Symptom Clusters in Patients With Advanced Cancer: A Prospective Longitudinal Cohort Study to Examine Their Stability and Prognostic Significance.

This study's purpose was to assess symptom cluster (SC) stability during disease progression and determine their strength of association with survival in patients with advanced cancer . Consecutively eligible patients with advanced cancer not receiving cancer-specific treatment and referred to a Tertiary Palliative Care Clinic were enrolled in a prospective cohort study. At first consultation (D0) and in subsequent consultations at day 15 (D15) and day 30 (D30), patients rated 9 symptoms through the Edmonton Symptom Assessment System scale (0-10) and 10 others using a Likert scale (1-5). Principal components factor analysis with varimax rotation was used to determine SCs at each consultation. Of 318 patients with advanced cancer, 301 met eligibility criteria with a median age of 69 years (range 37-94). Three SCs were identified: neuro-psycho-metabolic (NPM), gastrointestinal, and sleep impairment, with some variations in their constitution over time. Exploratory factor analysis accounted for 40% of variance of observed variables in all SCs. Shorter median survival was observed continuously for NPM cluster (D0 23 vs. 58 days, P < .001; D15 41 vs. 104 days, P=.004; D30 46 vs. 114 days, P = .002), although the presence of 2 or more SCs on D0 and D15 also had prognostic significance (D0: 21 vs. 45 days, P = .005; D30: 50 vs. 96 days, P = .040). In a multivariable model, NPM cluster (D0 hazard ratio estimate: HR 1.64; 95%CI, 1.17-2.31; P = .005; D15 HR: 2.51; 95%CI, 1.25-5.05; P = .009; D30 HR: 3.9; 95%CI, 1.54-9.86; P = .004) and hospitalization (D0 HR: 2.27; 95%CI, 1.47-3.51; P < .001; D15 HR: 2.43; 95%CI, 1.18-5.01; P = .016; D30 HR: 3.41; 95%CI, 1.35-8.62; P = .009) were independently and significantly associated with worse survival. Three clinically relevant SCs were identified, and their constitution had small variations, maintaining a stable set of nuclear symptoms through disease progression. Presence of the NPM cluster and hospitalization maintained their prognostic value over time.

The Risk of Distant Metastases in Patients With Clinical Complete Response Managed by Watch and Wait After Neoadjuvant Therapy for Rectal Cancer: The Influence of Local Regrowth in the International Watch and Wait Database.

BACKGROUND: Nearly 30% of patients with rectal cancer develop local regrowth after initial clinical complete response managed by watch and wait. These patients might be at higher risk for distant metastases. OBJECTIVE: This study aimed to investigate risk factors for distant metastases using time-dependent analyses. DESIGN: Data from an international watch and wait database were retrospectively reviewed. Cox regression analysis was used to determine risk factors for worse distant metastases-free survival. Conditional survival modeling was used to investigate the impact of risk factors on the development of distant metastases. SETTING: Retrospective, multicenter database. PATIENTS: A total of 793 patients (47 institutions) with rectal cancer and clinical complete response to neoadjuvant treatment from the International Watch & Wait Database were included. MAIN OUTCOME MEASURES: Distant metastases-free survival. RESULTS: Of the 793 patients managed with watch and wait (median follow-up 55.2 mo)' 85 patients (10.7%) had distant metastases. Fifty-one of 85 patients (60%) had local regrowth at any time. Local regrowth was an independent factor associated with worse distant metastases-free survival in the multivariable model. Using conditional estimates, patients with local regrowth without distant metastases for 5 years (from decision to watch and wait) remained at higher risk for development of distant metastases for 1 subsequent year compared to patients without local regrowth (5-year conditional distant metastases-free survival 94.9% vs 98.4%). LIMITATIONS: Lack of information on adjuvant chemotherapy, salvage surgery for local regrowth, and heterogeneity of individual surveillance/follow-up strategies used may have affected results. CONCLUSIONS: In patients with clinical complete response managed by watch and wait, development of local regrowth at any time is a risk factor for distant metastases. The risk of distant metastases remains higher for 5 years after development of local regrowth. See Video Abstract at http://links.lww.com/DCR/C53. EL RIESGO DE METSTASIS A DISTANCIA EN PACIENTES CON RESPUESTA CLNICA COMPLETA MANEJADA POR WATCH AND WAIT DESPUS DE LA TERAPIA NEOADYUVANTE PARA EL CNCER DE RECTO LA INFLUENCIA DEL NUEVO CRECIMIENTO LOCAL EN LA BASE DE DATOS INTERNACIONAL WATCH AND WAIT: ANTECEDENTES:Casi el 30 % de los pacientes con cáncer de recto desarrollan un nuevo crecimiento local después de la respuesta clínica completa inicial manejada por watch and wait. Estos pacientes podrían tener un mayor riesgo de metástasis a distancia.OBJETIVO:Investigar los factores de riesgo de metástasis a distancia mediante análisis dependientes del tiempo.DISEÑO:Se revisó retrospectivamente los datos de la base de datos internacional de Watch and Wait. Se utilizó el análisis de regresión de Cox para determinar los factores de riesgo de peor sobrevida libre de metástasis a distancia. Se utilizó un modelo de sobrevida condicional para investigar el impacto de los factores de riesgo en el desarrollo de metástasis a distancia. El tiempo transcurrido hasta el evento se calculó utilizando la fecha de decisión para watch and wait y la fecha del nuevo crecimiento local para el diagnóstico de metástasis a distancia.ESCENARIOBase de datos multicéntrica retrospectiva.PACIENTES:Se incluyeron un total de 793 pacientes (47 instituciones) con cáncer de recto y respuesta clínica completa al tratamiento neoadyuvante de la base de datos internacional de Watch and Wait.PRINCIPALES MEDIDAS DE RESULTADO:Desarrollo de metástasis a distancia.RESULTADOS:De los 793 pacientes tratados con watch and wait (mediana de seguimiento de 55,2 meses), 85 (10,7%) tenían metástasis a distancia. 51 de 85 (60%) tuvieron recrecimiento local en algún momento. El recrecimiento local fue un factor independiente asociado a una peor supervivencia libre de metástasis a distancia en el modelo multivariable. Además, al usar estimaciones condicionales, los pacientes con recrecimiento local sin metástasis a distancia durante 5 años (desde la decisión de watch and wait) permanecieron en mayor riesgo de desarrollar metástasis a distancia durante un año subsiguiente en comparación con los pacientes sin recrecimiento local (sobrevida libre de metástasis a distancia a 5 años: recrecimiento local 94,9% frente a no recrecimiento local 98,4%).LIMITACIONES:La falta de información relacionada con el uso de quimioterapia adyuvante, las características específicas de la cirugía de rescate para el nuevo crecimient o local y la heterogeneidad de las estrategias individuales de vigilancia/seguimiento utilizadas pueden haber afectado los resultados observados.CONCLUSIONES:En pacientes con respuesta clínica completa manejados por Watch and Wait, el desarrollo de recrecimiento local en cualquier momento es un factor de riesgo para metástasis a distancia. El riesgo de metástasis a distancia sigue siendo mayor durante 5 años después del desarrollo de un nuevo crecimiento local. Consulte Video Resumen en http://links.lww.com/DCR/C53. (Traducción-Dr. Felipe Bellolio).

Positive and negative experiences of caregiving in dementia: The role of sense of coherence.

OBJECTIVES: Sense of coherence (SOC) is increasingly recognized as an important health determinant, particularly for mental health. Part of the evidence comes from informal caregivers in diverse clinical conditions. The extent to which SOC influences caregiving outcomes, however, is relatively under-researched in dementia, particularly regarding positive experiences. We analysed the association of SOC with dementia caregivers' subjective burden, psychological distress and positive aspects of care. METHODS/DESIGN: This is a secondary analysis of cross-sectional data from the Lisbon study of Families of Persons with Dementia, involving a convenience sample of 99 primary caregivers of community-dwelling patients of neurology and psychiatry services. SOC was assessed with the Orientation for Life Scale. Measures of caregivers' outcomes were: the Zarit Burden Interview, the General Health Questionnaire for psychological distress and the Positive Aspects of Caregiving scale. Analyses controlled for demographics, caregiving arrangements, objective burden, social support, patients' neuropsychiatric symptoms and dementia stage. RESULTS: Lower SOC was associated with higher psychological distress (p = 0.001). No significant associations were found for subjective burden (p = 0.081) or positive aspects of caregiving (p = 0.688). Additional analyses showed that lower SOC was associated with less emotional support (p < 0.001) and past psychiatric illness (p = 0.044). CONCLUSIONS: These findings support previous research suggesting that SOC is protective for psychological distress, and extend evidence to the positive aspects of care in dementia. The cross-sectional design and small-scale convenience sampling preclude both causality presumptions and generalizability. SOC assessments may be useful to define subgroups of dementia caregivers at risk for anxiety and depression.

The impact of indoor air quality on respiratory health of older people living in nursing homes: spirometric and exhaled breath condensate assessments.

In the Portuguese Geriatric Study of the Health Effects of Indoor Air Quality in Senior Nursing Homes, we aimed to evaluate the impact of indoor air contaminants on the respiratory symptoms and biomarkers in a sample of elderly living in nursing homes. A total of 269 elderly answered a health questionnaire, performed a spirometry and 150 out of these collected an exhaled breath condensate sample for pH and nitrites analysis. The study included the evaluation of indoor chemical and microbiological contaminants. The median age of the participants was 84 (78-87) years and 70.6% were women. The spirometric data indicated the presence of airway obstruction in 14.5% of the sample. Median concentrations of air pollutants did not exceed the existing standards, although increased peak values were observed. In the multivariable analysis, each increment of 100 µg/m3 of total volatile organic compounds was associated with the odds of respiratory infection in the previous three months ( OR̂ =1.05; 95% CI: 1.00-1.09). PM2.5 concentrations were inversely associated with pH values ( ß̂ = -0.04, 95%: -0.06 to -0.01, for each increment of 10 µg/m3). Additionally, a direct and an inverse association were found between total bacteria and FEV1/FVC and FVC, respectively.

CHOROIDAL THICKNESS IN DIABETIC PATIENTS WITHOUT DIABETIC RETINOPATHY.

PURPOSE: To compare choroidal thickness (CT) between diabetic patients without diabetic retinopathy and a nondiabetic group. To explore how CT relates to disease duration, mean arterial pressure, glycemia, glycosylated hemoglobin, intraocular pressure, and ocular pulse amplitude. METHODS: Choroidal thickness was assessed using a spectral-domain optical coherence tomography and enhanced depth mode at 13 locations (subfoveal and 3 measurements 500 µm apart in 4 directions-nasal, temporal, superior, and inferior). Linear regression models were used. RESULTS: One hundred seventy-five patients were recruited (125 diabetic patients without diabetic retinopathy and 50 nondiabetic patients). In diabetic patients, although without statistical significance, CT showed a trend to be thicker in all locations (6.16-24.27 µm). Choroidal thickness was negatively associated with age (P < 0.001) in both groups, but only in the diabetic group, it was positively associated to ocular pulse amplitude (with a mean increase between 8.5 µm and 11.6 µm for each millimeter of mercury increase in ocular pulse amplitude). Diabetic patients' CT seems to stabilize after 150 months of diabetes, increase with higher glycemia levels (>160 mg/dL) while showing no fluctuation with glycosylated hemoglobin and mean arterial pressure. CONCLUSION: There seems to be a thickening of the choroid in diabetic patients without diabetic retinopathy. Moreover, this tissue may be functionally different in diabetes, as the pattern of associations seems to differ between groups.

Extended-release niacin increases anti-apolipoprotein A-I antibodies that block the antioxidant effect of high-density lipoprotein-cholesterol: the EXPLORE clinical trial.

AIMS: Extended-release niacin (ERN) is the most effective agent for increasing high-density lipoprotein-cholesterol (HDL-C). Having previously identified anti-HDL antibodies, we investigated whether ERN affected the antioxidant capacity of HDL and whether ERN was associated with the production of antibodies against HDL (aHDL) and apolipoprotein A-I (aApoA-I). METHODS: Twenty-one patients older than 18 years, with HDL-C ≤40 mg dl-1 (men) or ≤50 mg dl-1 (women) were randomly assigned to receive daily ERN (n = 10) or placebo (n = 11) for two sequential 12-week periods, with 4 weeks of wash-out before cross-over. Primary outcome was change of paraoxonase-1 (PON1) activity and secondary outcomes were changes in aHDL and aApoA-I antibodies. Clinical Trial Unique Identifier: EudraCT 2006-006889-42. RESULTS: The effect of ERN on PON1 activity was nonsignificant (coefficient estimate 20.83 U l-1 , 95% confidence interval [CI] -9.88 to 51.53; P = 0.184). ERN was associated with an increase in HDL-C levels (coefficient estimate 5.21 mg dl-1 , 95% CI 1.16 to 9.25; P = 0.012) and its subclasses HDL2 (coefficient estimate 2.46 mg dl-1 , 95% CI 0.57 to 4.34; P = 0.011) and HDL3 (coefficient estimate 2.73 mg dl-1 , 95% CI 0.47 to 4.98; P = 0.018). ERN was significantly associated with the production of aApoA-I antibodies (coefficient estimate 0.25 µg ml-1 , 95% CI 0.09-0.40; P = 0.001). aApoA-I titres at baseline were correlated with decreased PON activity. CONCLUSIONS: The rise in HDL-C achieved with ERN was not matched by improved antioxidant capacity, eventually hampered by the emergence of aApoA-I antibodies. These results may explain why Niacin and other lipid lowering agents fail to reduce cardiovascular risk.

The Association Between Antihypertensive Medication and Blood Pressure Control in Patients with Obstructive Sleep Apnea.

Obstructive sleep apnea and hypertension are closely related diseases. The lowering effect of continuous positive airway pressure (CPAP) on blood pressure (BP) control is modest and concomitant antihypertensive therapy is still required. However, the best antihypertensive regimen for BP control in patients with OSA remains unknown. We aimed to investigate a hypothetical association between ongoing antihypertensive medication and BP control rates in patients with OSA. We conducted a prospective observational study in a cohort of 205 patients with OSA and hypertension who underwent a sleep study and 24-h ambulatory blood pressure monitoring (ABPM). Ongoing antihypertensive medication profile was recorded. Logistic regression models were used to investigate the association between antihypertensive regimen and BP control, before (n = 205) and, when applicable, after CPAP adaptation (n = 90). One hundred and fifty-five patients (155/205) were being treated with 31 different antihypertensive regimens. At baseline, the antihypertensive regimens and the number of antihypertensive drugs were not associated with BP control (p = 0.847; p = 0.991). After CPAP adaptation, a decrease in median night-time systolic and diastolic BP was observed (p = 0.001; p = 0.006). Nevertheless, the lack of association between antihypertensive regimens and the number of antihypertensive drugs and BP control remained (p = 0.864; p = 0.800). Our findings confirm that although CPAP improves nocturnal BP, this improvement is not sufficient to control blood pressure for 24 h. This study shows, for the first time, that in patients with OSA, there is no association between BP control and both the antihypertensive regimen and the number of antihypertensive drugs.

Stomach cancer incidence in Southern Portugal 1998-2006: a spatio-temporal analysis.

Stomach cancer belongs to the most common malignant tumors in Portugal. Main causal factors are age, dietary habits, smoking, and Helicobacter pylori infections. As these factors do not only operate on different time dimensions, such as age, period, or birth cohort, but may also vary along space, it is of utmost interest to model temporal and spatial trends jointly. In this paper, we analyze incidence of stomach cancer in Southern Portugal between 1998 and 2006 for females and males jointly using a spatial multivariate age-period-cohort model. Thus, we avoid age aggregation and allow the exploration of heterogeneous time trends between males and females across age, period, birth cohort, and space. Model estimation is performed within a Bayesian setting assuming (gender specific) smoothing priors. Our results show that the posterior expected rate of stomach cancer is decreasing for all counties in Southern Portugal and that males around 70 have a two times higher risk of getting stomach cancer compared with their female counterparts. We further found that, except for some few counties, the spatial influence is almost constant over time and negligible in the southern counties of Southern Portugal.

Impact of psychosis on Portuguese caregivers: a cross-cultural exploration of burden, distress, positive aspects and clinical-functional correlates.

PURPOSE: Further cross-cultural comparisons are needed on caregiving consequences of chronic psychotic disorders. The EPSILON study (European Psychiatric Services: Inputs Linked to Outcome Domains and Needs) involved five European countries, but not Portugal. We aimed to analyse the impact of severe mental illness in a Portuguese sample and to provide support to comparisons with some of the EPSILON results, focusing on the north-European Dutch centre. METHODS: We studied 108 caregiver-patient dyads by a consecutive sampling of people with schizophrenia-spectrum disorders in psychiatric outpatient services. Relatives' assessments included the Involvement Evaluation Questionnaire, European version (IEQ), the 12-item General Health Questionnaire (GHQ-12); the loss, stigma and positive aspects' subscales of the Experience of Caregiving Inventory, and the Social Network and Family Coping Questionnaires. Patients were assessed regarding symptoms, disability and global functioning. RESULTS: Caregiving rewards and negative consequences co-existed. On the IEQ, 49.1% reported negative consequences and rank order of domain scores was worrying > urging > tension > supervision. More than one-third of caregivers were psychologically distressed according to GHQ screenings. Involvement Evaluation Questionnaire scores were correlated with caregivers' distress, stigma, loss, patient's involvement and other ways of coping, and patients' variables. Some of these failed to be included in a regression model. CONCLUSIONS: Many of these Portuguese caregivers were at risk regarding burden and psychological distress. In comparison with other European samples, caregiving arrangements and assessments were typical of Mediterranean countries, as Italy or Spain. All IEQ scores were significantly higher than those in the Netherlands. On account of small numbers, caution is needed in the interpretation of associations.

Caregiving in severe mental illness: the psychometric properties of the Involvement Evaluation Questionnaire in Portugal.

BACKGROUND: Despite the achievements of previous research, caregiving assessments in severe mental illness should be crossculturally validated in order to define risk groups or to evaluate family work. This study reports on the psychometric properties of the European version of the Involvement Evaluation Questionnaire (IEQ-EU) in Portugal. METHODS: A Portuguese translation of the IEQ-EU was developed according to the 'European Psychiatric Services: Inputs Linked to Outcome Domains and Needs' (EPSILON) group guidelines. We then studied 194 caregivers who were related to patients with schizophrenia spectrum disorders in psychiatric outpatient services. All relatives were assessed using the IEQ-EU. In order to describe the corresponding patients' sample, the majority (n = 162) was evaluated with the World Health Organization Disability Assessment Schedule (WHO-DAS II); 108 patients were also assessed with the Brief Psychiatric Rating Scale (BPRS) and the Global Assessment of Functioning (GAF). RESULTS: The factor structure of the Portuguese version of the questionnaire was similar to the original; internal consistency was good, with Cronbach's α ranging from 0.71 to 0.87 in the IEQ-EU scales (total score and domains: tension, supervision, worrying, urging); test-retest reliability yielded intraclass correlation coefficients (ICCs) from 0.80 to 0.94, concerning the same scores. Ecological validity was confirmed. Most caregiving consequences were reported on the worrying domain of the IEQ-EU. CONCLUSIONS: Validity and reliability of the Portuguese IEQ-EU translation were established. Specifically the four IEQ-EU subscale domains seem to be valid in Portugal.

Audiological biomarkers of tinnitus in an older Portuguese population.

Tinnitus is a phantom sound perceived in the absence of external acoustic stimulation. It is described in a variety of ways (e.g., buzzing, ringing, and roaring) and can be a single sound or a combination of different sounds. Our study evaluated associations between audiological parameters and the presence or severity of tinnitus, to improve tinnitus diagnosis, treatment, and prognosis. Our sample included 122 older participants (63 women and 59 men), aged 55-75 years from the Portuguese population, with or without sensory presbycusis and with or without tinnitus. All participants underwent a clinical evaluation through a structured interview, Ear, Nose, and Throat observation, and audiological evaluation (standard and extended audiometry, psychoacoustic tinnitus evaluation, auditory brainstem responses, and distortion product otoacoustic emissions). The Tinnitus Handicap Inventory was used to measure tinnitus symptom severity. Our data confirmed that the odds of developing tinnitus were significantly higher in the presence of noise exposure and hearing loss. Also, participants who had abrupt tinnitus onset and moderate or severe hyperacusis featured higher odds of at least moderate tinnitus. However, it was in the ABR that we obtained the most exciting and promising results, namely, in wave I, which was the common denominator in all findings. The increase in wave I amplitude is a protective factor to the odds of having tinnitus. Concerning the severity of tinnitus, the logistic regression model showed that for each unit of increase in the mean ratio V/I of ABR, the likelihood of having at least moderate tinnitus was 10% higher. Advancing knowledge concerning potential tinnitus audiological biomarkers can be crucial for the adequate diagnosis and treatment of tinnitus.

Retinal and choroidal thickness changes in systemic lupus erythematosus patients: a longitudinal study.

BACKGROUND/OBJECTIVES: To prospectively evaluate changes in peripapillary retinal nerve fibre layer (pRNFL), in all macular layers and in choroidal thickness (CT) in a cohort of systemic lupus erythematosus (SLE) patients without ophthalmologic manifestations. To associate those changes with ophthalmic characteristics, disease activity state, medication and systemic comorbidities. SUBJECTS/METHODS: Prospective cohort study of 68 previously diagnosed SLE patients. In two study visits (V1 and V2) at least 12 months apart, patients underwent a complete ophthalmologic examination including spectral domain-optical coherence tomography (SD-OCT) and an autoimmune disease specialist assessment. Automatic retinal segmentation was performed. pRNFL was determined globally and in the six peripapillary sectors and each macular layer thickness was determined in the nine early treatment diabetic retinopathy study (ETDRS) subfields. CT was manually measured at 13 locations in the posterior pole. Only one eye per patient was randomly selected for inclusion. Generalised linear mixed effects models were employed. RESULTS: Sixty-five patients completed the study. The median follow-up time was twelve months. At V2, pRNFL was significantly thinner globally (p = 0.006) and in the temporal inferior sector (p = 0.017). Patients under chronic medication with anticoagulants or antihypertensives had significantly thinner pRNFL in some locations. No significant changes were observed in macular layers or choroidal thickness between study visits. CONCLUSIONS: SLE patients presented early SD-OCT signs of neurodegeneration, evidenced by a progressive reduction in pRNFL thickness. Regardless of study visit, baseline chronic medication with anticoagulants or antihypertensives was associated with lower pRNFL thickness, accounting for a deleterious effect of cardiovascular risk factors.

Caregiving experiences and knowledge about dementia in Portuguese clinical outpatient settings.

BACKGROUND: Important public health and clinical issues remain unanswered concerning disease-related knowledge and caregiving experiences in dementia. The aim of this study is to describe these dimensions in Portuguese clinical settings and analyze the link between knowledge and burden, and also between knowledge and positive caregiving experiences. METHODS: We studied a non-randomized sample of 116 caregivers of outpatients with ICD10-DCR diagnosis of dementia. Comprehensive assessments included Dementia Knowledge Questionnaire (DKQ), Zarit Burden Interview (ZBI), Caregiving Activity Survey (CAS), Positive Aspects of Caregiving (PAC) and General Health Questionnaire-12 (GHQ). Portuguese translations for DKQ, ZBI and PAC scales had been developed; validity aspects were documented, as well as test-retest reliability coefficients for ZBI (ICC = 0.93) and PAC (ICC = 0.85). RESULTS: Most caregivers were close relatives, female and living with the patient. Although positive aspects of care were reported, burden and distress levels were moderate to high. Knowledge needs were not striking. Distress was moderately correlated to burden, but no associations were found between caregivers' knowledge and ZBI, PAC or GHQ. DKQ scores did not predict PAC nor ZBI scores. A relationship was found between ZBI, as dependent variable, and PAC, GHQ and CAS. CONCLUSIONS: A large proportion of caregivers in this sample, albeit informed about dementia, were at risk of high burden and distress. Knowledge about dementia may not be protective of burden per se, nor did it influence positive aspects of caregiving.

A comparison of primary and secondary caregivers of persons with dementia.

Having 2 or more relatives involved in the informal care of people with dementia is frequent worldwide. There are, however, few comparisons of primary and secondary caregivers and even fewer of those who are caring for the same person. Our study aimed to contrast these 2 experiences of caregiving. We compared 2 related samples of 61 primary and 61 secondary family caregivers of the same persons with dementia in a nonrandomized cross-sectional study. Caregivers' main outcome assessments were the Zarit Burden Interview (for subjective burden), the General Health Questionnaire (for psychological distress), and the Positive Aspects of Caregiving scale. We controlled for caregiver variables (e.g., demographics, caregiving arrangements, social support, sense of coherence) and the neuropsychiatric symptoms of dementia. Subjective burden was higher in primary than secondary caregivers (p = .013), but positive aspects of caregiving did not differ (p = .150). Psychological distress was high at clinically relevant levels in primary and secondary caregivers, without statistically significant differences between groups (p = .456). The findings demonstrate that notwithstanding the difficulties faced by primary caregivers, secondary caregivers may also experience clinically significant distress. Therefore, their needs for assistance and support should be addressed more systematically. These findings call for systemic family-focused interventions in dementia that address the support each person provides or might provide, as well as the psychological distress each person may feel. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Neurodegeneration in systemic lupus erythematosus: layer by layer retinal study using optical coherence tomography.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic, autoimmune and multisystemic disease. Recent studies with functional and structural magnetic resonance imaging and cognitive tests report an unexpectedly high frequency of central nervous system involvement, even in patients with asymptomatic SLE. The purpose of this study was to identify early signs of retinal neurodegeneration by comparing the thickness of the peripapillary retinal nerve fiber layer (pRNFL) and all macular layers between patients with SLE without ophthalmologic manifestations and healthy controls. The effect of disease duration and systemic comorbidities was also studied. METHODS: Cross-sectional study, in which all participants underwent a complete ophthalmologic evaluation including retinal segmentation analysis with spectral domain-optical coherence tomography. Patients with SLE also received a detailed autoimmune disease specialist evaluation to assess the disease activity state and systemic involvement. For pRNFL thickness, the global and six peripapillary sectors were determined. Each macular layer thickness was determined in the nine Early Treatment Diabetic Retinopathy Study (ETDRS) subfields. A multiple linear regression analysis was performed to control for the effect of potential demographic, ophthalmic and systemic confounders. A second multivariable analysis, including patients with SLE only, was performed to assess the effect of disease-specific variables on the outcome measures. RESULTS: Sixty-eight eyes of 68 patients with SLE and 50 eyes of 50 healthy controls were considered. The pRNFL was significantly thinner in the SLE group globally (p = 0.026) and in the temporal superior (p = 0.007) and temporal (p = 0.037) sectors. In patients with SLE, chronic medication for hypercholesterolemia, hypertension and anticoagulants were associated with a significant thinning of the pRNFL. Patients with SLE presented significant thinning in the photoreceptor layer in five ETDRS areas (p < 0.05). Shorter disease duration was associated with greater photoreceptor thinning in all ETDRS subfields. Neuropsychiatric SLE, higher disease activity and cardiovascular risk factors were associated with a thinner photoreceptor layer. No differences were observed in overall retinal thickness or the remaining macular layers. CONCLUSION: Patients with SLE present early signs of retinal neurodegeneration, as evidenced by a reduction in the photoreceptor layer and pRNFL. These signs are more pronounced in patients with higher cardiovascular risk burden or neuropsychiatric involvement.

Efavirenz concentrations in HIV-infected patients with and without viral hepatitis.

AIMS: Data on efavirenz in HIV/viral hepatitis co-infected patients is non-consensual, probably due to liver function heterogeneity in the patients included. METHODS: A case control study was performed on 27 HIV-infected patients, with controlled and homogenous markers of hepatic function, either mono-infected or co-infected with HBV/HCV, to ascertain the influence of viral hepatitis on efavirenz concentrations over a 2-year follow-up period. RESULTS: No differences were found in efavirenz concentrations between groups both during and at the end of the follow-up period: control (2.43 +/- 1.91 mg l(-1)) vs. co-infected individuals (2.37 +/- 0.37 mg l(-1)). CONCLUSION: It was concluded that HBV/HCV infections in themselves do not predispose to an overexposure to efavirenz.

Reference values for spirometry in elderly individuals: a cross-sectional study of different reference equations.

BACKGROUND: Spirometry is the single most important test for the evaluation of respiratory function. The results are interpreted by comparing measured data with predicted values previously obtained from a reference population. Reference equations for spirometry have been discussed previously. The aim of this study was to compare reference values based on National Health and Nutrition Assessment Survey (NHANES III), European Community of Steel and Coal (ECSC), and Global Lung Initiative (GLI) equations in an elderly sample population. METHODS: Subjects from the Geriatric Study on Health Effects of Air Quality in elder care centres who met the inclusion criteria were enrolled. Spirometry was performed according to international guidelines. The forced vital capacity, forced expiratory volume in 1 s, and FEV1/FVC ratio were reported as percentages of the predicted value, and the lower limit of normality was calculated. RESULTS: Out of 260 elderly patients, 69.6% were women; the mean age was 83.0 ± 6.46 years with an age range of 65-95 years. The lowest %FVC and %FEV1 values were obtained using the GLI reference equations. However, when NHANES III equations were used, the FEV1/FVC ratio was higher than ratios obtained from GLI and ECSC equations. The prevalence of airway obstruction was highest using ECSC equations, while GLI equations demonstrated more restrictive defects. CONCLUSIONS: The present study showed meaningful differences in the reference values, and consequently, in the results obtained using NHANES III, ECSC, and GLI reference equations. The spirometry interpretation was also influenced by the reference equations used.

Antibodies against HDL Components in Ischaemic Stroke and Coronary Artery Disease.

Quantitative and qualitative defects of high-density lipoprotein (HDL) are important in atherogenesis. In this study, we investigated whether antibodies against HDL components had additional value to conventional cardiovascular risk factors for the diagnosis of ischaemic stroke (IS) and coronary artery disease (CAD). Cross-sectional study was conducted on 53 patients with IS, 51 with CAD and 55 healthy controls, and in vitro studies to validate findings of the clinical study. We determined serum immunoglobulin G (IgG) antibodies against HDL (aHDL), apolipoproteins (aApoA-I, aApoA-II and aApoC-I) and paraoxonase-1 (aPON1) as well as PON1 activity (PON1a), total antioxidant capacity and biomarkers of endothelial activation (serum nitric oxide metabolites, 3-nitrotyrosine, VCAM-1 and ICAM-1); in vitro assays tested the capacity of IgG aHDL purified from high titer patients to inhibit PON1a and to reverse protective effect of HDL on endothelial cells. IgG aHDL, aApoA-I and aPON1 were higher in IS and CAD than controls (p < 0.001), predicted negatively PON1a and positively VCAM-1 and ICAM-1. By adding IgG aHDL and aApoA-I to a traditional cardiovascular risk factors model for IS and by adding IgG aHDL in a similar model for CAD, we obtained better discrimination of IS and CAD from healthy controls. IgG aHDL purified from IS and CAD inhibited PON1a by 38% (p < 0.01) and abrogated the protective effect of HDL on VCAM-1 expression by 126% compared with non-specific human IgG (p < 0.001). IgG against HDL components interfere with the antioxidant and anti-inflammatory properties of HDL and may represent novel biomarkers for vascular disease that need to be investigated in prospective studies.