Anticipation of age at onset in multiple sclerosis: methodologic pitfalls.

BACKGROUND/AIM: There are several reports that claim anticipation in complex or polygenic diseases such as multiple sclerosis (MS), Crohn disease or schizophrenia. The aim of the present study was to assess age at onset of MS during the last 60 years in the region of Costa de Ponent (Barcelona, Spain) showing how apparent changes in age at onset between generations can be an artefact of analysis based on cohorts that have not been followed enough time. METHODS: The study comprised 1100 patients diagnosed of MS. The method used to correct for follow-up time bias involves constructing comparison cohorts that had been observed for the same amount of time. To ensure equal follow-up times, we restricted our analysis to patients whose onset was by 37 years of age (percentile 75) and were at least 37 years old. We analysed differences in age at onset using log-rank test to compare survival curves estimated by Kaplan-Meier method. RESULTS: Age at onset decreases progressively from older to younger generations. However, when adjustment to equal follow-up time was done, anticipation in age at onset was not found. CONCLUSION: Anticipation of age at onset is undetectable when adjusted for follow-up time.

Oral health-related quality of life and nutritional status.

OBJECTIVES: This study examines whether oral health-related quality of life (OHRQoL) is associated with malnutrition risk in the elderly. METHODS: A cross-sectional study was designed using a representative sample of Spaniards over 65 years old. Data on sociodemographics and oral health status were gathered by interview and examination. Oral health-related quality of life was evaluated using the Geriatric Oral Health Assessment Index (GOHAI), and malnutrition risk using the Mini Nutritional Assessment (MNA). RESULTS: The final sample included 2,860 elderly, 41.7 percent males and 58.3 percent females, with a mean age of 73.7 +/- 6.8 years. Mean GOHAI score was 52.1 +/- 7.2, with 70.7 percent of the sample needing oral health care according to this index. The mean MNA score was 24.0 +/- 3.31; 3.5 percent of the elderly were malnourished, 31.5 percent were at risk of malnutrition, and 65.0 percent were considered adequately nourished. A strong association was found between mean GOHAI and MNA scores.

Prevalence of dementia subtypes in El Prat de Llobregat, Catalonia, Spain: the PRATICON study.

BACKGROUND: Studies on dementia subtypes show a wide variation in the prevalence of Alzheimer's disease (AD) and vascular dementia (VD) worldwide. However, studies reporting on Lewy body dementia (LBD) and frontotemporal dementia (FTD) are sparse. AIMS: To describe the prevalence of dementia and subtypes. METHOD: A 34% sample of 5,150 subjects aged 70 years and over in El Prat de Llobregat (Barcelona) were screened by the Mini-Mental State Examination. When scoring <24, participants were assessed to establish a diagnosis. RESULTS: There were 165 subjects diagnosed with dementia (prevalence of 9.4%). Subtypes of dementia were: AD 69.1%, VD 12.7%, LBD 9.1%, FTD 3% and secondary dementia 1.8%. Prevalences were: AD 6.5%, VD 1.2%, LBD 0.9% and FTD 0.3%. CONCLUSIONS: AD and VD were the most common type of dementia. Prevalence of dementia, AD and FTD were similar to those reported, while prevalence of VD and LBD were lower.

Weight loss and quality of life in patients surviving 2 years after gastric cancer resection.

BACKGROUND: Malnutrition is common in patients undergoing gastric cancer resection, leading to weight loss, although little is known about how this impacts on health-related quality of life (HRQL). This study aimed to explore the association between HRQL and weight loss in patients 2 years after curative gastric cancer resection. METHODS: Consecutive patients undergoing curative gastric cancer resection and surviving at least 2 years without disease recurrence were recruited. Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the specific module for gastric cancer (STO22) before and 2 years postoperatively and associations between HRQL scores and patients with and without ≥ 10% body weight loss (BWL) were examined. RESULTS: A total of 76 patients were included, of whom 51 (67%) had BWL ≥10%. At 2 years postoperatively, BWL ≥10% was associated with deterioration of all functional aspects of quality of life, with persistent pain (21.6%), diarrhoea (13.7%) and nausea/vomiting (13.7%). By contrast, none of the patients with BWL <10% experienced severe nausea/vomiting, pain or diarrhoea. CONCLUSIONS: Disabling symptoms occurred more frequently in patients with ≥10% BWL than in those with <10% BWL, with a relevant negative impact on HRQL. A cause-effect relationship between weight loss and postoperative outcome remains unsolved.

Photodynamic therapy with intravitreal triamcinolone in predominantly classic choroidal neovascularization: one-year results of a randomized study.

PURPOSE: To determine whether intravitreal triamcinolone acetonide (IVTA) improves the efficacy of photodynamic therapy (PDT) with verteporfin in predominantly classic subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). DESIGN: Prospective randomized study. PARTICIPANTS: Sixty-one patients with predominantly classic subfoveal CNV secondary to AMD. METHODS: Patients were randomized to receive PDT (n = 30) or PDT followed by approximately 11 mg IVTA (n = 31), with retreatment every 3 months when leakage was documented by fluorescein angiography. At baseline and each follow-up visit, best-corrected visual acuity (VA) was measured with Early Treatment Diabetic Retinopathy Study charts by a certified examiner masked to the patient's treatment, lesion size on fluorescein angiography, and foveal thickness on optical coherence tomography. MAIN OUTCOME MEASURES: Mean change in VA (logarithm of the minimum angle of resolution [logMAR]) from baseline, percentage of patients losing fewer than 15 letters (3 lines) of VA, mean change in lesion size, mean change in foveal thickness, and retreatment rate. RESULTS: At the 12-month follow-up, VA (mean logMAR change from baseline) was significantly better (P = 0.001) in the group of patients who received combined therapy. Seventy-four percent of patients treated with combined therapy compared with 61% treated with verteporfin alone lost fewer than 15 letters of VA (P = 0.78). Reduction in lesion size (P = 0.001) and in foveal thickness (P = 0.03) was significantly greater with combined therapy than with verteporfin. Retreatment rate was significantly lower (P = 0.04) in the combined therapy group. Triamcinolone-related adverse events included glaucoma (25.8%) and cataract progression (32%). CONCLUSIONS: Combined PDT and IVTA therapy seemed to be more effective than PDT alone for managing predominantly classic subfoveal lesions secondary to AMD. The triamcinolone-related adverse events included glaucoma and cataract progression.

[Postoperative pain management in a tertiary care hospital: initial situation prior to starting a quality assurance program]. / Atención del dolor postoperatorio en un hospital de tercer nivel: situación inicial previa a la implantación de un programa de calidad.

OBJECTIVE: To characterize the initial situation in postoperative pain management among the services General and Vascular surgery as the first step in developing a program to improve postoperative analgesia. METHODS: An anonymous questionnaire with 14 items covered the characteristics of postoperative pain, information received about analgesic treatments and requesting medication, and degree of satisfaction. The questionnaire was filled in during an early postoperative interview with all patients undergoing surgery in the aforementioned departments. RESULTS: A total of 158 patients were interviewed; 89% were from the general surgery department and 11% from vascular surgery. At 24 hours after surgery, 18% were free of pain, 35% had mild pain, and 47% had moderate or intense pain. Nonsteroidal anti-inflammatory drugs were the most frequently used postoperative analgesics, in 94% of patients, and the dosage and timing had been prescribed for 74%. Thirty-six percent of the patients asked for an analgesic to be administered. The correlation between degree of greatest pain and request for an analgesic was statistically significant (P < 0.001). CONCLUSIONS: Postoperative pain is an area in which improvements can be implemented to provide better care and treatment of surgical patients, particularly since there are efficacious analgesic treatments for pain control that are presently not being used. The custom of prescribing pain medication on demand should be avoided in all surgical procedures that are known to produce postoperative pain.

Postoperative complications do not impact on recurrence and survival after curative resection of gastric cancer.

BACKGROUND: We assessed the impact of complications on recurrence and survival after curative gastric cancer resection. METHODS: Patients undergoing R0 resections between 1990 and 2009 were identified in a prospectively maintained database and were categorized by presence of any complication Clavien-Dindo (CD) ≥ II, sepsis or intra-abdominal sepsis. Cox regression analyses to relate complications and clinico-pathological variables to time to recurrence (TTR) and overall survival (OS) were performed. RESULTS: A total of 271 patients were included with a median follow-up of 149.9 months (range 140.1-159.9). Complications CD ≥ II occurred in 162 (59.8%) patients, sepsis in 66 (22.5%), and intra-abdominal sepsis in 37 (13.6%). Recurrence developed in 88 (32.4%) patients. Independent predictors of short TTR were pTNM stage (IIIB-IIIC vs. IA-IIA) (hazard ratio [HR] = 37.55, 95% confidence interval [CI] 17.57-80.24; p < 0.001), D1 lymphadenectomy (HR = 3.14, 95% CI 1.94-5.07; p < 0.001), and male gender (HR = 1.65, 95% CI 1.06-2.57; p = 0.026). pTNM stage (IIIB-IIIC vs. IA-IIA, HR = 10.28, 95% CI 6.51-16.23; p < 0.001), male gender (HR = 1.64, 95% CI 1.17-2.31; p = 0.005), age (HR = 1.03, 95% CI 1.02-1.05; p < 0.001), and adjuvant therapy (HR = 0.55, 95% CI 0.37-0.83; p = 0.004) were identified as independent predictors of OS.. CONCLUSIONS: Evidence provided by this study does not support a negative impact of postoperative complications CD ≥ II, sepsis, and intra-abdominal sepsis on the oncologic outcome after curative gastric cancer resection.

Long-term clinical outcome of paraneoplastic cerebellar degeneration and anti-Yo antibodies.

The outcome of 34 women with anti-Yo-associated paraneoplastic cerebellar degeneration was reviewed. Three patients had not developed cancer after more than 4 years of follow-up. The only independent predictor for survival was the type of associated tumor (risk ratio, 1.79; 95% CI, 1.02 to 3.12). Median survival was 100 months for patients with breast cancer and 22 for those with gynecologic cancer. Although paraneoplastic cerebellar degeneration leads to the diagnosis of cancer in 63% of the patients, cancer progression was the cause of death in 52%.

14-3-3 protein in the CSF as prognostic marker in early multiple sclerosis.

Axonal damage probably occurs early in the evolution of MS. Five of 38 (13%) patients had a positive assay for the neuronal 14-3-3 protein in the CSF obtained at the first clinically isolated syndrome suggestive of MS. A positive 14-3-3 assay was the only independent predictor for a shorter time to conversion to clinical definite MS (risk ratio 4.1; 95% CI 1.1 to 15) and to reach an Expanded Disability Status Scale (EDSS) > or =2 at the end of follow-up (odds ratio 14.8; 95% CI 2.86 to 76.8). The detection of the 14-3-3 protein in the CSF at the first neurologic event suggestive of MS may be a useful predictor of short-term evolution.

Recipient body surface area as a predictor of posttransplant renal allograft evolution.

BACKGROUND: The aim of the present study was to analyze whether minor differences in recipient body surface area have any predictive value on renal allograft evolution. METHODS: For this study, we considered 236 pairs of recipients who received a kidney from the same donor at our center between March 1985 and December 1995. Pairs in whom at least one patient presented any of the following events were excluded: graft loss during the first year of follow-up, diabetes mellitus, noncompliance with treatment, chronic pyelonephritis, and recurrent or de novo glomerulonephritis. Recipients of each pair were classified as large or small according to their body surface area (BSA). The percentage difference of BSA in each pair was calculated, and two cohorts of pairs were defined: BSA difference < or = 10% (n=76 pairs) and BSA difference >10% (n=70 pairs). RESULTS: The large recipients of the cohort with a BSA difference >10% showed a higher incidence of posttransplant delayed graft function (22/70 vs. 12/70, P=0.075), hypertension at 1 year of follow-up (51/70 vs. 35/70, P=0.006), and a higher serum creatinine level at 1-year follow-up (173 vs. 142 micromol/L, P=0.003), whereas in the cohort with a BSA difference < or = 10%, posttransplant evolution in large and small recipients was not different. Multivariate analysis showed that recipient BSA was an independent predictor of delayed graft function, posttransplant hypertension, and serum creatinine at 1-year follow-up. CONCLUSIONS: Relatively small differences in recipient BSA influence renal allograft evolution. Consequently, our data support that recipient size should be taken into consideration for renal allograft allocation.

The impact of donor age on liver transplantation: influence of donor age on early liver function and on subsequent patient and graft survival.

BACKGROUND: The urgent need to increase the organ donor pool has led to the expansion of criteria for donor selection. The aim of this study was to analyze the influence of donor age on early graft function, subsequent graft loss, and mortality after liver transplantation (LT). METHODS: Data on LT were evaluated retrospectively in a population-based cohort of 400 LTs in 348 patients. Of these, 21 (5%) were from donors >70 years old. Pretransplantation donor and recipient characteristics and the evolution of recipients were analyzed. The influence of donor age as a risk factor was assessed using univariate and multivariate analyses. RESULTS: Actuarial graft survival was 89% at 1 month after LT, 81% after 6 months, and 59% after 60 months. Multivariate analysis demonstrated that only donor age (>70 years old) was associated with a higher risk of long-term graft loss (relative risk [RR]=1.4, 95% confidence interval [CI]=1-1.9; P=0.03) and mortality (RR=1.7, 95% CI=1.2-2.3; P=0.01). Graft survival of septuagenarian livers was 80% at 1 month after LT, 56% after 6 months, and 25% after 54 months. Actuarial survival analysis (Kaplan-Meier curves) also demonstrated worse evolution in recipients of livers from old donors (log-rank test, P<0.001). CONCLUSIONS: Advanced donor age is associated with lower graft and recipient survival.

Protocol renal allograft biopsies and the design of clinical trials aimed to prevent or treat chronic allograft nephropathy.

BACKGROUND: The minimum sample size to perform a clinical trial aimed to modify the natural history of chronic allograft nephropathy (CAN) is very large. Since the presence of chronic tubulointerstitial damage in renal protocol biopsy specimens is an independent predictor of late outcome, we evaluated whether protocol biopsies could facilitate the design of trials aimed to prevent or treat CAN. METHODS: Two hundred eighty-two protocol biopsy specimens were obtained 3 months after transplantation in 280 patients with serum creatinine levels <300 micromol/L, proteinuria <1000 mg/day, and stable function. The specimens were evaluated according to the Banff criteria. RESULTS: Graft survival depended on the presence of CAN and renal transplant vasculopathy (RTV). Thus, biopsy specimens were classified as: (a) no CAN (n=174); (b) CAN without RTV (n=87); and (c) CAN with RTV (n=21). Graft survival at 10 years was 95%, 82%, and 41%, respectively (P=0.001). Total serum cholesterol before transplantation was 4.5+/-1.1, 4.6+/-1.1, and 5.3+/-1.6 mmol/L, respectively (P=0.009) and it was the only predictor of RTV. Power analysis (beta=20%, alpha=5%) was done to evaluate whether protocol biopsies can facilitate the design of clinical trials aimed either to prevent or treat CAN. We showed that the most feasible approach would be to use the presence of CAN as the primary efficacy end point in a prevention trial. To demonstrate a 50% reduction in the incidence of CAN at 3 months, 570 patients would be required. CONCLUSIONS: Protocol biopsies may allow a reduction of sample size and especially the time of follow-up in a trial aimed to prevent CAN.

The deleterious effect of donor high plasma sodium and extended preservation in liver transplantation. A multivariate analysis.

The aim of this study was to analyze the donor risk factors associated with second orthotopic liver transplantation (reOLT) and graft loss after OLT within 1 month. A total of 649 OLTs performed in 11 centers in Spain during the period from 1992 to 1993 were analyzed retrospectively. Eleven donor and recipient variables were studied. Biochemical evolution of the OLT, biliary and arterial complications, patient status (alive, retransplanted, or dead), and follow-up were also recorded. Bivariate study demonstrated that extended preservation ( > 12 hr) was associated with increased biliary complications (P = 0.02), and lower prothrombin time (P = 0.04). In a logistic model regression for biliary complications, ischemia > 12 hr was an independent risk factor (odds ratio = 2.2, 95% confidence interval [CI] = 1.1-4.3). The multivariate Cox proportional model of potential risk factors showed that only urgent reOLT (relative risk [RR] = 2.7, 95% CI = 1.4-5.4) was independently associated with higher 30-day mortality. Donor plasma sodium > 155 mmol/L (RR = 1.4, 95% CI = 1.0-2.2) and incompatible ABO graft (RR = 3.2, 95% CI = 1.3-7.9) were independently associated with increased rate of reOLT before 30 days. Donor plasma sodium > 155 mmol/L (RR = 2, 95% CI = 1.1-3.6) and incompatible graft (RR = 3.3, 95% CI = 1.4-8.2) were independently associated with graft loss (death or reOLT) before 1 month. We conclude that cold ischemia should be kept less than 12 hr in order to avoid biliary complications. Donors over 60 years old or with plasma sodium > 155 should be carefully evaluated before OLT.

Secretion and dual regulation between epidermal growth factor and transforming growth factor-beta1 in MDA-MB-231 cell line in 42-hour-long cultures.

MDA-MB-231 is a breast cancer cell line which possesses large quantities of epidermal growth factor (EGF) receptors and specific high-affinity transforming growth factor-beta1 (TGF-beta1) receptors. We have established that these cells secrete constitutively measurable levels of EGF and TGF-beta1 in conditioned medium. The constitutive secretion of EGF decreased over time in culture (42 h), while the constitutive secretion of TGF-beta1 remained constant. TGF-beta1 secretion in EGF-treated cells was lower than in controls (P < 0.0001), but EGF concentrations were not modified after TGF-beta1 supplement. We postulate that in MDA-MB-231 cell line there is a dual regulation between both growth factors.

Water metabolism disturbances at different stages of primary thyroid failure.

The aim of the present study was to study salt and water metabolism in thyroid deficiency. We performed an oral water loading test (OWL) and a hypertonic 5% saline infusion test (HSI) in 16 patients with overt primary hypothyroidism before replacement treatment (PRE group) and after, in eight patients with subclinical hypothyroidism (SUB group) and in 16 normal individuals (CG group). In the PRE group, a lower free water clearance was detected in the OWL (P < 0.022), with lower plasma osmolality (OWL: P < 0.005; HSI: P < 0.001) and arginine vasopressin (AVP) (OWL: P < 0.001; HSI: P < 0.001) than the CG group, across both tests; they normalized with the replacement treatment. The same plasma abnormalities were detected in the SUB group with the HSI. Although the AVP and thirst thresholds did not differ between the groups, the lag between them was lower in the PRE (4.1+/-3.2 mOsm/kg) and SUB group (2.6+/-2.1 mOsm/kg) than in the CG group (13.3+/-9.2 mOsm/kg) (P < 0.05). There were no differences in atrial natriuretic hormone (ANH), plasma renin activity (PRA) and plasma aldosterone among the groups. These results indicate that plasma hypo-osmolality and low levels of AVP are present in primary hypothyroidism, and indeed are already present in the subclinical phase of the disease. An overlap between the thresholds of thirst and AVP seem to play a role in these abnormalities, but ANH, PRA and plasma aldosterone do not appear to contribute.

Nutrient intake and gastric cancer risk: a case-control study in Spain.

A case-control study of dietary factors and gastric cancer was conducted between September 1986 and March 1989 in the Barcelona metropolitan area, Spain. In all 117 cases with histologically confirmed diagnosis of gastric adenocarcinoma were matched on sex, age and possession of a telephone to 234 population controls. Of the controls 188 (80.3%) were selected by random digit telephone dialing and 46 (19.7%) by neighbourhood of residence. Information about frequency and amount of consumption of 89 alimentary items was gathered by questionnaire, and cases and controls were interviewed in their homes by trained interviewers. The gastric cancer risk decreased in proportion to vitamin C intake. In multivariate analysis adjusting for major covariables, energy and vitamin A intake, the estimated odds ratio (OR) for the upper quartile of vitamin C intake was 0.3 (95% confidence interval [CI]: 0.1-0.8). After adjustment for major covariables, calories and vitamin C intake, vitamin A did not show significant association with the gastric cancer risk. Our findings are consistent with previous case-control studies and with the hypothesis that vitamin C may inhibit the intragastric nitrosation process.

End-of-life preferences in elderly patients admitted for heart failure.

BACKGROUND: Heart failure is increasing in prevalence and incidence, with considerable mortality among the elderly. AIM: To determine preferences concerning cardiopulmonary-resuscitation (CPR) and end-of-life care in elderly patients hospitalized for heart failure. DESIGN: Prospective interview-based survey. METHODS: Patients >64 years old admitted for acute heart failure were interviewed to address their preferences regarding end-of-life care and cardio-pulmonary resuscitation (CPR) when facing the last stages of their disease. RESULTS: We interviewed 80 patients (mean age 79 years; 58% women). Thirty-two (40%) expressed a wish not to have CPR. Only two had previously discussed their CPR preferences with their physicians. When recovery from the illness was considered unlikely, 40 (50%) participants preferred to receive treatment at home, 32 (40%) preferred in-hospital management, and 8 (10%) were unsure. Thirty-three patients (41%) expressed a desire for spiritual support, 38 (48%) said not and the remaining 9 (11%) were indifferent. DISCUSSION: Advance planning of end-of-life procedures and doctor-patient communication regarding these items remains poor and must be improved.

Serum albumin as indicator of clinical evolution in patients on parenteral nutrition. Multivariate study.

BACKGROUND AND AIMS: The aim of this study is to establish whether serum albumin concentration at the beginning of parenteral nutrition is related to morbidity and mortality. METHODS: In this cohort study spanning four years, a number of patients were classified into twelve groups, depending on their clinical status at the beginning of parenteral nutrition. Their serum albumin concentration and other clinical parameters were then measured and twelve multiple logistic regression models were thus generated in order to model the relationship between initial albumin concentration and risk of morbidity/mortality. RESULTS: 1953 (84%) of the 2321 patients studied were hypoalbuminemic. In six models, this condition was associated with a significant increase in the risk of nosocomial infection. However, no model could be associated to significant risk of renal failure, and only patients with previous hepatopathy were at risk for hepatic failure. In seven models, there was a significant increase in mortality. CONCLUSIONS: Serum albumin concentration at the beginning of parenteral nutrition is related to mortality and morbidity associated with nosocomial infection in some groups of the study.

Changes in diet and mortality from selected cancers in southern Mediterranean countries, 1960-1989.

Mortality trends of breast, colorectal, ovarian and prostate cancer in Spain, Italy, Greece, Yugoslavia, and England and Wales are presented. Figures are discussed with regard to patterns of consumption of fat-containing foods in these countries. An increase of all cancer site mortality is shown in southern European countries, whereas in England and Wales a decrease in ovarian and colorectal cancer among women is observed. Consumption of milk, meat and animal fat products increased in all Mediterranean countries but decreased in England and Wales. Some differences regarding cancer mortality and food consumption patterns among southern European countries are pointed out. This markedly divergent fat consumption pattern between northern and southern Europe appears to antedate and be associated with their substantial differences in ovarian and colorectal cancer mortality trends, and to a lesser extent with breast cancer.