A double blind randomized controlled trial investigating efficacy and safety of varenicline for smoking cessation in patients with type 2 diabetes: study protocol.

Reducing exposure to cigarette smoke is an imperative for public health and for diabetic patients. Patients with diabetes who continue to smoke face challenges at quitting and the delivery of effective smoking cessation interventions is a major unmet need. The high-affinity α4ß2 nicotinic acetylcholine receptor partial agonist varenicline in combination with counseling is effective for smoking cessation, but evidence in patients with diabetes is limited. A clinical trial of varenicline targeted specifically at smokers with T2DM is warranted. This randomized, double blind, placebo-controlled trial will be the first study to test efficacy and safety of varenicline in smokers with type 2 diabetes mellitus (T2DM) over the course of 52 weeks. We hypothesize that varenicline treatment (1 mg BID, administered for 12 weeks) would increase quit rates, maintain smoking abstinence up to 1 year after treatment, and be well-tolerated in T2DM smokers intending to quit. Efficacy end points will include carbon monoxide-confirmed continuous abstinence rate (CAR) and 7-day point prevalence of abstinence. The results of this RCT will help inform medical/health authorities and physicians worldwide whether an optimally varenicline-treated cohort of T2DM patients who smoke will experience significant success rates, without significant side effects.Trial registration NCT01387425 ( https://clinicaltrials.gov/ct2/show/NCT01387425 ).

Adjuvant radiotherapy on older and oldest elderly rectal cancer patients.

The purpose of this study was to evaluate the impact of radiotherapy in terms of feasibility and activity in the patients aged > or = 75 with advanced rectal cancer. From January 2002 to December 2006, 41 consecutive patients (27 men and 14 women) aged > or = 75 received radiotherapy for local advanced rectal cancer, 9 in a pre-operative and 22 in a post-operative setting. Sixteen patients received concomitant chemotherapy. Variables considered were age, co-morbidities, evaluated according to the adult co-morbidity evaluation index (ACE-27), surgery versus no surgery, and timing of radiotherapy. The median age was 80.5 years (range 75-90). A total of 19.5% of the patients had no co-morbidity, 48.8% mild, 17.1% moderate, and 14.6% had severe co-morbidities. Thirty-nine subjects (95.1%) were submitted to surgery. All patients but one completed the planned radiation schedule. At a median follow-up of 23.1 months, the 2- and 4-year overall survival rates were 71.8% and 61.6%, respectively. There was a better survival for patients with no or mild co-morbidities (p=0.002) and a good performance status (p=0.003). The cancer-free survival at 2 and 4 years was 78.9% and 26.4%, respectively. No difference in acute and late toxicity rates was found between patients with different ACE-27 indexes. We conclude that compliance with radiotherapy is good and rate of toxicity is acceptable in elderly patients. Patients with no or mild co-morbidities have a significantly better survival. Increasing severity of co-morbidity may sufficiently shorten remaining life expectancy to cancel gains with adjuvant radiotherapy. Further prospective trials are needed to confirm these results.

Therapeutic options for elderly diabetic subjects: open label, randomized clinical trial of insulin glargine added to oral antidiabetic drugs versus increased dosage of oral antidiabetic drugs.

Glycemic control in elderly persons with type 2 diabetes mellitus (T2DM) is challenging because they are more likely to have other age-associated medical conditions and to experience hypoglycemia during intensive therapy. A best therapeutic strategy for these patients has not yet been defined. We investigated the efficacy and safety of adding once-daily insulin glargine to patients' current oral antidiabetic drugs (OAD) regimen, compared to increasing the OAD doses. The study enrolled patients aged 65 years or more, with poor glycemic control. Patients were randomized to two groups and entered a 3-week titration period in which their actual therapy was adjusted to meet the study's glycemic goals, by either adding insulin glargine to current therapy (group A, 27 patients) or increasing current OAD dosages (group B, 28 patients). Thereafter, therapies were continued unchanged for a 24-week observation period. The mean therapeutic dosage of insulin glargine in group A was 14.9 IU/day (SD = 5.0 IU/day). During the observation period, mean levels of glycosylated hemoglobin (HbA1c) reduced by 1.5% in group A and 0.6% in group B (P = 0.381). An HbA1c level <7.0% was achieved by five patients in each group. Mean fasting blood glucose levels reduced by 29 and 15% in groups A and B, respectively (P = 0.029). Group A had fewer total hypoglycemic events (23 vs. 79, P = 0.030) and fewer patients experiencing any such event (9 vs. 17, P = 0.045). Neither a serious hypoglycemic event nor other adverse event occurred. These results suggest that, compared to increasing OAD dosage, the addition of insulin glargine to current OAD therapy is as effective but safer in terms of the risk for hypoglycemia in elderly patients with T2DM.

Patterns of medical diagnosis and treatment of migraine and probable migraine in a health plan.

The objectives of this study were to assess the proportion of subjects with strict migraine (SM, migraine with and without aura), probable migraine (PM), and all migraine (AM, SM and PM pooled together), who receive a medical diagnosis or a specific treatment within a health plan. Eligible participants were 18-55-year participants of a non-profit health maintenance organization (HMO) who had received out-patient, emergency department, or in-patient care from a physician within the past year. We used a validated computer-assisted telephone interview (CATI) survey to identify SM, PM and controls (received out-patient, emergency department, or in-patient care from a physician for any reason within the past year, but did not have SM or PM). Medical and prescription drug claims for the 24-month period were linked to participant files. Among 8579 respondents, we identified 1265 SM sufferers and 1252 PM sufferers, which were compared with 960 randomly selected controls. Just 194 (15.3%) SM, 21 (1.7%) PM, and 215 (8.5%) AM sufferers received an in-patient or out-patient primary migraine claim in the previous 24 months, compared with six (0.5%) controls; 240 (18.9%) SM, 39 (3.1%) PM, 279 (11.1%) AM sufferers, and eight controls (0.6%) received any migraine claim. There were claims for migraine drugs (ICD-9 code for triptans or ergot compounds) for just 140 (11.1%) SM and 34 (2.7%) PM sufferers, and migraine analgesics (butalbital and isomethepthene compounds), for 6.3% SM and 2.2% PM sufferers (0.7% of the controls). Migraine preventives were used for a larger number of SM and PM sufferers (19.6% and 13.1%), but also for controls (10.5%), indicating that they were probably used for other medical reasons. Both SM and PM are underdiagnosed and undertreated within a health plan. Educational strategies should focus on physician education addressing diagnosing the full spectrum of migraine and physician management of migraine with specific migraine therapy in appropriate patients.

Prevalence and impact of migraine and probable migraine in a health plan.

BACKGROUND: A large number of headache sufferers with features of migraine fail to meet criteria for strict migraine (SM; migraine with or without aura) but do meet criteria for probable migraine (PM). OBJECTIVES: To estimate the prevalence of PM, to compare the epidemiologic profiles of SM and PM, and to assess the disability and impact on the health-related quality of life (HRQoL) of these patients. METHODS: Computer-assisted telephone interviews in a sample recruited from a mixed model health maintenance organization were used. SM, PM, and control subjects were identified. Also assessed were demographic features, disability, HRQoL, and depression. RESULTS: The 1-year prevalence for SM was 14.7% (19.2% in women and 6.6% in men); for PM, it was 14.6% (15.9% in women, 12.6% in men). Most subjects with PM (82%) did not meet the associated symptom criteria for migraine. HRQoL was reduced in the PM, SM, and all migraine (AM; SM and PM pooled together) groups compared with controls. The proportion of subjects with high disability was elevated in PM (13%), SM (31%), and AM (22%) groups vs controls (3.7%; p < 0.0001). CONCLUSIONS: Within a health plan, probable migraine is a prevalent form of migraine, with symptom and epidemiologic profiles that overlap with strict migraine. Although strict migraine prevalence was consistent with previous studies, a probable migraine prevalence higher than previously reported was found, perhaps reflecting a difference between health plan and population samples.

Suicides and the third age.

The phenomenon of suicide represents a complex problem, the specific aspects of which should be examined by a multifactorial analysis, particularly in the elderly subjects. Although the research on risk factors continues to grow, only a limited knowledge is available on the biological changes increasing the risk for suicide. Similarly, limited information is at our disposal about the contributing psychosocial processes extending beyond the demographic factors. Although the best explored population is the elderly using primary care services, no proven interventions are known for the time being, although some efforts to test certain approaches reaching these older adults are under way. Apparently even more, continued efforts are needed to change the attitudes toward the mental illnesses and their treatments in general, in order to reach the older adults who are still outside of the health care services.

Evaluation of oxidative stress in diabetic patients after supplementation with a standardised red orange extract.

Diabetes mellitus is associated with a high oxidative stress level, resulting from an imbalance between free radicals or reactive oxygen species production and the antioxidant systems. Inhibition of these oxidative processes by co-adjuvant therapy could therefore prevent, or at least delay, the onset and/or the development of long-term diabetic complications. Dietary supplementation with plant biophenols may be a successful strategy to decrease this risk of pathological complications. The Red Orange Complex (ROC) is a standardized red orange extract containing, as its main active principles, phenolic compounds (anthocyanins, flavanones and hydroxycinnamic acids) as well as ascorbic acid. The aim of the present preliminary study was to evaluate the effects of short-term (2 mo) dietary supplementation with ROC (50 mg/d, orally) on some serum non-invasive biomarkers of oxidative stress (total antioxidant status, or TAS, levels of thiol groups and levels of free radicals) in a group of 33 patients with Type 2 diabetes, in comparison with a group of 28 healthy volunteers. The results obtained demonstrate that in diabetic patients supplementation with ROC can improve blood levels of thiol groups on proteins (an indirect measurement of glutathione activity in serum); furthermore, it can elicit a marked decrease in serum free radical levels, in patients with high blood oxidative stress status. However, ROC supplementation appeared unable to modify serum TAS. Finally, the glycemic profile remained stable during the study period in all subjects, and no unpleasant side effects were reported. In conclusion, the treatment of diabetic patients with ROC might be of therapeutic benefit in order to protect against diabetes complications that are partially due to uncontrolled lipid oxidation. D

The prevalence of various arrhythmias in normotensive and hypertensive elderly patients.

The prevalence of the most frequent arrhythmias was studied in a geriatric day hospital. Patients older than 65 years have been considered, of them 118 were normotensive and 56 hypertensive subjects. Comparison of the two groups revealed no statistically significant difference either in the frequency of occurrence or in the type of arrhythmias. Dividing the hypertensive patients in the Lown's classes, only those of class 3 or over displayed a considerably higher frequency of arrhythmias than the normotensive subjects. The results demonstrate the age-dependent increase of the prevalence of arrhythmias in general, and the increased occurrence of complex ventricular types in the hypertensive subjects.

The leisure time and the third age: the experience of a geriatric day hospital.

Leisure time represents an important part of the so-called 'successful aging' and contributes to overcome the problems related to the reduction of the social roles, favoring a better subjective adaptation to old age. In this work we observed the elderly population frequenting our Day Hospital, by estimating the affective sphere (geriatric depression scale, GDS), the autosufficiency (activity of daily living, ADL; and instrumental activity of daily living, IADL) and the schooling years in correlation with the type and length of leisure time activities during the day. These data have been compared with those of the national statistics (ISTAT). The analyses revealed a very wide diffusion of the utilization of mass media and a large interindividual differentiation of the modes of using leisure time. The correlations between the indices of affectivity and autosufficiency show an effect on the types of leisure time activities, while the scholarity of the subjects has no influence on it. These results suggest considering leisure time as an indispensable part of the relational life of elderly subjects, having an important 'valency' for the affective sphere and the individual expectations and needs.

The care of elderly, terminally ill oncological patients in caregiving sanitary residences.

A panoramic survey is outlined regarding the care system of terminally ill oncologic patients with particular regard to the elderly. National and international experiences are considered offering a caregiving service out of hospital, in small dwelling centers being able to relieve the sufferings of the last days of life. The caregiving sanitary residences and hospices are inserted in a network of services for the elderly oncological patients, representing an adequate answer for the problems. In those structures there is a need of proper professional sanitary figures and standardized lodgings, which may be of importance in the maintenance of a good quality of life. In addition, this study emphasizes the caregiving activity of the family and the needs of the caregivers, as well as the proper instruction of them through courses of specialization. New figures should be inserted in the hospices, like the volunteers, the animators and spiritual assistants; their help is inevitably necessary to assure a better care during the last days of life.

On the importance of multidimensional evaluation of elderly oncologic patients.

The role of comorbidity and the psycho-affective attitudes have been studied in 108 elderly oncological patients, in comparison with 25 elderly subjects without tumor pathologies. The results have revealed positive correlations between the activity of daily living (ADL), as well as the instrumental activity of daily living (IADL) scales and the comorbidity both in the oncological subjects and the controls. The performance status defined by the eastern cooperative oncology group (ECOG-PS) positively correlated with the parameters of ADL and IADL scales, demonstrating an increased vulnerability and fragility of the oncological patients in their everyday activities. An increased psychological fragility of the oncological patients has also been revealed by the scores of the geriatric depression scale (GDS), which might be cause and consequence at the same time of the disease itself. In addition, the polypathologies are not associated with an increased gravity of the tumor stage, although there have been 2.5 accompanying pathologies, mainly diseases of osteoarticular and cardial character. The correction of functional damages of various organs due to aging or concomitant or previous diseases is a period of fundamental importance for an adequate oncological therapy. The principal goal of any intervention in the elderly oncological patient should certainly be an improvement of the quality of life, including an alleviation of the impact of the diagnostic and therapeutic procedures on it.

Helicobacter pylori and prurigo nodularis.

BACKGROUND/AIMS: Numerous data have suggested that there may be a relationship between Helicobacter pylori (H. pylori) infection and extragastric diseases, including dermatological pathologies. We studied some cases of Hide's Prurigo Nodularis (NP), a very itchy skin disease of unknown origin, in order to asses whether there is a pathogenic correlation between PN and H. pylori infection. METHODOLOGY: Prurigo Nodularis had been diagnosed clinically and histologically in 42 outpatients (27 females and 15 males with mean age of 62 +/- 5 years). All patients were screened for H. pylori infection by esophagogastroduodenoscopy, histologic examination and specific immuno-enzymatic determination. Specific pharmacological treatment was administered to all patients with H. pylori infection. RESULTS: H. pylori colonization was observed in 40/42 patients examined and 32/40 patients presented some immunologic alterations. After the pharmacological treatment, endoscopy and rapid urease test confirmed eradication of H. pylori in 39/40 cases; itching was greatly reduced in the latter and microscopic examination of repeated skin biopsies revealed an improved histologic picture in patients affected by PN associated with H. pylori infection. CONCLUSIONS: The concomitant presence of skin disease, H. pylori infection and immune disorders infers that there may be a pathogenic connection between bacterial infection and the inflammatory alteration of PN. We believe that the pharmacologic treatment induced remission of the skin lesions by direct control of H. pylori chronic infection; in fact, H. pylori may have triggered or enhanced the vasculitis which, in turn, may have enhanced the clinical signs and inflammatory histologic component of PN.

Echocardiographic studies on elderly patients with white coat hypertension to evaluate cardiac organ damages.

This case-control study was aimed at evaluating the distribution of some echocardiographic signs of cardiac organ damages in elderly patients with white coat hypertension (WCH), as compared with a normotensive group of elderly. Correlations between the signs of cardiac organ damages and the clinical and ambulatory blood pressure parameters (obtained by means of a 24-h monitoring) have also been evaluated. The first screening covered 258 elderly subjects of both sexes, aged from 65 to 82 years, with clinical diagnosis of hypertension (systolic and diastolic blood pressures being higher than 160 and 95 mmHg, respectively). Of this group, 116 subjects remained in the final pool, and their echocardiographic parameters were compared with 33 normotensive (N) subjects. Out of the 116 clinically hypertensive patients, 29 (25%) displayed WCH, according to the established criteria. Variance analyses on the ranks followed by Dunn's test revealed no statistically significant differences between the N and WCH groups, while the hypertensive group (H) proved to be significantly different from both the N and the WCH groups. In addition to the descriptive statistics, an analysis of correlations between the pressure variables and the echocardiographic parameters has also been performed by means of a forward-stepwise multiple linear regression method. The models generated by this regression analysis covered only the ambulatory diurnal systolic pressure, and the clinical diastolic pressure in most of the cases of the echocardiographic parameters, taken as independent variables. In all these cases, the standardizecl correlation coefficient of the diurnal systolic pressure was always higher than that of the clinical diastolic pressure, indicating that the echocardiographic parameters depend more strongly on the first than on the second pressure value.

Early endothelial alterations in non-insulin-dependent diabetes mellitus.

The high incidence of cardiovascular morbidity and mortality in non-insulin-dependent diabetes mellitus with albuminuria cannot be fully explained by the presence of standard cardiovascular risk factors. We assessed some pathogenic factors of diabetic vascular atherosclerotic damage in 72 non-insulin-dependent diabetes mellitus patients controlled by diet alone and 60 healthy controls. Our study aim was to assess the early onset of these alterations and to correlate them with the presence of microalbuminuria. We determined their incidence in two carefully selected groups of diabetic patients without clinical signs of cardiovascular risk and complications, where diet alone achieved glycometabolic balance. Microalbuminuric patients had an alterated oxide-reductive balance and elevated values of plasminogen activator inhibitor, tissue plasminogen activator, von Willebrand factor, endothelin-1 and betathromboglobulin compared with the normoalbuminuric diabetics and controls. Our findings support the hypothesis that a state of endothelial dysfunction characterized by altered oxide-reductive balance, modified hemostasis and changes in the endothelial barrier properties occurs much earlier in non-insulin-dependent diabetic patient especially in diabetics with microalbuminuria. In addition, alterations in the oxide-reductive balance, and hemostasis occur early and may be an underlying cause of microangiopathic complications in microalbuminuric diabetics.

The effects of caloric restriction and controlled physical exercise on hypertension in the elderly.

The overweight and sedentary life style are associated with elevated blood pressure values in the elderly patients. The first step in the therapy of arterial hypertension should be hygienic-behavioral measures in order to modify the life style of the patients. The present study evaluates the independent effects of caloric restriction and physical exercise on the blood pressure and on the anti-hypertensive treatment in elderly subjects with mild-moderate hypertension. The number of enrolled patients was 74 in the age range of 61-72 years, showing up in our Geriatric Day Hospital. The results obtained confirm that the non-pharmacological measures represent a valid alternative to the pharmacological treatment of hypertension in the elderly patients, or may be applied in combination with the latter, in order to reduce the doses of pharmaca.

A diary model for monitoring blood pressure in the elderly.

Activity can significantly change blood pressure. Twenty four hour ambulatory blood pressure monitoring (Holter method) was introduced to optimize diagnosis and the changes in blood pressure. It was flanked by the purpose to use diaries to correlate symptoms and pressure changes, pressure changes and psychophysical activity, life style and drugs. The diary model adopted by us for 380 elderly subjects between 65 and 85 years old is divided into four main sections: 1. general activities (8 items); 2. situational variations (7 items); 3. correlation between symptoms and pressure changes; 4. drug treatment and pressure changes. The aim of our study was to assess the compliance of the elderly to keeping a diary. Our results showed that compliance was satisfactory in 352/380 subjects (93%).

Comparison of ambulatory and clinical blood pressures, and their correlation with organic heart damage, in the elderly.

Casual blood pressure (BP) measurements may sometimes indicate the presence of cardiovascular morbidity and mortality, but the correlations between BP values and the subsequent occurrence of such complications are low. This may depend on the known inability of casual BP measurements to reflect accurately the 24-hour mean and overall profile of the BP. In this study, electrocardiography (ECG) of left ventricular muscle mass was related to various measures of BP during circadian ambulatory BP monitoring in 156 hypertensive and non-hypertensive elderly patients. Multiple regression analysis performed to establish the presence of left ventricular hypertrophy (LVH) revealed that the product of ambulatory systolic BP x diastolic BP (p = 0.027) and ambulatory diastolic BP were significant variables. Clinical pressure variables were not significant. Multiple linear regression analysis to establish the degree of LVH in function of the pressure variables generated a model where the variables included are the product of ambulatory systolic BP x diastolic BP (p = 2.7 x 10(-8)), ambulatory systolic BP (p = 7.8 x 10(-6)) and ambulatory diastolic BP (p = 2.4 x 10(-6)). Results obtained agree with the literature and revealed that LVH evaluated using ECG-Romhilt-Estes score was correlated in terms of presence/absence of organ damage and in terms of score to ambulatory monitoring values.

[The prevalence of white coat hypertension in patients over 60 who came to a day hospital]. / Prevalenza di white coat hypertension in ultrasessantenni afferenti ad un day hospital.

Over the last thirty years white coat hypertension has been the object of numerous studies which suggest that the interactions between doctor and patient and environmental, psychological circumstances suffice to determine a significant increase of arterial pressure in subjects who are generally normotense. The aim of this study was to evaluate the prevalence of white coat hypertension in elderly subjects with hypertension which had been diagnosed recently using the traditional sphygmomanometric method three times in the space of one week. We divided 69 patients (age range 60 to 82 years) into three groups depending on their clinic pressures, i.e. patients with isolated systolic, systo-diastolic or diastolic hypertension. Non invasive 24 h pressure ambulatory monitoring was performed in each subject using a Takeda recorder TM 2420 and adopting a protocol for single measurements at 15 minutes intervals between 08.00 and 20.00 (daytime measurements) and 30 minutes intervals between 20.00 and 08.00 (night-time measurements). Ambulatory monitoring with less than 60 recordings, and those where measurements were not taken for over 60 minutes during the day or 90 minutes during the night were excluded from the study, and the mean daytime and 24 h pressure load was calculated. Monitoring conducted in 60 subjects (39 males and 21 females) was considered valid. Statistical analysis of the mean arterial pressure values of each subject determined by the two methods was performed using a t-test.(ABSTRACT TRUNCATED AT 250 WORDS)