Evaluating the Sputum Bacteriological Profile of Lower Respiratory Tract Infections With Bartlett Score Analysis in a Tertiary Care Hospital in Southern Karnataka.

INTRODUCTION: Lower respiratory tract infections (LRTIs) are one of the most commonly encountered infections with significant mortality and morbidity. Sputum is the most frequently obtained sample for LRTI diagnosis. However, sputum samples carry the risk of being non-representative due to the risk of contamination with oral colonizers. To overcome the dilemma with respect to representative sampling, the use of a scoring system such as the Bartlett scoring system is emphasized. This study probes the bacterial profile of sputum samples among patients presenting with LRTIs and their antibiotic susceptibility profile in relation to the Bartlett scoring system. METHODOLOGY: Retrospective data for a period of three years, comprising 4960 sputum samples from patients presenting with LRTI, were collected to study the bacterial profile and antibiogram in comparison with the sputum quality analyzed by the Bartlett scoring system. RESULTS: Out of the 4960 sputum samples analyzed from patients with LRTI, 31.18% yielded the growth of bacterial pathogens, and 98.64% of the sputum samples yielding pathogenic growth had a significant Bartlett score. CONCLUSION: Sputum samples are non-invasive representative samples of lower airway infective pathologies. Sputum quality assessment by Bartlett scoring serves as a proxy marker to rule out respiratory colonization and aid culture-based diagnosis.

Primary Anterior Thoracic Wall Abscess with Osteomyelitis by Salmonella paratyphi A : Case Report.

Salmonella enterica serovar Typhi and Paratyphi have been imputed in the causation of enteric fever. Cardiovascular and extraintestinal Salmonella infections have been documented among immunocompromised individuals. Rarely these pathogens are ascribed in the causation of extraintestinal infections among immunocompetent hosts due to hematogenous seeding. We report a case of anterior chest wall abscess with osteomyelitis in an immunocompetent adult by Salmonella paratyphi A without any prior predisposing conditions or gastrointestinal symptoms. The patient underwent incision and drainage of the loculated pus and the involved costochondral junction was curetted. Medical management was guided by automated antibiotic susceptibility testing. Patient responded well to treatment and was discharged with no residual morbidities. Prompt diagnosis complements appurtenant treatment and thereby averts defunct consequential sequelae.

Bridging Access to Pediatric Pain Care: Telehealth Utilization.

OBJECTIVES: To evaluate subsequent shifts to patient access to tertiary pain management care following shelter-in-place (SIP) and increased telehealth during the COVID-19 pandemic. MATERIALS AND METHODS: Retrospective naturalistic design was used. Data for this study were extracted from a retrospective review of the Pediatric-Collaborative Health Outcomes Information Registry, with additional demographic information collected using chart review. Participants were 906 youth who received an initial evaluation either in-person (n=472) within the 18 months before SIP or through telehealth (n=434) within the 18 months after SIP during the COVID-19 pandemic. Patient variables to assess access included geographic distance from the clinic, ethnic and racial diversity, and patient's insurance type. Descriptive characteristics for each group were analyzed using χ 2 test, percentage change, and t -test analyses. RESULTS: Data indicated that transitioning to telehealth resulted in maintained access rates between groups as measured by race and ethnic diversity as well as distance traveled from the clinic. A trend toward increase in government-funded insurance was found, though no statistically significant differences were identified between telehealth and in-person visits. Though the majority of participants (in-person: 52.75%; telehealth 55.81%) lived within 50 miles of the clinic, results indicated that telehealth allowed for a statistically significant increase in evaluation access for families living further from the clinic within a 50-mile radius. DISCUSSION: Overall, accessibility to pediatric pain management through telehealth during SIP was maintained despite significant declines in overall access to health care, with some trends in increased accessibility for patients with government insurance.

A nurse practitioner-led telehealth protocol to improve diabetes outcomes in primary care.

BACKGROUND: Diabetes-related complications contribute to a costly health burden in the United States. Telehealth (TH) is a tool that can increase access to care and offer ongoing support for chronic disease self-management. LOCAL PROBLEM: A primary care practice in Texas needed a method to manage an influx of patients with uncontrolled diabetes and improve type 2 diabetes outcomes using nurse practitioner (NP) TH appointments. METHODS: Thirty patients meeting inclusion criteria participated in monthly TH check-ins and followed monthly for 3 months. Baseline and postintervention diabetes laboratory studies (hemoglobin A1c [HbA1c], estimated glomerular filtration rate, and microalbumin) were collected. INTERVENTIONS: During each monthly TH visit, an NP-led diabetes TH QI protocol was implemented. The Telehealth Usability Questionnaire was administered to patients after the 3-month intervention. RESULTS: The TH QI protocol resulted in an overall ∼1% reduction in HbA1c. Over 73% of participants experienced various reductions of HbA1c, of which 2.3% achieved a postintervention HbA1c <7%, indicating controlled diabetes. Kidney function indicated by eGFR improved by 7 ml/min/1.73 m2 in 83% of participating patients. At the end of the 3-month intervention, 84% of participants expressed overall satisfaction with TH appointments. CONCLUSIONS: Interventions using TH to improve chronic disease may be useful in diabetes outcomes and self-management. Monthly TH visits can improve patient outcomes, reduce complications, and enhance the patient-provider relationship. Preventive self-care activities and long-term use of TH visits for self-management are implications for future studies.

A Semiparametric Bayesian Approach to Epidemics, with Application to the Spread of the Coronavirus MERS in South Korea in 2015.

We consider incomplete observations of stochastic processes governing the spread of infectious diseases through finite populations by way of contact. We propose a flexible semiparametric modeling framework with at least three advantages. First, it enables researchers to study the structure of a population contact network and its impact on the spread of infectious diseases. Second, it can accommodate short- and long-tailed degree distributions and detect potential superspreaders, who represent an important public health concern. Third, it addresses the important issue of incomplete data. Starting from first principles, we show when the incomplete-data generating process is ignorable for the purpose of Bayesian inference for the parameters of the population model. We demonstrate the semiparametric modeling framework by simulations and an application to the partially observed MERS epidemic in South Korea in 2015. We conclude with an extended discussion of open questions and directions for future research.

Comparison of pain and psychosocial correlates among Hispanic and Non-Hispanic White youth with chronic pain.

Introduction: Despite well-documented pain disparities among adults from non-White and Hispanic groups, less is known about pain disparities in non-White and Hispanic pediatric populations. Objectives: We compare pain and related psychosocial factors at the individual (pain intensity, pain interference, pain catastrophizing, co-occurring symptoms), social (peer relations), and systemic (health insurance) levels among Hispanic and Non-Hispanic White (NHW) youth with chronic pain. Methods: Eight hundred thirty-seven (71.4% female) Hispanic (n = 268, 32%) and NHW (n = 569, 68%) youth ages 8 to 17 years (M = 14.00; SD = 2.54) completed a survey at their initial visit to a pain clinic. Independent sample t tests investigated mean differences in psychosocial factors at the individual and social levels. Chi-squared tests investigated differences at the systemic level. Bivariate correlations for each group were compared using Fisher r-to-z transformations. Results: Hispanic youth reported higher levels of pain intensity (t[811] = -2.75, P = 0.006). Groups did not differ in reports of other individual or social factors. Non-Hispanic White youth were more likely to have private insurance (OR, 5.66). All examined variables were significantly correlated among NHW youth. Correlations were weaker or nonsignificant among Hispanic youth. Fisher r-to-z transformations revealed these group differences to be significant. Conclusion: Hispanic youth report higher pain levels than NHW counterparts and lower likelihood of having private insurance. Pain and psychosocial factors correlate differently among the 2 groups highlighting a need to better understand the chronic pain experiences of diverse youth because models derived primarily from NHW populations may not generalize across ethnic and racial groups.

Assessment of antibacterial and anti-biofilm effects of zinc ferrite nanoparticles against Klebsiella pneumoniae.

In response to the emergence of drug resistance and limited therapeutic options, researchers are in action to look for more effective and sustainable antimicrobial practices. Over few years, novel nanoparticles are proving to be potent and promising for effectively dealing with ever- evolving microbial pathogens and diseases. In the present investigation, antibacterial and anti-biofilm efficiencies of zinc ferrite nanoparticles (ZnFe2O4 NPs) are explored against opportunistic pathogens Klebsiella pneumoniae (K. pneumoniae). Results of the present study demonstrate that the ZnFe2O4 NPs endow an excellent antibacterial efficiency with a maximum zone of inhibition i.e.16 mm. The reactive oxygen species (ROS)-induced bacterial damage is caused by the ZnFe2O4 NPs. Subsequently, intracellular cytoplasmic leakage of sugar and protein confirms their ability to disturb the membrane integrity of bacteria. This study also demonstrates the prominent efficiency of ZnFe2O4 NPs in an anti-biofilm study by inhibiting biofilm formation up to 81.76% and reducing mature biofilm up to 56.22% at 75 µg/mL the minimum inhibitory concentration value. Therapeutic possibilities of the ZnFe2O4 NPs in antimicrobial applications are discussed which are helpful to overcome the challenges associated with biofilm infectivity.

Comparative evaluation of oral lesions: Tale - the Covid 19 Tells

Introduction & ObjectivesThe COVID-19 pandemic has been raging across the globe since early January 2020. India has reported over 27 million cases and more than 3, 00,000 deaths. This study was planned to analyze the differences in demographic, clinical features and oral manifestations of COVID 19 patients hospitalized during COVID-19 pandemic. MethodsThis observational pilot study had total 36 participants, 12 each of mild, moderate and severe RT-PCR positive COVID cases hospitalized during COVID 19 pandemic. All demographic, clinical features, treatment details and oral manifestations were noted from first day of admission to hospital till treatment completion with follow up of minimum 7 days. ResultsMean age of the patients was 39.44 {+/-}9.13 years with M: F ratio of 5:4. Most common clinical presentation was fever, shortness of breath and treatment involved was symptomatic with supplemental oxygen & mechanical ventilation. Most common oral site involved was tongue & oral lesions observed were herpes labialis, mucositis, burning sensation, dryness of oral cavity, angular chelitis, aphthous ulcers, geographic tongue, fissuring of tongue, candidiasis, coated tongue, sublingual varicosity, & scalloped tongue. Interpretation and ConclusionAll demographic, clinical and oral manifestations were significantly different in mild, moderate and severe cases of covid hospitalized patients. Though clinical symptoms were improved, oral lesions were worsened. Oral Lesions seen in covid patients were associated with multiple drug therapy for illness along with poor oral hygiene, but further etiology for lesions needs to be evaluated. Sublingual varicosity was observed in our hospitalised covid patients, but large sample observation is required for confirmation of findings and may be an early oral feature for covid detection. Prevention is always better than cure, so all patients positive for Covid should have a full mouth examination. Oral health should be priority during overall management of COVID patients and dentists should be a part of Covid management team.

Application of inline variable pathlength technology for rapid determination of dynamic binding capacity in downstream process development of biopharmaceuticals.

Determination of dynamic binding capacity (DBC) for capture purification chromatographic step is usually the first experiment to be performed during downstream process development of biopharmaceuticals. In this work, we investigated the application of inline variable pathlength technology using FlowVPE for rapid determination of DBC on affinity resins for protein capture and proved its comparability with offline titer methods. This work also demonstrated that variable pathlength technology for DBC determination can be successfully applied to different classes of monoclonal antibodies and fusion proteins. This enabled rapid screening of affinity resins and optimization of the capture chromatography step. Hence, use of inline variable pathlength technology eliminated the dependency on offline titer data, traditionally used for DBC determination and accelerated overall process development timelines with less cost.

Clinical Utility of CAT Administered PROMIS Measures to Track Change for Pediatric Chronic Pain.

Patient Reported Outcomes (PROs) are utilized in clinical registries and trials, necessitating development of benchmarks to enhance interpretability. This study aimed to 1) examine if PROMIS measures administered via computer adaptive testing (CAT) were responsive to change, and 2) highlight one method of assessing clinically significant change for youth seen in a tertiary pain clinic. Clinically significant change was achieved if patients had significantly reliable pre-to-post-changes greater than Reliable Change Index (RCI) value and reported decreased symptoms by at least one severity level (e.g., moderate to mild). Participants were 328 youth (8-17 years old) seen in a tertiary pediatric pain management clinic. Small to moderate effect sizes were noted across PROMIS measures (except Peer Relations). Reliable magnitudes of change were estimated for this sample as approximately 6 point reduction for Pain Interference and Mobility, 9 for Fatigue, and 11 for Anxiety and Depression. Depending on the measure, 10 to 24% were categorized as improved, 3 to 6% as deteriorated, and 68 to 81% were either not clinically elevated at baseline or remained unchanged at 3 months. Overall, PROMIS CAT measures demonstrated responsiveness to change over time. Estimation of clinically significant change offers preliminary yet rigorous benchmarks for evaluating treatment response and sets the stage for understanding treatment effects. PERSPECTIVE: This study assesses responsiveness of CAT administered PROMIS measures and highlights one methodological approach of presenting clinical significance for assessing treatment outcomes in pediatric chronic pain. These benchmarks will allow clinicians and researchers to evaluate treatment response utilizing PROs while allowing for a deeper understanding of treatment effects.

Structural evidence of the oxidation of iodide ion into hyper-reactive hypoiodite ion by mammalian heme lactoperoxidase.

Lactoperoxidase (1.11.1.7, LPO) is a mammalian heme peroxidase found in the extracellular fluids of mammals including plasma, saliva, airway epithelial lining fluids, nasal lining fluid, milk, tears, gastric juices, and intestinal mucosa. To perform its innate immune action against invading microbes, LPO utilizes hydrogen peroxide (H2 O2 ) to convert thiocyanate (SCN- ) and iodide (I- ) ions into the oxidizing compounds hypothiocyanite (OSCN- ) and hypoiodite (IO- ). Previously determined structures of the complexes of LPO with SCN- , OSCN- , and I- show that SCN- and I- occupy appropriate positions in the distal heme cavity as substrates while OSCN- binds in the distal heme cavity as a product inhibitor. We report here the structure of the complex of LPO with IO- as the first structural evidence of the conversion of iodide into hypoiodite by LPO. To obtain this complex, a solution of LPO was first incubated with H2 O2 , then mixed with ammonium iodide solution and the complex crystallized by the addition of PEG-3350, 20% (wt/vol). These crystals were used for X-ray intensity data collection and structure analysis. The structure determination revealed the presence of four hypoiodite ions in the substrate binding channel of LPO. In addition to these, six other hypoiodite ions were observed at different exterior sites. We surmise that the presence of hypoiodite ions in the distal heme cavity blocks the substrate binding site and inhibits catalysis. This was confirmed by activity experiments with the colorimetric substrate, ABTS (2,2'-azino-bis(3-ethylbenzthiazoline-sulfonic acid)), in the presence of hypoiodite and iodide ions.

Evaluating Telehealth Implementation in the Context of Pediatric Chronic Pain Treatment during COVID-19.

Telehealth has emerged as a promising healthcare delivery modality due to its ability to ameliorate traditional access-level barriers to treatment. In response to the onset of the novel coronavirus (COVID-19) pandemic, multidisciplinary pain clinics either rapidly built telehealth infrastructure from the ground up or ramped up existing services. As the use of telehealth increases, it is critical to develop data collection frameworks that guide implementation. This applied review provides a theoretically-based approach to capitalize on existing data sources and collect novel data to inform virtually delivered care in the context of pediatric pain care. Reviewed multisource data are (1) healthcare administrative data; (2) electronic chart review; (3) clinical health registries; and (4) stakeholder feedback. Preliminary telehealth data from an interdisciplinary pediatric chronic pain management clinic (PPMC) serving youth ages 8-17 years are presented to illustrate how relevant implementation outcomes can be extracted from multisource data. Multiple implementation outcomes were assessed, including telehealth adoption rates, patient clinical symptoms, and mixed-method patient-report telehealth satisfaction. This manuscript provides an applied roadmap to leverage existing data sources and incorporate stakeholder feedback to guide the implementation of telehealth in pediatric chronic pain settings through and beyond COVID-19. Strengths and limitations of the modeled data collection approach are discussed within the broader context of implementation science.

Cryoablation Without Excision for Low-Risk Early-Stage Breast Cancer: 3-Year Interim Analysis of Ipsilateral Breast Tumor Recurrence in the ICE3 Trial.

BACKGROUND: The ICE3 trial is designed to evaluate the safety and efficacy of breast cryoablation, enabling women older than 60 years with low-risk early-stage breast cancers to benefit from a nonsurgical treatment and to avoid the associated surgical risks. METHODS: The ICE3 trial is a prospective, multi-center, single-arm, non-randomized trial including women age 60 years or older with unifocal, ultrasound-visible invasive ductal carcinoma size 1.5 cm or smaller and classified as low to intermediate grade, hormone receptor (HR)-positive, and human epidermal growth factor receptor 2 (HER2)-negative. Ipsilateral breast tumor recurrence (IBTR) at 5 years was the primary outcome. A 3-year interim analysis of IBTR was performed, and the IBTR probability was estimated using the Kaplan-Meier method. RESULTS: Full eligibility for the study was met by 194 patients, who received successful cryoablation per protocol. The mean age was 75 years (range, 55-94 years). The mean tumor length was 8.1 mm (range, 8-14.9 mm), and the mean tumor width was 7.4 mm (range, 2.8-14 mm). During a mean follow-up period of 34.83 months, the IBTR rate was 2.06% (4/194 patients). Device-related adverse events were reported as mild in 18.4% and moderate in 2.4% of the patients. No severe device-related adverse events were reported. More than 95% of the patients and 98% of the physicians reported satisfaction with the cosmetic results at the clinical follow-up evaluation. CONCLUSIONS: Breast cryoablation presents a promising alternative to surgery while offering the benefits of a minimally invasive procedure with minimal risks. Further study within a clinical trial or registry is needed to confirm cryoablation as a viable alternative to surgical excision for appropriately selected low-risk patients.

Representing Route Familiarity Using the Abstraction Hierarchy Framework.

Familiarity with a route is influenced by levels of dynamic and static knowledge about the route and the route network such as type of roads, infrastructure, traffic conditions, purpose of travel, weather, departure time, etc. To better understand and develop route choice models that can incorporate more meaningful representations of route familiarity, OBDII devices were installed in the vehicles of 32 drivers, 65 years and older, for a period of three months. Personalized web-based trip diaries were used to provide older drivers with post-trip feedback reports about their risky driving behaviors, and collect feedback about their route familiarity, preferences, and reasons for choosing the route driven vs. an alternate low-risk route. Feedback responses were analyzed and mapped onto an abstraction hierarchy framework, which showed that among older drivers, route familiarity depends not only on higher abstraction levels such as trip goals, purpose, and driving strategies, but also on the lower levels of demand on driving skills, and characteristics of road type. Additionally, gender differences were identified at the lower levels of the familiarity abstraction model, especially for driving challenges and the driving environment. Results from the analyses helped highlight the multi-faceted nature of route familiarity, which can be used to build the necessary levels of granularity for modelling and interpretation of spatial and contextual route choice recommendation systems for specific population groups such as older drivers.

Clinical Correlates of Opioid Prescription Among Pediatric Patients With Chronic Pain.

INTRODUCTION: Up to 17%-20% of pediatric patients with chronic pain are prescribed opioid pharmacotherapy and face an increased risk of opioid misuse in adulthood. Little is known about the way clinical presentation may influence which children with chronic pain are prescribed opioids. This study examines the associations between child's and caregiver's report of child's pain, physical function, and socioemotional indices with opioid prescriptions in pediatric patients initiating treatment for chronic pain. METHODS: Participants were 1,155 pediatric patients (71.26% female, n=823) aged 8-17 years and 1 of their caregivers (89% mothers) who presented for evaluation at a tertiary care pediatric pain clinic. Data were collected from 2015 to 2019 and analyzed in 2020. RESULTS: Binary logistic regression analyses investigated the relative contribution of child's demographic, pain, and Patient-Reported Outcome Measurement Information System measures to opioid prescription status; separate models were conducted for child's and caregiver's report. Across child and caregiver models, findings were that child's age (older), pain duration (longer; child's report only), and increased physical limitations (mobility challenges and pain interference; caregiver's report only) were the most salient clinical correlates of positive opioid status. Contrary to the existing literature on adults with chronic pain, socioemotional indices (anxiety, depression, peer functioning) were nonsignificant. CONCLUSIONS: A greater understanding of how clinical presentation may relate to prescribed opioid pharmacotherapy informs the field's conceptualization of the sequelae of opioid use and misuse in the context of pediatric chronic pain.

Fetal brain small vessel disease 1 caused by a novel mutation in the COL4A1 gene.

A singleton fetus was referred to fetal magnetic resonance imaging (MRI) at 25 weeks due to mild ventriculomegaly and an abnormal fetal echocardiogram showing cardiomegaly, right ventricular hypertrophy and tricuspid insufficiency. Patchy areas of ischemic infarction, extensive subacute and chronic hemorrhage not respecting vascular territories, encephaloclastic cysts and closed lip schizencephaly were identified. Cataract was detected postnatally. The anomalies were caused by a pathogenic mutation (c.353 G>A; p.G118D) in the COL4A1 gene. The phenotype seen in this case, i.e. small vessel cerebral disease with or without ocular anomalies caused by COL4A1 mutations, is likely an underrecognized cause of perinatal stroke. The pattern of abnormalities reported herein should prompt strong consideration for diagnosis and molecular testing.

Controlled loading of albumin-drug conjugates ex vivo for enhanced drug delivery and antitumor efficacy.

To harness the intrinsic transport properties of albumin yet improve the therapeutic index of current in situ albumin-binding prodrugs, we developed albumin-drug conjugates with a controlled loading that achieved better antitumor efficacy. Here, model drug monomethyl auristatin E (MMAE) was conjugated ex vivo to Cys34 of albumin via a cathepsin B-sensitive dipeptide linker to ensure that all drug would be bound specifically to albumin. The resulting albumin-drug conjugate with a drug to albumin ratio (DAR) of 1 (ALDC1) retained the native secondary structure of albumin compared to conjugate with a higher DAR of 3 (ALDC3). ALDC1 exhibited improved drug release and cytotoxicity compared to ALDC3 in vitro. Slower plasma clearance and increased drug exposure over time of ALDC1 were observed compared to ALDC3 and MMAE prodrug. In single dose studies with MIA PaCa2 xenografts, cohorts treated with ALDC1 had the highest amount of MMAE drug in tumor tissues compared to other treatment arms. After multiple dosing, ALDC1 significantly delayed the tumor growth compared to control treatment arms MMAE, MMAE-linker conjugate and ALDC3. When dosed with the maximum tolerated dose of ALDC1, there was complete eradication of 83.33% of the tumors in the treatment group. Ex vivo conjugated ALDC1 also significantly inhibited tumor growth in an immunocompetent syngeneic mouse model that better recapitulates the phenotype and clinical features of human pancreatic cancers. In summary, site-specific loading of drug to albumin at 1:1 ratio allowed the conjugate to better maintain the native structure of albumin and its intrinsic properties. By conjugating the drug to albumin prior to administration minimized premature cleavage and instability of the drug in plasma and enabled higher drug accumulation in tumors compared to in situ albumin-binding prodrugs. This strategy to control drug loading ex vivo ensures complete drug binding to the albumin carrier and achieves excellent antitumor efficacy, and it has the potential to greatly improve the outcomes of anticancer therapy.

Diabetes in Appalachia: providers' perspectives.

BACKGROUND: Southeastern Appalachian Ohio has more than double the national average of diabetes and a critical shortage of healthcare providers. Paradoxically, there is limited research focused on primary care providers' experiences treating people with diabetes in this region. This study explored providers' perceived barriers to and facilitators for treating patients with diabetes in southeastern Appalachian Ohio. METHODS: We conducted in-depth interviews with healthcare providers who treat people with diabetes in rural southeastern Ohio. Interviews were transcribed, coded, and analyzed via content and thematic analyses using NVivo 12 software (QSR International, Chadstone, VIC, Australia). RESULTS: Qualitative analysis revealed four themes: (1) patients' diabetes fatalism and helplessness: providers recounted story after story of patients believing that their diabetes was inevitable and that they were helpless to prevent or delay diabetes complications. (2) Comorbid psychosocial issues: providers described high rates of depression, anxiety, incest, abuse, and post-traumatic stress disorder among people with diabetes in this region. (3) Inter-connected social determinants interfering with diabetes care: providers identified major barriers including lack of access to providers, lack of access to transportation, food insecurity, housing insecurity, and financial insecurity. (4) Providers' cultural understanding and recommendations: providers emphasized the importance of understanding of the values central to Appalachian culture and gave culturally attuned clinical suggestions for how to use these values when working with this population. CONCLUSIONS: Evidence-based interventions tailored to Appalachian culture and training designed to increase the cultural competency and cultural humility of primary care providers may be effective approaches to reduce barriers to diabetes care in Appalachian Ohio.