Noninvasive detection of any-stage cancer using free glycosaminoglycans.

Cancer mortality is exacerbated by late-stage diagnosis. Liquid biopsies based on genomic biomarkers can noninvasively diagnose cancers. However, validation studies have reported ~10% sensitivity to detect stage I cancer in a screening population and specific types, such as brain or genitourinary tumors, remain undetectable. We investigated urine and plasma free glycosaminoglycan profiles (GAGomes) as tumor metabolism biomarkers for multi-cancer early detection (MCED) of 14 cancer types using 2,064 samples from 1,260 cancer or healthy subjects. We observed widespread cancer-specific changes in biofluidic GAGomes recapitulated in an in vivo cancer progression model. We developed three machine learning models based on urine (Nurine = 220 cancer vs. 360 healthy) and plasma (Nplasma = 517 vs. 425) GAGomes that can detect any cancer with an area under the receiver operating characteristic curve of 0.83-0.93 with up to 62% sensitivity to stage I disease at 95% specificity. Undetected patients had a 39 to 50% lower risk of death. GAGomes predicted the putative cancer location with 89% accuracy. In a validation study on a screening-like population requiring ≥ 99% specificity, combined GAGomes predicted any cancer type with poor prognosis within 18 months with 43% sensitivity (21% in stage I; N = 121 and 49 cases). Overall, GAGomes appeared to be powerful MCED metabolic biomarkers, potentially doubling the number of stage I cancers detectable using genomic biomarkers.

Determinants of post discharge mortality among hospitalized COVID-19 patients.

Background & objectives: The post-acute effects of COVID-19 are continually being updated. This investigation was conducted to evaluate the determinants of post discharge mortality in hospitalized COVID-19 patients, especially 18-45 yr of age. Methods: A series of three nested case-control analyses was conducted on follow up data collected in the National Clinical Registry for COVID-19 between September 2020 and February 2023 from 31 hospitals. Matching (1:4) was done by the date of hospital admission ±14 days for the following comparisons: (i) case-patients reported as dead vs. controls alive at any contact within one year follow up; (ii) the same in the 18-45 yr age group and (iii) case-patients reported as dead between the first and one year of follow up vs. controls alive at one year post discharge. Results: The one year post discharge mortality was 6.5 per cent (n=942). Age [≤18 yr: adjusted odds ratio (aOR) (95% confidence interval [CI]): 1.7 (1.04, 2.9); 40-59 yr: aOR (95% CI): 2.6 (1.9, 3.6); ≥60 yr: aOR (95% CI): 4.2 (3.1, 5.7)], male gender [aOR (95% CI): 1.3 (1.1, 1.5)], moderate-to-severe COVID-19 [aOR (95% CI): 1.4 (1.2, 1.8)] and comorbidities [aOR (95%CI): 1.8 (1.4, 2.2)] were associated with higher odds of post-discharge one-year mortality, whereas 60 per cent protection was conferred by vaccination before the COVID-19 infection. The history of moderate-to-severe COVID-19 disease [aOR (95% CI): 2.3 (1.4, 3.8)] and any comorbidities [aOR (95% CI): 3 (1.9, 4.8)] were associated with post-discharge mortality in the 18-45-yr age bracket as well. Post COVID condition (PCC) was reported in 17.1 per cent of the participants. Death beyond the first follow up was associated with comorbidities [aOR (95%CI): 9.4 (3.4, 26.1)] and reported PCC [aOR (95% CI): 2.7 (1.2, 6)]. Interpretation & conclusions: Prior vaccination protects against post discharge mortality till one year in hospitalized COVID-19 patients. PCC may have long term deleterious effects, including mortality, for which further research is warranted.

Analysis of Predictors and Outcomes of COVID-19 Patients Requiring ICU Admission from COVID-19 Registry, India.

Background: Patients admitted to intensive care units (ICUs) with severe coronavirus disease (COVID-19) are associated with high mortality. The present retrospective, multicenter study describes the predictors and outcomes of COVID-19 patients requiring ICU admission from COVID-19 Registry of Indian Council of Medical Research (ICMR), India. Materials and methods: Prospectively collected data from participating institutions were entered into the electronic National Clinical Registry of COVID-19. We enrolled patients aged >18 years with COVID-19 pneumonia requiring ICU admission between March 2020 and August 2021. Exclusion criteria were negative in RT-PCR report, death within 24 hours of ICU admission, or incomplete data. Their demographic and laboratory variables, ICU severity indices, treatment strategies, and outcomes were analyzed. Results: A total of 5,865 patients were enrolled. Overall mortality was 43.2%. Non-survivors were older (58.2 ± 15.4 vs 53.6 ± 14.7 years; p = 0.001), had multiple comorbidities (33.2% vs 29.5%, p = 0.001), had higher median D-dimer (1.56 vs 1.37, p = 0.015), higher CT severity index (16.8 ± 5.2 vs 13.5 ± 5.47, p = 0.001) and longer median hospital stay (10 vs 8 days, p = 0.001) and ICU stay (5 vs 4 days, p = 0.001), compared with survivors.On multivariate analysis, high CRP (HR 1.008, 95% CI: 1.006-1.010, p = 0.001) and high D-dimer (HR 1.089, 95% CI: 1.065-1.113, p < 0.001) were associated with invasive mechanical ventilation while older age (HR 1.19, CI: 1.001-1.038, p = 0.039) and high D-dimer (HR-1.121, CI: 1.072-1.172, p = 0.001) were independently associated with mortality and while the use of prophylactic low molecular weight heparin (LMWH) (HR 0.647, CI: 0.527-0.794, p = 0.001) lowered mortality. Conclusion: Among 5,865 COVID-19 patients admitted to ICU, mortality was 43.5%. High CRP and D-dimers were independently associated with the need for invasive mechanical ventilation while older age and high D-dimer were associated with higher mortality. The use of prophylactic LMWH independently reduced mortality. How to cite this article: Kajal K, Singla K, Puri GD, Bhalla A, Mukherjee A, Kumar G, et al. Analysis of Predictors and Outcomes of COVID-19 Patients Requiring ICU Admission from COVID-19 Registry, India. Indian J Crit Care Med 2023;27(8):552-562.

Characterizing the third wave of COVID-19: An analysis from the National Clinical Registry of COVID-19.

Background & objectives: Data from the National Clinical Registry for COVID-19 (NCRC) were analyzed with an aim to describe the clinical characteristics, course and outcomes of patients hospitalized with COVID-19 in the third wave of the pandemic and compare them with patients admitted earlier. Methods: The NCRC, launched in September 2020, is a multicentre observational initiative, which provided the platform for the current investigation. Demographic, clinical, treatment and outcome data of hospitalized COVID-19 patients were captured in an electronic data portal from 38 hospitals across India. Patients enrolled during December 16, 2021 to January 17, 2022 were considered representative of the third wave of COVID-19 and compared with those registered during November 15 to December 15, 2021, representative of the tail end of the second wave. Results: Between November 15, 2021 and January 17, 2022, 3230 patients were recruited in NCRC. Patients admitted in the third wave were significantly younger than those admitted earlier (46.7±20.5 vs. 54.6±18 yr). The patients admitted in the third wave had a lower requirement of drugs including steroids, interleukin (IL)-6 inhibitors and remdesivir as well as lower oxygen supplementation and mechanical ventilation. They had improved hospital outcomes with significantly lower in-hospital mortality (11.2 vs. 15.1%). The outcomes were better among the fully vaccinated when compared to the unvaccinated or partially vaccinated. Interpretation & conclusions: The pattern of illness and outcomes were observed to be different in the third wave compared to the last wave. Hospitalized patients were younger with fewer comorbidities, decreased symptoms and improved outcomes, with fully vaccinated patients faring better than the unvaccinated and partially vaccinated ones.

POEMS Syndrome: Clinical and Laboratory Approach Towards Diagnosis.

Polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes (POEMS) syndrome is a rare multisystem paraneoplastic disorder. Here we describe a case of a 50 year old post-menopausal female who presented with chief complaints of difficulty in walking, getting up from squatting position and tingling sensation of bilateral lower limbs since 1 month. Additional unusual features in the patient included hepatosplenomegaly, endocrinal involvement in the form of hypothyroidism and elevated estradiol levels for her age. There were skin changes in the form of hyperpigmentation. M protein was not noted on serum electrophoresis but was visible on serum protein immunofixation (IgA lambda). She was investigated as a case of polyneuropathy and later a provisional clinical diagnosis of POEMS was made based on the presence of major and minor criteria. The patient was managed with methyl prednisolone, calcium carbonate and vit D3 and topical antibiotics for local infections.

Clinical profile of hospitalized COVID-19 patients in first & second wave of the pandemic: Insights from an Indian registry based observational study.

Background & objectives: India witnessed a massive second surge of COVID-19 cases since March 2021 after a period of decline from September 2020. Data collected under the National Clinical Registry for COVID-19 (NCRC) were analysed to describe the differences in demographic and clinical features of COVID-19 patients recruited during these two successive waves. Methods: The NCRC, launched in September 2020, is an ongoing multicentre observational initiative, which provided the platform for the current investigation. Demographic, clinical, treatment and outcome data of hospitalized, confirmed COVID-19 patients were captured in an electronic data portal from 41 hospitals across India. Patients enrolled during September 1, 2020 to January 31, 2021 and February 1 to May 11, 2021 constituted participants of the two successive waves, respectively. Results: As on May 11, 2021, 18961 individuals were recruited in the registry, 12059 and 6903 reflecting in-patients from the first and second waves, respectively. Mean age of the patients was significantly lower in the second wave [48.7 (18.1) yr vs. 50.7 (18.0) yr, P<0.001] with higher proportion of patients in the younger age group intervals of <20, and 20-39 yr. Approximately 70 per cent of the admitted patients were ≥ 40 yr of age in both waves of the pandemic. The proportion of males were slightly lower in second wave as compared to the first [4400 (63.7%) vs. 7886 (65.4%), P=0.02]. Commonest presenting symptom was fever in both waves. In the second wave, a significantly higher proportion [2625 (48.6%) vs. 4420 (42.8%), P<0.003] complained of shortness of breath, developed ARDS [422(13%) vs. 880 (7.9%), P<0.001], required supplemental oxygen [1637 (50.3%) vs. 4771 (42.7%), P<0.001], and mechanical ventilation [260 (15.9%) vs. 530 (11.1%), P<0.001]. Mortality also significantly increased in the second wave [OR: 1.35 (95% CI: 1.19, 1.52)] in all age groups except in <20 yr. Interpretation & conclusions: The second wave of COVID-19 in India was slightly different in presentation than the first wave, with a younger demography, lesser comorbidities, and presentation with breathlessness in greater frequency.

Use of convalescent plasma for COVID-19 in India: A review & practical guidelines.

Convalescent plasma (CP) therapy is one of the promising therapies being tried for COVID-19 patients. This passive immunity mode involves separating preformed antibodies against SARS-CoV-2 from a recently recovered COVID-19 patient and infusing it into a patient with active disease or an exposed individual for prophylaxis. Its advantages include ease of production, rapid deployment, specificity against the target infectious agent, and scalability. In the current pandemic, it has been used on a large scale across the globe and also in India. However, unequivocal proof of efficacy and effectiveness in COVID-19 is still not available. Various CP therapy parameters such as donor selection, antibody quantification, timing of use, and dosing need to be considered before its use. The current review attempts to summarize the available evidence and provide recommendations for setting up CP protocols in clinical and research settings.

Quality of Patient Education Materials on Safe Opioid Management in the Acute Perioperative Period: What Do Patients Find Online?

OBJECTIVE: Guidelines on postoperative pain management recommend inclusion of patient and caregiver education on opioid safety. Patient education materials (PEMs) should be written at or below a sixth grade reading level. We designed this study to compare the readability of online PEMs related to postoperative opioid management produced by institutions with and without a regional anesthesiology and acute pain medicine (RAAPM) fellowship. METHODS: With institutional review board exemption, we constructed our cohort of PEMs by searching RAAPM fellowship websites from North American academic medical centers and identified additional websites using structured Internet searches. Readability metrics were calculated from PEMs using the TextStat 0.4.1 textual analysis package for Python 2.7. The primary outcome was the Flesch-Kincaid Grade Level (FKGL), a score based on words per sentence and syllables per word. We also compared fellowship-based and nonfellowship PEMs on the presence or absence of specific content-related items. RESULTS: PEMs from 15 fellowship and 23 nonfellowship institutions were included. The mean (SD) FKGL for PEMs was grade 7.84 (1.98) compared with the recommended sixth grade level (P < 0.001) and was not different between groups. Less than half of online PEMs contained explicit discussion of opioid tapering or cessation. Disposal and overdose risk were addressed more often by nonfellowship PEMs. CONCLUSIONS: Available online PEMs related to opioid management are beyond the recommended reading level, but readability metrics for online PEMs do not differ between fellowship and nonfellowship groups. More than two-thirds of RAAPM fellowship programs in North America are lacking readable online PEMs on safe postoperative opioid management.

Replacement of Fascia Iliaca Catheters with Continuous Erector Spinae Plane Blocks Within a Clinical Pathway Facilitates Early Ambulation After Total Hip Arthroplasty.

OBJECTIVE: The optimal continuous peripheral nerve block (CPNB) technique for total hip arthroplasty (THA) that maximizes both analgesia and mobility is unknown. Continuous erector spinae plane (ESP) blocks were implemented at our institution as a replacement for fascia iliaca (FI) catheters to improve our THA clinical pathway. We designed this study to test the hypothesis that this change will increase early postoperative ambulation for elective primary THA patients. METHODS: We identified all consecutive primary unilateral THA cases six months before and six months after the clinical pathway change to ESP catheters. All other aspects of the THA clinical pathway and multimodal analgesic regimen including perineural infusion protocol did not change. The primary outcome was total ambulation distance (meters) on postoperative day 1. Other outcomes included total ambulation on postoperative day 2, combined two-day ambulation distance, pain scores, opioid consumption, inpatient length of stay, and minor and major adverse events. RESULTS: Eighty-eight patients comprised the final sample (43 FI and 45 ESP). Postoperative day 1 total ambulation distance was greater for the ESP group compared with the FI group (median [10th-90th percentiles] = 24.4 [0.0-54.9] vs 9.1 [0.7-45.7] meters, respectively, P = 0.036), and two-day ambulation distance was greater for the ESP group compared with the FI group (median [10th-90th percentiles] = 68.6 [9.0-128.0] vs 46.6 [3.7-104.2] meters, respectively, P = 0.038). There were no differences in pain scores, opioid use, or other outcomes. CONCLUSIONS: Replacing FI catheters with continuous ESP blocks within a clinical pathway results in increased early ambulation by elective primary THA patients.

Utilisation, equity and determinants of full antenatal care in India: analysis from the National Family Health Survey 4.

OBJECTIVES: We examined the utilisation, equity and determinants of full antenatal care (ANC), defined as 4 or more antenatal visits, at least one tetanus toxoid (TT) injection and consumption of iron folic acid (IFA) for a minimum of 100 days, in India. METHODS: We analysed a sample of 190,898 women from India's National Family Health Survey 4. Concentration curves and concentration index were used to assess equity in full ANC utilisation. Multivariable logistic regression model was used to examine the factors associated with full ANC utilisation. RESULTS: In India, 21% of pregnant women utilised full ANC, ranging from 2.3-65.9% across states. Overall, 51.6% had 4 or more ANC visits, 30.8% consumed IFA for atleast 100 days, and 91.1% had one or more doses of tetanus toxoid. Full ANC utilisation was inequitable across place of residence, caste and maternal education. Registration of pregnancy, utilisation of government's Integrated Child Development Services (ICDS) and health insurance coverage were associated with higher odds of full ANC utilisation. Lower maternal education, lower wealth quintile(s), lack of father's participation during antenatal visits, higher birth order, teenage and unintended pregnancy were associated with lower odds of full ANC utilisation. CONCLUSIONS: Full ANC utilisation in India was inadequate and inequitable. Although half of the women did not receive the minimum recommended ANC visits, the utilisation of TT immunisation was almost universal. The positive association of full ANC with ICDS utilisation and child's father involvement may be leveraged for increasing the uptake of full ANC. Strategies to address the socio-demographic factors associated with low and inequitable utilisation of full ANC are imperative for strengthening India's maternal health program.

Lupus retinopathy: a marker of active systemic lupus erythematosus.

Retinopathy in the context of systemic lupus erythematosus (SLE) is associated with severe disease and poorer prognosis. We studied retinopathy in our cohort of Indian lupus patients. Four hundred and thirty-seven patients fulfilling the Systemic Lupus International Collaborating Clinics-American College of Rheumatology-2012 criteria, attending the department of Clinical Immunology were enrolled under this cross-sectional study. A comprehensive clinical (including ophthalmological) examination and immunological profile were performed. Retinopathy was defined if cotton-wool spots, haemorrhages, vasculitis, retinal detachment or optic disc changes as papilledema, optic atrophy were present. Disease activity was assessed using SLE disease activity index (SLEDAI). Mean age of participants was 28.06 ± 9.7 years (93.1% females); median disease duration 12 months (Interquartile range-IQR 6.36). Forty-five (10.3%) had SLE associated retinopathy. Autoimmune haemolytic anaemia [31.1 vs 14.5%, p value 0.004, odd's ratio-OR (95% confidence interval-CI) 2.65 (1.33-5.29)], serositis [33.3 vs 18.9%, p value 0.023, OR (CI) 2.14 (1.11-4.10)], lupus nephritis [62.2 vs 40.8%, p value 0.006, OR (CI) 2.38 (1.26-4.50)], seizures [28.9 vs 12.8%, p value 0.004, OR (CI) 2.77 (1.36-5.65)] and median SLEDAI score (24 vs 12, p < 0.01) were significantly higher in those with retinopathy. On adjusted binary logistic regression, autoimmune hemolytic anemia, lupus nephritis and presence of antibodies to Smith antigen were predictors for retinopathy. Retinopathy is common in SLE, a marker of active disease with frequent renal involvement and should be screened for in all patients with lupus.

Availability and Readability of Online Patient Education Materials Regarding Regional Anesthesia Techniques for Perioperative Pain Management.

OBJECTIVE: Patient education materials (PEM) should be written at a sixth-grade reading level or lower. We evaluated the availability and readability of online PEM related to regional anesthesia and compared the readability and content of online PEM produced by fellowship and nonfellowship institutions. METHODS: With IRB exemption, we constructed a cohort of online regional anesthesia PEM by searching Websites from North American academic medical centers supporting a regional anesthesiology and acute pain medicine fellowships and used a standardized Internet search engine protocol to identify additional nonfellowship Websites with regional anesthesia PEM based on relevant keywords. Readability metrics were calculated from PEM using the TextStat 0.1.4 textual analysis package for Python 2.7 and compared between institutions with and without a fellowship program. The presence of specific descriptive PEM elements related to regional anesthesia was also compared between groups. RESULTS: PEM from 17 fellowship and 15 nonfellowship institutions were included in analyses. The mean (SD) Flesch-Kincaid Grade Level for PEM from the fellowship group was 13.8 (2.9) vs 10.8 (2.0) for the nonfellowship group (p = 0.002). We observed no other differences in readability metrics between fellowship and nonfellowship institutions. Fellowship-based PEM less commonly included descriptions of the following risks: local anesthetic systemic toxicity (p = 0.033) and injury due to an insensate extremity (p = 0.003). CONCLUSIONS: Available online PEM related to regional anesthesia are well above the recommended reading level. Further, fellowship-based PEM posted are at a higher reading level than PEM posted by nonfellowship institutions and are more likely to omit certain risk descriptions.

Defining the Role of Physiotherapy in Palliative Care in Multiple Sclerosis.

With increasing prevalence of multiple sclerosis worldwide, India too has transitioned from low to medium prevalence region. This increases the overall burden of a number of people suffering from a chronic progressive disorder. Such scenario underlines the need for an early comprehensive and holistic patient management plan, aiming to provide a better quality of life. The presented case is one such example of a patient-centered, and interdisciplinary team approach for better management of a patient suffering from an incurable, progressive disorder. As physiotherapists tend to spend a considerable amount of time with their patients on a regular basis, it becomes imperative to view all the patient related problems from a wider angle and endeavor to address each of them individually/collaboratively. In a palliative care setting, physiotherapy can no longer be considered as only physical symptom management approach but a patient care approach considering their entire physical, emotional, psychosocial, and spiritual needs. This novel case report shall serve as a guiding strategy for physiotherapists to work in the domain of palliative care.

The Barrier to Accessing Dental Healthcare Services Among the Institutionalized Visually Impaired Adults: A Qualitative Study.

Many studies have focused on the overall oral health of people with visual impairment, but there is a dearth of studies on the barriers to accessing dental healthcare services among institutionalized visually impaired people. Therefore, the current study aims to assess the barriers to accessing dental healthcare services among institutionalized visually impaired people. METHODS: A qualitative study design was conducted over the course of 10 months among institutionalized visually impaired individuals. A semi-structured interview was conducted among the participants. Interviews were audio-recorded, transcribed, translated, and qualitatively analyzed using MAXQDA software, version 22.0 (VERBI Software, Berlin). RESULTS: A total of 20 participants participated in the study. Three levels were used to classify the investigated barriers: the individual's level, which pertains to the obstacles they encountered in receiving oral health care and their viewpoints on the way that care is provided; the interpersonal degree and the system level, in order to determine the broader components and their impact. CONCLUSION: This study gives insight into the problems people have in assessing the dental services and facilities available. Three levels were used to identify the barriers among the study participants. Six themes emerged in the study that described their problems, which affected their mental health directly.

Assessment of Oral Health Status among the Sevayats of Shree Sakhigopal Temple, Puri - A Cross-sectional Study.

Aim: To assess the oral health status of the Sevayats of Sakhigopal temple, Puri, Odisha. Methodology: An assessment of the oral health status of 111 Sevayats at the Sakhigopal temple in Puri was carried out using a cross-sectional survey. The World Health Organization oral health assessment form for adults (2013) was used to collect data. Chi-square test and one-way analysis of variance were the statistical tests used for the investigation using Statistical Package for the Social Sciences 27 version. When the P value was less than 0.05, it was deemed statistically significant. Results: The mean DMFT of all the participants was 3.70 ± 1.71. The prevalence of caries was 91%. Bleeding and periodontal pocket were present in 82.9% and 83.8% of Sevayats, respectively. Conclusion: There was a higher prevalence of dental caries and periodontal disease among the subjects.

Assessment of oral health status amongst postal employees of Bhubaneswar city: A cross-sectional study.

Introduction: Upholding good dental health has wider effects on productivity and performance at work in addition to being crucial for individual well-being. Because it can affect both their personal well-being and productivity at work, post office workers' oral health is therefore a critical issue of concern. Hence, evaluating Bhubaneswar city post office workers' dental health is the study's aim. Materials and Methodology: With the aid of the WHO 2013 oral health assessment form, a cross-sectional study involving 171 regular post office workers was undertaken. Using the Chi-square test and an ANOVA for pertinent variables, the data were analysed using SPSS statistical software version 27.0. Potential confounding variables were adjusted using multiple logistic regression analysis. Results: The survey included a total of 171 post office personnel, of which 76.6% were men and 23.4% were women. The participants' periodontal health revealed that 67.7% had deep periodontal pockets, 18.7% had shallow ones, and 95.3% had bleeding gums. The mean DMFT of the study participants was 4.10 ± 3.149. Conclusion: Among post office workers, tobacco use and oral health conditions represent a crucial junction of variables that call for caution and preventative action.

Nitrosamines crisis in pharmaceuticals - Insights on toxicological implications, root causes and risk assessment: A systematic review.

The presence of N-nitroso compounds, particularly N-nitrosamines, in pharmaceutical products has raised global safety concerns due to their significant genotoxic and mutagenic effects. This systematic review investigates their toxicity in active pharmaceutical ingredients (APIs), drug products, and pharmaceutical excipients, along with novel analytical strategies for detection, root cause analysis, reformulation strategies, and regulatory guidelines for nitrosamines. This review emphasizes the molecular toxicity of N-nitroso compounds, focusing on genotoxic, mutagenic, carcinogenic, and other physiological effects. Additionally, it addresses the ongoing nitrosamine crisis, the development of nitrosamine-free products, and the importance of sensitive detection methods and precise risk evaluation. This comprehensive overview will aid molecular biologists, analytical scientists, formulation scientists in research and development sector, and researchers involved in management of nitrosamine-induced toxicity and promoting safer pharmaceutical products.

Corrigendum to "Nitrosamines crisis in pharmaceuticals - Insights on toxicological implications, root causes and risk assessment: A systematic review" [J. Pharm. Anal. 14 (2024) 100919].

[This corrects the article DOI: 10.1016/j.jpha.2023.12.009.].