Diagnostic Stewardship in Clinical Microbiology: An Indispensable Component of Patient Care.

Emerging infectious diseases and increasing resistance to available antimicrobials are mapping the evolution of clinical microbiology and escalating the nature of undertakings required. Rapid diagnosis has become the need of the hour, which can affect diagnostic algorithms and therapeutic decisions simultaneously. Subsequently, the concept of 'diagnostic stewardship' was introduced into clinical practice for coherent implementation of available diagnostic modalities to ensure that these new rapid diagnostic technologies are conserved, rather than consumed as part of health care resources, with a view to improve the patient care and reduce Turnaround Time (TAT) and treatment expense. The present study highlights the requisite of diagnostic stewardship and outlines the infectious disease diagnostic modalities that can assist in its successful implementation. Diagnostic stewardship promotes precise, timely diagnostics, from the initial specimen collection and identification to reporting with appropriate TAT, so as to enable timely management of the patient. The main aim of diagnostic stewardship is to optimize the right choice of diagnostic test for the right patient to attain clinically significant reports with the least possible TAT for timely management and the least expected adverse effects for the patient, community, and the healthcare system. This underlines the requisite of a multifaceted approach to make technological advancements effective and successful for implementation as a part of diagnostic stewardship for the best patient care.

The Multifaceted Impact of Gallstones: Understanding Complications and Management Strategies.

Gallstones, or cholelithiasis, represent a prevalent gastrointestinal disorder characterized by the formation of calculi within the gallbladder. This review aims to provide a comprehensive analysis of the complications associated with gallstones, with a focus on their pathophysiology, clinical manifestations, diagnostic methodologies, and management strategies. Gallstone-related complications encompass a broad spectrum, including biliary colic, acute cholecystitis, choledocholithiasis, acute pancreatitis, and cholangitis. The pathogenesis of these complications primarily involves biliary obstruction and subsequent infection, leading to significant morbidity and potential mortality. Diagnostic evaluation of gallstone complications employs various imaging techniques, such as ultrasonography, magnetic resonance cholangiopancreatography (MRCP), and endoscopic retrograde cholangiopancreatography (ERCP), each with distinct advantages and limitations. Therapeutic approaches are discussed, ranging from conservative management with pharmacotherapy and bile acid dissolution agents to interventional procedures like extracorporeal shock wave lithotripsy (ESWL) and percutaneous cholecystostomy. Surgical management, particularly laparoscopic cholecystectomy, remains the gold standard for definitive treatment. Additionally, advancements in endoscopic techniques, including endoscopic sphincterotomy (EST) and cholangioscopy, are highlighted. This review synthesizes current research findings and clinical guidelines, aiming to enhance the understanding and management of gallstone-related complications among healthcare professionals, thereby improving patient outcomes and reducing the burden of this common ailment.

COVID-19 pandemic - Cocktail of variants, a study from Northern India.

Context: The aim of the study was to identify and monitor the circulating strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the samples received at our center and update the existing national and international genomic surveillance data. Introduction: SARS-CoV-2 is no exception to the basic nature of the viruses ability to change and evolve. Since its first report in December 2019 from Wuhan, China, multiple variants of the virus have emerged and been reported. Five variants of concern have been recognized and reported by the Centers for Disease Control and Prevention, which are associated with variable degrees of transmissibility and mortality. Materials and Methods: Nasopharyngeal and oropharyngeal swabs received in viral transport medium at the Viral Research Diagnostic Laboratory were processed for reverse transcription-polymerase chain reaction for SARS-CoV-2. Whole genome sequencing (WGS) was performed for selective positive samples using Oxford Nanopore sequencing technology, using MinKNOW software for data acquisition. Statistical Analysis: The clades were assigned using Nextclade v2.4.1 software. The statistical analysis was calculated using OpenEpi version 3, an open-source calculator, and two by two. Results: Variants reported over the study period included Alpha, Kappa, Delta, and Omicron. Delta dominated in the year 2021, while Omicron was the dominant variant in 2022. In both the dominant variants, asymptomatics contributed to around 30-40% of positives. Intensive care unit admissions and mortality were higher in the Delta variant, while vaccination history and travel history were higher in the patients with Omicron variant. Conclusion: The trend tracking of these variants has been important in view of public health, enabling early interventions to control the spread of the disease and foresight in preparation for the situation.

Logic "AND Gate Circuit" Based Mussel Inspired Polydopamine Nanocomposite as Bioactive Antioxidant for Management of Oxidative Stress and Neurogenesis in Traumatic Brain Injury.

In the intricate landscape of Traumatic Brain Injury (TBI), the management of TBI remains a challenging task due to the extremely complex pathophysiological conditions and excessive release of reactive oxygen species (ROS) at the injury site and the limited regenerative capacities of the central nervous system (CNS). Existing pharmaceutical interventions are limited in their ability to efficiently cross the blood-brain barrier (BBB) and expeditiously target areas of brain inflammation. In response to these challenges herein, we designed novel mussel inspired polydopamine (PDA)-coated mesoporous silica nanoparticles (PDA-AMSNs) with excellent antioxidative ability to deliver a new potential therapeutic GSK-3ß inhibitor lead small molecule abbreviated as Neuro Chemical Modulator (NCM) at the TBI site using a neuroprotective peptide hydrogel (PANAP). PDA-AMSNs loaded with NCM (i.e., PDA-AMSN-D) into the matrix of PANAP were injected into the damaged area in an in vivo cryogenic brain injury model (CBI). This approach is specifically built while keeping the logic AND gate circuit as the primary focus. Where NCM and PDA-AMSNs act as two input signals and neurological functional recovery as a single output. Therapeutically, PDA-AMSN-D significantly decreased infarct volume, enhanced neurogenesis, rejuvenated BBB senescence, and accelerated neurological function recovery in a CBI.

Student Satisfaction and Physical Health Effects of Online Learning Among Medical and Paramedical Undergraduates in Northern India: A Cross-Sectional Study.

BACKGROUND: Online modality of pedagogy was introduced in many medical institutes globally, especially during the COVID-19 pandemic. However, these techniques were not evaluated, either with respect to effectiveness or student satisfaction in terms of promoting successful educational outcomes. The current study was conducted to identify determinants of student satisfaction with respect to online learning, in the post-pandemic era. METHODS: A pilot-tested and validated online questionnaire was administered to 370 medical/paramedical students who attended online classes during the pandemic. The students were selected randomly from four different streams of a medical university, representing all the years of study. The questionnaire included Likert-type questions and was divided into two parts: socio-demographic profile and satisfaction with online learning. RESULTS: The response rate was 81.4%. Overall satisfaction with online learning among students was 35.9% and the areas of most satisfaction for students were user-friendliness of the online portal (65.5%), self-directed responsibilities assigned to pupils (49.9%), faculty accessibility/availability (48.8%) and timely evaluation, test and feedback (47.9%). The areas of most dissatisfaction were lack of personal effect as compared to offline learning (n=71, 23.6%), effect on social life (n=54, 17.9%), and feeling of not belonging to the online session (n=38, 12.6%). Multiple regression analysis demonstrated that having previous exposure to online courses and having a separate room led to more satisfaction, whereas the emergence of health problems led to poor satisfaction with the course. The duration of previous exposure to online courses was not a statistically significant predictor of satisfaction. One or more health problems were reported by 176 (58.5%) of the respondents. Some of the common health problems reported were eye strain (72.8%), headache (56.1%), insomnia (47.2%), stress (35.2%), muscle fatigue (22.6) and tingling sensation (10.6%). CONCLUSION: Adopting a combination of online and offline approaches, i.e., blended pedagogy, involving different methods to involve students and their feedback are important to ensure student satisfaction.

A cautionary tale of pseudo-Cryptococcus infection in neonates.

We report a tale of two cases of neonates, where India Ink preparation of cerebrospinal fluid (CSF) received in glass vials was suggestive of Cryptococcus; however, the absence of correlation and report of cases sequentially from the same unit raised alarm bells. Repeat smears using routine in-house and newly prepared stains were prepared and repeat sampling was collected in a strictly sterile specimen container, which resulted in negative microscopy for repeat samples (uncentrifuged and centrifuged). The source of contamination was found to be non-sterile glass vials used for CSF collection. This report underlines the requisite to maintain an aseptic chain from sample collection to processing, to prevent reporting of pseudo-infections that can upset diagnostic accuracy, especially when the aseptic chain has not been maintained.

Variations in the Position of Mandibular Foramen in Temporomandibular Ankylosis Patients.

Aim: To evaluate the variation in the position of the mandibular foramen and mandibular canal in patients with and without temporomandibular joint ankylosis. Materials and Methods: 100 temporomandibular joints were evaluated of which 50 joints were ankylosed joints (Group A) and the rest 50 were normal joints (Group B) without ankylosis. These groups were further divided into those with growing potential (less than 18 years) and those without growing potential (above 18 years). The position of the mandibular foramen was measured from its center to the glenoid fossa, sigmoid notch, coronoid notch, gonion and posterior border on CBCT scans. The position of the mandibular canal was measured from the outer aspect of the canal to the lower border of the mandible, buccal and lingual cortical plates and the alveolus in the region of the 1st, 2nd and 3rd molars. Results: The mean distance of the foramen from the base of the skull in Group A was 19.01 mm while the same for Group B was 31.26 mm. The mandibular foramen was found to be closer to the occlusal plane (5.43 mm) in Group A as compared to the mean distance of 6.21 mm reported in Group B. There was no significant difference in the position of the foramen from the posterior border, gonion and sigmoid notch between the groups. The mental foramen was seen more commonly posterior to the 2nd premolar and closer to the first molar region in Group A while in Group B it was seen anterior or near the 2nd premolar. In Group A, the mean distance of the canal to the buccal cortical plate in the 1st and 2nd molar regions was 3.65 mm and 5.76 mm, respectively, while in Group B it was 6.09 mm and 6.59 mm. The canal was further away from the lower border in ankylosis cases (8.79 mm) than the control group (7.41 mm). On comparing the unaffected side in unilateral cases with the normal mandible, the canal and the foramen location were similar to that of a normal mandible with the values in the lower range that is usually seen in normal mandibles. Conclusion: Ankylosis of the mandible is a debilitating condition especially when it develops in an individual prior completion of growth as it can affect the mandibular anatomy. Understanding the variations that accompany a deranged mandible can assist the surgeon in planning of surgical procedures in a manner that limits the possible complications resulting from surgery.

Insights into changing patterns of extrapulmonary tuberculosis in North India.

PURPOSE: Tuberculosis is one of the dreadful infections and India contributes to substantial burden of TB cases globally. Though majority of cases are pulmonary, extra-pulmonary tuberculosis (EPTB) share significant burden, more in HIV-positive persons. Despite the striking burden, very few studies have been conducted in India and present study was undertaken to determine trends of EPTB at our tertiary care centre. METHODS: This was a retrospective study conducted over a period of 4 years 3 months. Diagnosis of EPTB was based on suspected clinical features, with positive micobiological evidence with cartridge based nucleic acid amplification test (CBNAAT) with/without microscopy. RESULTS: A total of 10,560 samples (pulmonary and extra-pulmonary) were received during the study period, of which 3972 were extrapulmonary. Of these, a total of 18% were noted to be positive for EPTB. Trend of positivity revealed highest burden in 2018 and a decline was noted over the years, however, rise in cases was noted in 2022. Pleural, meningitis, musculoskeletal, peritoneal and pericardial TB was more common in males, while lymphadenitis was more common in females (p value: <0.0001). Pleural TB (31%) was the most common presentation, followed by lymphadenitis. A gradual decline in lymphadenitis was noted with significantly increasing trend only for musculoskeletal TB. Rifampicin resistance was detected in 7.45% of positive samples, of which the maximum rate of resistance was noted in lymph node aspirates (11.11%), followed by musculoskeletal and pleural samples. CONCLUSION: The present study showed a gradual decline in positivity of EPTB cases over the years. Younger productive age group with more propensity to transmit infection was the most commonly affected, with pleural TB as the most common presentation. Rare presentations of EPTB also contributed major share. Higher rates of resistance underline requisite to strengthen ongoing programs, to achieve the End TB strategy by 2025.

Prevalence of co-existent COVID-19-associated pulmonary aspergillosis (CAPA) and its impact on early mortality in patients with COVID-19-associated pulmonary mucormycosis (CAPM).

BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.

Small-molecule inhibition of the METTL3/METTL14 complex suppresses neuroblastoma tumor growth and promotes differentiation.

The N6-methyladenosine (m6A) RNA modification is an important regulator of gene expression. m6A is deposited by a methyltransferase complex that includes methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14). High levels of METTL3/METTL14 drive the growth of many types of adult cancer, and METTL3/METTL14 inhibitors are emerging as new anticancer agents. However, little is known about the m6A epitranscriptome or the role of the METTL3/METTL14 complex in neuroblastoma, a common pediatric cancer. Here, we show that METTL3 knockdown or pharmacologic inhibition with the small molecule STM2457 leads to reduced neuroblastoma cell proliferation and increased differentiation. These changes in neuroblastoma phenotype are associated with decreased m6A deposition on transcripts involved in nervous system development and neuronal differentiation, with increased stability of target mRNAs. In preclinical studies, STM2457 treatment suppresses the growth of neuroblastoma tumors in vivo. Together, these results support the potential of METTL3/METTL14 complex inhibition as a therapeutic strategy against neuroblastoma.

Antibiotic Resistant Biofilms and the Quest for Novel Therapeutic Strategies.

Antimicrobial resistance (AMR) is one of the major leading causes of death around the globe. Present treatment pipelines are insufficient to overcome the critical situation. Prominent biofilm forming human pathogens which can thrive in infection sites using adaptive features results in biofilm persistence. Considering the present scenario, prudential investigations into the mechanisms of resistance target them to improve antibiotic efficacy is required. Regarding this, developing newer and effective treatment options using edge cutting technologies in medical research is the need of time. The reasons underlying the adaptive features in biofilm persistence have been centred on different metabolic and physiological aspects. The high tolerance levels against antibiotics direct researchers to search for novel bioactive molecules that can help combat the problem. In view of this, the present review outlines the focuses on an opportunity of different strategies which are in testing pipeline can thus be developed into products ready to use.

Ratiometric Fluorescent Probe Promotes Trans-differentiation of Human Mesenchymal Stem Cells to Neurons.

Development of multifunctional theranostics is challenging and crucial for deciphering complex biological phenomena and subsequently treating critical disease. In particular, development of theranostics for traumatic brain injury (TBI) and understanding its repair mechanism are challenging and highly complex areas of research. Recently, there have been interesting pieces of research work demonstrated that a small molecule-based neuroregenerative approach using stem cells has potential for future therapeutic lead development for TBI. However, these works demonstrated the application of a mixture of multiple molecules as a "chemical cocktail", which may have serious toxic effects in the differentiated cells. Therefore, development of a single-molecule-based potential differentiating agent for human mesenchymal stem cells (hMSCs) into functional neurons is vital for the upcoming neuro-regenerative therapeutics. This lead could be further extraploted for the design of theranostics for TBI. In this study, we have developed a multifunctional single-molecule-based fluorescent probe, which can image the transdifferentiated neurons as well as promote the differentiation process. We demonstrated a promising class of fluorescent probes (CP-4) that can be employed to convert hMSCs into neurons in the presence of fibroblast growth factor (FGF). This fluorescent probe was used in cellular imaging as its fluorescence intensity remained unaltered for up to 7 days of trans-differentiation. We envision that this imaging probe can have an important application in the study of neuropathological and neurodegenerative studies.

Increased electrode impedance as an indicator for early detection of deep brain stimulation (DBS) hardware Infection: Clinical experience and in vitro study.

BACKGROUND: When deep brain stimulation (DBS) infections are identified, they are often too advanced to treat without complete hardware removal. New objective markers to promptly identify DBS infections are needed. We present a patient with GPi (globus pallidus interna) DBS for dystonia, where the electrode impedance unexpectedly increased 3-months post-operatively, followed by serologic and hematologic markers of inflammation at 6-months, prompting explantation surgery. We recreated these conditions in a laboratory environment to analyze the pattern of changing of electrical impedance across the contacts of a DBS lead following Staphylococcus biofilm formation. METHODS: A stainless-steel culture chamber containing 1 % brain heart infusion agar was used. A DBS electrode was dipped in peptone water containing a strain of S. aureus and subsequently introduced into the chamber. The apparatus was incubated at 37 °C for 6 days. Impedance was measured at 24hr intervals. A control experiment without S. Aureus inoculation was used to determine changes in impedance over a period of 6-days. RESULTS: The mean monopolar impedance on day-1 was 751.8 ± 23.8 Ω and on day-3 was 1004.8 ± 68.7 Ω, a 33.7 % rise (p = 0.007). A faint biofilm formation could be seen around the DBS lead by day-2 and florid growth by day-3. After addition of the linezolid solution, a 15.9 % decrease in monopolar impedance was observed from day 3-6 (p = 0.003). CONCLUSION: This study gives insight into impedance trends following a hardware infection in DBS. Increased impedance outside expected norms may be valuable for early prediction of infection. Furthermore, timely management using antibiotics might reduce the frequency of infection-related explant surgeries.

Salmonella Typhi: A Review of Antibiogram Journey in Developing Countries.

BACKGROUND: Typhoid fever poses a significant health challenge in low- and middleincome countries (LMiCs), impacting millions of individuals across various age groups. Its prevalence is particularly pronounced in South Asia. Factors contributing to its transmission in South Asia include rapid unplanned urbanization, urban-rural disparities, provision of poor water and sanitation facilities, and open defecation. The mortality rate of typhoid fever is up to 1%, and those who survive have a protracted period of poor health and carry an enormous financial burden. The treatment is further complicated by the emerging antibiotic resistance leaving few treatment options in hands. This issue has become more urgent due to the further emergence of extended drug-resistant (XDR) and multidrug-resistant (MDR) typhoid strains, as well as their subsequent global spread. Fluoroquinolone-resistant Salmonella spp. is currently classified by the World Health Organization (WHO) as a high (Priority 2) pathogen. As a result, establishing minimum inhibitory concentrations (MIC) according to the latest guidelines may prove effective in treating typhoid fever and minimizing the rising threat of drug resistance.

Unsupervised machine learning to investigate trajectory patterns of COVID-19 symptoms and physical activity measured via the MyHeart Counts App and smart devices.

Previous studies have associated COVID-19 symptoms severity with levels of physical activity. We therefore investigated longitudinal trajectories of COVID-19 symptoms in a cohort of healthcare workers (HCWs) with non-hospitalised COVID-19 and their real-world physical activity. 121 HCWs with a history of COVID-19 infection who had symptoms monitored through at least two research clinic visits, and via smartphone were examined. HCWs with a compatible smartphone were provided with an Apple Watch Series 4 and were asked to install the MyHeart Counts Study App to collect COVID-19 symptom data and multiple physical activity parameters. Unsupervised classification analysis of symptoms identified two trajectory patterns of long and short symptom duration. The prevalence for longitudinal persistence of any COVID-19 symptom was 36% with fatigue and loss of smell being the two most prevalent individual symptom trajectories (24.8% and 21.5%, respectively). 8 physical activity features obtained via the MyHeart Counts App identified two groups of trajectories for high and low activity. Of these 8 parameters only 'distance moved walking or running' was associated with COVID-19 symptom trajectories. We report a high prevalence of long-term symptoms of COVID-19 in a non-hospitalised cohort of HCWs, a method to identify physical activity trends, and investigate their association. These data highlight the importance of tracking symptoms from onset to recovery even in non-hospitalised COVID-19 individuals. The increasing ease in collecting real-world physical activity data non-invasively from wearable devices provides opportunity to investigate the association of physical activity to symptoms of COVID-19 and other cardio-respiratory diseases.

The new Xpert Mycobacterium tuberculosis/rifampicin (MTB/Rif) Ultra assay in comparison to Xpert MTB/Rif assay for diagnosis of tuberculosis in children and adolescents.

BACKGROUND: Microbiological diagnosis of pediatric tuberculosis (TB) using conventional microbiological techniques has been challenging due to paucibacillary nature of the disease. Molecular methods using cartridge-based tests like Xpert, have immensely improved diagnosis. A novel next-generation cartridge test, Xpert Ultra, incorporates two additional molecular targets and claims to have much lower detection limit. We attempted to compare the two techniques in presumptive pediatric TB patients. OBJECTIVES: The aim of this study was to compare the diagnostic performance of Xpert MTB/Rif Ultra with Xpert MTB/Rif for the detection of pediatric TB. STUDY DESIGN: This is an observational comparative analytical study. METHODS: Children under 15 years of age with presumptive TB were enrolled. Appropriate specimens were obtained (sputum, induced sputum or gastric aspirate for suspected pulmonary TB, cerebrospinal fluid for suspected tubercular meningitis and pleural fluid for suspected tubercular pleural effusion), subjected to smear microscopy, mycobacterial culture, Xpert and Xpert ultra tests and other appropriate diagnostic investigations. RESULTS: Out of 130 enrolled patients, 70 were diagnosed with TB using a composite reference standard (CRS). The overall sensitivity of Xpert was 64.29% [95% confidence interval (CI) 51.93-75.93%] and that of Xpert Ultra was 80% (95% CI 68.73-88.61%) with 100% overall specificity for both. The sensitivity of Xpert and Xpert Ultra in pulmonary specimens (n = 112) was 66.67% and 79.37% and in extrapulmonary specimens (n = 18) was 42.86% and 85.71%, respectively. CONCLUSION: Our study found Ultra to be more sensitive than Xpert for the detection of Mycobacterium tuberculosis in children. Our findings support the use of Xpert Ultra as initial rapid molecular diagnostic test in children under evaluation for TB.

Comparing feature selection and machine learning approaches for predicting CYP2D6 methylation from genetic variation.

Introduction: Pharmacogenetics currently supports clinical decision-making on the basis of a limited number of variants in a few genes and may benefit paediatric prescribing where there is a need for more precise dosing. Integrating genomic information such as methylation into pharmacogenetic models holds the potential to improve their accuracy and consequently prescribing decisions. Cytochrome P450 2D6 (CYP2D6) is a highly polymorphic gene conventionally associated with the metabolism of commonly used drugs and endogenous substrates. We thus sought to predict epigenetic loci from single nucleotide polymorphisms (SNPs) related to CYP2D6 in children from the GUSTO cohort. Methods: Buffy coat DNA methylation was quantified using the Illumina Infinium Methylation EPIC beadchip. CpG sites associated with CYP2D6 were used as outcome variables in Linear Regression, Elastic Net and XGBoost models. We compared feature selection of SNPs from GWAS mQTLs, GTEx eQTLs and SNPs within 2 MB of the CYP2D6 gene and the impact of adding demographic data. The samples were split into training (75%) sets and test (25%) sets for validation. In Elastic Net model and XGBoost models, optimal hyperparameter search was done using 10-fold cross validation. Root Mean Square Error and R-squared values were obtained to investigate each models' performance. When GWAS was performed to determine SNPs associated with CpG sites, a total of 15 SNPs were identified where several SNPs appeared to influence multiple CpG sites. Results: Overall, Elastic Net models of genetic features appeared to perform marginally better than heritability estimates and substantially better than Linear Regression and XGBoost models. The addition of nongenetic features appeared to improve performance for some but not all feature sets and probes. The best feature set and Machine Learning (ML) approach differed substantially between CpG sites and a number of top variables were identified for each model. Discussion: The development of SNP-based prediction models for CYP2D6 CpG methylation in Singaporean children of varying ethnicities in this study has clinical application. With further validation, they may add to the set of tools available to improve precision medicine and pharmacogenetics-based dosing.

Hand hygiene with interventions: an observational study from a tertiary care institute over 2 years.

Background: Appropriate adherence to hand hygiene (HH) practices by health care workers (HCWs) reduces the transmission of pathogens and subsequently the incidence of hospital acquired infections (HAIs), in health care settings. Strict monitoring and auditing of this simple and cost-effective intervention is very important, as it significantly contributes in reducing the HAIs. Material and methods: A retrospective observational study, evaluating the HH audits from June 2021 till May 2023 in a tertiary health care facility in North India. HH audits were conducted in the ICUs and wards daily, by the trained infection control nurses (ICNs), using direct observation method based on World health organization (WHO) hand hygiene observational forms. HH total adherence (HHTAR), partial adherence (HHPAR) and complete adherence rate (HHCAR) were analyzed in Microsoft Excel sheet. HHTAR rates were compared among different profession, moments and the month wise trend was also observed over the period. Results: A total of 24,740 HH opportunities were observed. The compliance rate for HHCAR, HHPAR and HHTAR were 20.3%, 41.5% and 61.4% respectively. Overall better compliance was reported from the ICUs, profession-specific compliance was highest among nurses (62.8%) and doctors (61.5%). Significant increase in adherence rate was appreciated post intervention 46.1% to 67.3%, (p value < 0.01). Conclusions: Continuous monitoring and reinforcement with timely feedback for intervention and regular auditing is a necessity to improve and maintain the appropriate HH practices among the HCWs. Low- and middle-income countries need to focus more on this simple and promising measure to combat the increasing HAI rates.

Comparative in vitro activities of seven new beta-lactams, alone and in combination with beta-lactamase inhibitors, against clinical isolates resistant to third generation cephalosporins

We examined the drug susceptibility pattern of Gram-negative bacilli to seven new beta-lactams. A total of 277 non-duplicate gramnegative bacilli strains belonging to the Enterobacteriaceae family, Pseudomonas and Acinetobacter species, isolated from various clinical samples were tested for susceptibility to imipenem, piperacillin/tazobactam, cefoperazone/sulbactam, ticarcillin/clavulanate, cefdinir, cefepime and cefpirome with the disk diffusion technique. The percentage resistance was low for imipenem (7.2 percent), piperacillin/tazobactam (2.8 percent), cefoperazone/sulbactam (5.4 percent). However, a high frequency of resistance was observed to ticarcillin/clavulanate (83.9 percent), cefdinir (70.6 percent), cefepime (45.5 percent) and cefpirome (84.4 percent). We conclude that imipenem, piperacillin/tazobactam and cefoperazone/sulbactam are effective antibiotics in our environment, whereas ticarcillin/clavulanate, cefdinir, cefepime and cefpirome are relatively uneffective.