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OBJECTIVE: The relationships among depression, personality factors, stress, and cognitive decline in the elderly are complex. Depressed elders score higher in neuroticism than nondepressed older individuals. Independently, the presence of neuroticism and the number of stressful life events are each associated with worsening cognitive decline in depressed older adults. Yet little is known about combined effects of changes in neuroticism and changes in stress on cognitive decline among older depressed adults. DESIGN: Longitudinal observational study. SETTING: Academic Health Center. PARTICIPANTS: The authors examined 62 participants in the Neurobiology of Late-life depression (NBOLD) study to test the hypothesis that, compared with older depressed subjects who experience improved neuroticism and lower psychosocial stressors over time, those with worsening neuroticism and greater psychosocial stressors will demonstrate more cognitive decline. MEASUREMENTS: The authors measured neuroticism using the NEO-Personality Inventory-Revised at baseline and 1 year. Study psychiatrists measured depression using the Montgomery-Ǻsberg Depression Rating Scale. At annual assessments, subjects reported the number of psychosocial stressors in the prior year and completed a neuropsychological evaluation. Participants completed a detailed neuropsychological battery at baseline and annually over 3 years. The battery included a test of delayed story memory (Logical Memory-2 or LMII). The outcome 3-year change in cognitive scores was regressed against 3-year change scores of neuroticism and number of psychosocial stressors, plus their interaction, while adjusting for sex, age, race, education, baseline cognitive score, and 3-year change in MADRS score as covariates. RESULTS: In multivariable linear regression analysis with the above covariates, the interaction effect of 3-year change in Total Neuroticism score and 3-year change in Total Stressors on change in LMII performance was statistically significant (B = -0.080[95%CL: -0.145 to -0.015], T = -2.48, df = 52, p = 0.017). Further exploration of this finding showed that 1) when total stressors increased by 2 or more over 3 years, LMII change was inversely associated with neuroticism change; and 2) when neuroticism improved less, LMII change score was inversely associated with total stressor change. There were no other significant interactions between stress and neuroticism on cognition. CONCLUSION: Our findings document the importance of tracking change in neuroticism and monitoring psychosocial stress over the long-term course of treatment in geriatric depression. Both factors exert important combined effects on memory over time. Future studies in larger samples are needed to confirm our results and to extend them to examine both cognitive change and development of dementia.
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Disfunción Cognitiva , Humanos , Anciano , Neuroticismo , Disfunción Cognitiva/etiología , Personalidad , Pruebas Neuropsicológicas , CogniciónRESUMEN
OBJECTIVES: The relationships among depression, personality factors, and cognitive decline in the elderly are complex. Depressed elders score higher in neuroticism than nondepressed older individuals. Presence of neuroticism worsens cognitive decline in depressed older adults. Yet little is known about changes in neuroticism among older adults being treated for depression and the impact of these changes on cognitive decline. DESIGN: Longitudinal observational study. SETTING: Academic Health Center. PARTICIPANTS: We examined 68 participants in the neurobiology of late-life depression (LLD) study to test the hypothesis that older depressed subjects with more improvement in neuroticism would experience less cognitive decline compared with those with less change in neuroticism. MEASUREMENTS: We measured neuroticism using the NEO-Personality Inventory-Revised at baseline and 1 year. Study psychiatrists measured depression using the Montgomery-Åsberg depression rating scale (MADRS). Global cognitive performance was measured using the Consortium to Establish a Registry for Alzheimer's disease (CERAD) battery at baseline and annually over 3 years. Regression models of 1-year change in neuroticism and 3-year change in CERAD included sex, age, race, education, and 1-year change in MADRS score as covariates. RESULTS: We found that among older adults, 1-year change in neuroticism was inversely associated with 3-year change in CERAD total score. CONCLUSIONS: Our findings challenge the notion of longitudinal stability of measures of personality, especially among older depressed individuals. They highlight the importance of repeated personality assessment, especially of neuroticism, in the management of LLD. Future studies in larger samples followed for longer periods are needed to confirm our results and to extend them to examine both cognitive change and development of dementia.
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Enfermedad de Alzheimer , Trastornos de la Personalidad , Anciano , Cognición , Humanos , Neuroticismo , Personalidad , Inventario de PersonalidadRESUMEN
BACKGROUND: Clostridium difficile is a gram-positive, anaerobic, and spore-forming bacillus, which is responsible for the majority of antibiotic-associated diarrhea and colitis. OBJECTIVE: Determine if fecal microbiota transplantation (FMT) is effective in a population sample from Connecticut. METHODS: We report the clinical experience of 92 consecutive patients from one gastroenterology practice in central Connecticut treated by colonoscopy with FMT for infection with Clostridium difficile from 2012 to 2017. The analyses are based on clinical follow-up up to 3 months after the FMT procedure and on medical chart review. RESULTS: Overall, complete recovery occurred in 86% of patients. As previously reported in a limited number of previous studies, community-acquired cases were more common than hospital-acquired cases, and community-acquired cases were more likely to be female. CONCLUSIONS: Consistent with some previous reports, we found the following: the source of the donor for FMT did not make a difference in recovery: material from nonrelatives was as effective as from close relatives; and the presence of multiple comorbidities did not make a difference in recovery: patients with 2 or more comorbidities did as well as those with one or none.
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Clostridioides difficile/patogenicidad , Infecciones por Clostridium/microbiología , Infecciones por Clostridium/terapia , Trasplante de Microbiota Fecal , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Probabilidad , Donantes de Tejidos , Resultado del TratamientoRESUMEN
Familial adenomatous polyposis (FAP) is a genetic disorder characterized by the development of hundreds of polyps throughout the colon. Without prophylactic colectomy, most individuals with FAP develop colorectal cancer at an early age. Treatment with EPA in the free fatty acid form (EPA-FFA) has been shown to reduce polyp burden in FAP patients. Since high-purity EPA-FFA is subject to rapid oxidation, a stable form of EPA compound has been developed in the form of magnesium l-lysinate bis-eicosapentaenoate (TP-252). We assessed the chemopreventive efficacy of TP-252 on intestinal tumor formation using ApcΔ14/+ mice and compared it with EPA-FFA. TP-252 was supplemented in a modified AIN-93G diet at 1, 2 or 4% and EPA-FFA at 2.5% by weight and administered to mice for 11 weeks. We found that administration of TP-252 significantly reduced tumor number and size in the small intestine and colon in a dose-related manner and as effectively as EPA-FFA. To gain further insight into the cancer protection afforded to the colon, we performed a comprehensive lipidomic analysis of total fatty acid composition and eicosanoid metabolites. Treatment with TP-252 significantly decreased the levels of arachidonic acid (AA) and increased EPA concentrations within the colonic mucosa. Furthermore, a classification and regression tree (CART) analysis revealed that a subset of fatty acids, including EPA and docosahexaenoic acid (DHA), and their downstream metabolites, including PGE3 and 14-hydroxy-docosahexaenoic acid (HDoHE), were strongly associated with antineoplastic activity. These results indicate that TP-252 warrants further clinical development as a potential strategy for delaying colectomy in adolescent FAP patients.
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Neoplasias del Colon/patología , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/farmacología , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Poliposis Adenomatosa del Colon/complicaciones , Animales , Quimioprevención/métodos , Neoplasias del Colon/etiología , Neoplasias del Colon/prevención & control , Estabilidad de Medicamentos , Ácido Eicosapentaenoico/química , Ácidos Grasos , Femenino , Masculino , Ratones , Ratones MutantesRESUMEN
PURPOSE: Clinicians use tamsulosin, an α1-adrenoceptor antagonist, to manage symptomatic benign prostatic hyperplasia (BPH). Because α1-adrenoceptors are also present in the brain, the potential exists for adverse effects on cognitive functions. We explored the association between tamsulosin use and dementia risk. METHODS: We used Medicare data (2006-2012) to conduct a cohort study among patients aged ≥65 years and diagnosed with BPH. Men taking tamsulosin (n = 253 136) were matched at a 1:1 ratio using propensity-scores to each of 6 comparison cohorts: patients who used no BPH-medication (n = 180 926), and patients who used the following alternative-BPH-medications: doxazosin (n = 28 581), terazosin (n = 23 858), alfuzosin (n = 17 934), dutasteride (n = 34 027), and finasteride (n = 38 767). Assessment began following the first fill of BPH-medication to identify incident dementia by ICD-9 diagnosis codes. We estimated hazard ratios (HR) and 95% confidence intervals (CI) for dementia using Cox proportional hazard regression for each of the 6 propensity-score-matched cohort-pairs. RESULTS: The median follow-up period for all cohorts was 19.8 months. After propensity-score matching, the tamsulosin cohort had an incidence of dementia of 31.3/1000 person-years compared with only 25.9/1000 person-years in the no-BPH-medication cohort. The risk of dementia was significantly higher in the tamsulosin cohort, when compared with the no-BPH-medication cohort (HR [95% CI]: 1.17 [1.14, 1.21]) and each of the alternative-BPH-medication cohorts: doxazosin (1.20 [1.12, 1.28]), terazosin (1.11 [1.04, 1.19]), alfuzosin (1.12 [1.03, 1.22]), dutasteride (1.26 [1.19, 1.34]), and finasteride (1.13 [1.07, 1.19]). The significance of these findings persisted in sensitivity analyses. CONCLUSION: Tamsulosin may increase the risk of dementia in older men with BPH.
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Inhibidores de 5-alfa-Reductasa/administración & dosificación , Antagonistas de Receptores Adrenérgicos alfa 1/efectos adversos , Demencia/epidemiología , Hiperplasia Prostática/tratamiento farmacológico , Tamsulosina/efectos adversos , Inhibidores de 5-alfa-Reductasa/efectos adversos , Antagonistas de Receptores Adrenérgicos alfa 1/administración & dosificación , Factores de Edad , Anciano , Anciano de 80 o más Años , Demencia/inducido químicamente , Dutasterida/administración & dosificación , Dutasterida/efectos adversos , Finasterida/administración & dosificación , Finasterida/efectos adversos , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Medicare/estadística & datos numéricos , Estudios Retrospectivos , Factores de Riesgo , Tamsulosina/administración & dosificación , Estados Unidos/epidemiologíaRESUMEN
AIMS: The current study was conducted to investigate how changes in the content of a social media ad, user engagement values associated with the ad and user-generated comments (UGCs) associated with the ad can influence the appeal (i.e. source appeal, informational appeal and emotional appeal) of a social media ad. SHORT SUMMARY: Facebook beer ads that violated the guidelines of a relevant marketing code were rated as more emotionally appealing compared to Facebook beer ads that did not violated the guidelines. Increased emotional appeal in beer advertising increases the probability that the ad will be remembered and influence future drinking occasions. METHODS: A 2 (ad regulatory compliance: compliant vs. non-compliant) × 2 (user engagement: low vs. high) × 2 (UGC congruence: pro- vs anti-alcohol) mixed factorial experiment was conducted with 120 young adults, 21-24 years old. Each participant viewed four Facebook beer ads that were previously evaluated for thematic content and regulatory compliance. Participants were randomized to view either high or low user engagement values and either pro- or anti-drinking user-generated comments. After each ad exposure, ad appeal was assessed. Statistical analysis was conducted using hierarchical linear modeling. Models were adjusted for demographics, Alcohol Use Disorders Identification Test (AUDIT) scores and Facebook involvement. RESULTS: Source appeal (P = 0.034) and informational appeal (P < 0.001) were significantly higher among ads that were compliant with existing advertising regulations. Emotional appeal was significantly higher among ads that were non-compliant (P = 0.004). The effect of user engagement and UGCs were non-significant (p's > 0.05). Additionally, AUDIT scores (p's < 0.01) and Facebook involvement scores (p's < 0.01) were positively associated with all forms of ad appeal. CONCLUSION: The appeal of Facebook beer ads may be primarily determined by ad content. Increased emotional appeal in advertising caused by non-compliant advertising may increase the probability that the ad will be remembered and influence future drinking occasions.
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Publicidad/legislación & jurisprudencia , Publicidad/métodos , Consumo de Bebidas Alcohólicas/legislación & jurisprudencia , Consumo de Bebidas Alcohólicas/psicología , Cerveza , Red Social , Femenino , Humanos , Aplicación de la Ley/métodos , Masculino , Adulto JovenRESUMEN
ABSTRACTNeuroticism in older adults is common yet understudied, particularly its effects on depression treatment outcomes. We hypothesized that presence of high neuroticism would be associated with lower 12-week remission rates in older depressed sertraline-treated patients. In this longitudinal cohort study, 43 depressed older adults completed the Revised NEO Personality Inventory (NEO PI-R). A study psychiatrist administered the Montgomery Ǻsberg Depression Rating Scale (MADRS), and the Cumulative Illness Rating Scale (CIRS, a measure of medical burden) at baseline, and the MADRS at each clinical visit. All subjects began open-label sertraline treatment and were followed over 12 weeks with clinically indicated flexible dosing and an option to switch antidepressants. We used regression analyses to examine factors related to 12-week remission of depression (MADRS score < 8) and final MADRS score. We found that higher total neuroticism (odds ratio (OR) = 0.963, 95% confidence interval (CI) = 0.928-1.000) and a neuroticism subscale, stress vulnerability (OR = 0.846, 95% CI = 0.728-0.983), were associated with lower likelihood of remission among both the intention-to-treat group and sertraline completers. Findings remained significant after controlling for baseline MADRS and CIRS score. In conclusion, assessment of personality, particularly features of neuroticism, may be important in management of late-life depression. Future studies should determine if depressed patients high in neuroticism may benefit from psychotherapy focusing on emotional regulation and stress management.
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Depresión , Neuroticismo , Sertralina , Anciano , Antidepresivos/administración & dosificación , Antidepresivos/efectos adversos , Depresión/diagnóstico , Depresión/tratamiento farmacológico , Depresión/psicología , Relación Dosis-Respuesta a Droga , Monitoreo de Drogas/métodos , Resistencia a Medicamentos , Femenino , Humanos , Enfermedades de Inicio Tardío , Masculino , Persona de Mediana Edad , Inventario de Personalidad , Escalas de Valoración Psiquiátrica , Inducción de Remisión/métodos , Sertralina/administración & dosificación , Sertralina/efectos adversos , Resultado del TratamientoRESUMEN
IN BRIEF Several contraindications limit the use of metformin, most notably the risk of lactic acidosis. This article reports on an examination of a population of patients with diabetes with preserved renal function to evaluate provider compliance with guidelines on metformin use and to identify factors that contributed when practice diverged from recommendations. It found that metformin was withheld from approximately one-third of these patients because of 1) an existent contraindication to metformin, 2) patient behavior or preference, or 3) provider preference or bias based on patient or personal factors. Although providers generally follow current recommendations for the use of metformin, deviations from guidelines in practice are common.
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PURPOSE: Based on suggestive findings from a recent study of high-risk Japanese patients, we sought to determine whether the risk of colorectal polyps associated with smoking may be modified by daily use of aspirin in an analysis of a large US screening population. METHODS: This is a cross-sectional study of 2,918 consecutive colonoscopy patients at a university hospital over a 30-month period. Data were abstracted from electronic medical records. Multivariate models of polyp counts were used to examine the competing risks of smoking and aspirin use. Models were further stratified by polyp location (proximal vs. distal) and pathologic subtype (dysplastic vs. serrated). RESULTS: Incidental rate of polyps was higher among active smokers [incidence rate ratio (IRR) 1.72; 95 % confidence interval (CI) 1.46-2.02] and lower among daily aspirin users (IRR 0.73; 95 % CI 0.61-0.86) compared to those who used neither. Smoking interacts significantly with aspirin use resulting in loss of aspirin protection (IRR 1.69; 95 % CI 1.28-2.24). Stratified analyses demonstrate that aspirin specifically reduces the risk of traditional dysplastic adenomas (IRR 0.72; 95 % CI 0.61-0.86) not serrated/hyperplastic polyps (IRR 0.92; 95 % CI 0.72-1.17) and that the modification of aspirin protection by smoking is primarily observed within the distal colorectum (p < 0.03). CONCLUSIONS: We report for the first time, in a typical risk US clinical population, a lack of protective association of aspirin for polyps among active smokers. Future prospective studies are recommended to confirm this mitigating effect in order to improve the precision of the growing evidence base about the chemopreventive benefit of aspirin in colorectal cancer.
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Antiinflamatorios no Esteroideos/uso terapéutico , Aspirina/uso terapéutico , Pólipos del Colon/prevención & control , Fumar , Anciano , Pólipos del Colon/epidemiología , Colonoscopía , Estudios Transversales , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , RiesgoRESUMEN
BACKGROUND: Natriuresis with polyuria is common after aneurysmal subarachnoid hemorrhage (aSAH). Previous studies have shown an increased risk of symptomatic cerebral vasospasm or delayed cerebral ischemia (DCI) in patients with hyponatremia and/or the cerebral salt wasting syndrome (CSW). However, natriuresis may occur in the absence of hyponatremia or hypovolemia and it is not known whether the increase in DCI in patients with CSW is secondary to a concomitant hypovolemia or because the physiology that predisposes to natriuretic peptide release also predisposes to cerebral vasospasm. Therefore, we investigated whether polyuria per se was associated with vasospasm and whether a temporal relationship existed. METHODS: A retrospective review of patients with aSAH was performed. Exclusion criteria were admission more than 48 h after aneurysmal rupture, death within 5 days, and the development of diabetes insipidus or acute renal failure. Polyuria was defined as > 6 liters of urine in a 24 h period. Vasospasm was defined as a mean velocity > 120 m/s on Transcranial Doppler Ultrasonography (TCDs) or by evidence of vasospasm on computerized tomography (CT) or catheter angiography. Multivariable logistic regression was performed to assess the relationship between polyuria and vasospasm. RESULTS: 95 patients were included in the study. 51 had cerebral vasospasm and 63 met the definition of polyuria. Patients with polyuria were significantly more likely to have vasospasm (OR 4.301, 95% CI 1.378-13.419) in multivariate analysis. Polyuria was more common in younger patients (52 vs 68, p <.001) but did not impact mortality after controlling for age and disease severity. The timing of the development of polyuria was clustered around the diagnosis of vasospasm and patients with polyuria developed vasospasm faster than those without polyuria. CONCLUSIONS: Polyuria is common after aSAH and is significantly associated with cerebral vasospasm. The development of polyuria may be temporally related to the development of vasospasm. An increase in urine volume may be a useful clinical predictor of patients at risk for vasospasm.
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Natriuresis/fisiología , Poliuria/orina , Hemorragia Subaracnoidea/orina , Vasoespasmo Intracraneal/orina , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Poliuria/etiología , Estudios Retrospectivos , Hemorragia Subaracnoidea/complicaciones , Vasoespasmo Intracraneal/etiologíaRESUMEN
BACKGROUND: We sought to investigate the relationship between neuroticism and depression in an elderly cohort. In this paper, we describe the methods of an National Institute of Mental Health-NIMH-supported study and present findings among the cohort enrolled to date. METHODS: We used the NEO Personality Inventory to assess neuroticism, and we employed several cognitive neuroscience-based measures to examine emotional control. RESULTS: Compared with a group of 27 non-depressed older control subjects, 33 older depressed subjects scored higher on measures of state and trait anxiety and neuroticism. On our experimental neuroscience-based measures, depressed subjects endorsed more negative words compared with controls on an emotional characterization test. In addition, we found a significant group-by-congruency effect on an emotional interference test where subjects were asked to identify the face's emotional expression while ignoring the words "fear" or "happy" labeled across the face. CONCLUSION: Thus, in this preliminary work, we found significant differences in measures of neuroticism and emotional controls among older adults with and without depression.
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Envejecimiento/psicología , Trastornos de Ansiedad/diagnóstico , Ansiedad/diagnóstico , Depresión/complicaciones , Trastornos de la Personalidad/diagnóstico , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Acontecimientos que Cambian la Vida , Imagen por Resonancia Magnética , Masculino , Neuroticismo , Inventario de Personalidad , Escalas de Valoración Psiquiátrica , Estados UnidosRESUMEN
Hyaluronic acid (HA) injections are used to treat osteoarthritis of the hip but their efficacy has not been clearly established. The purpose of this meta-analysis was to determine the effect of HA injections on hip pain. There were twenty-three studies that met our criteria and the mean decrease in visual analog scores (VAS) was -1.97 (95% CL, 2.83 to -1.12, P<0.0001). However, the clinical relevance of this change is difficult to determine since the decrease in VAS was only -0.27 in the six randomized trials in the study and the duration of follow-up in most studies was less than six months. Multicenter randomized trials are needed to determine the true efficacy of HA injections in decreasing pain associated with hip osteoarthritis.
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Articulación de la Cadera , Ácido Hialurónico/administración & dosificación , Osteoartritis de la Cadera/tratamiento farmacológico , Viscosuplementos/administración & dosificación , Humanos , Inyecciones Intraarticulares , Resultado del TratamientoRESUMEN
BACKGROUND: Throughout the coronavirus (COVID-19) pandemic, research revealed people of color were more likely to be infected, have severe illness, and die due to the virus. However, some areas in the USA are now reporting a new shift; lower Black and Hispanic COVID-19 mortality rates compared to their White counterparts. Research indicates that this shift is the result of COVID-19's impact on disparities by race. In this paper, we analyze death data to determine if the new shift has occurred locally. Specifically, we examined COVID-19 prevalence and related death data in Connecticut by comparing race/ethnicity through two periods of time: one before and one after the first case of the Omicron variant of COVID-19. METHODS: This cross-sectional epidemiological analysis to examine cases and deaths by racial/ethnic status utilizes Connecticut data from March 2020 to February 2022. The following assumption is applied: expected pre-Omicron cases and deaths from March 5, 2020 to November 27, 2021 are equal to the number of cases and deaths during Omicron cases and deaths from November 28, 2021 to February 17, 2022. Race/ethnicity are operationalized as non-Hispanic White, non-Hispanic Black, and Hispanic. RESULTS: Pre-Omicron (March 5, 2020 to November 27, 2021) compared to the monthly aged adjusted COVID-19 case rate for Whites (394/10,000 populations), Blacks had a higher rate (501/10,000 populations), and Hispanics had the highest (585/10,000 populations). During the Omicron period (November 28 to February 17, 2022), significant changes in COVID-19 case rates were observed in all three ethnic groups, but the biggest changes were observed in Hispanics, followed by Blacks, and then Whites. The rate ratios further showed a remarkable reduction of 47% in case rates (from 1.0 pre-Omicron and from 1.47 during Omicron, p < 0.0001) for Hispanics, when compared to that of Whites. While Blacks showed a significant, smaller reduction of 5% in case rates (from 1.27 pre-Omicron and from 1.22 during the Omicron, p < 0.001) when compared to Whites. Regarding COVID-19-related mortality, the racial differences were similar. CONCLUSIONS AND RELEVANCE: By examining Connecticut's COVID-19 death and case data, this study identified the new shift that occurred locally. The current shift may be anchored in the evolution of the COVID-19 virus, public health guidelines/policies, and the degree to which populations have complied with public health recommendations.
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COVID-19 , Humanos , Negro o Afroamericano , COVID-19/etnología , COVID-19/mortalidad , Estudios Transversales , SARS-CoV-2 , Estados Unidos/epidemiología , Blanco , Hispánicos o LatinosRESUMEN
BACKGROUND & AIMS: Porphyria cutanea tarda (PCT) is an iron-related disorder caused by reduced activity of hepatic uroporphyrinogen decarboxylase; it can be treated by phlebotomy or low doses of hydroxychloroquine. We performed a prospective pilot study to compare the efficacy and safety of these therapies. METHODS: We analyzed data from 48 consecutive patients with well-documented PCT to characterize susceptibility factors; patients were treated with phlebotomy (450 mL, every 2 weeks until they had serum ferritin levels of 20 ng/mL) or low-dose hydroxychloroquine (100 mg orally, twice weekly, until at least 1 month after they had normal plasma levels of porphyrin). We compared the time required to achieve a normal plasma porphyrin concentration (remission, the primary outcome) for 17 patients treated with phlebotomy and 13 treated with hydroxychloroquine. RESULTS: The time to remission was a median 6.9 months for patients who received phlebotomy and 6.1 months for patients treated with hydroxychloroquine treatment (6.7 and 6.5 mo for randomized patients), a difference that was not significant (log-rank, P = .06 and P = .95, respectively). The sample size was insufficient to confirm noninferiority of hydroxychloroquine treatment (hazard ratio, 2.19; 95% confidence interval, 0.95-5.06) for all patients. Patients who received hydroxychloroquine had substantially better compliance. There were no significant side effects of either treatment. CONCLUSIONS: Hydroxychloroquine, 100 mg twice weekly, is as effective and safe as phlebotomy in patients with PCT, although noninferiority was not established. Given these results, higher-dose regimens of hydroxychloroquine, which have more side effects, do not seem justified. Compliance was better and projected costs were lower for hydroxychloroquine than phlebotomy treatment. Long-term studies are needed to compare durability of response. ClinicalTrials.gov number, NCT01573754.
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Inhibidores Enzimáticos/administración & dosificación , Hidroxicloroquina/administración & dosificación , Flebotomía/métodos , Porfiria Cutánea Tardía/tratamiento farmacológico , Porfiria Cutánea Tardía/cirugía , Adulto , Anciano , Inhibidores Enzimáticos/efectos adversos , Femenino , Humanos , Hidroxicloroquina/efectos adversos , Masculino , Persona de Mediana Edad , Flebotomía/efectos adversos , Plasma/química , Porfirinas/sangre , Estudios Prospectivos , Resultado del TratamientoRESUMEN
Objective: We recently initiated microcracks, i.e. micron-scale cracks in the collagen networks of cartilage, using both single low-energy impacts and unconfined, cyclic compressions. We also tracked the propagation of microcracks after cyclic compressions simulating 12,000 walking strides. In this study, we aimed to determine the effect of one or more genipin treatments on: (1) the initiation of microcracks under mechanical impacts and (2) the subsequent propagation of microcracks under cyclic, unconfined compression. We hypothesized that treatments with genipin would improve the resistance of cartilage to microdamage, specifically reducing both the initiation of microcracks under impact loading and the propagation of microcracks under cyclic compression. Design: We tested 49 full-thickness, cylindrical osteochondral specimens. We incorporated one or two doses of genipin in between mechanical treatments, i.e. single low-energy mechanical impacts to initiate microcracks and unconfined, cyclic compressions to propagate microcracks. We also imaged specimens using second harmonic generation confocal microscopy, and analyzed the resulting images to quantify changes in morphologies (length, width, and depth) and orientations of microcracks. Finally, we used separate mixed-regression modeling to evaluate the effects of genipin treatments on mechanically induced microcracks. Results: Specimens treated with genipin presented significantly longer and marginally deeper microcracks after mechanical impacts. Two doses of genipin caused significantly longer and wider microcracks under propagation verses one dose. Conclusions: Our results do not support our hypothesis: unfortunately treatments with genipin, and the resulting mechanisms of cross-linking, do not provide resistance to microdamage, quantified as the initiation and propagation of microcracks.
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BACKGROUND: With recent COVID-19 vaccination rates relatively high in the USA, the USA still maintains the most documented cases globally,[1] even though COVID-19 cases, hospitalization, and mortality have been declining. However, the health burden has been largely felt in communities involving racial and ethnic minorities. Thus, in order to provide a clearer picture of what is happening in Black, Indigenous, and people of color communities, we examined the racial/ethnic differences of monthly COVID-19 deaths in Connecticut. METHODS: This is an epidemiological study analyzing mortality data from March 1, 2020, to February 28, 2021, obtained from the Connecticut State Department of Public Health. The data include cause of death (COVID-19 death identified by ICD-10 code U071), race/ethnicity (non-Hispanic White (White), non-Hispanic Black (Black), and Hispanic), sex, and age. Both crude and age-adjusted rates were reported by racial/ethnic groups. To compare age-adjusted rates between racial groups, with estimated age-adjusted death counts as outcomes, between-racial group rate ratios, 95% confidence intervals, and p values significant at < 0.05 were derived from the Poisson regression model. RESULTS: From March 2020 to May 2020 (wave 1) of COVID-19 cases, the COVID-19-related mortality rates were the highest for all three race groups (Whites, Blacks, and Hispanics) with statistical group differences (p < 0.05). Blacks had the highest rates of deaths followed by Hispanics and then Whites. Further, more Whites died in a nursing home when compared to Blacks and Hispanics. From June 2010 to October 2020 (wave 2), COVID-19 mortality declined significantly for all three race groups with no statistical differences between groups. COVID-19 deaths in nursing homes declined for all three racial/ethnic groups. From November 2020 to February 2021 (wave 3), COVID-19 mortality rates were significantly higher compared to wave 2 but lower than wave 1 for all three race groups. The mortality rates for Blacks and Hispanics were higher than Whites. Hispanics had the highest rates of deaths, followed by Blacks, and then Whites (p < 0.05). Whites showed the lowest mortality rates among all three racial/ethnic groups. CONCLUSIONS: In summary, COVID-19 health disparities among Black and Hispanic populations were evident in this study. Blacks and Hispanics had significantly higher mortality rates when compared to Whites. Blacks had the highest mortality rates during wave 1, and in wave 3, Hispanics has the highest mortality rates. Our data are important because they show monthly COVID-19 deaths data by race. Data reported this way gives a better and more accurate understanding of what is really happening in Black, Indigenous, and people of color populations.
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COVID-19 , Población Negra , Vacunas contra la COVID-19 , Connecticut/epidemiología , Hispánicos o Latinos , Humanos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Historically, Blacks and Hispanics have had lower opioid-involved overdose death rates in Connecticut (CT). We examined if a shift has taken place where rates of Black fatal overdoses have now surpassed Whites in the state. METHODS: Drug overdose fatality rates were calculated by number of deaths per year per 100,000 population from 2012 to 2019 in Connecticut. Measures were by race (White, Hispanic, Black, and Asian or Pacific Islander), age groups, and types of drugs, including fentanyl, heroin, cocaine, and other opioids. Poisson regression was used to test the interactions (race × age); joinpoint regression analysis was used to evaluate trend lines of fatality rate by racial/ethnic group within each age group with a significance level of p < 0.05. RESULTS: Drug overdose fatality rates in CT from 2012 to 2019 showed a significant increase for all races combined, estimated 3.6 deaths per 100,000 population per year. For Whites, overdose deaths were 4.6 per year from 2012 to 2017 with no change from 2017 to 2019. The overdose fatality rate for Hispanics was 3.0 and for Asian or Pacific Islanders 0.6 per year from 2012 to 2019. For Blacks, the death rates were statistically flat between 2012 and 2014; however, from 2015 to 2019, this group saw the largest average increase of 6.0 overdose deaths per 100,000 population each year. By 2019, the overdose fatality rate was higher in Blacks than in Whites, (39 vs. 38 per 100,000, respectively). Further, Blacks ages 50 years and over reported the highest overdose fatality rates among all race/age groups, an increase of 8.5 deaths per 100,000 population since 2014. CONCLUSIONS AND RELEVANCE: Connecticut is a microcosm of the opioid overdose trend in the New England region of our country. The majority of overdose deaths in CT involved illicit drugs, fentanyl, heroin, and cocaine, rather than prescription drugs. Blacks 50-years-old and over showed the fastest growing overdose death rates. Opioid deaths are now shifting to the Black community, creating an urgent public health crisis.
Asunto(s)
Cocaína , Sobredosis de Droga , Analgésicos Opioides , Connecticut/epidemiología , Sobredosis de Droga/epidemiología , Fentanilo , Heroína , Humanos , Persona de Mediana EdadRESUMEN
Older adults represent a vulnerable population with elevated risk for numerous morbidities. To explore the association of the microbiome with aging and age-related susceptibilities including frailty and infectious disease risk, we conducted a longitudinal study of the skin, oral, and gut microbiota in 47 community- or skilled nursing facility-dwelling older adults vs. younger adults. We found that microbiome changes were not associated with chronological age so much as frailty: we identified prominent changes in microbiome features associated with susceptibility to pathogen colonization and disease risk, including diversity, stability, heterogeneity, and biogeographic determinism, which were moreover associated with a loss of Cutibacterium (C.) acnes in the skin microbiome. Strikingly, the skin microbiota were also the primary reservoir for antimicrobial resistance, clinically important pathobionts, and nosocomial strains, suggesting a potential role particularly for the skin microbiome in disease risk and dissemination of multidrug resistant pathogens.
Asunto(s)
Fragilidad , Microbioma Gastrointestinal , Infecciones , Microbiota , Humanos , Anciano , Fragilidad/epidemiología , Estudios Longitudinales , Susceptibilidad a Enfermedades/microbiologíaRESUMEN
Porphyria cutanea tarda (PCT) is a cutaneous porphyria with sporadic (type 1) and familial (type 2) subtypes, both resulting from decreased hepatic uroporphyrinogen decarboxylase (UROD) activity. Environmental and genetic factors are involved in the development of PCT, and genetic variants in the cytochrome P450 (CYP ) genes, CYP1A1 and CYP1A2, have been implicated. We investigated the association between PCT and variants in CYP1A1, CYP1A2 and CYP2E1, and the glutathione-S-transferase (GST ) genes, GSTM1 and GSTT1. PCT diagnosis was based on urinary or plasma porphyrin profiles. Patients were classified as type 1 or 2 PCT based on UROD mutation analysis. The CYP1A2*1F promoter A allele frequency was significantly higher (P < 0.022) and the A/A genotype frequency marginally higher in PCT patients overall (P < 0.057), with the A/A genotype significantly more common in type 1 PCT (P < 0.043). The presence of the wild-type GSTM1 allele also was associated significantly with PCT (P < 0.019). Neither hemochromatosis (HFE) mutations, tobacco smoking, hepatitis C and HIV infection, ethanol consumption, nor estrogen use were associated with these allelic variants. Age at onset was significantly lower in type 2 PCT patients (P < 0.001), as observed previously. Thus, positive associations between PCT and the CYP1A2*1F promoter A allele and A/A genotype and the wild-type GSTM1 allele indicates that these functional hepatic biotransformation enzymes are risk factors for the development of this disease.