BREAKTHROUGH HIV-1 INFECTION IN SETTING OF LONG-ACTING CABOTEGRAVIR FOR PrEP

Background: Long-acting cabotegravir (CAB-LA) is highly effective as HIV PrEP and superior to daily oral F/TDF in sexually active adults. We report a 28-yearold gender diverse patient assigned male at birth who acquired HIV-1 91 days after transitioning from F/TAF to CAB-LA despite on-time dosing. Method(s): Electronic medical records were reviewed to assess patient history and CAB-LA administration details. Plasma 4th generation HIV-1/2 Ag/Ab combination immunoassay and HIV-1 RNA quantitative PCR were performed at each injection visit. Result(s): Patient was on daily F/TAF for ten months prior to CAB-LA with acceptable adherence, missing 1 dose per week. Their medical history included hypothyroidism on levothyroxine and unconfirmed hypogonadism with illicit use of IM testosterone cypionate complicated by significantly elevated total testosterone levels. They were sexually active with cisgender men, endorsing condomless oral and anal sex with one primary partner and 20-30 unique partners per month. In the past 6 months, patient was diagnosed with syphilis and mpox. Patient was given 600mg of CAB-LA into their left gluteal medius on Day 0, 27, and 91. Day 0 and 27, plasma HIV 1/2 Ag/Ab was non-reactive and HIV-1 RNA PCR was not detected. Patient reported flu-like illness on Day 76 with positive SARS-COV-2 PCR;they completed a five-day course of nirmatrelvirritonavir with rapid resolution of symptoms. At the third injection of 600mg CAB-LA on Day 91, their plasma HIV 1/2 Ag/Ab was non-reactive but the HIV-1 RNA PCR test was detected at 1.48log c/mL. On repeat testing on Day 100, plasma HIV 1/2 Ag/Ab was reactive with HIV-1 Ab detected on differentiation assay and HIV-1 RNA PCR was detected at 1.30 log c/mL. Patient's primary partner was living with HIV resistant to NRTIs (65R, 118I) and INSTIs (92G) with undetectable plasma HIV-1 RNA for the past 24 months. Patient's viremia was below the threshold to perform standard HIV-1 sequencing;HIV-1 DNA qualitative PCR and HIV-1 proviral DNA resistance testing are currently pending. Patient ultimately started on F/TAF/DRV/COBI and DTG on Day 112. Conclusion(s): This patient's history suggests HIV-1 infection despite on-time and appropriate CAB-LA injections. To our knowledge, this is the first case of CAB-LA PrEP failure outside the setting of a clinical trial and highlights the diagnostic and management challenges that may arise with such breakthrough infections in the real world.

IDF2022-0635 Can COVID-19 infection provoke new-onset A-beta+ KPD (ketosis-prone diabetes)? - Insights from an Indian prospective study

Background COVID-19 as a trigger for A-beta+ ketosis-prone diabetes (KPD) [1,2] in previously normoglycemic individuals presenting with new-onset DKA, has been sparsely studied. Aim To study prospective changes in insulin secretion and insulin resistance in suspected A-beta+ KPD patients presenting with COVID-associated new-onset DKA. Method 22 previously non-diabetic, antibody-negative patients with new-onset DKA and RT-PCR positive COVID-19 (suspected A-beta + KPD), were followed up for one year. They were compared with 20 Type 1A and 18 Type 2 DM patients, with serial assessments (0,6 and 12 months) of insulin secretion rates (ISR) and multi-tissue insulin resistance (IR). 75-g OGTT with serial glucose, insulin and C-peptide estimation (0,15, 30,45, 60,90,120, 150 and 180 minutes) was used to derive IS, while hepatic and peripheral IR was calculated based on study by Ghani et al. [3]. Results At baseline, ISR in suspected KPD (n = 22) was significantly reduced but similar to Type 1A DM(p = 0.15). Serial ISR demonstrated complete recovery in 17 (77%) patients who became insulin independent at one-year follow-up (remission), while 5(23%) patients continued to require insulin (non-remission). KPD patients showed significant hepatic and peripheral IR at baseline compared to Type 1A DM (p < 0.05). The remission group (n = 17) showed significantly enhanced recovery of hepatic and peripheral insulin sensitivity at 6 and 12 months follow-up (all p < 0.01) compared to the non-remission (n = 5) group, with IR in the latter being comparable to Type 2 DM at follow-up (all p > 0.05). Younger age, lower BMI, initial severity of DKA and inflammation (IL-6 levels), along-with reduced 25-hydroxy-Vitamin-D levels were factors associated with poorer recovery of beta-cell secretion amongst the KPD patients. Conclusion This is the first prospective study to demonstrate progressive recovery of p-cell secretion in new-onset A-beta + KPD provoked by COVID-19 infection in Indian adults, with a distinctly different profile from Type 1A DM.Copyright © 2023 Elsevier B.V.

Analysis of Communicable Disease Symptoms Using Bag-of-Neural Network at Edge Networks

Considering the increasing growth of communicable diseases worldwide such as COVID-19, it is recommended to stay at home for patients with fewer chronic health problems. In recent times, the high chance of COVID-19 spread and the lack of an excellent remote monitoring system make the situation challenging for hospital administrators. Inspired by these challenges, in this paper, we develop a new edge-centric healthcare framework for remote health monitoring and disease prediction using Wearable Sensors (WSs) and advanced Machine Learning (ML) model, namely Bag-of-Neural Network (BoNN), respectively. The epidemic model collects the health symptoms of the patient using various a set of WSs and preprocesses the data in distributed edge devices for preparing a useful dataset. Finally, the proposed BoNN model is applied over the refined dataset for detecting COVID-19 disease at centralized cloud servers using a set of random neural networks. To demonstrate the efficiency of the proposed BoNN model over the standard ML models, the system is fine-tuned and trained over a synthetic COVID-19 dataset before being evaluated on a benchmark Brazil COVID-19 dataset using various performance metrics. The experimental results demonstrate that the proposed BoNN model achieves 99.8% accuracy while analyzing the Brazil dataset. © 2001-2012 IEEE.

Clinical profile and outcome of pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 series in Eastern India

Objective: The objective of this study is to delineate the characteristics and outcome of Pediatric Inflammatory Multisystem Syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARSCoV2) infection (PIMS-TS) in Eastern Indian settings. Materials and Methods: We conducted a prospective observational multicentric study from May 2020 to August 2020, collecting data on clinical profile, investigation findings, and outcome of the children aged 1 month-12 years admitted with the features of coronavirus disease 2019 (COVID-19) related hyperinflammation satisfying criteria for PIMS-TS from three tertiary care hospitals of Kolkata. Results: A total of 38 patients fulfilling the criteria of PIMS-TS were recruited. The median age of the study population was 5 years (1.9-8 years). Gastrointestinal symptoms were present in 33 (86.6%) of patients. Nasopharyngeal swab for COVID-19 reverse transcriptase-polymerase chain reaction was positive in 19 (50%) of patients, and immunoglobulin G antibody against COVID-19 was found in 12 (66.6%) of patients, whereas 19 (50%) of patients had a positive contact history of SARS-Co-V2 exposure. The features of Kawasaki, like illness with coronary changes, were seen in 12 (32%) cases, whereas myocarditis with ejection fraction <55% was reported in 17 (45%) of patients. Intensive care admissions were needed in 27 (71%) patients, and inotropes were given in 18 (47%), whereas four patients required mechanical ventilator support. Immunotherapy was used in 32 (84%) of patients. The outcome was good, with one death. Conclusions: PIMS TS has varied clinical presentation ranging from milder cases to severe cardiac dysfunction with shock. However, timely intervention and prompt initiation of immunomodulators can improve the prognosis. © 2022 by the Author(s).

A Structural Intervention Improves ID Fellow Wellness Amid a Pandemic

Background. Infectious Disease (ID) physicians have historically had higher levels of burnout compared to other medical specialties. Fellows are not immune to the pressures that attendings experience in the course of clinical care. The Accreditation Council for Graduate Medical Education now requires programs to formally promote well-being amongst trainees. We created a structural intervention to improve fellow well-being and conducted a before-and-after study demonstrating effectiveness. Methods. We restructured our institution's inpatient ID clinical services, which increased attending presence on weekends and afternoons to help with clinical volume. A survey including the Maslach Burnout Inventory for Medical Personnel (MBI-HSS(MP)) and wellness metrics was completed by our 5 fellows before and after the intervention. Consult volume and efficiency were assessed before and after the intervention. Descriptive statistics, paired t-tests or Wilcoxon signed-rank tests were utilized as appropriate for data normality. Qualitative survey responses were coded into key domains until saturation was reached for analysis. Results. Post-intervention MBI-HSS(MP) mean scores significantly improved for emotional exhaustion (EE) [3.3 to 2.3, p-value .0089]. Personal accomplishment and depersonalization metrics improved but were not significant. Survey items assessing time for education, learning to service balance, satisfaction and wellness all improved but were not significant (Table 1). Consult volume was the most frequent domain associated with dissatisfaction, and was described as the most improved domain since intervention (Table 2). Clinical work volumes were the same, if not higher, in the post intervention period (Table 3). All 5 fellows completed surveys before and after the intervention. The pre and post intervention means with standard errors (SE) or frequency of responses are listed in the table as well as p- values for Wilcoxon-signed rank or paired t-test (depending on normality of that variable). For 'education versus service balance' fellows used a visual analogue scale (0-100) to assess their views of balance of education (lower values) to service (higher values) while on General Infectious Disease consults (GID). Fellows were asked to rate their 'satisfaction' with GID on a visual analogue scale from 0-100 with lower values as dissatisfaction and higher values as satisfaction. EE, DP, and PA are metrics used in the Maslach Burnout Inventory for Medical Personnel (MBI-SS(MP)). The values of the MBI questions are mean responses across items in their respective inventories, with higher values for EE and DP meaning more frequent negative experiences, and higher values for PA meaning more frequent positive experiences. For MBI, scores indicate how frequently feelings occur: 1, a few times/year;2, monthly;3, a few times monthly;4, weekly;5, a few times/week. Fellows were also asked to give the frequency at which they were able to teach or complete responsibilities at home (such as childcare, cleaning, cooking, grocery shopping) while on GID. Responses truncated only to frequencies selected by respondents. Responses to the last two questions were numerically coded for statistical analysis. * Indicates statistical significance (p < .05). Free text survey responses were analyzed by authors, resulting in the generation of key conceptual response domains;this process continued until saturation was reached, leading to the coding of text responses as above. Examples from text responses included in parenthesis. Prompt 1 was given to the 5 fellows before and after the intervention leading to 10 responses. Prompt 2 was given to the 5 fellows only following intervention. Variables were assessed pre and post intervention. Max list size is the maximum number of patients on the general infectious disease (GID) consult service, bumped consults is the number of consults not seen until the following work day, curbside consults is the number of consults where recommendations were given without seeing the patient, last rec is the t me of delivery of the last recommendation, pages is the raw number of pages received in a day by the GID fellow and COVID-19 census is the total number of patients admitted to our center with COVID-19. *Indicates statistical significance (p < .05) by paired t-test. IQR signifies inter-quartile range. Conclusion. We found that an intervention addressing structural contributors to burnout was effective in reducing EE and perception of clinical volume. This finding was significant despite stable to increased clinical volumes and the added stress of the cotemporaneous Omicron outbreak of COVID-19.

A Case Of Serology-negative, Bartonella Peliosis Hepatitis in a Poorly Controlled Patient with HIV Presenting with Altered Mental Status, Unintentional Weight Loss, and Reduced Appetite

INTRODUCTION: Despite reductions in AIDSrelated opportunistic infections (OIs) due to advancements in antiretroviral therapy (ART), providers must still be aware of signs and symptoms of OI's in newly diagnosed patients and those with poor medication adherence. We describe in this case a patient with advanced HIV who presented with altered mentation, weight loss, and fever of unknown origin found to have serology negative, peliosis hepatitis due to presumed Bartonella henselae. CASE DESCRIPTION: A 28 year old male with known HIV, off ART for many months presented to the emergency department with acute psychosis. Family endorsed paranoia and reduced functional capacity for one week in addition to yellowing of his eyes, reduced appetite, dry cough, and subjective fevers. Also reported unintentional fifty pound weight loss over 6 months. Vital signs were within normal limits. CBC was significant for lymphopenia, thrombocytopenia, and normocytic anemia. Comprehensive metabolic panel revealed transaminitis, direct & indirect hyperbilirubinemia, and normal renal function. CD4 count was 4.72 cells/mul, HIV viral load was 402,000 copies/mL, and SARS-CoV2 PCR was negative. Broad blood, urine, sputum & cerebral spinal fluid infectious studies were all nondiagnostic. CT of the abdomen and pelvis revealed hepatosplenomegaly and generalized lymphadenopathy. MRCP showed scattered T2 hyperintense foci throughout the liver and spleen. MRI brain revealed pontine hyperintense FLAIR signaling. Transjugular liver biopsy pathology revealed peliosis hepatis with a positive Warthyn Starry stain with occasional bacteria that were consistent with Bartonella species. Patient was initiated on appropriate antibacterial therapy for the Peliosis hepatitis and reinitiated ART. Patient's mentation clinically improved and was discharged home. DISCUSSION: Bartonella infections in patients with AIDS are heterogeneous in their presentation and may affect almost every organ system. It is an indolent organism difficult to grow on standard culture techniques. In patients with AIDS, up to approximately 25% of patients may have negative serologies on presentation.'.

A Prospective Characterization of Metabolic and Metabolomic Profiles of COVID-19–Associated New-Onset Diabetes Patients Presenting with DKA from India

Background: Recent evidence suggests a bidirectional relationship between COVID-infection and new-onset diabetes (NOD) presenting with DKA. Methodology: This one-year prospective study comprised of 29 COVID-negative DKA (controls) and 52 COVID-positive-DKA patients (18 NOD, 15 T1DM ,T2DM) . NOD were previously normoglycemic and negative for GAD/IA-2/ZnT8 autoantibodies. After 75g- OGTT with estimation of glucose, C-peptide, FFA and insulin at 0,15, 30,45, 60,90 ,120, 150 and 180minutes, Insulin secretion rate (ISR) [C-peptide-deconvolution] , Hepatic insulin sensitivity [AUC-glucose × AUC-insulin during first 30-minutes of OGTT ], Peripheral insulin sensitivity [ dG/dt ÷ mean plasma insulin concentration;dG/dt rate of decline in plasma glucose concentration]were calculated alongwith Metabolomics and Adipose tissue gene expression. All tests were performed at admission and 4, 8, and 12-months of followup. Results: At baseline, ISR in NOD was significantly reduced than controls (p=0.001) but similar to T1DM (p=0.15) . Nearly 83% (n=17) of NOD with DKA had near-complete recovery of ISR on follow-up compared to T1DM (all p<0.01) ,with non-remitters (n=3) having significantly worse admission Hba1c and IL-6 (all p<0.01) . NOD had significantly increased hepatic and peripheral insulin resistance compared to T1DM (all p<0.05) ,but similar to T2DM (all p>0.05) . Their Metabolomics revealed increased inflammatory phosphatidylcholines, that correlated with peripheral glucose uptake (p<0.01) ,while RNA sequencing showed significantly enhanced WNT5A , TLR4 (Toll-like Receptor-4) and RETN (resistin) than T1DM and T2DM (both p=0.001) . Conclusion: Our study provides novel insights into COVID-associated NOD with DKA. Majority have near-complete recovery of insulin secretion while simultaneous multi-tissue insulin resistance and inflammatory adipose tissue profiles persist as drivers of hyperglycemia.

Analysis of Communicable Disease Symptoms using Bag-of-Neural Network at Edge Networks

Considering the increasing growth of communicable diseases worldwide such as COVID-19, it is recommended to stay at home for patients with fewer chronic health problems. In recent times, the high chance of COVID-19 spread and the lack of an excellent remote monitoring system make the situation challenging for hospital administrators. Inspired by these challenges, in this paper, we develop a new edge-centric healthcare framework for remote health monitoring and disease prediction using Wearable Sensors (WSs) and advanced Machine Learning (ML) model, namely Bag-of-Neural Network (BoNN), respectively. The epidemic model collects the health symptoms of the patient using various a set of WSs and preprocesses the data in distributed edge devices for preparing a useful dataset. Finally, the proposed BoNN model is applied over the refined dataset for detecting COVID-19 disease at centralized cloud servers using a set of random neural networks. To demonstrate the efficiency of the proposed BoNN model over the standard ML models, the system is fine-tuned and trained over a synthetic COVID-19 dataset before being evaluated on a benchmark Brazil COVID-19 dataset using various performance metrics. The experimental results demonstrate that the proposed BoNN model achieves 99.8% accuracy while analyzing the Brazil dataset. IEEE

Mass media in creating awareness among agricultural labours during COVID-19 pandemic in Birbhum, West Bengal

In the crisis period due to global health threat caused by COVID-19 pandemic in the last few months of 2020 and the imposed lockdown in India, mass media played a very crucial role to make the countless mass of recipients aware and conscious about what is happening throughout the world. The study aims to find out informative role of mass media over traditional media in creating awareness about agriculture during the pandemic and exposure to mass media by the Santals of Birbhum District, West Bengal. Telephonic questionnaire through mobile contact was applied to collect quantitative data from 100 Santal agricultural labours of both local and migrant (50 male, 50 female) from 4 selected villages. It was observed that, though availability of mass media with the Santals was limited, however, their accessibility to mass media like TV or mobile phone was found somewhat better in creating awareness and consciousness about agricultural activities during the pandemic period among the Santals. Mean value of agricultural information consumption based on mass media of female Santals (X2= 109.43) was better than the male Santals (X1= 106.18). 't' value, which was 3.40, much more than the significant level, indicated that the agricultural information consumption based on mass media of female Santals is greater than that of male Santals in COVID-19 pandemic. Study finally suggested for balanced combination of traditional media and mass media in developing more awareness and consciousness among the Santals in the epidemic and pandemic period.

Outcome of Neonates Born to COVID-Positive Women at 6 Months of Age

OBJECTIVES: To compare clinical and neurodevelopmental outcome at the age of 6 months for neonates born to SARS-CoV-2-positive mothers. METHODS: Neonates of SARS-CoV-2 positive mothers, admitted in our hospital were assessed for growth, neurodevelopment by Amiel-Tison method, and Developmental Profile (DP3) at discharge as part of another study (July 2020). This data were retrieved and babies followed-up at the age of 6 months. Composite adverse outcome was death within 6 months post discharge or DP3 score <70 and hearing/visual deficit. RESULTS: Out of 131 enrolled at discharge, 127 (97%) were followed up. SARs-CoV-2 positive neonates (Group I;19, 15%) had more symptoms (P=0.012), sepsis (P=0.014), pneumonia (P=0.029), longer hospital stay (P<0.001) following birth compared to group II (SARs-CoV-2 negative neonates;108, 85%). No baby in group I met definition of composite adverse outcome, while in group II it was 0.9% (1 child with DP3 <70 with hearing deficit) (P=1.0) without any difference in hospital readmission, growth, DP3 scores, or tone abnormalities. CONCLUSIONS: There is no difference in growth, neurodevelopment, and hospital readmission in early infancy among infected and non-infected babies born to SARS-CoV-2 positive mothers.

Outcome of Neonates Born to COVID Positive Women at 6 Months of Age

OBJECTIVE: To compare clinical and neurodevelopmental outcome at the age of 6 months for neonates born to SARS-CoV-2-positive mothers. METHODS: Neonates of SARS-CoV-2 positive mothers, admitted in our hospital more assessed for growth, neurodevelopment by Amiel-Tison method, and Developmental Profile (DP3) at discharge part of another study (July 2020). This data were retrieved and babies followed-up at the age of 6 months. Composite adverse outcome was death within 6 months post discharge or DP3 score <70 and hearing/visual deficit. RESULTS: Out of 131 enrolled at discharge, 127 (97%) were followed up. Group I (19, 15%) had more symptoms (P=0.012), sepsis (P=0.014), pneumonia (P=0.029), longer hospital stay (P<0.001) following birth compared to group II (108, 85%). No baby in group I met definition of composite adverse outcome, while in group II it was 0.9% (1 child with DP3 <70 with hearing deficit) (P=1.0) without any difference in hospital readmission, growth, DP3 scores, or tone abnormalities. CONCLUSION: There is no difference in growth, neurodevelopment, and hospital readmission in early infancy among infected and non-infected babies born to SARS-CoV-2 positive mothers.