Mental Health among Geriatric Healthcare Workers in Italy during the COVID-19 Pandemic: Results from a National Survey.

OBJECTIVES: This study aimed to investigate the psychological impact of the COVID-19 pandemic on healthcare workers (HCWs) in geriatric settings. DESIGN: Online cross-sectional survey. SETTINGS AND PARTICIPANTS: 394 geriatric HCWs in Italy. MEASUREMENTS: The survey was developed by a multidisciplinary team and disseminated in April 2022 to the members of two geriatric scientific societies (Italian Society of Geriatrics and Gerontology and Italian Association of Psychogeriatrics). The survey examined the experiences related to the COVID-19 pandemic, as well as psychological burden and support. Work-related anxiety and distress related to the pandemic were studied using the SAVE-9 scale (Stress and Anxiety to Viral Epidemics). RESULTS: Three hundred sixty-four participants (92.4%) changed their job activity during the pandemic and about half (50.9%) failed to cope with this change, 58 (14.7%) had increased work-related anxiety, and 39 (9.9%) work-related stress levels. Three hundred forty (86.3%) participants reported acute stress reaction symptoms, including irritability, depressed mood, headache, anxiety, and insomnia, and 262 (66.5%) required psychological support, mainly from friends/relatives (57.9%) and/or colleagues (32.5%). Furthermore, 342 participants (86.8%) recognized they would benefit from informal and formal psychological support in case of future similar emergencies. CONCLUSIONS: This study highlights the high psychological burden experienced by geriatric HCWs in Italy during the COVID-19 pandemic and emphasizes the need for supportive interventions.

Overnight switch from rasagiline to safinamide in Parkinson's disease patients with motor fluctuations: a tolerability and safety study.

BACKGROUND AND PURPOSE: When switching between monoamine oxidase type B (MAO-B) inhibitors, a 15-day suspension period is a precautionary measure to avoid a serotonin syndrome and hypertensive crisis. However, this indication results in a major inconvenience for parkinsonian patients because of the worsening of their clinical condition. In routine clinical practice, neurologists often perform a substitution of these two drugs without solution of continuity (i.e. overnight), to avoid worsening of fluctuations and prolonged OFF periods. Therefore, a safety open label study was performed to investigate the possible risks of switching overnight from rasagiline to safinamide. METHODS: The study population included 20 advanced patients with Parkinson's disease on stable treatment with rasagiline and levodopa (alone or in combination with other anti-parkinsonian medication). The possible occurrence of serotonin syndrome and hypertension was monitored through a strict clinical observation and a 24-h Holter recording (ABPM) performed twice, whilst subjects were on rasagiline and immediately after switching to safinamide. RESULTS: No cases of serotonin syndrome or hypertensive crisis occurred during the study. Changes that were not significant occurred in the primary end-point: 24-h mean blood pressure (BP) had a mild +4.4% increase in the ABPM2 versus ABPM1 (P = 0.17), 24-h systolic and diastolic BP values were slightly higher at ABPM2 compared to ABPM1 (respectively +3.3%, P = 0.13; and 5.4%, P = 0.08) and 24-h systolic BP variability was unchanged between the two ABPM evaluations (from 8.6 ± 2.9 to 8.9 ± 1.8; P = 0.27). CONCLUSION: The results of the present study confirm that the overnight switch from rasagiline to safinamide is safe and well tolerated by patients.

Multiple hormonal and metabolic deficiency syndrome in chronic heart failure: rationale, design, and demographic characteristics of the T.O.S.CA. Registry.

Recent evidence supports the concept that progression of chronic heart failure (CHF) depends upon an imbalance of catabolic forces over the anabolic drive. In this regard, multiple hormonal deficiency syndrome (MHDS) significantly has impacts upon CHF progression, and is associated with a worse clinical status and increased mortality. The T.O.S.CA. (Trattamento Ormonale nello Scompenso CArdiaco; Hormone Therapy in Heart Failure) Registry (clinicaltrial.gov = NCT02335801) tests the hypothesis that anabolic deficiencies reduce survival in a large population of mild-to-moderate CHF patients. The T.O.S.CA. Registry is a prospective multicenter observational study coordinated by "Federico II" University of Naples, and involves 19 centers situated throughout Italy. Thyroid hormones, insulin-like growth factor-1, total testosterone, dehydroepiandrosterone , and insulin are measured at baseline and every year for a patient-average follow-up of 3 years. Subjects with CHF are divided into two groups: patients with one or no anabolic deficiency, and patients with two or more anabolic deficiencies at baseline. The primary endpoint is the composite of all-cause mortality and cardiovascular hospitalization. Secondary endpoints include the composite of all-cause mortality and hospitalization, the composite of cardiovascular mortality and cardiovascular hospitalization, and change of VO2 peak. Patient enrollment started in April 2013, and was completed in July 2017. Demographics and main clinical characteristics of enrolled patients are provided in this article. Detailed cross-sectional results will be available in late 2018. The T.O.S.CA. Registry represents the most robust prospective observational trial on MHDS in the field of CHF. The study findings will advance our knowledge with regard to the intimate mechanisms of CHF progression and hopefully pave the way for future randomized clinical trials of single or multiple hormonal replacement therapies in CHF.

Effects of testosterone on the Q-T interval in older men and older women with chronic heart failure.

The Q-Tc interval duration on the electrocardiogram is recognized to differ between the sexes. In vitro data and data from humans before and after puberty and menopause suggest that sex hormones play a role in the longer Q-Tc intervals in women, or conversely, the shorter Q-Tc intervals in men. Direct investigations of sex hormone effects on the Q-Tc interval in humans, however, are limited and reach conflicting conclusions. Our objective was to determine effects of testosterone on ECG Q-T intervals of older men and older women. ECG's from 84 older men and older women in double-blind placebo-controlled investigations of testosterone supplementation for the treatment of chronic heart failure (CHF) were analysed. Thirty men received 1000mg intramuscular long-acting testosterone undecanoate and 28 men received saline at 0, 6 and 12weeks. ECG's were recorded at baseline and 12weeks. Sixteen women received transdermal testosterone (33µg) and 10 women received matching placebo twice weekly for 24 weeks with ECG's at baseline and after 24weeks. Testosterone, but not placebo, shortened Q-T and Q-Tc intervals without heart rate changes. Q-T intervals decreased from 385±28 (mean±SD) to 382±28 ms (p<0.002) and Q-Tc intervals decreased from 398±26 to 392±27 (p<0.006) in men on testosterone. In women, Q-T intervals decreased from 400±25 to 397±23ms (p=0.06) and Q-Tc intervals from 415±26 to 409±27ms (p=0.3) on testosterone. Q-T intervals were longer in women compared with men under all conditions (p<0.03). The data support a direct effect of testosterone to shorten Q-T intervals in older men and older women in the absence of HR changes or hypogonadal status. Mean decreases are small and unlikely to affect risks of arrhythmic events in patients receiving Q-T prolonging medications.

Assessment of environmental pollutants in ten southern Italy harbor sediments.

In 2003-2006, the distribution of macronutrients and pollutants of environmental interest was investigated in surficial sediments collected from 10 southern Italy harbors selected in four different regions. About 167 stations were sampled to determine levels of total organic carbon, total nitrogen, total phosphorous, trace elements (Al, Cd, Pb, Ni, Cr, Cu, Zn, Hg, As), short- and long-chain aliphatic hydrocarbons (Hy C > 12 and Hy C < 12), and concentrations of persistent organic pollutants (polychlorinated biphenyls, polycyclic aromatic hydrocarbons [PAHs], p-p-Dichlorodiphenyldichloroethylene (4,4'-DDE), and Hexachlorobenzene (HCB). General relationships between studied variables and harbors systems were explored by multivariate statistical approaches. Results show that wide fluctuations are reported for all variables both among harbors and inside each studied system. Principal components analysis suggests that major significance in explaining total average variability is due to lead, copper, zinc, silts, sands, and PAHs. No significance has been observed when testing nonmetric multidimensional scaling distributions relating with the factor "region," while performing analyses on factor "main human activity," a higher significance is observed. These results suggest a strong relationship between the main human use of marine systems and observed pollution levels in sediments.

Dynamic adaptation of cardiac baroreflex sensitivity to prolonged exposure to microgravity: data from a 16-day spaceflight.

This study explored the process of arterial baroreflex adaptation to microgravity, starting from the first day of flight, during the 16-day STS-107 Columbia Space Shuttle mission. Continuous blood pressure (BP), ECG, and respiratory frequency were collected in four astronauts on ground (baseline) and during flight at days 0-1, 6-7, and 12-13, both at rest and during moderate exercise (75 W) on a cycle ergometer. Sensitivity of the baroreflex heart rate control (BRS) was assessed by sequence and spectral alpha methods. Baroreflex effectiveness index (BEI); low-frequency (LF) power and high-frequency (HF) power of systolic BP (SBP), diastolic BP (DBP), and R-R interval (RRI); the RRI LF/HF ratio; and the RRI root mean square of successive differences (RMSSD) index were also estimated. We found that, at rest, BRS increased in early flight phase, compared with baseline (means +/- SE: 18.3 +/- 3.4 vs. 10.4 +/- 1.2 ms/mmHg; P < 0.05), and it tended to return to baseline in subsequent days. During exercise, BRS was lower than at rest, without differences between preflight and in-flight values. At rest, in the early flight phase, RMSSD and RRI HF power increased (P < 0.05) compared with baseline, whereas LF powers of SBP and DBP decreased. No statistical difference was found in these parameters during exercise before vs. during flight. These findings demonstrate that heart rate baroreflex sensitivity and markers of cardiac vagal modulation are enhanced during early exposure to microgravity, likely because of the blood centralization, and return to baseline values in subsequent flight phases, possibly because of the fluid loss. No deconditioning seems to occur in the baroreflex control of the heart.

Chronic administration of Sildenafil improves markers of endothelial function in men with Type 2 diabetes.

OBJECTIVE: Diabetic patients have a reduced endothelial response to phosphodiesterase-5 inhibitors. The aim of this study was to determine the effects of chronic therapy with sildenafil on endothelial function in patients with Type 2 diabetes mellitus (DM2). METHODS: In a double-blind, placebo-controlled parallel design, 20 patients without erectile dysfunction randomly received a loading dose of sildenafil (100 mg) for 3 days, followed by either sildenafil 25 mg three times a day (t.d.s.) for 4 weeks or sildenafil 25 mg t.d.s. for 4 days followed by placebo t.d.s. for 3 weeks. RESULTS: After 1 week, flow-mediated dilatation (FMD) improved significantly (> 50% compared with baseline) in patients allocated to both sildenafil arms (62 and 64%, respectively). In patients allocated to chronic sildenafil, a progressive increase in percentage of patients with FMD improvement was noted (78, 86 and 94% at 2, 3 and 4 weeks, respectively) while a progressive decrease in the placebo group occurred (45, 18 and 6% at 2, 3 and 4 weeks, respectively). At the end of the study, a significant improvement in FMD compared with baseline was noted after chronic sildenafil (FMD from 6.8 +/- 0.5 to 12.5 +/- 0.7%, P = 0.01 vs. baseline). A decrease in endothelin-1 levels and an increase in nitrite/nitrate levels were found after chronic sildenafil; significant changes from baseline in C-reactive protein, interleukin 6, intercellular adhesion molecule and vascular adhesion molecule levels were also found. CONCLUSIONS: In DM2 patients, daily sildenafil administration improves endothelial function and reduces markers of vascular inflammation, suggesting that the diabetes-induced impairment of endothelial function may be improved by prolonged phosphodiesterase-5 inhibition.

Arsenic-resistant bacteria isolated from contaminated sediments of the Orbetello Lagoon, Italy, and their characterization.

AIMS: The aim of this study was to isolate arsenic-resistant bacteria from contaminated sediment of the Orbetello Lagoon, Italy, to characterize isolates for As(III), As(V), heavy metals resistance, and from the phylogenetic point of view. METHODS AND RESULTS: Enrichment cultures were carried out in the presence of 6.75 mmol l(-1) of As(III), allowing isolation of ten bacterial strains. Four isolates, ORAs1, ORAs2, ORAs5 and ORAs6, showed minimum inhibitory concentration values equal or superior to 16.68 mmol l(-1) and 133.47 mmol l(-1) in the presence of As(III) and As(V), respectively. Isolate ORAs2 showed values of 1.8 mmol l(-1) in the presence of Cd(II) and 7.7 mmol l(-1) of Zn(II), and isolate ORAs1 pointed out a value of 8.0 mmol l(-1) in the presence of Cu(II). Analysis of 16S rRNA gene sequences revealed that they can be grouped in the three genera Aeromonas, Bacillus and Pseudomonas. Phylogenetic analysis of the four more arsenic-resistant strains was also performed. CONCLUSION: Isolates are highly resistant to both As(III) and As(V) and they could represent good candidates for bioremediation processes of native polluted sediments. SIGNIFICANCE AND IMPACT OF THE STUDY: This study provides original results on levels of resistance to arsenic and to assigning genera of bacterial strains isolated from arsenic-polluted sediments.

Menopause and cardiovascular disease: the evidence.

Menopause is a risk factor for cardiovascular disease (CVD) because estrogen withdrawal has a detrimental effect on cardiovascular function and metabolism. The menopause compounds many traditional CVD risk factors, including changes in body fat distribution from a gynoid to an android pattern, reduced glucose tolerance, abnormal plasma lipids, increased blood pressure, increased sympathetic tone, endothelial dysfunction and vascular inflammation. Many CVD risk factors have different impacts in men and women. In postmenopausal women, treatment of arterial hypertension and glucose intolerance should be priorities. Observational studies and randomized clinical trials suggest that hormone replacement therapy (HRT) started soon after the menopause may confer cardiovascular benefit. In contrast to other synthetic progestogens used in continuous combined HRTs, the unique progestogen drospirenone has antialdosterone properties. Drospirenone can therefore counteract the water- and sodium-retaining effects of the estrogen component of HRT via the renin-angiotensin-aldosterone system, which may otherwise result in weight gain and raised blood pressure. As a continuous combined HRT with 17beta-estradiol, drospirenone has been shown to significantly reduce blood pressure in postmenopausal women with elevated blood pressure, but not in normotensive women. Therefore, in addition to relieving climacteric symptoms, drospirenone/17beta-estradiol may offer further benefits in postmenopausal women, such as improved CVD risk profile.

Low testosterone levels are associated with coronary artery disease in male patients with angina.

Historically, high androgen levels have been linked with an increased risk for coronary artery disease (CAD). However, more recent data suggest that low androgen levels are associated with adverse cardiovascular risk factors, including an atherogenic lipid profile, obesity and insulin resistance. The aim of the present study was to evaluate the relationship between plasma sex hormone levels and presence and degree of CAD in patients undergoing coronary angiography and in matched controls. We evaluated 129 consecutive male patients (mean age 58+/-4 years, range 43-72 years) referred for diagnostic coronary angiography because of symptoms suggestive of CAD, but without acute coronary syndromes or prior diagnosis of hypogonadism. Patients were matched with healthy volunteers. Out of 129 patients, 119 had proven CAD; in particular, 32 of them had one, 63 had two and 24 had three vessel disease, respectively. Patients had significantly lower levels of testosterone than controls (9.8+/-6.5 and 13.5+/-5.4 nmol/l, P<0.01) and higher levels of gonadotrophin (12.0+/-1.5 vs 6.6+/-1.9 IU/l and 7.9+/-2.1 vs 4.4+/-1.4, P<0.01 for follicle-stimulating hormone and luteinizing hormone, respectively). Also, both bioavailable testosterone and plasma oestradiol levels were lower in patients as compared to controls (0.84+/-0.45 vs 1.19+/-0.74 nmol/l, P<0.01 and 10.7+/-1.4 vs 13.3+/-3.5 pg/ml, P<0.05). Hormone levels were compared in cases with one, two or three vessel disease showing significant differences associated with increasing severity of coronary disease. An inverse relationship between the degree of CAD and plasma testosterone levels was found (r=-0.52, P<0.01). In conclusion, patients with CAD have lower testosterone and oestradiol levels than healthy controls. These changes are inversely correlated to the degree of CAD, suggesting that low plasma testosterone may be involved with the increased risk of CAD in men.

Metabolic syndrome.

Metabolic and non metabolic cardiovascular risk factors tend to cluster in the same individual. The association of the cardiovascular risk factors is referred as metabolic syndrome (MS). This syndrome is associated with an increased risk of accelerated atherosclerosis and cardiovascular events. The cluster of cardiovascular risk factors of the MS includes: insulin resistance with or without glucose intolerance or diabetes, abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, a proinflammatory and prothrombotic state. MS is one of the major issues in the management of cardiovascular disease because of its epidemic proportion and its impact on increasing risk of developing both cardiovascular disease and type 2 diabetes. The main therapeutic goal in the management of patients with the MS is to reduce risk for clinical cardiovascular events and to prevent type 2 diabetes. In particular, for individuals with established diabetes, risk factors management must be intensified to reduce their higher cardiovascular risk. Lifestyle changes have a critical role in the clinical management of the risk factors predisposing to MS, such as overweight/obesity, physical inactivity. A large body of evidence suggests the use of Metformin and Acarbose for the treatment of the syndrome as these drugs have consistently shown to reduce cardiovascular events and mortality. Most anti-hypertensive drugs have unfavorable metabolic profile while b-blockers, centrally acting agents and drugs targeting the renin angiotensin system should always be considered for the treatment of hypertension in patients with MS.

Metformin improves endothelial function in patients with metabolic syndrome.

BACKGROUND: Metabolic Syndrome (MS) is associated with impaired endothelial function and increased cardiovascular risk. Insulin resistance is a key feature of MS and plays an important role in the pathogenesis of endothelial dysfunction. Aim of the present study was to evaluate the effect of metformin on endothelial function and insulin resistance, assessed by the homeostasis model (HOMA-IR, homeostasis model assessment-insulin resistance), in patients with MS. METHODS: Sixty-five subjects (37 men and 28 women, mean age 54 +/- 6 years) with MS were allocated to receive metformin 500 mg twice daily (n = 32) or placebo (n = 33) for 3 months. Before and after treatment we assessed endothelial function, using flow-mediated dilatation of the brachial artery, and HOMA-IR. RESULTS: Patients who received metformin demonstrated statistically significant improvement in endothelium-dependent vasodilation compared with those treated with placebo (from 7.4 +/- 2.1% to 12.4 +/- 1.9% vs. 7.3 +/- 2.5% to 6.9 +/- 2.7%, P = 0.0016, metformin vs. placebo respectively), without significant effect on endothelium-independent response to sublingual glyceryl trinitrate (P =0.32). Metformin improved insulin resistance compared with placebo group (HOMA-IR from 3.39 to 2.5 vs. 3.42 to 3.37; 26% reduction in HOMA-IR, P = 0.01). An association between the improvement in insulin resistance and the improvement in endothelial function (r = -0.58, P = 0.0016) was found. CONCLUSION: Metformin improves both endothelial function and insulin resistance in patients with MS. These findings support the central role of insulin resistance in the development of endothelial dysfunction and the role of metformin for the treatment of patients with MS.

[Growth hormone secretion in heart failure]. / La secrezione dell'ormone della creascita nello scompenso cardiaco.

Growth hormone is a pituitary polypeptide hormone regulating growth in paediatric age as well as inducing anabolic actions directly or IGF-I mediated in adult age. Particularly, in many animals GH and IGF-I receptors were observed in cardiac myocyte membrane. GH modifies left ventricle structure and function. As concerns spontaneous GH secretion, some data suggest that pituitary gland can have a compensatory role on endocrine response to heart failure. Heart failure stage was directly correlated to nocturnal GH levels. All GH spontaneous night secretion parameters as well as IGF-I levels showed a range between normal people and very high spontaneous secretion. Therefore in these patients there are either a GH peripheric resistance or a reduction of the activity of GH/IGF-I axis. Anyhow in our patients, GH 24 hour infusion was inducing a 5 fold increase in GH concentration and a 50% increase in basal IGF-I levels. Anker et al. suggested to evaluate nutritional state in heart failure patients, observing no differences in non-cachectic patients vs controls, while cachectic patients presented a typical GH resistance syndrome. Interestingly, cardiovascular effects of GH administration seem to be only marginally correlated to hemodynamic basal state. On the other hand basal hormonal setting of the patient seems to correlate to the GH-induced cardiovascular response. In fact, low basal IGF-I but high basal GH patients presented the worst endocrine and cardiovascular response to GH infusion. In literature there are controversial data about GH treatment in patients with chronic heart failure. The heterogeneity of the population could be the reason for this discrepancy. Besides very different IGF-I responses to GH have been reported. Therefore, as there is good clinical evidence that GH acute infusion can improve heart failure, it seems to be necessary firstly to evaluate the basal endocrine status of the patients. Particularly attention should be given to those patients that present a peripheric GH resistance. On the other hand, those patients with a reduced pituitary GH reserve are supposed to have very beneficial effects from GH treatment.

Preliminary observations on the effects of acute infusion of growth hormone on coronary vasculature and on myocardial function and energetics of an isolated and blood-perfused heart.

Recent studies have shown that growth hormone (GH) deficiency may deteriorate post-ischemic myocardial reperfusion damage. Furthermore, GH has been reported to be a promising therapeutic option in the treatment of chronic myocardial dysfunction. However, the exact mechanisms of action of GH on the cardiovascular system, particularly in the acute setting, are still unclear. The aim of our study consisted of monitoring the acute effects of GH infusion on isolated blood-perfused rabbit heart according to dose-response pattern and during ischemic conditions to test its anti-ischemic property. Seven blood-donors perfused isolated hearts were used as experimental model. The mechanical and metabolic data of the isolated organs were continuously monitored. Under aerobic conditions, dose-response curves were initially tested after intracoronary infusion of GH at increasing dosages (1, 2, 3 mg/l). After a stabilization period, the effects of GH infusion (5 mg/kg) administered 30 minutes prior to acute global myocardial ischemia (30 minutes) were also investigated. At the doses tested, GH did not induce any changes either in the developed or in the diastolic pressures of the isolated organ. However, transient reduction of the coronary perfusion pressure was observed at the dosage of 3 mg/l. During the ischemia/reperfusion study, at the dosages used in this study, GH did not modify either the degree of stunning in the early reperfusion or the recovery of the developed pressure at the end of reperfusion. In addition, GH did not prevent either the increase of diastolic pressure during ischemia or the release of lactate and CPK during reperfusion. Tissue content of high-energy phosphates was also not changed by GH infusion. In our experimental model, acute GH infusion did not reduce the ischemic/reperfusion damage of the myocardium. However, GH transiently induced coronary vasodilation without modifying the myocardial contractility. Acute effects of GH appear, therefore, to predominantly relate to vascular dilation suggesting that the effects on myocardial contractility may require long-lasting intake being likely linked to enhancement of specific protein synthesis or gene expression of cardiac myocytes.

Chromogranin A in heart failure; a novel neurohumoral factor and a predictor for mortality.

BACKGROUND: In chronic heart failure, several hormonal systems are activated with diagnostic and prognostic implications. We tested the hypotheses that serum Chromogranin-A (CgA) -- a 49 kDa acid protein present in the secretor granules of neuroendocrine cells -- is increased in chronic heart failure and that CgA levels are a predictive factor for mortality. METHOD AND RESULTS: In 160 patients with chronic heart failure, we measured serum CgA and other neuroendocrine hormones. The results showed that CgA is increased in chronic heart failure and the increase is related to the clinical severity of the syndrome: CgA levels in New York Heart Failure (NYHA) class II (median 146.9 ng x ml(-1), inter-quartiles 108.3-265.5) were significantly higher (P<0.05) than in class I (median 109.7 ng x ml(-1), inter-quartiles 96.7-137.6), and significantly lower (P<0.05) than in class III (median 279.0 ng x ml(-1), inter-quartiles 203.6-516.1). Class IV patients showed the highest serum levels of CgA (median 545.0 ng. ml(-1), inter-quartiles 231.8-1068.3), being statistically significantly different from class III patients (P<0.001). The association between survival and some recognized variables of prognostic significance, including CgA was also studied. The results showed that ejection fraction, noradrenaline, atrial natriuretic peptide, NYHA class and CgA were significant univariate prognosticators; however, in the multivariate analysis by the Cox proportional-hazard model, CgA and NYHA class were the only independent predictive factors for mortality (P<0.005, RR=1.22, 95% CI=1.06-1.41 and P=0.04, RR=1.58, 95% CI=1.02-2.46, respectively). CONCLUSIONS: CgA is a pro-hormone, precursor of several active fragments likely to exert biological effects in chronic heart failure. CgA serum levels are increased in patients with chronic heart failure and are a predictive factor for mortality.

[Potential cost reductions for the National Health Service through a telecardiology service dedicated to general practice physicians]. / Riduzione potenziale dei costi per il Servizio Sanitario Nazionale mediante un servizio di telecardiologia dedicato ai medici di medicina generale.

BACKGROUND: Rising health care costs resulted in increasing pressure on the health care system and stimulated new strategies for improving the efficiency of care. A telecardiology service provides a useful support to general practitioners in the management of cardiac patients and contributes to the optimization of health care costs in terms of appropriateness of hospital admission and diagnostic testing. The aim of our study was to evaluate the reduction in the number of referrals to the Emergency Department and to cardiological evaluation resulting from the employment of a telecardiology service by general practitioners. METHODS: Eight hundred and ninety-one consecutive calls arrived to the receiving station of the telecardiology service were analyzed. One hundred and fifty general practitioners received a portable electrocardiographer (Card-Guard 7100, Rehovot, Israel) transferring, by a mobile or fixed telephone, a 12-lead ECG to a receiving station, where a cardiologist was available for reporting and for interactive teleconsultation. At the onset of the phone call, a question was asked to the general practitioner: "What would you have done without the telecardiology service?". The possible answers were: "No actions"; "Referral to the Emergency Department"; "Cardiological consultancy"; "Further investigations". Then we collected the history, risk factors, symptoms and therapy of the patients; the general practitioner sent the ECG tracing by phone. RESULTS: Eight hundred and ninety-one patients were enrolled (402 males, 489 females, mean age 59 +/- 19 years); 465 (52%) patients were symptomatic; 36.4% had no evidence of previous cardiac disease, 35.1% had systemic hypertension, 10.6% had ischemic cardiac disease, 3.7% had atrial fibrillation, and 11.9% other diseases. ECG was normal in 55%. The general practitioners would have sent to the Emergency Department 106 patients (11.9%), and requested further investigations in 717 patients (80.5%). The cardiologist of the telecardiology service solved the problems of the general practitioners in 657 cases (73.7%), sent 56 patients (6.3%) to the Emergency Department, and asked for further investigations in 178 patients (20%), with a reduction of 47% of Emergency Department admission (p < 0.001) and of 95% of further investigations (p < 0.0001) respectively. The cost analysis showed a reduction, between the two modalities, varying from Itl 22,760,000 and Itl 140,060,000 for 891 calls. CONCLUSIONS: Telemedicine is a useful tool for the support of general practitioners' daily activity, with a possible cost reduction due to increased appropriateness of hospital admission and of diagnostic testing.

Retrovirus-mediated gene transfer and galactocerebrosidase uptake into twitcher glial cells results in appropriate localization and phenotype correction.

Galactocerebrosidase (GALC) is deficient in all tissues from human patients and animal models with globoid cell leukodystrophy (GLD) or Krabbe disease. The deficiency results in decreased lysosomal catabolism of certain galactolipids including galactosylceramide and psychosine that are synthesized maximally during myelination. According to current theories, the accumulation of psychosine in humans and animals with GLD induces oligodendrocyte degeneration and myelination ceases. Transduction of oligodendrocytes from twitcher mice with a retroviral vector containing the GALC cDNA can correct the enzyme deficiency in these cells. Our data show that twitcher astrocytes and oligodendrocytes can internalize exogenous GALC, as well as donate the enzyme to the mutant glial cells. Antibodies against human GALC localized the GALC antigen in retrovirally transduced cells and cells receiving enzyme via cell to cell secretion and uptake to the lysosomal fraction. In fact immunocytochemical studies in transduced oligodendrocytes revealed that the GALC colocalizes in vesicles lysosomal-associated membrane protein-2 (LAMP2) (+). Moreover, labeling cells with anti-GALC and a marker for oligodendrocytes demonstrated that, upon differentiation, transduced, twitcher oligodendrocytes attained the normal branched process configuration, while untransduced cells show only abnormal morphology. Phenotype correction in mutant oligodendrocytes has also been observed after enzyme transfer. These studies indicate that GALC activity supplied to cultured oligodendrocytes from twitcher mice by different methods can correct the pathological phenotype of these cells.