial, all of whom were randomly assigned a ketogenic diet: one child (who also had dystonic cerebral palsy) was found not breathing at home; one child died suddenly and unexpectedly at home; and one child went into cardiac arrest during routine surgery under anaesthetic. The deaths were judged unrelated to treatment by local principal investigators and confirmed by the data safety monitoring committee. INTERPRETATION: In this phase 4 trial, a ketogenic diet did not differ in efficacy and tolerability to a further antiseizure medication, and it appears to be safe to use in infants with drug-resistant epilepsy. A ketogenic diet could be a treatment option in infants whose seizures continue despite previously trying two antiseizure medications. FUNDING: National Institute for Health and Care Research.

Primary Care Counseling of Parents Regarding Childhood Screen Media Use.

Parental beliefs and motivation are instrumental in improving childhood digital media use (DMU). Parents (n = 611) completed questionnaires about childhood DMU assessing knowledge, interest in counseling, motivation to change, self-efficacy, and beliefs. Less than a third correctly recognized screen time limits. Twenty-seven percent received childhood DMU information from a doctor, while 46% stated they would like such information. Only 2% had a doctor-recommended DMU plan. Interest in DMU topics, motivation to improve, and management self-efficacy were moderate. Top negative beliefs were addiction to DMU (52%), sleep problems (39%), obesity (33%), social skills (33%), and inappropriate content (32%). Differences between age categories existed for social (48%, P = .01) and language (14%, P = .01) concerns (highest for toddlers), attention concerns (27%, P = .02; highest in preschoolers), and depression (13%, P < .001) and low self-esteem (8%, P = .04; highest in teens). Findings support further development of approaches to address DMU, tailored by age-specific common parental views.

Adoption of AI-Enabled Tools in Social Development Organizations in India: An Extension of UTAUT Model.

Social development organizations increasingly employ artificial intelligence (AI)-enabled tools to help team members collaborate effectively and efficiently. These tools are used in various team management tasks and activities. Based on the unified theory of acceptance and use of technology (UTAUT), this study explores various factors influencing employees' use of AI-enabled tools. The study extends the model in two ways: a) by evaluating the impact of these tools on the employees' collaboration and b) by exploring the moderating role of AI aversion. Data were collected through an online survey of employees working with AI-enabled tools. The analysis of the research model was conducted using partial least squares (PLS), with a two-step model - measurement and structural models of assessment. The results revealed that the antecedent variables, such as effort expectancy, performance expectancy, social influence, and facilitating conditions, are positively associated with using AI-enabled tools, which have a positive relationship with collaboration. It also concluded a significant effect of AI aversion in the relationship between performance expectancy and use of technology. These findings imply that organizations should focus on building an environment to adopt AI-enabled tools while also addressing employees' concerns about AI.

Expression of serum proteins in noise induced hearing loss workers of mining based industry.

Noise Induced Hearing Loss (NIHL) is caused by excessive noise exposure due to occupational activities thus affects communication and quality of life. Prolonged occupational and environmental exposure to loud noise damages key molecules present in the micro-machinery of the ear which are required for the mechano-electrical transduction of sound waves in cochlea. Specific proteins are known to be associated with hearing loss and related structural and functional disabilities in the human inner, outer hair cells and cochlea. Rationale of this study was to identify the cochlear proteins associated with the pathophysiology of NIHL using proteomic approaches in mining based industrial workers. Total (n = 210) samples were collected from mining based industrial workers of central India. Subjects were categorized based on audiometric analysis. Proteome changes of the host serum were investigated using one and two-dimensional electrophoresis in combination with LC-MS/MS and MALDI-TOF-MS. Up-regulated 46 cochlear proteins among confirmed NIHL cases were identified by MASCOT. Shrinkage discriminant analysis provided top 25 discriminating feature proteins namely myosin, transthyretin, SERPIN, CCDC50, enkurin, transferin etc. The identified potential proteins may be used as biomarkers for early detection and to understand the pathogenic mechanism of NIHL. Evaluation of these biomarkers in follow-up cases may further aid in improving NIHL diagnosis. SIGNIFICANCE: Human proteome study in Noise Induced Hearing Loss (NIHL) cases has not been published till date. This study represents most comprehensive proteomic analysis in NIHL cases taken from Indian mine workers. The identified key twenty-five discriminating feature proteins which are upregulated when an individual develops (or is in stage of development of) NIHL, provides insights into the potential roles of these varied proteins in disease progression. The proteins thus identified by proteomic approach may be used as early diagnostic biomarker to predict the occurrence of disease at very early stage.

Unexpected case of cryptococcal meningoencephalitis in a patient with long-standing well-controlled HIV infection.

Cryptococcal meningoencephalitis (CM) classically occurs in individuals with advanced HIV infection, solid organ transplants, or other immunocompromising conditions. We report a case of fatal CM in a 78-year-old woman with well-controlled HIV infection who had delayed diagnosis, persistently elevated intracranial pressure and pleocytosis of the cerebrospinal fluid. Initial suspicion for CM was low due to her relatively high CD4+ T cell counts, which likely contributed to greater inflammation.

Bacterial and fungal coinfections in COVID-19 patients hospitalized during the New York City pandemic surge.

We observed bacterial or fungal coinfections in COVID-19 patients admitted between March 1 and April 18, 2020 (152 of 4,267, 3.6%). Among these patients, mortality was 57%; 74% were intubated; 51% with bacteremia had central venous catheters. Time to culture positivity was 6-7 days, and 79% had received prior antibiotics. Metallo-ß-lactamase-producing E. cloacae coinfections occurred in 5 patients.

Analysis of catheter utilization, central line associated bloodstream infections, and costs associated with an inpatient critical care-driven vascular access model.

BACKGROUND: Central line-associated bloodstream infections (CLABSI) carry serious risks for patients and financial consequences for hospitals. Avoiding unnecessary temporary central venous catheters (CVC) can reduce CLABSI. Critical Care Medicine (CCM) is often consulted to insert CVC when alternatives are unavailable. We aim to describe clinical and financial implications of a CCM-driven vascular access model. METHODS: In this retrospective, observational cohort study, all CLABSI and a sample of CCM consults for CVC insertion on adult medical-surgical inpatient units were reviewed in 2019. Assessment of CVC appropriateness and financial analysis of labor, reimbursement, and attributable CLABSI cost was conducted. RESULTS: Of 554 CCM consult requests, 75 (13.5%) were for CVC and 36 (48.0%) resulted in CVC insertion; 6 (16.7%) CVC were avoidable. Three CLABSI occurred in avoidable CVC with estimated annual attributable cost of $165,099. Estimated annual CCM consultant cost for CVC was $78,094 generating $110,733 in reimbursement. Overall estimated annual loss was $132,460. DISCUSSION: Reliance on CCM for intravenous access resulted in avoidable CVC, CLABSI, inefficient physician effort, and financial losses; nurse-driven vascular access models offer potential cost savings and risk reduction. CONCLUSIONS: CCM-driven vascular access models may not be cost-effective; alternatives should be considered for utilization reduction, CLABSI prevention, and financial viability.

Chronic disease prevention evaluation in Ontario's public health system: a qualitative needs assessment.

OBJECTIVES: Building evaluation capacity for chronic disease prevention (CDP) is a critical step in ensuring the effectiveness of CDP programming over time. In this article, we highlight the findings of the qualitative arm of a mixed-methods needs assessment designed to assess the gaps and areas of strength within Ontario's public health system with respect to CDP evaluation. METHODS: We conducted 29 interviews and focus groups with representatives from 25 public health units (PHUs) and analyzed the data using thematic analysis. We sought to understand what gaps and challenges exist in the Ontario public health system around CDP evaluation. RESULTS: Challenges facing Ontario's PHUs in CDP evaluation include variation and centralization of capacity to evaluate, as well as competing priorities limiting the development of evaluative thinking. Participating PHUs identified the need for evaluation capacity building (ECB) strategies grounded in an understanding of the unique contexts in which they work and a desire for guidance in conducting a complex and thoughtful evaluation. Moving forward, PHUs noted a desire for a strong system of knowledge sharing and consultation across the public health system, including through strengthening existing partnerships with community collaborators. CONCLUSION: These results support the case for ECB strategies that are adaptive and context-sensitive and equip PHUs with the skills required to evaluate complex CDP programming.

RéSUMé: OBJECTIFS: Le renforcement des capacités en évaluation dans le domaine de la prévention des maladies chroniques (PMC) est crucial pour assurer l'efficacité des programmes visant à prévenir les maladies chroniques au fil du temps. Dans cet article, nous rapportons les résultats du volet qualitatif d'une analyse des besoins utilisant les méthodes mixtes conçues pour rendre compte des lacunes et des forces du système de santé publique de l'Ontario en matière d'évaluation de programmes de PMC. MéTHODES: Nous avons d'abord mené 29 entretiens et groupes de discussion auprès de 25 unités de santé publique (USP) pour ensuite analyser les données recueillies par une analyse thématique de contenu. Nous avons cherché à identifier les lacunes, les forces et les défis qui existent dans le système de santé publique de l'Ontario en matière d'évaluation de programmes de PMC. RéSULTATS: Les défis auxquels sont confrontées les USP de l'Ontario en matière d'évaluation de programmes de PMC comprennent la centralisation et les variations dans les capacités à réaliser l'évaluation ainsi que les priorités concurrentes qui limitent le développement de la pensée évaluative. Les organisations participantes souhaitent des stratégies de renforcement des capacités en évaluation qui tiennent compte des différents contextes dans lesquelles elles travaillent ainsi qu'un soutien dans la réalisation d'évaluations complexes. Pour aller de l'avant, les USP souhaitent également mettre en place un système efficace d'échanges d'informations et de consultations à travers le système de santé publique, notamment en renforçant les partenariats existants dans le milieu communautaire. CONCLUSION: Ces résultats appellent l'élaboration de stratégies de renforcement des capacités en évaluation qui sont flexibles, sensibles au contexte et qui dotent les USP des compétences requises en matière d'évaluation de programmes de PMC.

Micro-computed tomographic analysis of the marginal adaptation of a calcium silicate-based cement to radicular dentin after removal of three different intracanal medicaments - An in vitro study.

CONTEXT: This study focuses on the marginal adaptation of a calcium silicate-based cement to the root dentin after retrieval of different intracanal medicaments. AIM: This study compared the marginal adaptation of a calcium silicate-based cement to radicular dentin in the apical third of the root canal following the use of three different intracanal medicaments. MATERIALS AND METHODS: Forty single-rooted premolar teeth (n = 40) were decoronated 13 mm above the root apices; then, 3 mm of the root tips were resected to standardize the root length. Orthograde cleaning and shaping were done using the rotary files and apical enlargement using peeso reamers. Depending on the intracanal medicament used, the samples were equally divided into four groups: Group 1 - control, Group 2 - Metapex, Group 3 - triple antibiotic paste (TAP), and Group 4 - calcium hydroxide with Propolis. Subsequently, the medicament was removed and a 3 mm apical barrier of BiodentineTM was placed and later scanned using an ex vivo micro-computed tomography scanner. STATISTICAL ANALYSIS USED: One-way ANOVA F-test and Tukey's post hoc test were used. RESULTS: Maximum adaptation was seen in control group (0.65) > Propolis (1.47) > TAP (4.37) > Metapex (5.25); a high statistically significant difference between the four groups was found (P < 0.001) with regard to the external voids between BiodentineTM and radicular dentin. CONCLUSION: On comparison of the marginal adaptation of Biodentine to root canal dentin following the use of three different intracanal medicaments, maximum adaptation was seen in Group 1, followed by Group 4, Group 3, and Group 2.

Cochlear Proteins Associated with Noise-induced Hearing Loss: An Update.

Noise-induced hearing loss (NIHL) is one of the major occupational disease that has influence on the quality of life of mining workers. Several reports suggest NIHL is attributed to noise exposure at workplace and approximately 16% of hearing loss is due to it. NIHL occurs as a result of exposure to high-level noise (>85 dB) in the workplace. Noise disrupts proteins present in the micromachinery of the ear that is required for mechano-electric transduction of sound waves. High-level noise exposure can lead to hearing impairment owing to mechanical and metabolic exhaustion in cochlea, the major organ responsible for resilience of sound. Several key proteins of cochlea include tectorial membrane, inner hair cells, outer hair cells, and stereocilia are damaged due to high-level noise exposure. Numerous studies conducted in animals have shown cochlear proteins involvement in NIHL, but the pertinent literature remains limited in humans. Detection of proteins and pathways perturbed within the micromachinery of the ear after excessive sound induction leads toward the early identification of hearing loss. The situation insisted to present this review as an update on cochlear proteins associated with NIHL after an extensive literature search using several electronic databases which help to understand the pathophysiology of NIHL.

Pancreas as an Occult Source of Recurrent Salmonella enteritidis Bacteremia in an Immunocompromised Patient.

Salmonella infection usually presents as gastroenteritis and enteric fever. Some cases of bacteremia can lead to invasion of different organ systems and become occult sources for recurrence. Almost all organs of the body can be affected and have been reported in the literature. We report a rare case of repeated Salmonella enteritidis infection in a patient with systemic lupus erythematosus. She was treated with intravenous and oral antibiotics but still had recurrence of fevers and bacteremia. After a thorough workup, pancreatic abscesses were identified and drained with abscess culture revealing Salmonella enteritidis. She was then treated with a prolonged course of antibiotics and finally cleared the infection. This case demonstrates that nontyphoid Salmonella can be invasive and cause persistent infection. This is particularly pertinent in immunocompromised patients who are at an increased risk of infection. An aggressive workup and prolonged antibiotic course might be beneficial for this subset of patients.

Impact of socioeconomic status and living condition on latent tuberculosis diagnosis among the tribal population of Melghat: A cohort study.

AIMS: To study socioeconomic status (SES) and living conditions (LC) as risk factors for latent tuberculosis infection (LTBI) and their impact on QuantiFERON-TB gold (QFT-G) and tuberculin skin test (TST) outcome for determining a better diagnostic test for LTBI in the malnourished tribal population of Melghat. SETTINGS AND DESIGN: Six hundred sixty nine participants matching the inclusion criteria were recruited from 10 tribal villages of Melghat region, India. SUBJECTS AND METHODS: Complete information related to various risk factors and test outcome was obtained on 398 participants, which was analyzed as per predefined conceptual framework. Factors were classified based on their relevance either at individual or household level, and subsequently based on the possibility of intervention. Data were partitioned into concordant and discordant sets depending on test agreement. RESULTS: In concordant set, the two tests revealed that LTBI was significantly associated with smoking (adjusted odds ratio [aOR]: 2.64 [95% confidence interval [CI]: 1.03-6.79]), tobacco usage (aOR: 2.74 [95% CI: 1.50-4.99]), and malnourishment (aOR: 1.97 [95% CI: 1.12-3.48]) after basic adjustment. Inclusion of latent variable SES and LC in the model has mediating effect on the association of above factors with LTBI. Further, the association of SES and LC with LTBI in concordant set was unaltered in presence of other cofactors. From discordant set, results of QFT-G corroborated with that of concordant set. CONCLUSIONS: Poor SES and LC can be considered as strong risk factors linked with LTBI as compared to malnourishment, which is often targeted in such communities. Further, our study showed QFT-G test as a reliable tool in screening of LTBI in the tribal population of Melghat, India.

Neopterin: A candidate biomarker for the early assessment of toxicity of aluminum among bauxite dust exposed mine workers.

INTRODUCTION: Bauxite ore is a major source of aluminum (Al) which contains approximately 35-60% Al by weight. Occupational and environmental bauxite dust exposure may cause toxicity by interaction with human biological systems resulting in oxidative stress (OS) and cell death. A neopterin derivative as an antioxidant is able to modulate cytotoxicity by the induction of OS. MATERIALS AND METHODS: A total of 273 subjects were selected for blood collection from three different major Al producing bauxite mines and were categorized into three groups as experimental (Exp) (n = 150), experimental controls (ExC) (n = 73) and control (Con) (n = 50). Whole blood and serum samples were used for measurement of Al, neopterin, urea and creatinine values. Statistical analysis was performed using R-2.15.1 programming language. RESULTS AND DISCUSSION: The result showed that age, body mass index and the behavioral habits, that is, smoking, tobacco and alcohol consumption have possible effects on neopterin level. Serum neopterin levels were found to be significantly higher (P <0.0001) in the experimental group as compared to other groups. Significantly positive correlation (P < 0.0001) was observed between neopterin and creatinine. It was also observed that neopterin level increases as the duration of exposure increases. CONCLUSION: On the basis of findings it was concluded that exposure to bauxite dust (even at low levels of Al) changes biochemical profile leading to high levels of serum neopterin. Levels of serum neopterin in workers exposed to bauxite dust were probably examined for the 1(st) time in India. The outcome of this study suggested that serum neopterin may be used as potential biomarker for early detection of health risks associated with bauxite dust exposed population.

Serum 25-Hydroxyvitamin D Levels are not Associated with Adverse Outcomes in Clostridium Difficile Infection.

Clostridium difficile infection (CDI) is a significant source of healthcare-associated morbidity and mortality. This study investigated whether serum 25-hydroxyvitamin D is associated with adverse outcomes from CDI. Patients with CDI were prospectively enrolled. Charts were reviewed and serum 25-hydroxyvitamin D was measured. The primary outcome was a composite definition of severe disease: fever (temperature >38°C), acute organ dysfunction, or serum white blood cell count >15,000 cells/µL within 24-48 hours of diagnosis; lack of response to therapy by day 5; and intensive care unit admission; colectomy; or death within 30 days. Sixty-seven patients were included in the final analysis. Mean (±SD) serum 25-hydroxyvitamin D was 26.1 (±18.54) ng/mL. Severe disease, which occurred in 26 (39%) participants, was not associated with serum 25-hydroxyvitamin D [odds ratio (OR) 1.00; 95% confidence interval (CI) 0.96-1.04]. In the adjusted model for severe disease only serum albumin (OR 0.12; 95%CI 0.02-0.64) and diagnosis by detection of stool toxin (OR 5.87; 95%CI 1.09-31.7) remained independent predictors. We conclude that serum 25-hydroxyvitamin D is not associated with the development of severe disease in patients with CDI.

Latent TB infection diagnosis in population exposed to TB subjects in close and poor ventilated high TB endemic zone in India.

BACKGROUND: The present study was designed to investigate the utility of Quantiferon TB gold (QFT-G) and Tuberculin skin test (TST) for diagnosis of latent TB infection (LTBI) in high crowding TB endemic zone of Nagpur, India and their comparison with associated risk factors. METHODS: Out of 342 eligible participants, QFT-G and TST were performed in 162 participants. RESULTS: The prevalence of LTBI observed according to QFT-G and TST was 48% and 42% respectively, with an agreement of 52.47%. QFT-G positivity was associated with age while TST positivity was associated with body mass index (BMI). Duration of exposure emerged as a key risk factor significantly associated with both the tests. CONCLUSION: The prevalence of LTBI was quite high in the studied zone as detected by both the evaluated tests and thus, the combination of both the tests will be best predictive for LTBI in such high TB endemic regions.

Heat shock proteins: possible biomarkers in pulmonary and extrapulmonary tuberculosis.

Tuberculosis (TB) and Tuberculous meningitis (TBM) caused by Mycobacterium tuberculosis (MTB) continue to be a major cause of morbidity and mortality. Therefore there is a need to explore potential biomarkers and heat shock proteins [Hsp(s)] could be one such candidate. We found that host (Hsp 25, Hsp 60, Hsp 70 and Hsp 90) and MTB Hsp(s) (Hsp 16, Hsp 65 and Hsp 71) to be an important feature of the immune response in human clinical samples of pulmonary and extrapulmonary TB patients and in MTB infected monocytes. Notably, the host (Hsp 25, Hsp 70 and Hsp 90) and MTB (Hsp 16, Hsp 65 and Hsp 71) Hsp(s) increases significantly in the clinical samples as well as in cell line model after TB infection. Collectively, results revealed that alteration in immune response leads to a change in the both host and MTB Hsp profile, highlighting them as possible biomarkers for the disease.

Mycobacterial dormancy regulon protein Rv2623 as a novel biomarker for the diagnosis of latent and active tuberculous meningitis.

The present study was designed to investigate Rv2623 antigen, a major dormancy regulon protein of Mycobacterium tuberculosis (MTB) in CSF of suspected latent and active tuberculous meningitis (TBM) patients. A total of 100 CSF samples from TBM (n = 31), suspected latent TBM (n = 22), and suitable noninfectious control subjects (n = 47) were collected and evaluated for Rv2623 antigen level using ELISA protocol. A significantly high (P < 0.05) mean absorbance was observed in samples of suspected latent TBM and active TBM patients as compared to non-TBM control patients. However, no significant difference in Rv2623 level was observed between suspected latent TBM and TBM patients. Our preliminary findings suggest that Rv2623 may be useful as a potential biomarker for the diagnosis of the latent as well as active TBM infection. Futher evaluation of this biomarker in large number of samples is therefore needed to confirm the result.

Laboratory investigations on the diagnosis of tuberculosis in the malnourished tribal population of melghat, India.

BACKGROUND: Malnutrition is a major risk factor for the development of tuberculosis (TB). In India, Melghat is among the tribal regions which consist of highest number of malnutrition cases. Because of the paucity of TB data from these malnourished areas there is an urgent need for the development and evaluation of improved TB diagnostic tests. In the present study, three in house developed diagnostic tests namely TB-Ag(antigen) ELISA, Adenosine deaminase (ADA) estimation and IS6110 polymerase chain reaction (PCR) assay were investigated for the detection of Mycobacterium tuberculosis (M. tb.) infection. METHODS: For investigation, blood samples were collected from 128 study subjects from six villages of Melghat tribal area and evaluated using three in house developed assays, namely TB-Ag ELISA, ADA estimation and IS6110 PCR. RESULTS: The TB-Ag ELISA method yielded 83% sensitivity and 94% specificity. The ADA and PCR assay gave a sensitivity of 61% and 49% and specificity of 62% and 98% respectively. A considerable good agreement of 82.81% (k=0.472) between TB-Ag ELISA and PCR was observed. The overall sensitivity of TB-Ag ELISA was significantly higher (p<0.05) than the ADA and PCR while PCR yielded highest specificity among all the three evaluated tests. CONCLUSIONS: We concluded that the routine use of TB-Ag ELISA can be useful for screening of suspected TB patients in the malnourished population where sophisticated laboratory set up is difficult.