RESUMEN
BACKGROUND: The management and outcomes of nontuberculous mycobacterial (NTM) infections in solid organ transplant (SOT) recipients are poorly characterized. We aimed to describe the management and 1-y mortality of these patients. METHODS: Retrospective, multinational, 1:2 matched case-control study included SOT recipients aged 12 y old or older diagnosed with NTM infection between January 1, 2008, and December 31, 2018. Controls were matched on transplanted organs, NTM treatment center, and posttransplant survival at least equal to the time to NTM diagnosis. The primary aim was 1-y mortality after NTM diagnosis. Differences between cases and controls were compared using the log-rank test, and Cox regression models were used to identify factors associated with mortality at 12 mo among cases. RESULTS: In 85 patients and 169 controls, the median age at the time of SOT was 54 y (interquartile range, 40-62 y), 59% were men, and the lungs were the most common site of infection after SOT (57.6%). One-year mortality was significantly higher in cases than in controls (20% versus 3%; P < 0.001), and higher mortality was associated with lung transplantation (hazard ratio 3.27; 95% confidence interval [1.1-9.77]; P = 0.034). Median time (interquartile range) from diagnosis to treatment initiation (20 [4-42] versus 11 [3-21] d) or the reduction of net immunosuppression (36% versus 45%, hazard ratio 1.35 [95% CI, 0.41-4.43], P = 0.618) did not differ between survivors and those who died. CONCLUSIONS: NTM disease in SOT recipients is associated with a higher mortality risk, especially among lung transplant recipients. Time to NTM treatment and reduction in net immunosuppression were not associated with mortality.
RESUMEN
Cisplatin (CDDP) is an FDA-approved chemotherapeutic drug used for treating various solid tumors. Despite of its effectiveness towards chemotherapy, it faces several challenges, such as multi-drug resistance (MDR) and significant damage to the normal tissues. To address these challenges, various nanoformulations were developed to improve the delivery and safety of CDDP. One of the limitation in these CDDP loaded nanoformulations is that the effective CDDP loading concentrations are very poor. Therefore, this leaves a grand challenge to develop an effective strategy to carry higher concentrations of CDDP molecules, and also simultaneously exhibit very unique properties. Herein, we have developed an one-pot synthesis of Cisplatin encapsulated Plasmonic blackbody (CiP), which offers a double play for near infrared (NIR) light activatable chemo-photothermal therapy in destructing cancer cells as well as mediate catalytic reduction of 4-nitrophenol (4-NP). The CiP nanoformulation exhibits superior light absorbing capabilities in the NIR region with an appreciable photothermal conversion efficiency of 41%. Further, NIR light activatable combinatorial therapeutic approach of CiP was demonstrated against ovarian cancer cells and as a catalyst for the reduction of model pollutant 4-nitrophenol. Our findings highlight the potential of CiP as a versatile platform for light-activated combinatorial cancer therapy and environmental pollutant remediation.
RESUMEN
BACKGROUND: Despite increasing morbidity and mortality from non-communicable diseases (NCD) globally, health systems in low- and middle-income countries (LMICs) have limited capacity to address these chronic conditions, particularly in sub-Saharan Africa (SSA). There is an urgent need, therefore, to respond to NCDs in SSA, beginning by applying lessons learned from the first global response to any chronic disease-HIV-to tackle the leading cardiometabolic killers of people living with HIV (PLHIV). We have developed a feasible and acceptable package of evidence-based interventions and a multi-faceted implementation strategy, known as "TASKPEN," that has been adapted to the Zambian setting to address hypertension, diabetes, and dyslipidemia. The TASKPEN multifaceted implementation strategy focuses on reorganizing service delivery for integrated HIV-NCD care and features task-shifting, practice facilitation, and leveraging HIV platforms for NCD care. We propose a hybrid type II effectiveness-implementation stepped-wedge cluster randomized trial to evaluate the effects of TASKPEN on clinical and implementation outcomes, including dual control of HIV and cardiometabolic NCDs, as well as quality of life, intervention reach, and cost-effectiveness. METHODS: The trial will be conducted in 12 urban health facilities in Lusaka, Zambia over a 30-month period. Clinical outcomes will be assessed via surveys with PLHIV accessing routine HIV services, and a prospective cohort of PLHIV with cardiometabolic comorbidities nested within the larger trial. We will also collect data using mixed methods, including in-depth interviews, questionnaires, focus group discussions, and structured observations, and estimate cost-effectiveness through time-and-motion studies and other costing methods, to understand implementation outcomes according to Proctor's Outcomes for Implementation Research, the Consolidated Framework for Implementation Research, and selected dimensions of RE-AIM. DISCUSSION: Findings from this study will be used to make discrete, actionable, and context-specific recommendations in Zambia and the region for integrating cardiometabolic NCD care into national HIV treatment programs. While the TASKPEN study focuses on cardiometabolic NCDs in PLHIV, the multifaceted implementation strategy studied will be relevant to other NCDs and to people without HIV. It is expected that the trial will generate new insights that enable delivery of high-quality integrated HIV-NCD care, which may improve cardiovascular morbidity and viral suppression for PLHIV in SSA. This study was registered at ClinicalTrials.gov (NCT05950919).
RESUMEN
Background: Fixed, large volume resuscitation with intravenous fluids (IVFs) in septic shock can cause inadvertent hypervolemia, increased medical interventions, and death when unguided by point-of-care ultrasound (POCUS). The primary study objective was to evaluate whether total IVF volume differs for emergency department (ED) septic shock patients receiving POCUS versus no POCUS. Methods: We conducted a retrospective observational cohort study from 7/1/2018 to 8/31/2021 of atraumatic adult ED patients with septic shock. We agreed upon a priori variables and defined septic shock as lactate ≥4 and hypotension (SBP <90 or MAP <65). A sample size of 300 patients would provide 85% power to detect an IVF difference of 500 milliliters between POCUS and non-POCUS cohorts. Data are reported as frequencies, median (IQR), and associations from bivariate logistic models. Results: 304 patients met criteria and 26% (78/304) underwent POCUS. Cardiac POCUS demonstrated reduced ejection fraction in 15.4% of patients. Lung ultrasound showed normal findings in 53% of patients. The POCUS vs. non-POCUS cohorts had statistically significant differences for the following variables: higher median lactate (6.7 [IQR 5.2-8.7] vs. 5.6], p = 0.003), lower systolic blood pressure (77.5 [IQR 61-86] vs. 85.0, p < 0.001), more vasopressor use (51% vs. 34%, p = 0.006), and more positive pressure ventilation (38% vs. 24%, p = 0.017). However, there were no statistically significant differences between POCUS and non-POCUS cohorts in total IVF volume ml/kg (33.02 vs. 32.1, p = 0.47), new oxygen requirement (68% vs. 59%, p = 0.16), ED death (3% vs. 4%, p = 0.15), or hospital death (31% vs. 27%, p = 0.48). There were similar distributions of lactate, total fluids, and vasopressors in patients with CHF and severe renal failure. Conclusions: Among ED patients with septic shock, POCUS was more likely to be used in sicker patients. Patients who had POCUS were given similar volume of crystalloids although these patients were more critically ill. There were no differences in new oxygen requirement or mortality in the POCUS group compared to the non-POCUS group.
RESUMEN
BACKGROUND: Integrase inhibitors (INSTIs) have been associated with poorer cognition in people with HIV (PWH). We examined the impact of switching to INSTIs on neuropsychological (NP) outcomes in PWH 40 years of age and older. METHODS: From the AIDS Clinical Trials Group observational cohort study, HAILO, we identified PWH who switched to INSTIs, had ≥2 NP assessments before and at least 1 after switch, and maintained viral suppression while on INSTIs. NP performance was assessed with a composite score (NPZ4) including Hopkins Verbal Learning Test (HVLT-R), Digit Symbol test (DSY), Trail Making A, and Trail Making B, while adjusting for covariates and learning effects. Outcomes changes from preswitch and postswitch periods were estimated using piecewise linear mixed models. RESULTS: Among 395 PWH (mean age 54 years, 81% male, 20% Hispanic, and 29% Black) NPZ4 increased preswitch and postswitch. There was no difference in slopes between periods for NPZ4 [preswitch 0.036/year (95% CI: 0.03 to 0.043); postswitch 0.022/year (95% CI: 0.006 to 0.005); P = 0.147]. All tests scores improved preswitch (P < 0.01). Postswitch, Trail Making A and DSY increased (all P < 0.01) without differences in rate of change (all P > 0.05). HVLT-R had a nonsignificant decrease postswitch (P = 0.22), resulting in a significant preswitch vs postswitch difference in slopes (P = 0.03). CONCLUSIONS: NP performance improved regardless of INSTI use. There was an attenuation of improvement in verbal memory in the postswitch vs preswitch period. The clinical significance of these changes is unclear but, overall, INSTIs did not have a consistent detrimental effect on NP outcomes.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Inhibidores de Integrasa VIH , Humanos , Masculino , Persona de Mediana Edad , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/uso terapéutico , Inhibidores de Integrasa VIH/farmacología , Cognición , Fármacos Anti-VIH/uso terapéutico , IntegrasasRESUMEN
BACKGROUND: Preliminary evidence suggests that digital mental health intervention (Wysa for Chronic Pain) can improve mental and physical health in people with chronic musculoskeletal pain and coexisting symptoms of depression or anxiety. However, the behavioral mechanisms through which this intervention acts are not fully understood. OBJECTIVE: The purpose of this study was to identify behavioral mechanisms that may mediate changes in mental and physical health associated with use of Wysa for Chronic Pain during orthopedic management of chronic musculoskeletal pain. We hypothesized that improved behavioral activation, pain acceptance, and sleep quality mediate improvements in self-reported mental and physical health. METHODS: In this prospective cohort, pilot mediation analysis, adults with chronic (≥3 months) neck or back pain received the Wysa for Chronic Pain digital intervention, which uses a conversational agent and text-based access to human counselors to deliver cognitive behavioral therapy and related therapeutic content. Patient-reported outcomes and proposed mediators were collected at baseline and 1 month. The exposure of interest was participants' engagement (ie, total interactions) with the digital intervention. Proposed mediators were assessed using the Behavioral Activation for Depression Scale-Short Form, Chronic Pain Acceptance Questionnaire, and Athens Insomnia Scale. Outcomes included Patient-Reported Outcomes Measurement Information System Anxiety, Depression, Pain Interference, and Physical Function scores. A mediation analysis was conducted using the Baron and Kenny method, adjusting for age, sex, and baseline mediators and outcome values. P<.20 was considered significant for this pilot study. RESULTS: Among 30 patients (mean age 59, SD 14, years; 21 [70%] female), the mediation effect of behavioral activation on the relationship between increased intervention engagement and improved anxiety symptoms met predefined statistical significance thresholds (indirect effect -0.4, 80% CI -0.7 to -0.1; P=.13, 45% of the total effect). The direction of mediation effect was generally consistent with our hypothesis for all other proposed mediator or outcome relationships, as well. CONCLUSIONS: In a full-sized randomized controlled trial of patients with chronic musculoskeletal pain, behavioral activation, pain acceptance, and sleep quality may play an important role in mediating the relationship between use of a digital mental health intervention (Wysa for Chronic Pain) and improved mental and physical health. TRIAL REGISTRATION: ClinicalTrials.gov NCT05194722; https://clinicaltrials.gov/ct2/show/NCT05194722.
RESUMEN
In India, oral cancers are the major cause of cancer-related death. Tongue and buccal mucosa being the major subsites in oral cancer have varying clinicopathological presentations. This study is intended to know the difference in clinicopathological behavior of these two subsites. This retrospective study included 474 patients of which 232 patients had tongue cancer and 242 patients had buccal alveolar complex (BAC) cancer. Comparison between the pathological characters including pattern of nodal involvement was analyzed. Disease-free survival (DFS) and factors influencing the DFS were analyzed and compared using Cox regression analysis. Mean age of the study population was 52.7 years. Tongue oral squamous cell carcinoma (OSCC) differed significantly from BAC OSCC in terms of age of presentation, tumor staging, and perineural invasion. Among neck nodal involvement, tongue OSCC commonly involved level IIa (p < 0.001) whereas BAC involved level Ib (p < 0.001). At a median follow-up of 27 months, 141 patients had disease recurrence, tongue OSCC commonly recurred in neck (p = 0.008), and BAC OSCC relapsed at primary site (p = 0.001). Patients older than 45 years with BAC cancer had lesser risk of recurrence (HR, 0.30; 95% CI, 0.2-0.5; p < 0.0001). Pathological tumor stage in tongue cancer (HR, 14.9; 95% CI, 2.6-84.8; p = 0.002) and grade of tumor differentiation in BAC OSCC (HR, 9.2; 95% CI, 1.9-43.3; p < 0.005) were the most significant factors that influenced tumor recurrence. There was a significant difference in factors influencing disease recurrence among tongue and BAC OSCC. Also, pattern of nodal metastasis and pattern of recurrence were different. Hence, further research on OSCC may be done site specific. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-023-01750-8.
RESUMEN
Nontuberculous mycobacteria (NTM) infections are caused by environmental exposure. We describe spatial distribution of NTM infections and associations with sociodemographic factors and flooding in Missouri, USA. Our retrospective analysis of mycobacterial cultures reported to the Missouri Department of Health and Social Services surveillance system during January 1, 2008-December 31, 2019, detected geographic clusters of infection. Multilevel Poisson regression quantified small-area geographic variations and identified characteristics associated with risk for infection. Median county-level NTM infection rate was 66.33 (interquartile range 51-91)/100,000 persons. Risk of clustering was significantly higher in rural areas (rate ratio 2.82, 95% CI 1.90-4.19) and in counties with >5 floodings per year versus no flooding (rate ratio 1.38, 95% CI 1.26-1.52). Higher risk for NTM infection was associated with older age, rurality, and more flooding. Clinicians and public health professionals should be aware of increased risk for NTM infections, especially in similar environments.
Asunto(s)
Infecciones por Mycobacterium no Tuberculosas , Micobacterias no Tuberculosas , Humanos , Missouri/epidemiología , Infecciones por Mycobacterium no Tuberculosas/epidemiología , Infecciones por Mycobacterium no Tuberculosas/microbiología , Micobacterias no Tuberculosas/aislamiento & purificación , Micobacterias no Tuberculosas/fisiología , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Factores de Edad , Inundaciones , Población Rural , Masculino , Femenino , Persona de Mediana Edad , Anciano , Punto Alto de Contagio de EnfermedadesRESUMEN
Although Worst pattern of invasion (WPOI) is one of the histopathological (HP) markers that has been utilized in risk stratification of oral squamous cell carcinoma (OSCC) patients, its potential as an independent predictive factor for lymph node metastasis (LNM) and prognosis is least analyzed. Aim of the study is to analyze the relationship of various HP parameters to WPOI, their propensity for lymph node metastasis and prognostic value. This retrospective study included 140 patients diagnosed with resectable OSCC who underwent definitive surgery. Multiparametric HP risk assessment was done on the postoperative specimen and patients were categorized as low-risk WPOI (Type 1-3), and high-risk group (type 4 and 5). After categorization, 36.1% patients had low-risk WPOI and 63.9% had high-risk WPOI. Significant association was noted between WPOI and patient's age (p = 0.001), nodal stage (p = 0.001), lymphovascular invasion (LVI) (p = 0.006) and neural invasion (p = 0.001). 87% patients with nodal metastasis had high risk WPOI. LVI (p = 0.014) and WPOI (p < 0.001) had significant predictive role in LNM. High-risk WPOI and bone involvement were found to be predictive factors for overall survival, and only high risk WPOI had strong correlation with disease free survival having significant poor prognosis. Analyzing WPOI is essential in reporting HP specimens in OSCC. High-risk WPOI can act as an independent predictor for LNM, early recurrence and poor prognosis. Incorporation of WPOI into TNM staging is recommended to improve clinician's ability to prognosticate and individualize treatment strategies.
RESUMEN
BACKGROUND: Risk factors for nontuberculous mycobacteria (NTM) infections after solid organ transplant (SOT) are not well characterized. Here we aimed to describe these factors. METHODS: Retrospective, multinational, 1:2 matched case-control study that included SOT recipients ≥12 years old diagnosed with NTM infection from 1 January 2008 to 31 December 2018. Controls were matched on transplanted organ, NTM treatment center, and post-transplant survival greater than or equal to the time to NTM diagnosis. Logistic regression on matched pairs was used to assess associations between risk factors and NTM infections. RESULTS: Analyses included 85 cases and 169 controls (59% male, 88% White, median age at time of SOT of 54 years [interquartile range {IQR} 40-62]). NTM infection occurred in kidney (42%), lung (35%), heart and liver (11% each), and pancreas transplant recipients (1%). Median time from transplant to infection was 21.6 months (IQR 5.3-55.2). Most underlying comorbidities were evenly distributed between groups; however, cases were older at the time of NTM diagnosis, more frequently on systemic corticosteroids and had a lower lymphocyte count (all P < .05). In the multivariable model, older age at transplant (adjusted odds ratio [aOR] 1.04; 95 confidence interval [CI], 1.01-1.07), hospital admission within 90 days (aOR, 3.14; 95% CI, 1.41-6.98), receipt of antifungals (aOR, 5.35; 95% CI, 1.7-16.91), and lymphocyte-specific antibodies (aOR, 7.73; 95% CI, 1.07-56.14), were associated with NTM infection. CONCLUSIONS: Risk of NTM infection in SOT recipients was associated with older age at SOT, prior hospital admission, receipt of antifungals or lymphocyte-specific antibodies. NTM infection should be considered in SOT patients with these risk factors.
Asunto(s)
Infecciones por Mycobacterium no Tuberculosas , Trasplante de Órganos , Humanos , Masculino , Persona de Mediana Edad , Niño , Femenino , Estudios de Casos y Controles , Receptores de Trasplantes , Estudios Retrospectivos , Antifúngicos , Infecciones por Mycobacterium no Tuberculosas/microbiología , Trasplante de Órganos/efectos adversos , Factores de Riesgo , Micobacterias no TuberculosasRESUMEN
BACKGROUND: Oral squamous cell carcinoma (OSCC) remains the most common cancer among Indian men. OSCC involving the tongue and bucco alveolar complex (BAC) behaves differently. Nevertheless, the differences in clinical features and symptoms between the two subsites and their relation to pathology remain largely unexplored. STUDY DESIGN: The study compared various clinical parameters and pathological factors between tongue cancer patients and patients with BAC cancer. RESULTS: Among 474 patients, 232 had tongue cancer and 242 had BAC cancer. Except for the ulcer, 30% of patients with OSCC were asymptomatic at presentation. Compared to tongue cancers, lesions confined to BAC present at an advanced stage (P = 0.006). Multivariate analysis showed that dysphagia in tongue cancer (P = 0.020) and external swelling or lesion in BAC cancers (P = 0.002) were significant predictors of an advanced stage of the disease. On histopathology, perineural invasion (PNI) was significantly associated with tongue (P = 0.008) compared to BAC cancers (P = 0.015). Cancers of the tongue with pain and referred otalgia had a significantly higher depth of invasion (DOI), compared to those without pain (DOI - no pain 6.9 mm, pain 9.9 mm, and referred otalgia 11.4 mm). CONCLUSIONS: Patients with OSCC present late and in an advanced stage of the disease. Among tongue cancers, clinical history of pain was significantly associated with DOI and PNI, the significance of which needs to be prospectively analyzed. Clinical history in OSCC can be used as predicting factor for an advanced pathological stage of the disease. It also had an influence on various pathological characters, which is subsite specific.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Neoplasias de la Lengua , Masculino , Humanos , Neoplasias de la Boca/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas/patología , Neoplasias de la Lengua/patología , Estudios Retrospectivos , Dolor de Oído/patología , Estadificación de Neoplasias , Invasividad Neoplásica/patología , Dolor/patología , Neoplasias de Cabeza y Cuello/patología , PronósticoRESUMEN
OBJECTIVE: To identify if disparate trends in the access and use of nursing home (NH) services among Black and Latino older adults compared with White older adults persist. Access was operationalized as the NHs that served Black, Latino, and White residents. Use was operationalized as the utilization of NH services by Black, Latino, and White residents. DESIGN: This was an observational study analyzing facility-level data from LTCfocus for 2011 to 2017. SETTING AND PARTICIPANTS: All NH residents present in US NHs participating in the Centers for Medicare and Medicaid Services program on the first Thursday in April in the years 2011 to 2017. NHs with fewer than 4500 bed-days per year are excluded in the LCTfocus dataset. Black, Latino, and White were the racial/ethnic groups of interest. METHODS: We calculated the mean percentage of each racial/ethnic group in NHs (Black, Latino, White) annually along with the number of NHs that provided care for these groups. We conducted a simple trend analysis using ordinary least squares to estimate the change in NH access and use by racial/ethnic group over time. RESULTS: Our NH sample ranged from 15,564 in 2011 to 14,956 in 2017. Latino residents' use of NHs increased by 20.47% and Black residents increased by 11.42%, whereas there was a 1.36% decrease in White residents' use of NHs. In this 7-year span, there was a 4.44% and 6.41% decline in the number of NHs that serve any Black and Latino older adults, respectively, compared with a 2.26% decline in NHs that serve only White older adults (access). CONCLUSIONS AND IMPLICATIONS: Our findings reveal a continued disproportionate rise in Black and Latino older adults' use of NHs while the number of NHs that serve this population have declined. This work can inform federal and state policies to ensure access to long-term care services and supports in the community for all older adults and prevent inappropriate NH closures.
Asunto(s)
Medicare , Casas de Salud , Anciano , Estados Unidos , Humanos , Hispánicos o Latinos , Grupos Raciales , EtnicidadRESUMEN
OBJECTIVES: Up to 15% of the 1.4 million US nursing home (NH) residents receive antibiotics daily. Antibiotic use in NHs is often inappropriate, contributing to quality and safety concerns as well as antibiotic resistance. Information technology (IT) maturity-defined as the extent to which facilities possess and use diverse technological devices and software that are integrated across resident care, clinical support, and administrative activities-may improve the tracking and reporting of antibiotic use in NH residents. Thus, this research explores trends in IT maturity over time and associations with antibiotic use in US NHs. DESIGN: Repeated cross-sectional study. SETTING AND PARTICIPANTS: Long-term resident assessments from a random sample of Medicare-certified US NHs over 4 consecutive years (2013-2017). METHODS: Three data sources were used: (1) 4 annual surveys measuring IT maturity, (2) Minimum Data Set (MDS) 3.0 assessments for resident characteristics, and (3) Certification and Survey Provider Enhanced Reporting data for facility characteristics. Nonadmission MDS assessments that were within a 90-day window of the IT survey were eligible. Descriptive statistics were examined. Bivariate and multivariate regressions using NH fixed effects were conducted controlling for resident and NH characteristics. RESULTS: There were 219,461 MDS assessments from 80,237 long-stay residents aged ≥65 years, living in 817 NHs. Trends in IT maturity increased significantly over 4 years. IT integration in administrative processes was positively associated with antibiotic use (AOR 1.072, 95% CI 1.025, 1.122). CONCLUSIONS AND IMPLICATIONS: IT components that integrate administrative activities, which can provide greater access to data sources across the organization as a whole, was associated with changes in antibiotic use. Further evaluation is needed to determine if antibiotic use is more appropriate with higher maturity such that policy makers can encourage IT with these capabilities to promote antibiotic stewardship.
Asunto(s)
Antibacterianos , Cuidados a Largo Plazo , Anciano , Antibacterianos/uso terapéutico , Estudios Transversales , Humanos , Tecnología de la Información , Medicare , Casas de Salud , Estados UnidosRESUMEN
Mycobacterium tuberculosis (M. tuberculosis) causes an enormous burden of disease worldwide. As a central aspect of its pathogenesis, M. tuberculosis grows in macrophages, and host and microbe influence each other's metabolism. To define the metabolic impact of M. tuberculosis infection, we performed global metabolic profiling of M. tuberculosis-infected macrophages. M. tuberculosis induced metabolic hallmarks of inflammatory macrophages and a prominent signature of cholesterol metabolism. We found that infected macrophages accumulate cholestenone, a mycobacterial-derived, oxidized derivative of cholesterol. We demonstrated that the accumulation of cholestenone in infected macrophages depended on the M. tuberculosis enzyme 3ß-hydroxysteroid dehydrogenase (3ß-Hsd) and correlated with pathogen burden. Because cholestenone is not a substantial human metabolite, we hypothesized it might be diagnostic of M. tuberculosis infection in clinical samples. Indeed, in 2 geographically distinct cohorts, sputum cholestenone levels distinguished subjects with tuberculosis (TB) from TB-negative controls who presented with TB-like symptoms. We also found country-specific detection of cholestenone in plasma samples from M. tuberculosis-infected subjects. While cholestenone was previously thought to be an intermediate required for cholesterol degradation by M. tuberculosis, we found that M. tuberculosis can utilize cholesterol for growth without making cholestenone. Thus, the accumulation of cholestenone in clinical samples suggests it has an alternative role in pathogenesis and could be a clinically useful biomarker of TB infection.
Asunto(s)
Interacciones Huésped-Patógeno , Macrófagos/metabolismo , Metabolómica , Mycobacterium tuberculosis/fisiología , Transducción de Señal , Tuberculosis/metabolismo , Animales , Humanos , Macrófagos/microbiología , RatonesRESUMEN
OBJECTIVES: Reducing inappropriate nursing home (NH) antibiotic usage by implementing stewardship programs is a national priority. Our aim is to evaluate the influence of antibiotic stewardship programs on antibiotic use rates in NHs over time. DESIGN: Retrospective, repeated cross-sectional analysis. SETTING AND PARTICIPANTS: Long-term residents not receiving hospice care in freestanding NHs that participated in 1 or both surveys in 2013 and 2017. METHODS: Survey data were merged with the Minimum Data Set and the Certification and Survey Provider Enhanced Reporting data. Our outcome was a binary indicator for antibiotic use. The main predictor was the NH antibiotic stewardship policy intensity. Using multivariate linear regression models adjusting for resident and facility characteristics that differed between the 2 years, we calculated antibiotic use rates in 2013 and 2017 for all residents, those with Alzheimer's disease, and those with any infection including urinary tract infections (UTIs). RESULTS: Our sample included 317,003 resident assessments from 2013 and 267,537 assessments from 2017, residing in 953 and 872 NHs, respectively. NH antibiotic stewardship policy intensity increased from 2013 to 2017 (P < .01) and among all NH residents, including those with Alzheimer's disease, antibiotic use rate decreased (P < .05), with 45% of the decline attributable to strengthening stewardship programs. For most residents, policy intensity was associated with decreased usage in residents with UTI. However, among Alzheimer's disease residents with a UTI, this association did not persist. CONCLUSIONS AND IMPLICATIONS: Although there was a decrease in antibiotic use in 2017, more time is needed to see the full impact of antibiotic stewardship policy into practice. Adjustments to programs that directly address barriers to implementation and appropriate UTI antibiotic use for residents with Alzheimer's disease are necessary to continue strengthening NH antibiotic stewardship and improve care.
Asunto(s)
Programas de Optimización del Uso de los Antimicrobianos , Antibacterianos/uso terapéutico , Estudios Transversales , Humanos , Casas de Salud , Políticas , Estudios RetrospectivosRESUMEN
BACKGROUND: Though work has been done studying nursing home (NH) residents with either advanced Alzheimer's disease (AD) or Alzheimer's disease related dementia (ADRD), none have distinguished between them; even though their clinical features affecting survival are different. In this study, we compared mortality risk factors and survival between NH residents with advanced AD and those with advanced ADRD. METHODS: This is a retrospective observational study, in which we examined a sample of 34,493 U.S. NH residents aged 65 and over in the Minimum Data Set (2011-2013). Incident assessment of advanced disease was defined as the first MDS assessment with severe cognitive impairment (Cognitive Functional Score equals to 4) and diagnoses of AD or ADRD. Demographics, functional limitations, and comorbidities were evaluated as mortality risk factors using Cox models. Survival was characterized with Kaplan-Maier functions. RESULTS: Of those with advanced cognitive impairment, 35 % had AD and 65 % ADRD. At the incident assessment of advanced disease, those with AD had better health compared to those with ADRD. Mortality risk factors were similar between groups (shortness of breath, difficulties eating, substantial weight-loss, diabetes mellitus, heart failure, chronic obstructive pulmonary disease, and pneumonia; all p < 0.01). However, stroke and difficulty with transfer (for women) were significant mortality risk factors only for those with advanced AD. Urinary tract infection, and hypertension (for women) only were mortality risk factors for those with advanced ADRD. Median survival was significantly shorter for the advanced ADRD group (194 days) compared to the advanced AD group (300 days). CONCLUSIONS: There were distinct mortality and survival patterns of NH residents with advanced AD and ADRD. This may help with care planning decisions regarding therapeutic and palliative care.
Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Enfermedad Pulmonar Obstructiva Crónica , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/terapia , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/epidemiología , Femenino , Humanos , Casas de Salud , Estudios RetrospectivosRESUMEN
Importance: Hospitalizations for infections among nursing home (NH) residents remain common despite national initiatives to reduce them. Cognitive impairment, which markedly affects quality of life and caregiving needs, has been associated with hospitalizations, but the association between infection-related hospitalizations and long-term cognitive function among NH residents is unknown. Objective: To examine whether there are changes in cognitive function before vs after infection-related hospitalizations among NH residents. Design, Setting, and Participants: This cohort study used data from the Minimum Data Set 3.0 linked to Medicare hospitalization data from 2011 to 2017 for US nursing home residents aged 65 years or older who had experienced an infection-related hospitalization and had at least 2 quarterly Minimum Data Set assessments before and 4 or more after the infection-related hospitalization. Analyses were performed from September 1, 2019, to December 21, 2020. Exposure: Infection-related hospitalization lasting 1 to 14 days. Main Outcomes and Measures: Using an event study approach, associations between infection-related hospitalizations and quarterly changes in cognitive function among NH residents were examined overall and by sex, age, Alzheimer disease and related dementias (ADRD) diagnosis, and sepsis vs other infection-related diagnoses. Resident-level cognitive function was measured using the Cognitive Function Scale (CFS), with scores ranging from 1 (intact) to 4 (severe cognitive impairment). Results: Of the sample of 20â¯698 NH residents, 71.0% were women and 82.6% were non-Hispanic White individuals; the mean (SD) age at the time of transfer to the hospital was 82 (8.5) years. The mean CFS score was 2.17, and the prevalence of severe cognitive impairment (CFS score, 4) was 9.0%. During the first quarter after an infection-related hospitalization, residents experienced a mean increase of 0.06 points in CFS score (95% CI, 0.05-0.07 points; P < .001), or 3%. The increase in scores was greatest among residents aged 85 years or older vs younger residents by approximately 0.022 CFS points (95% CI, 0.004-0.040 points; P < .05). The prevalence of severe cognitive impairment increased by 1.6 percentage points (95% CI, 1.2-2.0 percentage points; P < .001), or 18%; the increases were observed among individuals with ADRD but not among those without it. After an infection-related hospitalization, cognition among residents who had experienced sepsis declined more than for residents who had not by about 0.02 CFS points (95% CI, 0.00-0.04 points; P < .05). All observed differences persisted without an accelerated rate of decline for at least 6 quarters after infection-related hospitalization. No differences were observed by sex. Conclusions and Relevance: In this cohort study, infection-related hospitalization was associated with immediate and persistent cognitive decline among nursing home residents, with the largest increase in CFS scores among older residents, those with ADRD, and those who had experienced sepsis. Identification of NH residents at risk of worsened cognition after an infection-related hospitalization may help to ensure that their care needs are addressed to prevent further cognitive decline.
Asunto(s)
Disfunción Cognitiva/epidemiología , Hospitalización/estadística & datos numéricos , Infecciones/epidemiología , Casas de Salud , Factores de Edad , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/epidemiología , Estudios de Cohortes , Demencia/epidemiología , Femenino , Humanos , Estudios Longitudinales , Masculino , Medicare , Sepsis/epidemiología , Estados UnidosRESUMEN
Oral cancers are the leading cause of cancer-related death in Indian men. Currently steps to contain the transmission and treatment of COVID-19 pandemic have crippled the entire health care system. With hospitals running short of resources, the oncological practice became standstill, especially during the initial phase. This is a retrospective study among patients who presented to our tertiary care hospital in early 3 months of COVID-19 era(ECE) with respect to pre-COVID-19 era(PCE). The study includes patients discussed in multidisciplinary tumor board(MDT)(421 in ECE Vs 31 in PCE) and those who underwent surgery(192 in ECE Vs 26 in PCE). The presentation and outcomes of oral carcinoma were compared between the two eras. There was a significant drop in the number of patients who presented during ECE. Though mean age and gender remained comparable between groups, there was a statistical difference in relation to demographic profile of patient (p value < 0.001). Among operated during ECE, 80% had a significantly advanced tumor stage (p value < 0.034) and advanced composite stage (p value < 0.049). Among patients discussed in MDT during ECE, 38.7% were deemed inoperable which is double the number when compared with PCE (p value < 0.009). Results of our study showed a higher incidence of advanced stage disease during ECE, with many patient turning inoperable. Thus, the survival of newly diagnosed oral carcinoma patients will be worser. In the management of oral cancer both early stage and advanced stage should have the same priority. Immediate resumption of safe oncology services is mandatory to curtail the current issues.
RESUMEN
OBJECTIVE: Coronavirus disease 2019 (COVID-19) has disproportionately impacted nursing homes (NHs) with large shares of Black residents. We examined the associations between the proportion of Black residents in NHs and COVID-19 infections and deaths, accounting for structural bias (operationalized as county-level factors) and stratifying by urbanicity/rurality. DESIGN: This was a cross-sectional observational cohort study using publicly available data from the LTCfocus, Centers for Disease Control and Prevention Long-Term Care Facility COVID-19 Module, and the NYTimes county-level COVID-19 database. Four multivariable linear regression models omitting and including facility characteristics, COVID-19 burden, and county-level fixed effects were estimated. SETTING AND PARTICIPANTS: In total, 11,587 US NHs that reported data on COVID-19 to the Centers for Disease Control and Prevention and had data in LTCfocus and NYTimes from January 20, 2020 through July 19, 2020. MEASURES: Proportion of Black residents in NHs (exposure); COVID-19 infections and deaths (main outcomes). RESULTS: The proportion of Black residents in NHs were as follows: none= 3639 (31.4%), <20% = 1020 (8.8%), 20%-49.9% = 1586 (13.7%), ≥50% = 681 (5.9%), not reported = 4661 (40.2%). NHs with any Black residents showed significantly more COVID-19 infections and deaths than NHs with no Black residents. There were 13.6 percentage points more infections and 3.5 percentage points more deaths in NHs with ≥50% Black residents than in NHs with no Black residents (P < .001). Although facility characteristics explained some of the differences found in multivariable analyses, county-level factors and rurality explained more of the differences. CONCLUSIONS AND IMPLICATIONS: It is likely that attributes of place, such as resources, services, and providers, important to equitable care and health outcomes are not readily available to counties where NHs have greater proportions of Black residents. Structural bias may underlie these inequities. It is imperative that support be provided to NHs that serve greater proportions of Black residents while considering the rurality of the NH setting.
Asunto(s)
Negro o Afroamericano/estadística & datos numéricos , COVID-19/mortalidad , Casas de Salud , Estudios Transversales , HumanosRESUMEN
Background: An estimated 50% of nursing home (NH) residents experience hospital transfers in their last year of life, often due to infections. Hospital transfers due to infection are often of little clinical benefit to residents with advanced illness, for whom aggressive treatments are often ineffective and inconsistent with goals of care. Integration of palliative care and infection management (i.e., merging the goals of palliative care and infection management at end of life) may reduce hospital transfers for residents with advanced illness. Objectives: Evaluate the association between integration and (1) all-cause hospital transfers and (2) hospital transfers due to infection. Design: Cross-sectional observational study. Setting/Subjects: 143,223 U.S. NH residents, including 42,761 residents in the advanced stages of dementia, congestive heart failure (CHF), and chronic obstructive pulmonary disease (COPD). Measurement: Cross-sectional, nationally representative NH survey data (2017-2018) were combined with resident data from the Minimum Data Set 3.0 and Medicare inpatient data (2016-2017). NH surveys measured integration of palliative care and infection management using an index of 0-100. Logistic regression models were used to estimate the relationships between integration intensity (i.e., the degree to which NHs follow best practices for integration) and all-cause hospital transfer and transfer due to infection. Results: Among residents with advanced dementia, integration intensity was inversely associated with all-cause hospital transfer and transfer due to infection (p < 0.001). Among residents with advanced COPD, integration intensity was inversely associated with all-cause hospital transfer (p < 0.05) but not transfers due to infection. Among residents with advanced CHF, integration intensity was not associated with either outcome. Conclusions: NH policies aimed to promote integration of palliative care and infection management may reduce burdensome hospital transfers for residents with advanced dementia. For residents with advanced CHF and COPD, alternative strategies may be needed to promote best practices for infection management at end of life.