Preventive Service Usage and New Chronic Disease Diagnoses: Using PCORnet Data to Identify Emerging Trends, United States, 2018-2022.

Background: Data modernization efforts to strengthen surveillance capacity could help assess trends in use of preventive services and diagnoses of new chronic disease during the COVID-19 pandemic, which broadly disrupted health care access. Methods: This cross-sectional study examined electronic health record data from US adults aged 21 to 79 years in a large national research network (PCORnet), to describe use of 8 preventive health services (N = 30,783,825 patients) and new diagnoses of 9 chronic diseases (N = 31,588,222 patients) during 2018 through 2022. Joinpoint regression assessed significant trends, and health debt was calculated comparing 2020 through 2022 volume to prepandemic (2018 and 2019) levels. Results: From 2018 to 2022, use of some preventive services increased (hemoglobin A1c and lung computed tomography, both P < .05), others remained consistent (lipid testing, wellness visits, mammograms, Papanicolaou tests or human papillomavirus tests, stool-based screening), and colonoscopies or sigmoidoscopies declined (P < .01). Annual new chronic disease diagnoses were mostly stable (6% hypertension; 4% to 5% cholesterol; 4% diabetes; 1% colonic adenoma; 0.1% colorectal cancer; among women, 0.5% breast cancer), although some declined (lung cancer, cervical intraepithelial neoplasia or carcinoma in situ, cervical cancer, all P < .05). The pandemic resulted in health debt, because use of most preventive services and new diagnoses of chronic disease were less than expected during 2020; these partially rebounded in subsequent years. Colorectal screening and colonic adenoma detection by age group aligned with screening recommendation age changes during this period. Conclusion: Among over 30 million patients receiving care during 2018 through 2022, use of preventive services and new diagnoses of chronic disease declined in 2020 and then rebounded, with some remaining health debt. These data highlight opportunities to augment traditional surveillance with EHR-based data.

Lessons Learned From a Peer-Supported Differentiated Care and Nutritional Supplementation for People With TB in a Southern Indian State.

Two critical components of patient support systems for people with TB are regular counseling and locally managed nutritional support. As part of an ongoing differentiated TB care initiative called Tamil Nadu Kasanoi Erappila Thittam (meaning TB death-free initiative in Tamil, TN-KET) to reduce TB deaths, adults with TB with very severe undernutrition, respiratory insufficiency, or poor performance status are identified at diagnosis (triage-positive) and prioritized for referral, comprehensive clinical assessment, and inpatient care. Between January and June 2023, in 6 districts, a pilot exercise was conducted in which trained TB survivors, known as TB champions, provided baseline counseling and additional counseling (if required) to triage-positive people with TB at diagnosis. Additionally, people with TB with severe undernutrition were prioritized for nutritional supplementation for at least 3 months. Among 652 people with TB who were triage-positive at diagnosis, the program staff shared details of 145 (22%), and all were counseled by TB champions (baseline counseling). Program staff identified 74 (11%) triage-positive people with TB who required additional counseling (i.e., those refusing referral or admission or continued admission), and 71 (96%) were counseled by TB champions. Among these, 54 (76%) were admitted or readmitted and successfully discharged. In addition, among 1,042 people with TB with severe undernutrition, program staff shared details of 390 (38%), of which 60% received nutritional supplementation through the efforts of TB champions. We conclude that TB champions were able to provide quality and timely peer support through direct counseling and by mobilizing local resources for nutritional support. The engagement of TB champions can be further strengthened by establishing robust coordination mechanisms with the TB program. Lessons from this pilot will contribute to the Tamil Nadu State TB Cell's plans to expand the role of TB champions and enhance community participation to end TB in India.

Elevated Cortisol Levels and Manic Symptoms in a 16-Year-Old Female: A Case Report.

This case report presents the clinical presentation, diagnosis, and management of a 16-year-old female with elevated cortisol levels who was diagnosed with mania. The patient exhibited symptoms consistent with a manic episode, including extreme euphoria, decreased need for sleep, impulsivity, and heightened irritability. Laboratory investigations revealed an elevated morning cortisol level, prompting further psychiatric evaluation. A diagnosis of bipolar I disorder, manic episode, was made based on established criteria. The patient was initiated on mood stabilizers and antipsychotic medications alongside psychoeducation for the patient and her family. This case underscores the potential association between cortisol dysregulation and mood disorders, highlighting the importance of comprehensive assessment and personalized treatment approaches in adolescents with bipolar disorder. Further research is needed to elucidate the underlying mechanisms linking cortisol dysregulation and mood disturbances and explore novel therapeutic interventions targeting hypothalamic-pituitary-adrenal axis dysfunction.

Identifying Myoclonic Epilepsy Misdiagnosed as Psychogenic Nonepileptic Seizures: Challenges in Differential Diagnosis.

Psychogenic nonepileptic seizures (PNES) and epileptic seizures often present with similar clinical manifestations. This case report describes the diagnostic journey of a 24-year-old female initially diagnosed with PNES but later found to have myoclonic epilepsy upon comprehensive evaluation. The patient presented with recurrent episodes characterized by sudden loss of awareness, jerking movements, and urinary incontinence, often triggered by stressors. Initial assessment, including video-electroencephalography (EEG) monitoring, did not reveal epileptiform activity, leading to the provisional diagnosis of PNES. However, the persistence of symptoms and doubts regarding the diagnosis prompted further investigation, which uncovered generalized spike-and-wave discharges on repeat EEG studies. The diagnosis of myoclonic epilepsy was established based on these findings, and treatment with valproate resulted in a significant reduction in seizure frequency. This case underscores the importance of a thorough evaluation in distinguishing between seizure disorders and psychogenic manifestations, emphasizing the need for collaborations between neurology and psychology disciplines for accurate diagnosis and management.

A Rare Presentation of Delusional Parasitosis With Koro-Like Syndrome.

Delusional parasitosis (DP) with Koro-like syndrome poses a complex clinical challenge, demanding a comprehensive and empathetic approach from healthcare professionals. This exceptional combination of fixed beliefs about infestation and experiences of genital retraction can profoundly impact patients' well-being and daily functioning. The associated stigma and misconceptions further compound the difficulties faced by individuals struggling with these co-occurring conditions. Given the rarity of encountering both conditions simultaneously, navigating the diagnosis and treatment of delusional parasitosis with Koro-like syndrome requires a thorough understanding of its multifaceted nature. Embracing a holistic strategy encompassing psychoeducation, psychotherapy, and pharmacological interventions is essential for effectively addressing these dual conditions.

Quality of comprehensive assessment among severely ill TB patients referred after triaging in southern India.

To reduce TB deaths, Tamil Nadu, a southern Indian state, implemented the first state-wide differentiated TB care strategy starting April 2022. Triage-positive severely ill patients are prioritised for comprehensive assessment and inpatient care. Routine program data during October-December 2022 revealed that documentation of total score after comprehensive assessment was available in only 39%, possibly indicating poor quality of comprehensive assessment. We confirmed this using operational research. The case record form to record comprehensive assessment was used only in 26% and among these, the completeness and correctness in filling out the form were sub-optimal. There is a clear need to enhance the quality of comprehensive assessments.

Depuis avril 2022, le Tamil Nadu, un État du sud de l'Inde, a mis en œuvre la première stratégie de soins différenciés pour la TB à l'échelle de l'État afin de réduire le nombre de décès dus à la TB. Les personnes gravement malades ayant obtenu un résultat positif au triage sont prioritaires pour une évaluation complète et des soins hospitaliers. Les données du programme de routine entre octobre et décembre 2022 ont révélé que la documentation du score total après l'évaluation complète n'était disponible que dans 39% des cas, ce qui pourrait indiquer une mauvaise qualité de l'évaluation complète. Nous l'avons confirmé par le biais d'une recherche opérationnelle. Le formulaire de dossier pour enregistrer l'évaluation complète n'a été utilisé que dans 26% des cas et, parmi ceux-ci, l'exhaustivité et l'exactitude du remplissage du formulaire n'étaient pas optimales. Il est manifestement nécessaire d'améliorer la qualité de l'évaluation complète.

A Bird's-Eye Perspective: An Unusual Case of Very Late-Onset Schizophrenia-Like Psychosis With Visual Hallucinations Included in Its Manifestations Versus the Dementia Prodrome.

Very late-onset schizophrenia-like psychosis (VLOSLP) is still a paradox; certain characteristics such as episodic progression of psychosis including delusions and hallucinations involving various modalities, as well as the absence of negative symptoms, are strongly predictive of VLOSLP. We describe an interesting case of a 61-year-old male who presented with a second episode of psychosis along with mild to moderate cognitive impairment like having difficulty in buttoning for over eight months at our tertiary care hospital. Previously, during the first episode, he was treated by a private practitioner; adequate doses for an adequate duration of two atypical antipsychotics were given; and up to 25% global improvement was reported by the caregiver. During the current episode, he experienced delusions, in which he had a conviction that a "WIFI" was capable of "thought-making" functions. During the past four months, his delusions exacerbated and were accompanied by hallucinations of other modalities, like visual and kinesthetic hallucinations, which profoundly impacted his daily life. He used to hear voices. While listening to the voices, he also experienced voices coming out of his mouth. All these were experienced by him in clear consciousness daily for a few hours. All plausible medical causes of late-onset psychosis, such as neuroinflammatory/immunological disorders, were ruled out. Neuroimaging revealed T2-weighted image (T2WI)/fluid-attenuated inversion recovery (FLAIR) hyperintensity in bilateral subcortical and periventricular deep white matter, suggestive of small vessel ischemic changes in the brain. The diagnosis of VLOSLP is completely rationalized by evidence-based medicine. Hence, the role of cerebrovascular risk factors, as well as age-related neurobiological processes, in the pathogenesis of VLOSLP is discussed. Future research ought to emphasize identifying a particular biomarker that would be highly predictive for accurately diagnosing VLOSLP and giving it an identity to separate it from various overlapping clinical conditions such as dementia with Lewy bodies (DLB) and other types of dementia with psychosis so that the patient can be given specific treatment.

Association between Usage of Prophylactic AYUSH Medicines and Disease Severity in COVID-19 Patients: A Retrospective Cohort Study.

BACKGROUND: Prior vaccination is often studied for its impact on individuals' post-infection prognosis. Ayurveda, Yoga, Unani, Siddha and Homeopathy (AYUSH) medicines, advised by the Government of India as prophylaxis during the first wave of the coronavirus disease 2019 (COVID-19) pandemic, were consumed by the masses in 2020. A study was therefore undertaken to observe any association between the prior usage of AYUSH prophylactic medicines and post-infection severity as reported by recovered COVID-19 individuals. METHODS: This was a retrospective, multi-centre, cohort study conducted in 21 cities of India from 5th August to 30th November 2020. Data from recovered COVID-19 patients, of either sex or any age, captured information about AYUSH prophylactic medicines intake prior to infection, disease severity, symptomatology, duration of complaints, etc. The study participants were grouped into AYUSH intake and non-intake. Primary composite outcome was the disease clinical course. Secondary clinical outcomes were the rate of and time to clinical recovery. RESULTS: Data of 5,023 persons were analysed. Ayurveda or homeopathic prophylactic medicines were consumed by more than half of the study participants: that is, 56.85% (n = 1,556) and 56.81% (n = 1,555) respectively. The overall adjusted protective effect (PE) of AYUSH prophylactic intake against moderate/severe forms of COVID-19 disease was 56.7% (95% confidence interval [CI], 48.7 to 63.50; p < 0.001). Adjusted PE for homeopathy and Siddha was 52.9% (95% CI, 42.30 to 61.50; p < 0.001) and 59.8% (95% CI, 37.80 to 74.10; p < 0.001), respectively. A statistically significant association was found between AYUSH prophylactic medicine intake and clinical recovery more frequently by the 3rd day of illness (χ2 = 9.01; p = 0.002). Time to resolution of symptoms in the AYUSH intake group was on average 0.3 days earlier than in the non-intake group (p = 0.002). CONCLUSION: AYUSH prophylactics were associated with statistically significant levels of protection against COVID-19 disease severity. Amongst these, previous intake of homeopathy or Siddha medicines was associated with some protection against moderate/severe illness and with a somewhat quicker clinical recovery. Prospective studies with experimental research design are needed to validate the findings of this study. STUDY REGISTRATION: Clinical Trials Registry-India (CTRI/2020/08/027000).

The Association between Blood Test Trends and Undiagnosed Cancer: A Systematic Review and Critical Appraisal.

Clinical guidelines include monitoring blood test abnormalities to identify patients at increased risk of undiagnosed cancer. Noting blood test changes over time may improve cancer risk stratification by considering a patient's individual baseline and important changes within the normal range. We aimed to review the published literature to understand the association between blood test trends and undiagnosed cancer. MEDLINE and EMBASE were searched until 15 May 2023 for studies assessing the association between blood test trends and undiagnosed cancer. We used descriptive summaries and narratively synthesised studies. We included 29 articles. Common blood tests were haemoglobin (24%, n = 7), C-reactive protein (17%, n = 5), and fasting blood glucose (17%, n = 5), and common cancers were pancreatic (29%, n = 8) and colorectal (17%, n = 5). Of the 30 blood tests studied, an increasing trend in eight (27%) was associated with eight cancer types, and a decreasing trend in 17 (57%) with 10 cancer types. No association was reported between trends in 11 (37%) tests and breast, bile duct, glioma, haematological combined, liver, prostate, or thyroid cancers. Our review highlights trends in blood tests that could facilitate the identification of individuals at increased risk of undiagnosed cancer. For most possible combinations of tests and cancers, there was limited or no evidence.

Journey of Marijuana From "Folk Tales" to "Doors of Justice": A Comprehensive Review.

This comprehensive review delves into the intricate journey of marijuana in India, tracing its historical and cultural significance from ancient times to the present day. Despite its deep-rooted presence in religious rituals, traditional medicine, and cultural festivities, marijuana faces stringent prohibition under the Narcotic Drugs and Psychotropic Substances Act 1985. This review critically examines the current legal framework, highlighting its societal impacts and limitations. Through an evidence-based analysis, it advocates for a reevaluation of marijuana laws to align with contemporary realities, promoting public health, social equity, and economic development. By envisioning a future of evidence-based regulation and innovation, India can unlock the full potential of marijuana as a "miracle crop" for the betterment of its people and society.

Bridging the Gap: A Holistic View of Personality Factors in Individuals With and Without Alcohol Use.

This comprehensive review examines the intricate interplay between personality factors and alcohol use, shedding light on the dynamic relationship that shapes the initiation, progression, and outcomes of alcohol-related behaviors. The exploration encompasses vital personality traits such as sensation seeking, impulsivity, neuroticism, extroversion, agreeableness, conscientiousness, and openness to experience. The bidirectional nature of this association is underscored, emphasizing how personality influences and is influenced by alcohol consumption patterns. Protective personality factors, including resilience, emotional regulation, and social support, are identified as crucial elements in mitigating the risk of alcohol use disorders (AUDs). The implications for clinical practice advocate for tailored interventions that address individual personality profiles, while policy considerations highlight the need for targeted prevention efforts that acknowledge the diverse ways individuals respond to alcohol use. Furthermore, a call for future research emphasizes emerging perspectives, improved methodologies, and ongoing exploration of intervention strategies to advance our understanding of this complex relationship and refine approaches for prevention and treatment. As we navigate this evolving field, the insights gleaned hold promise for shaping more compelling and nuanced interventions to address the diverse needs of individuals affected by AUDs.

Navigating the Shadows: A Comprehensive Review of Suicide in the Geriatric Population.

This review critically examines the complex landscape of suicide within the geriatric population, defined as individuals aged 65 and older. By synthesizing existing research, we elucidate critical findings related to the prevalence, risk factors, and challenges associated with suicide in this demographic. Social isolation, mental health issues, and the intricate psychosocial dimensions of ageing emerge as pivotal factors contributing to the vulnerability of older individuals. The conclusion underscores a compelling call to action, urging collaborative efforts from healthcare professionals, policymakers, and communities to implement targeted prevention strategies. Our vision for the future involves building a supportive and resilient community for the geriatric population, emphasizing age-friendly policies, robust social support networks, and destigmatizing mental health discussions. Through this comprehensive exploration, we aim to contribute to a deeper understanding of suicide in the geriatric population and inspire effective interventions that prioritize the well-being and dignity of older individuals.

Exploring Body Image Dissatisfaction and Psychiatric Co-morbidities in Rural India: A Comprehensive Review.

This comprehensive review examines the intricate landscape of body image dissatisfaction (BID) in rural India, shedding light on the multifaceted factors influencing individual perceptions and societal expectations. Delving into cultural nuances, economic disparities, and gender-specific experiences, the study highlights the pervasive nature of BID across diverse age groups. Unveiling the complex interplay between BID and psychiatric co-morbidities, such as depression and anxiety, underscores the urgency of integrated mental health interventions. The review concludes with a resounding call to action for policymakers, healthcare professionals, and communities. It advocates for culturally sensitive mental health policies, targeted healthcare training, and community-driven initiatives to foster environments conducive to positive body image and mental well-being. By acknowledging these challenges and committing to collaborative solutions, this review aims to contribute to developing comprehensive strategies that address BID in rural India and pave the way for healthier and more resilient communities.

Prolinyl Phosphoramidates of Nucleotides with Increased Reactivity.

Nucleoside monophosphates (NMPs) are the subunits of RNA. They are incorporated into growing complementary strands when sequences are copied in enzyme-free reactions using organic leaving groups at the phosphates. Amino acids are rarely considered as leaving groups, but proline can act as a leaving group when N-linked to NMPs, so that prolinyl NMPs hydrolyze in aqueous buffer at 37 °C, with half-life times as short as 2.4 h, and they act as monomers in enzyme-free primer extension. Still, their level of reactivity is insufficient for practical purposes, requiring months for some extensions. Herein we report the synthesis of eight substituted prolinyl AMPs together with seven related compounds and the results of a study of their reactivity. A δ-carboxy prolinyl NMP was found to be converted with a half-life time of just 11 min in magnesium-free buffer, and a δ-isopropyl prolinyl NMP was shown to react sevenfold faster than its prolinyl counterpart in enzyme-free genetic copying of RNA. Our results indicate that both anchimeric and steric effects can be employed to increase the reactivity of aminoacidyl nucleotides, i.e. compounds that combine two fundamental classes of biomolecules in one functional entity.

Interferon-epsilon is a novel regulator of NK cell responses in the uterus.

The uterus is a unique mucosal site where immune responses are balanced to be permissive of a fetus, yet protective against infections. Regulation of natural killer (NK) cell responses in the uterus during infection is critical, yet no studies have identified uterine-specific factors that control NK cell responses in this immune-privileged site. We show that the constitutive expression of IFNε in the uterus plays a crucial role in promoting the accumulation, activation, and IFNγ production of NK cells in uterine tissue during Chlamydia infection. Uterine epithelial IFNε primes NK cell responses indirectly by increasing IL-15 production by local immune cells and directly by promoting the accumulation of a pre-pro-like NK cell progenitor population and activation of NK cells in the uterus. These findings demonstrate the unique features of this uterine-specific type I IFN and the mechanisms that underpin its major role in orchestrating innate immune cell protection against uterine infection.

Systemic and ocular outcomes in patients with young-onset type 2 diabetes.

PURPOSE: To analyze the systemic and ocular outcomes in patients with young-onset type 2 diabetes (YO-DM2) based on grade of presenting diabetic retinopathy (DR). METHODS: Retrospective cohort study analysis of empaneled patients with type 2 diabetes <40 years old with retinopathy screening within the Los Angeles Department of Health Services between 01/01/2017-07/01/2021 were included. Patients were stratified based on presenting severity of DR determined on fundus photographs or clinical examination. Patient's systemic co-morbidities and ocular outcomes were then compared across each group. Procedural (e.g. intravitreal injections) and surgical interventions (e.g. pars plana vitrectomy) were documented as performed by the treating physician. RESULTS: 2795 patients were screened from 12,456 patients diagnosed with diabetes younger than age 40 (22.4 %). Of these, 1496 patients were diagnosed with type 2 DM. 1084 (72.4 %) of patients presented without DR, 307 (20.5 %) presented with non-proliferative diabetic retinopathy (NPDR), and 105 (7.0 %) of patients presented with proliferative diabetic retinopathy (PDR). Increasing presenting diabetic retinopathy severity was associated with longer duration of diabetes, greater systemic comorbidities (e.g. diabetic foot disease, neuropathy, chronic kidney or end stage renal disease), worse baseline and final visual acuity, and required more procedural and surgical interventions. CONCLUSIONS: Worse presenting DR severity in patients young-onset type 2 diabetes was associated with greater comorbid systemic and ocular disease with worse visual acuity outcomes. <1 % of patients without diabetic retinopathy or with mild NPDR were likely to progress to PDR. Diabetic kidney disease was an independent risk factor for developing neovascular glaucoma and retinal detachments. Prompt evaluation and intervention in patients with YO-DM2 may help reduce the associated systemic and ocular morbidity.

Biotics: An emerging food supplement for health improvement in the era of immune modulation.

The involvement of the commensal microbiota in immune function is a multifold process. Biotics, such as probiotics, prebiotics, synbiotics, and paraprobiotics, have been subjected to animal and human trials demonstrating the association between gut microbes and immunity biomarkers leading to improvement in overall health. In recent years, studies on human microbiome interaction have established the multifarious role of biotics in maintaining overall health. The consumption of biotics has been extensively reported to help in maintaining microbial diversity, enhancing gut-associated mucosal immune homeostasis, and providing protection against a wide range of lifestyle disorders. However, the establishment of biotics as an alternative therapy for a range of health conditions is yet to be ascertained. Despite the fact that scientific literature has demonstrated the correlation between biotics and immune modulation, most in vivo and in vitro reports are inconclusive on the dosage required. This review provides valuable insights into the immunomodulatory effects of biotics consumption based on evidence obtained from animal models and clinical trials. Furthermore, we highlight the optimal dosages of biotics that have been reported to deliver maximum health benefits. By identifying critical research gaps, we have suggested a roadmap for future investigations to advance our understanding of the intricate crosstalk between biotics and immune homeostasis.

The vagus nerve in cardiovascular physiology and pathophysiology: From evolutionary insights to clinical medicine.

The parasympathetic nervous system via the vagus nerve exerts profound influence over the heart. Together with the sympathetic nervous system, the parasympathetic nervous system is responsible for fine-tuned regulation of all aspects of cardiovascular function, including heart rate, rhythm, contractility, and blood pressure. In this review, we highlight vagal efferent and afferent innervation of the heart, with a focus on insights from comparative biology and advances in understanding the molecular and genetic diversity of vagal neurons, as well as interoception, parasympathetic dysfunction in heart disease, and the therapeutic potential of targeting the parasympathetic nervous system in cardiovascular disease.

Genomic and epigenomic analysis of plasma cell-free DNA identifies stemness features associated with worse survival in AR -altered lethal prostate cancer.

Metastatic castration-resistant prostate cancer (mCRPC) resistant to androgen receptor (AR)-targeted agents is often lethal. Unfortunately, biomarkers for this deadly disease remain under investigation, and underpinning mechanisms are ill-understood. Here, we applied deep sequencing to ∼100 mCRPC patients prior to the initiation of first-line AR-targeted therapy, which detected AR /enhancer alterations in over a third of patients, which correlated with lethality. To delve into the mechanism underlying why these patients with cell-free AR /enhancer alterations developed more lethal prostate cancer, we next performed genome-wide cell-free DNA epigenomics. Strikingly, we found that binding sites for transcription factors associated with developmental stemness were nucleosomally more accessible. These results were corroborated using cell-free DNA methylation data, as well as tumor RNA sequencing from a held-out cohort of mCRPC patients. Thus, we validated the importance of AR /enhancer alterations as a prognostic biomarker in lethal mCRPC, and showed that the underlying mechanism for lethality involves reprogramming developmental states toward increased stemness.