Type 2 diabetes and health-related quality of life among older Medicare beneficiaries: The mediating role of sleep.

OBJECTIVE: To examine mediating effects of sleep quality and duration on the association between T2D and QoL among Medicare beneficiaries 65+. METHODS: Data from the Medicare Health Outcome Survey (2015-2020) were used. The outcome was QoL (physical and mental health component-summary scores [PCS and MCS]) measured by the Veterans-Rand-12. The main predictor was diagnosed T2D. Mediators were sleep duration and sleep quality. The effect modifier was race/ethnicity. Structural Equation Modeling was used to estimate moderated-mediating effects of sleep quality and duration across race/ethnicity. RESULTS: Of the 746,400 Medicare beneficiaries, 26.7% had T2D, and mean age was 76 years (SD ± 6.9). Mean PCS score was 40 (SD ± 12.2), and mean MCS score was 54.0 (SD ± 10.2). Associations of T2D with PCS and MCS were negative and significant. For all racial/ethnic groups, those with T2D reported lower PCS. For White, Black, Asian, and Hispanic beneficiaries only, those with T2D reported lower MCS. The negative impact of T2D on PCS and MCS was mediated through sleep quality, especially very bad sleep quality. CONCLUSION: Improving sleep may lead to improvement in QoL in elderly adults with T2D.

The variation in preventable hospitalization in patients with type 2 diabetes in Kentucky before and after the Medicaid expansion.

BACKGROUND: Hospitalizations are more resource intensive and expensive than outpatient care. Therefore, type 2 diabetes-related preventable hospitalization are a major topic of research efficiency in the healthcare system. OBJECTIVES: Analyze county level variation in type 2 diabetes-related preventable hospitalization rates in Kentucky before the Medicaid expansion (2010-2013) and after the Medicaid expansion (2014-2017). DESIGN: Geographic mapping and cluster analysis. SETTING: Data for a state of the United States of America. METHODS: We used the KID data to generate geographic mapping for type 2 diabetes-related preventable hospitalizations to visualize rates. We included all Kentucky discharges of age 18 years and older with the ICD9/10 principal diagnosis code for type 2 diabetes. Then, we conducted cluster analysis techniques to compare county-level variation in type 2 diabetes-related preventable hospitalization rates across Kentucky counties pre- and post-Medicaid expansion. MAIN OUTCOME AND MEASURES: County type 2 diabetes-related preventable hospitalization pre- and post-Medicaid expansion. RESULTS: From 2010-2017, type 2 diabetes-related preventable hospitalization discharge rates reduced significantly in the period of the post-Medicaid expansion (P=.001). The spatial statistics analysis revealed a significant spatial clustering of counties with similar rates of type 2 diabetes-related preventable hospitalization in the south, east, and southeastern Kentucky pre- and post-Medicaid expansion (positive z-score and positive Moran's Index value (P>.05). Also, there was a significant clustering of counties with low type 2 diabetes-related preventable hospitalization rates in the north, west, and central regions of the state pre-Medicaid expansion and post-Medicaid expansion (positive z-score and positive Moran's Index value (P>.05). CONCLUSION: Kentucky counties in the southeast have experienced a significant clustering of highly avoidable hospitalization rates during both periods. Focusing on the vulnerable counties and the economic inequality in Kentucky could lead to efforts to lowering future type 2 diabetes-related preventable hospitalization rates. LIMITATIONS: We used de-identified data which does not provide insights into the frequency of hospitalizations per patient. An individual patient may be hospitalized several times and counted as several individuals.

Diagnostic Accuracy of Fine Needle Aspiration Cytology as Compared to Histopathology in Parotid Gland Swelling.

BACKGROUND: The diagnosis of parotid swelling is challenging and investigations like imaging and needle aspiration cytology are helpful. The objective of this study was to determine the diagnostic accuracy of fine needle aspiration cytology (FNAC) as compared to the histopathology in parotid gland swelling. METHODS: It was a descriptive cross sectional study carried out in the Department of ENT-Head and Neck Surgery, Tribhuvan University Teaching Hospital, Institute of Medicine, Kathmandu by reviewing the medical record charts of the patients who had undergone surgery for parotid lesions during the study period of seven and half years. All patients whose fine needle aspiration cytology and histopathology reports were available were included in the study. The data were presented as mean, standard deviation, ratio and percentages. Microsoft excel was used for data analysis. RESULTS: There were 75 patients included in the study. The age ranged from nine years to 78 years and the mean age being 38.3 17.42 years. The male to female ratio was 1:1.78. The concordance rate between fine needle aspiration cytology and histopathology was 82.7%. The sensitivity and specificity of the fine needle aspiration cytology were 80% and 95% respectively. Similarly, the positive predictive and negative predictive values were 84% and 93% respectively. The diagnostic accuracy of the fine needle aspiration cytology was 91% for the parotid swelling in our study. CONCLUSIONS: The diagnostic accuracy of fine needle aspiration cytology for parotid swellings in our study was excellent. The result of fine needle aspiration cytology is helpful in deciding management plan for parotid lesions.

[PATIENT BLOOD MANAGEMENT - IT IS IMPOSSIBLE TO IGNORE THIS POLICY].

INTRODUCTION: Anemia is common and is an independent risk factor for morbidity and mortality, especially in pre- (30-40% of patients undergoing major surgery) or post-operative anemia (up to 80-90%). Using World Health Organization (WHO) criteria, in 2010 one quarter of the global population was anemic (1.9 billion people) and iron deficiency anemia (IDA( was and still remains the most common type of anemia worldwide, accounting for more than half of the total anemia burden. In a systematic analysis for the Global Burden of Disease Study 2016, IDA was the fourth leading cause of years lived with disability, particularly in women, thus highlighting prevention and treatment of IDA as a major public health goal. Red blood cells (RBC) transfusion is a common therapeutic intervention with considerable variation in clinical practice. More than 85 million units packed RBC (PRBC) are transfused annually worldwide. The principal indication for blood transfusion (BT) is anemia, yet a significant percentage of RBC transfusions are inappropriately overused. For many physicians and clinicians, across many different specialties, BT is still considered to be the first-line treatment when facing anemia. The Joint Commission along with the American Medical Association has included BT in a list of the five most overused therapeutic procedures in the United States. Restrictive blood transfusion (RBT) is an evidence-based policy, at least as effective, if not superior to the liberal policy of BT. Patient blood management (PBM) is a patient-centered systematic, evidence-based approach, supported by RBT. In this article we analyze the factors which influence the implementation of PBM.

Variation between surgeons in rate of reoperation after horizontal strabismus surgery among Medicare beneficiaries: associations with patient and surgeon characteristics and adjustable sutures.

Objective: To quantify variation between surgeons in reoperation rates after horizontal strabismus surgery, and to explore associations of reoperation rate with surgical techniques, patient characteristics, and practice type and volume. Methods: Fee-for-service payments in a national database to providers for Medicare beneficiaries having strabismus surgery on horizontal muscles between 2012 and 2020 were analyzed retrospectively to identify same calendar year reoperations. Multivariable linear regression was used to determine predictors of each surgeon's reoperation rate. Results: The reoperation rate for 1-horizontal muscle surgery varied between 0.0% and 30.8% among 141 surgeons. Just 7.8% of surgeons contributed over half of the reoperation events for 1-horizontal muscle surgery, due to the presence of high-volume surgeons with high reoperation rates. Surgeon seniority, gender, surgery volume, and use of adjustable sutures were not independently associated with surgeon reoperation rate. We explored associations of reoperation with patient characteristics, such as age and poverty. Surgeons in the South tended to have a higher reoperation rate (p=0.03) in a multivariable model. However, the multivariable model could only explain 16.3% of the inter-surgeon variation in reoperation rate for 1-horizontal muscle surgery. Discussion: Strabismus surgery is similar to other areas of medicine, in which large variations in outcomes between surgeons are observed. Future work can be directed towards explaining this variation. Conclusions: Patient-level analyses that fail to consider variation between surgeons will be dominated by a small number of high-reoperation, high-volume surgeons. Order-of-magnitude variations exist in reoperation rates among strabismus surgeons, the cause of which is largely unexplained.

The Promise of Therapeutic Psilocybin: An Evaluation of the 134 Clinical Trials, 54 Potential Indications, and 0 Marketing Approvals on ClinicalTrials.gov.

Introduction: Psilocybin, a tryptamine psychedelic, has been touted in the media both historically and recently as a potential game-changing mental health therapeutic. ClinicalTrials.gov has over one hundred and thirty psilocybin clinical trials listed covering the last twenty years. The single most important aspect of any therapeutic is to gain approval for marketing and thus enter the real-world phase of development. A typical new chemical entity progresses from inception to US Food and Drug Administration (FDA) approval in approximately 12 years and seeks approval for a single indication. Methods: An observational study was conducted with the available information on the ClinicalTrials.gov site to observe the extent of progress made demonstrating the clinical utility of psilocybin. Results: The results showed 134 psilocybin trials typically unblinded studies of 10-20 participants, recruited over years at a single site. Additionally, there have been only three advanced trials (1 Phase 2/3 and 2 Phase 3) submitted, and only in the last two years. Discussion: The hundreds of psilocybin clinical trials initiated over the past twenty years comprising a myriad of potential indications may actually be slowing this potential game-changing mental health therapeutic agent's approval and is costing excessive amounts of capital. To fully evaluate the actual potential of psilocybin, purposeful clinical trials need to be designed well, executed efficiently, and analyzed utilizing sequential and statistically valid processes for each potential indication. This will require a change from the current exploratory forays to defined, well-funded, sequential pharmaceutical development practices, including adequate and appropriate blinding of studies, statistical design to determine the number of participants and more importantly, professional expertise in conducting multicenter trials. Unfortunately, these results demonstrate little real progress towards FDA approval of psilocybin and a field with no clear direction forward.

Assessing the quality and reliability of YouTube videos as a source of information on inflammatory back pain.

Background: Inflammatory back pain is a chronic condition with localized pain, particularly in the axial spine and sacroiliac joints, that is associated with morning stiffness and improves with exercise. YouTube is the second most frequently used social media platform for accessing health information. This study sought to investigate the quality and reliability of YouTube videos on inflammatory back pain (IBP). Methods: The study design was planned as cross-sectional. A search was conducted using the term "inflammatory back pain," and the first 100 videos that met the inclusion criteria were selected on October 19, 2023. The data of the videos selected according to the inclusion and exclusion criteria in the study settings were examined. Videos with English language, with audiovisual content , had a duration >30 s, non-duplicated and primary content related to IBP were included in the study. A number of video parameters such as the number of likes, number of views, duration, and content categories were assessed. The videos were assessed for reliability using the Journal of the American Medical Association (JAMA) Benchmark criteria and the DISCERN tool. Quality was assessed using the Global Quality Score (GQS). Continuous variables were checked for normality of distribution using Shapiro-Wilk test and Kolmogorov-Smirnov test. Kruskal-Wallis test and Mann-Whitney U test were used to analyze the continuous data depending on the number of groups. Categorical data were analyzed using Pearson's chi-square test. Results: Reliability assessment based on JAMA scores showed 21% of the videos to have high reliability. Quality assessment based on GQS results showed 19% of the videos to have high quality. JAMA, DISCERN, and GQS scores differed significantly by source of video (p < 0.001, < 0.001, and = 0.002, respectively). Video duration had a moderate positive correlation with scores from the GQS (r = 0.418, p < 0.001), JAMA (r = 0.484, p < 0.001), and modified DISCERN (r = 0.418, p < 0.001). Conclusion: The results of the present study showed that YouTube offers videos of low reliability and low quality on inflammatory back pain. Health authorities have a responsibility to protect public health and should take proactive steps regarding health information shared on social media platforms.

Exploring the association between dietary Inflammatory Index and chronic pain in US adults using NHANES 1999-2004.

Chronic pain, a substantial public health issue, may be influenced by dietary patterns through systemic inflammation. This cross-sectional study explored the association between Dietary Inflammatory Index (DII) and chronic pain among 2581 American adults from NHANES data. The DII, ranging from - 4.98 to 4.69, reflects the inflammatory potential of the diet, with higher scores indicating greater pro-inflammatory capacity. Our findings showed no significant association between the continuous DII score and chronic pain prevalence. However, a nonlinear relationship emerged. When the DII was categorized, a significant association between higher DII scores (DII ≥ 2.5) and chronic pain prevalence was observed. The analysis uncovered a U-shaped pattern, with an inflection point at a DII score of - 0.9, indicating an association between both low and high levels of dietary inflammation are associated with higher pain prevalence. This nuanced interaction between dietary inflammation and chronic pain indicates the possibility of incorporating dietary modification into pain management strategies and underscores the need for further research into the long-term effects of diet on chronic pain.

A Clinical Nurse Specialist in Home Healthcare.

PURPOSE: Opportunities and challenges in home healthcare are discussed from the perspective of a gerontological clinical nurse specialist who has served as an expert clinician, administrator, and compliance director of a home health agency in the Midwest United States. DESCRIPTION: Home-based nursing care requires a distinct set of knowledge and skills centered on the home environment and the way the home health patient responds emotionally and physically to become confident and self-sufficient. A Theoretical Framework for Home-Based Professional Nursing Practice is presented identifying the 6 concepts (primacy of home, patient authority, patient self-management, caregivers as collaborators, interprofessional clinical team collaboration, nurse autonomy) that are building blocks to describe the experience of patients in their homes and interactions with providers. The quality of clinical care and documentation influence reimbursement for care and the financial survival of the home health agency. OUTCOME: Six management priorities both within the administrative office and the clinical teams are highlighted to improve quality of care, promote efficiency, and retain staff. CONCLUSION: Exciting opportunities are available for the clinical nurse specialist in home-based care.

Assessing Laboratory Method Validations for Informing Inference Across Survey Cycles in the National Health and Nutrition Examination Survey.

Background and objectives Laboratory tests conducted on survey respondents' biological specimens are a major component of the National Health and Nutrition Examination Survey. The National Center for Health Statistics' Division of Health and Nutrition Examination Surveys performs internal analytic method validation studies whenever laboratories undergo instrumental or methodological changes, or when contract laboratories change. These studies assess agreement between methods to evaluate how methodological changes could affect data inference or compromise consistency of measurements across survey cycles. When systematic differences between methods are observed, adjustment equations are released with the data documentation for analysts planning to combine survey cycles or conduct a trend analysis. Adjustment equations help ensure that observed differences from methodological changes are not misinterpreted as population changes. This report assesses the reliability of statistical methods used by the Division of Health and Nutrition Examination Surveys when conducting method validation studies to address concerns that adjustment equations are being overproduced (recommended too frequently). Methods Public-use 2017-2018 National Health and Nutrition Examination Survey laboratory data were used to simulate "new" measurements for 120 analytic method validation studies. Blinded studies were analyzed to determine the final adjustment recommendation for each study using difference plots, descriptive statistics, t-tests, and Deming regressions. Final recommendations were compared with simulated difference types to assess how often spurious results were observed. Concordance estimates (concordance, misclassification, sensitivity, specificity, and positive and negative predictive values) informed assessments. Results Adjustment equations were appropriately recommended for 75.0% of the studies, over-recommended for 5.8%, under-recommended for 15.8%, and recommended with an inappropriate technique for 3.3%. Across simulated difference types, sensitivity ranged from 65.9% to 84.4% and specificity from 74.7% to 97.5%. Conclusions Findings from this report suggest that the current methodology used by the Division of Health and Nutrition Examination Surveys performs moderately well. Based on these data and analyses, underadjustment was more prevalent than overadjustment, suggesting that the current methodology is conservative.

Births: Final Data for 2022.

Objectives- This report presents 2022 data on U.S. births by selected characteristics. Trends in fertility patterns and maternal and infant characteristics are described. Methods-Descriptive tabulations based on birth certificates of the 3.67 million births registered in 2022 are shown by maternal age, live-birth order, race and Hispanic origin, marital status, tobacco use, prenatal care, source of payment for the delivery, method of delivery, gestational age, birthweight, and plurality. Selected data by mother's state of residence and birth rates also are shown. Trends for 2010 to 2022 are presented for selected items, and by race and Hispanic origin for 2016-2022. Results-A total of 3,667,758 births occurred in the United States in 2022, essentially unchanged from 2021. The general fertility rate declined 1% from 2021 to 56.0 births per 1,000 females ages 15-44 in 2022. The birth rate for females ages 15-19 declined 2% from 2021 to 2022; birth rates fell 7% for women ages 20-24, rose 1% to 5% for women ages 25-29 and 35-44, and rose 12% for women ages 45-49 (the first increase since 2016). The total fertility rate declined less than 1% to 1,656.5 births per 1,000 women in 2022. Birth rates declined for unmarried women but increased for married women from 2021 to 2022. Prenatal care beginning in the first trimester declined to 77.0% in 2022; the percentage of women who smoked during pregnancy declined to 3.7%. The cesarean delivery rate was unchanged in 2022 (32.1%); Medicaid was the source of payment for 41.3% of births. The preterm birth rate declined 1% to 10.38%; the low birthweight rate rose 1% to 8.60%. The twin birth rate was unchanged in 2022 (31.2 per 1,000 births); the 2% decrease in the triplet and higher-order multiple birth rate.

Social media influences National Park visitation.

Visitation to National Parks in the United States increased by more than 25% since 2010, rising from roughly 70 to 90 million annual visitors. Anecdotes suggest that this increase was driven by the advent of social media in the early-to-mid 2010s, generating a new form of exposure for parks, and has led to concerns about overcrowding and degradation of environmental quality. However, there is little empirical evidence on the role of social media in influencing recreation decisions. Here, I construct a dataset on social media exposure (SME) for each National Park and relate that exposure to changes in visitation over the last two decades. High SME parks see visitation increase by 16 to 22% relative to parks with less exposure, which comes with a concomitant increase in revenue. Low SME parks have no, or negative, changes in visitation. These estimates account for unobserved park heterogeneity and are based on an instrumental variables strategy that predicts exposure with a park's online popularity prior to the social media era. Additional analysis suggests that recent social media posts that include media attachments increase visitation, while posts with negative sentiment reduce visitation. These results provide insight for the National Park Service-which faces more than $22 billion in deferred maintenance costs and is considering policy options to manage demand-as well as for management of recreation on other public lands.

Elements of successful NIH grant applications.

Is there a formula for a competitive NIH grant application? The Serenity Prayer may provide one: "Grant me the serenity to accept the things I cannot change, the ability to change the things I can, and the wisdom to know the difference." But how to tell the difference? In this Perspective, we provide an inclusive roadmap-elements of NIH funding. Collectively, we have over 30 y of peer review experience as NIH Scientific Review Officers in addition to over 30 y of program experience as NIH Program Officers. This article distills our NIH experience. We use Euclid's 13-book landmark, The Elements, as our template to humbly share what we learned. We have three specific aims: inform, guide, and motivate prospective applicants. We also address ways that support diversity and inclusion among applicants and young investigators in biomedical research. The elements we describe come from a wide range of sources. Some themes will be general. Some will be specific. All will be candid. The ultimate goal is a competitive application, serenity, and hopefully both.

Medicaid Eligibility Loss Among Dual-Eligible Beneficiaries Before and During COVID-19 Public Health Emergency.

Importance: Medicaid coverage loss can substantially compromise access to and affordability of health care for dual-eligible beneficiaries. The extent to which this population lost Medicaid coverage before and during the COVID-19 public health emergency (PHE) and the characteristics of beneficiaries more at risk for coverage loss are currently not well known. Objective: To assess the loss of Medicaid coverage among dual-eligible beneficiaries before and during the first year of the PHE, and to examine beneficiary-level and plan-level factors associated with heightened likelihood of losing Medicaid. Design, Setting, and Participants: This repeated cross-sectional study used national Medicare data to estimate annual rates of Medicaid loss among dual-eligible beneficiaries before (2015 to 2019) and during the PHE (2020). Individuals who were dual eligible for Medicare and Medicaid at the beginning of a given year and who continuously received low-income subsidies for Medicare Part D prescription drug coverage were included in the sample. Multivariable regression models were used to examine beneficiary-level and plan-level factors associated with Medicaid loss. Data analyses were conducted between March 2023 and October 2023. Exposure: Onset of PHE. Main Outcomes and Measures: Loss of Medicaid for at least 1 month within a year. Results: Sample included 56 172 736 dual-eligible beneficiary-years between 2015 and 2020. In 2020, most dual-eligible beneficiaries were aged over 65 years (5 984 420 [61.1%]), female (5 868 866 [59.9%]), non-Hispanic White (4 928 035 [50.3%]), full-benefit eligible (6 837 815 [69.8%]), and enrolled in traditional Medicare (5 343 537 [54.6%]). The adjusted proportion of dual-eligible beneficiaries losing Medicaid for at least 1 month increased from 6.6% in 2015 to 7.3% in 2019 and then dropped to 2.3% in 2020. Between 2015 and 2019, dual-eligible beneficiaries who were older (ages 55-64 years: -1.4%; 95% CI, -1.8% to -1.0%; ages 65-74 years: -2.0%; 95% CI, -2.5% to -1.5%; ages 75 and older: -4.5%; 95% CI, -5.0% to -4.0%), disabled (-0.8%; 95% CI, -1.1% to -0.6%), and in integrated care programs were less likely to lose Medicaid. In 2020, the disparities within each of these demographic groups narrowed significantly. Notably, while Black (0.6%; 95% CI, 0.2% to 0.9%) and Hispanic (0.7%; 95% CI, 0.3% to 1.2%) dual-eligible beneficiaries were more likely to lose Medicaid than their non-Hispanic White counterparts between 2015 and 2019, such gap was eliminated for Black beneficiaries and narrowed for Hispanic beneficiaries in 2020. Conclusions and Relevance: During the PHE, Medicaid coverage loss declined significantly among dual-eligible beneficiaries, and disparities were mitigated across subgroups. As the PHE unwinds, it is crucial for policymakers to implement strategies to minimize Medicaid coverage disruptions and racial and ethnic disparities, especially given that loss of Medicaid was slightly increasing over time before the PHE.

A Review of FDA-Approved Anti-HIV-1 Drugs, Anti-Gag Compounds, and Potential Strategies for HIV-1 Eradication.

Acquired immunodeficiency syndrome (AIDS) is an enormous global health threat stemming from human immunodeficiency virus (HIV-1) infection. Up to now, the tremendous advances in combination antiretroviral therapy (cART) have shifted HIV-1 infection from a fatal illness into a manageable chronic disorder. However, the presence of latent reservoirs, the multifaceted nature of HIV-1, drug resistance, severe off-target effects, poor adherence, and high cost restrict the efficacy of current cART targeting the distinct stages of the virus life cycle. Therefore, there is an unmet need for the discovery of new therapeutics that not only bypass the limitations of the current therapy but also protect the body's health at the same time. The main goal for complete HIV-1 eradication is purging latently infected cells from patients' bodies. A potential strategy called "lock-in and apoptosis" targets the budding phase of the life cycle of the virus and leads to susceptibility to apoptosis of HIV-1 infected cells for the elimination of HIV-1 reservoirs and, ultimately, for complete eradication. The current work intends to present the main advantages and disadvantages of United States Food and Drug Administration (FDA)-approved anti-HIV-1 drugs as well as plausible strategies for the design and development of more anti-HIV-1 compounds with better potency, favorable pharmacokinetic profiles, and improved safety issues.

Phytotherapy of Vulvovaginal Candidiasis: A Narrative Review.

Vulvovaginal candidiasis (VVC) is a real gynecological problem among women of reproductive age from 15 to 49. A recent analysis showed that 75% of women will have an occurrence at least once per year, while 5% are observed to have recurrent vaginal mycosis-these patients may become unwell four or more times a year. This pathology is caused in 85-90% of cases by fungi of the Candida albicans species. It represents an intractable medical problem for female patients due to pain and pruritus. Due to the observation of an increasing number of strains resistant to standard preparations and an increase in the recurrence of this pathology when using local or oral preferential therapy, such as fluconazole, an analysis was launched to develop alternative methods of treating VVC using herbs such as dill, turmeric, and berberine. An in-depth analysis of databases that include scientific articles from recent years made it possible to draw satisfactory conclusions supporting the validity of herbal therapy for the pathology in question. Although phytotherapy has not yet been approved by the Food and Drug Administration, it appears to be a promising therapeutic solution for strains that are resistant to existing treatments. There is research currently undergoing aimed at comparing classical pharmacotherapy and herbal therapy in the treatment of vaginal candidiasis for the purpose of increasing medical competence and knowledge for the care of the health and long-term comfort of gynecological patients.

Alzheimer's Amyloid Hypothesis and Antibody Therapy: Melting Glaciers?

The amyloid cascade hypothesis for Alzheimer's disease is still alive, although heavily challenged. Effective anti-amyloid immunotherapy would confirm the hypothesis' claim that the protein amyloid-beta is the cause of the disease. Two antibodies, aducanumab and lecanemab, have been approved by the U.S. Food and Drug Administration, while a third, donanemab, is under review. The main argument for the FDA approvals is a presumed therapy-induced removal of cerebral amyloid deposits. Lecanemab and donanemab are also thought to cause some statistical delay in the determination of cognitive decline. However, clinical efficacy that is less than with conventional treatment, selection of amyloid-positive trial patients with non-specific amyloid-PET imaging, and uncertain therapy-induced removal of cerebral amyloids in clinical trials cast doubt on this anti-Alzheimer's antibody therapy and hence on the amyloid hypothesis, calling for a more thorough investigation of the negative impact of this type of therapy on the brain.

Potential Therapeutic Targets to Modulate the Endocannabinoid System in Alzheimer's Disease.

Alzheimer's disease (AD), the most common neurodegenerative disease (NDD), is characterized by chronic neuronal cell death through progressive loss of cognitive function. Amyloid beta (Aß) deposition, neuroinflammation, oxidative stress, and hyperphosphorylated tau proteins are considered the hallmarks of AD pathology. Different therapeutic approaches approved by the Food and Drug Administration can only target a single altered pathway instead of various mechanisms that are involved in AD pathology, resulting in limited symptomatic relief and almost no effect in slowing down the disease progression. Growing evidence on modulating the components of the endocannabinoid system (ECS) proclaimed their neuroprotective effects by reducing neurochemical alterations and preventing cellular dysfunction. Recent studies on AD mouse models have reported that the inhibitors of the fatty acid amide hydrolase (FAAH) and monoacylglycerol (MAGL), hydrolytic enzymes for N-arachidonoyl ethanolamine (AEA) and 2-arachidonoylglycerol (2-AG), respectively, might be promising candidates as therapeutical intervention. The FAAH and MAGL inhibitors alone or in combination seem to produce neuroprotection by reversing cognitive deficits along with Aß-induced neuroinflammation, oxidative responses, and neuronal death, delaying AD progression. Their exact signaling mechanisms need to be elucidated for understanding the brain intrinsic repair mechanism. The aim of this review was to shed light on physiology and pathophysiology of AD and to summarize the experimental data on neuroprotective roles of FAAH and MAGL inhibitors. In this review, we have also included CB1R and CB2R modulators with their diverse roles to modulate ECS mediated responses such as anti-nociceptive, anxiolytic, and anti-inflammatory actions in AD. Future research would provide the directions in understanding the molecular mechanisms and development of new therapeutic interventions for the treatment of AD.

Efficacy of assisted partner services for people who inject drugs in Kenya to identify partners living with HIV and hepatitis C virus infection: a prospective cohort study.

BACKGROUND: People who inject drugs are at increased risk of both HIV and hepatitis C virus (HCV) infections but face barriers to testing and engagement in care. Assisted partner services are effective in locating people with HIV but are understudied among people who inject drugs. We assessed whether assisted partner services could be used to find, test for HIV and HCV infections, and link to care the partners of people who inject drugs in Kenya. METHODS: In this prospective study at eight sites offering harm-reduction services in Kenya, we enrolled people aged 18 years or older who inject drugs and were living with HIV (index participants) between Feb 27, 2018, and Nov 1, 2021. Index participants provided information about their sexual and injecting partners (ie, anyone with whom they had had sexual intercourse or injected drugs in the previous 3 years), and then community-embedded peer educators located partners and referred them for enrolment in the study (partner participants). All participants underwent testing for HCV infection, and partner participants also underwent HIV testing. Index and partner participants with HIV but who were not on antiretroviral therapy (ART) were linked with treatment services, and those positive for HCV were linked to treatment with direct-acting antivirals. We calculated the number of index participants whom we needed to interview to identify partner participants with HIV and HCV infection. FINDINGS: We enrolled 989 people living with HIV who inject drugs, who mentioned 4705 sexual or injecting partners. Of these 4705 partners, we enrolled 4597 participants, corresponding to 3323 unique individuals. 597 (18%) partner participants had HIV, of whom 506 (85%) already knew their status. 358 (71%) of those who knew they were HIV positive were virally suppressed. 393 (12%) partner participants were HCV antibody positive, 213 (54%) of whom had viraemia and 104 (26%) of whom knew their antibody status. 1·66 (95% CI 1·53-1·80) index participants had to be interviewed to identify a partner with HIV, and 4·24 (3·75-4·85) had to be interviewed to find a partner living with HIV who was unaware of their HIV status, not on ART, or not virally suppressed. To find a partner seropositive for HCV who did not know their antibody status, 3·47 (3·11-3·91) index participants needed to be interviewed. Among the 331 index and partner participants living with HIV who were not on ART at enrolment, 238 (72%) were taking ART at 6-month follow-up. No adverse events were attributed to study procedures. INTERPRETATION: Use of assisted partner services among people with HIV who inject drugs was safe and identified partners with HIV and HCV infections. Assisted partner services was associated with increased uptake of ART for both index participants and partners. FUNDING: US National Institutes of Health.