Strongyloides stercoralis infection in San Marino Republic: first epidemiological data from an observational study.

Strongyloides stercoralis is a neglected parasite that can cause death in immunocompromised individuals. There were no data on the epidemiology of S. stercoralis infection in San Marino Republic until two patients (one of whom died) were diagnosed with severe strongyloidiasis (hyperinfection) between September 2016 and March 2017. A serology test for Strongyloides spp. was introduced in routine practice in the laboratory of the State Hospital to test patients considered to be at risk for strongyloidiasis. Between August 2017 and August 2018, of 42 patients tested with serology, two (4.8%) were positive. An additional case was found by gastric biopsy. Two of the positive cases were presumably autochthonous infections (elderly people with no significant travel history), while the other was a probable imported case (young man born in Nigeria and settled in Europe since 2003). Epidemiology of strongyloidiasis in San Marino might be similar to Northern Italy, where a relevant proportion of cases was diagnosed in immigrants (mainly from sub-Saharan Africa) and in elderly Italians with eosinophilia. Screening for strongyloidiasis might be worthwhile in inhabitants of San Marino in the same categories of individuals, particularly those at risk of immune suppression.

Epidemiology of inflammatory bowel disease in the Republic of San Marino: The "EPIMICI - San Marino" study.

BACKGROUND: The burden of Crohn's disease (CD) and ulcerative colitis (UC) has never been estimated in the Republic of San Marino, the third smallest nation of the world. AIMS: To assess the occurrence and clinical features of CD and UC in San Marino during the last 35 years. METHODS: We retrospectively evaluated the prevalence, incidence, and main clinical aspects of CD and UC from 1980 to 2014, crossing data from various sources. RESULTS: Prevalence rates (per 100,000) on December 31, were 241 for CD (263 in males and 220 in females) and 311 for UC (370 in males and 255 in females). The specific incidence of UC steadily increased from 4.6 (95% CI: 1.5-10.6) in 1980-1984 to 12.4 (95% CI: 7.6-19.1) in 2010-2014; CD incidence showed a higher proportional increase, from 1.8 (95% CI: 0.2-6.6) in 1980-1984 to 17.9 (95% CI: 12.0-25.7) in 2010-2014. The main clinical features of CD and UC (activity and location at diagnosis, extra-intestinal manifestations, disease progression overtime, therapies, and hospitalizations) were analyzed. CONCLUSIONS: This study provides the first epidemiological report on CD and UC in San Marino, showing specific traits and overall higher prevalence and incidence rates than previously reported in neighbor Areas.

Multiple sclerosis in the Republic of San Marino, Italian peninsula: an incidence and prevalence study from a high-risk area.

Epidemiological studies on multiple sclerosis (MS) carried out in Southern Europe in the last years have shown a significant increase in the disease frequency. Previous surveys conducted in the Republic of San Marino, Northern Italian peninsula, identified that the population is at high risk for MS, with a prevalence of 51.6 per 100,000 population in 1982 and of 166.7 in 2005 and with a mean annual incidence of 7.9 per 100,000 for the period 1990-2005. The present work is a community-based intensive prevalence and incidence survey, by a complete enumeration approach, to update the prevalence and incidence of MS in the Republic of San Marino. The mean annual incidence for the period 2005-14 was 7.7 (95% CI 4.9-11.4) per 100,000, 3.3 (95% CI 1.1-7.6) for men and 11.9 (95% CI 7.2-18.6) for women. On 31 December 2014, 67 patients (19 men and 48 women), suffering from definite or probable MS and living in the Republic of San Marino, yielded a crude prevalence of 204.3 (95% CI 158.4-259.5) per 100,000, 117.8 (95% CI 70.9-183.7) for men and 288.2 (95% CI 212.4-383.3) for women. Our study has confirmed San Marino is an area at high risk for MS, in line with epidemiological data from continental Italy. The marked increase in MS prevalence over time in this population can be ascribable to increased survival and improved ascertainment, in the presence of a substantially stable, yet high, incidence rate.

Estimation of the prevalence of asymptomatic pancreatic cysts in the population of San Marino.

BACKGROUND: There has been a dramatic increase in the number of pancreatic cystic lesions observed in the past two decades but data regarding the prevalence of cysts in the general population are lacking. METHODS: All the individuals who undergo CT at the San Marino State Hospital are residents of the Republic of San Marino; their demographic distribution is available and precise. CT scans carried out over 1 year at the State Hospital were reviewed for asymptomatic pancreatic cysts. RESULTS: 1061 relevant CT scans were carried out on 814 patients; 762 individuals were eligible for the study and 650 patients underwent contrast-enhanced CT. Thirty-five patients had at least one cyst at contrast-enhanced CT (5.4%). The prevalence of cysts increased with increasing age up to 13.4% (95% CI 6.6-20) in individuals 80-89 years of age (p < .001). Cyst prevalence was significantly higher in patients who underwent CT for malignancy (p = .038) but this difference was no longer significant in multivariate analysis. The odds of a cyst being present increased by 1.05 (95% CI 1.02-1.09) for each increasing year of age (p = .002). Approximately a quarter of the patients with cysts died within 1 year after CT from non pancreas-related disease. The estimated standardized age-adjusted cyst prevalence is 2194 per 100,000 people. CONCLUSIONS: The likelihood of having a pancreatic cyst correlates with increasing age, not with the presence of extra-pancreatic malignancies. The estimated prevalence of CT-detectable asymptomatic pancreatic cysts in the general population is 2.2%.

Analgesic, antiulcer, antithrombotic drugs and organ damage: a population-based case-control study.

AIM: Oral medication is of paramount importance for pain treatment. Analgesics, antiulcer (AUDs) and antithrombotic drugs (ATDs) are often coprescribed in elderly people. Non-steroidal anti-inflammatory drugs (NSAIDs) require AUDs to lower the risk of peptic ulcer, and potentially interfere with ATDs. The aim of this study was to quantify the prevalence of NSAID use in patients with gastrointestinal, cardiac or kidney damage in the year 2013, compared to the general population. METHODS: We performed a population-based case-control study in the Republic of San Marino to evaluate the Odds-Ratios for upper gastrointestinal damage (gastroduodenal ulcers and/or erosions, GUE), ischemic heart disease (IHD), heart failure (HF), and renal function impairment (assessed using the CKD-EPI formula), in people who had taken AUDs, ATDs, or NSAIDs in the previous 90 days, versus people who had not taken such drugs in the same period of time. RESULTS: We found that AUDs decreased the OR for GUE (OR: 0.762; CI:0.598-0.972), while ATDs and NSAIDs increased the risk (OR: 1.238 and CI: 0.935-1.683; OR:1.203 and CI:0.909-1.592, respectively). NSAIDs seemed to increase the risk of IHD, although this was not statistically significant (OR=1.464; CI=0.592-3.621). AUDs and ATDs significantly increased the risk of renal function impairment (OR=1.369 and CI=1.187-1.579; OR=1.818 and CI=1.578-2.095, respectively), while this effect was not observed for NSAIDs. CONCLUSION: NSAIDs may induce gastrointestinal and cardiovascular damage, not only by themselves, but also when used concomitantly with common medications such as AUDs or ATDs, due to additive and/or synergistic effects. We performed a "pragmatic" analysis of the association of organ damage with use of NSAIDs/AUDs/ATDs, including patient age, treatment duration and dose, to allow for an immediate application of our findings to everyday clinical practice.

Canine leishmaniasis surveillance program in a San Marino Republic kennel.

The Republic of San Marino is an autonomous State that, in view of its geographical and environmental features, can be considered a part of the Northern Italian territory, where the canine leishmaniasis (CanL) is endemic. In the past, a CanL focus in the Republic's kennel was described. As a consequence of this epidemiological situation, a surveillance program was carried-out covering a 6-year period (2006-2012). A total of 1,094 sera were collected from 420 kennel dogs and examined for antibodies to Leishmania infantum by the indirect fluorescent antibody test (IFAT). Eighty-eight (21%) dogs resulted IFAT positive (antibody titre ≥1/40). The overall seroprevalence increased in the first 4 years (2006-2010), going from 5.5% to 26.8% and then decreased in the 2 following years going to 17.9%(2011) and 3.9% (2012). The cumulative incidence constantly increased from 0.6% to 2.6%. This trend could be attributed to a changed infection pressure due to the dog turnover in the kennels. According to the observed incidence values, the CanL focus seems to be stable, supported by autochthonous transmission, new case introduction and Leishmania spp. circulation in owned dogs in the same area.

Mass population screening for celiac disease in children: the experience in Republic of San Marino from 1993 to 2009.

BACKGROUND: Prevalence of celiac disease in developed countries is assessed about 1:100-1:150. The real prevalence is unknown because mass screenings are expensive and difficult to organize. Moreover celiac disease can affect people at every age and studies on asymptomatic subjects at different ages are not comparable. In this study we wanted to know the real prevalence of celiac disease in children in the Republic of San Marino. We also analysed concordance of different tests used and costs of mass screening. METHODS: The study started in 1993. From 1993 to 1997 children aged 6, 10 and 14 were screened. Since 1997 only children aged 6 were monitored, in order to have a homogeneous population. In fact, every child born since 1980 was taken into account. Children were recruited by classroom lists of students for general paediatric examination. Until 2005 the screening test was based on dosage of antibodies anti-gliadin (AGA) IgA and IgG on venous blood. Since 2006 these tests were replaced by anti-transglutaminase IgA antibodies (ATTG). Anti-endomysial antibodies (EMA) were performed if result of any between either AGA or ATTG tests was positive or borderline; if EMA was positive, then an endoscopy with histological examination was performed to confirm the final diagnosis. RESULTS: Attendance to paediatric examination was 96%, submission to blood test was 87%. 42 on 5092 (0,8%; 1:125) children resulted affected by celiac disease. Histology always confirmed diagnosis by serology except for two cases. AGA test (until 2005) yielded 28 on 4304 (0,7% 1:143); ATTG test (since 2006) revealed 14 positive cases on 788 (1,8%; 1:55) leading to a larger percentage of diagnosis. EMA antibodies always confirmed positivity of ATTG. CONCLUSIONS: Prevalence of celiac disease in children of Republic of San Marino is comparable to other North-European Countries. Sensitivity of ATTG proved much higher than that of anti-gliadin antibodies. Concordance between ATTG and EMA was 100%. Concordance between serology and histology was approximately 100%. Cost of screening was yearly about 5000 euros (250 children screened every year).

Multiple sclerosis in the Republic of San Marino: a prevalence and incidence study.

Studies on the distribution of multiple sclerosis (MS) carried out in Southern Europe in the last years have shown a significant increase in the frequency of the disease. A previous descriptive survey in the Republic of San Marino, northern Italian peninsula, published in 1984 established that this area is at high risk for MS. We updated the frequency estimates of the disease by adopting a complete enumeration approach. On 31 December 2005, 50 MS patients (36 women and 14 men) yielded a crude prevalence rate of 166.7 per 100, 000 (95% CI 123.7-220), 235.3 (95% CI 165-327.4) for women and 95.2 (95% CI 52-160) for men. The average incidence from 1990 to 2005 was 7.9 (95% CI 5.3-11.1) per 100,000, 11.7 (95% CI 7.6-17.3) for women and 3.9 (95% CI 1.7-7.7) for men. We did not detect any significant temporal trend over the study period. These results confirm that in San Marino the disease occurs more frequently than that suggested in the past and support the data on MS frequency in continental Italy. The marked increase in MS prevalence ratio is partly due to the increasing survival of patients and the accumulation of new incidence cases owing to the reduction in diagnostic latency for better quality of neurological diagnostic procedures. However, an increased incidence of the disease could be considered.

Hypertension prevalence, awareness, control and association with metabolic abnormalities in the San Marino population: the SMOOTH study.

BACKGROUND: The aim of the SMOOTH (San Marino Observational Outlooking Trial on Hypertension) study was to explore hypertension awareness, treatment and control and the associated metabolic abnormalities and risk factors in the population of San Marino, a small state in the Mediterranean area, for which limited evidence is available. METHODS: Nine general practitioners enrolled 4590 consecutive subjects (44% of the San Marino population age 40-75 years), seen in their office by collecting history, physical and laboratory data and office blood pressure (BP) measurements. RESULTS: Of these subjects, 2446 were normotensive and 2144 hypertensive; 62.3% of hypertensive patients were aware of their condition, 58.6% were treated (monotherapy 31.5%, combination therapy 27.1%), and 21.7% were controlled. Hypertension awareness and treatment were more frequent above age 50 and in females; BP control was similarly low in both genders. As compared to normotensives, hypertensive subjects were less frequently smokers (20.1 versus 27.8%), had greater body mass index (28.1 +/- 4.5 versus 25.8 +/- 3.7 g/m), and a higher prevalence of diabetes mellitus (15.8 versus 6.3%), lower high-density lipoprotein (HDL) cholesterol and higher prevalence of increased blood total cholesterol (66.1 versus 51.3%), triglycerides and serum uric acid. Values of subjects with 'high-normal' blood pressure were closer to those of hypertensive subjects. The prevalence of metabolic syndrome was higher in hypertensive than in normotensive subjects, and in treated than in untreated hypertensives. CONCLUSIONS: Even in a small Mediterranean country with high health-care standards, hypertension awareness, treatment and control are inadequate and hypertension clusters with metabolic abnormalities and risk factors as in non-Mediterranean areas.

Cluster headache: the history of the Cluster Club and a review of recent clinical research.

In September 2003, a scientific meeting was held in Rome to revive the International Cluster Headache Research Group (or "Cluster Club") tradition. This group of specialists was originally formed in the late 1970s by Ottar Sjaastad in order to promote research ideas, and to generate papers and other important information in this field. Its meetings, the last of which had taken place in 1994, had been informal events at which there was ample time for lively discussion. The last decade of the 20th century brought a significant increase in clinical and experimental research into cluster headache (CH), and this review summarizes some of the results of this research. The male preponderance of CH has been shown to be progressively decreasing over the years. Revised clinical criteria and a modern classification have been presented. First-degree relatives of probands with CH have been shown to have an increased risk of suffering from CH compared with the general population. Genetic analysis suggests that an autosomal dominant gene plays a role in some families. Functional neuroimaging has contributed to a better understanding of the pathophysiology of the condition. Positron emission tomography during provoked attacks has shown activation of the ipsilateral inferior posterior hypothalamus and it has been suggested that CH might be a functional neurovascular disorder of pacemaker or circadian regions in the hypothalamic grey matter. Subcutaneously administered sumatriptan has emerged as a highly effective acute treatment, but, in our opinion, the emphasis should be on attack prevention. Deep brain stimulation of the inferior posterior hypothalamic grey matter seems to be very promising as a novel treatment targeting the presumed central origin of pain attacks.

Prevalence and incidence of cluster headache in the Republic of San Marino.

Based on a preceding survey performed in 1985, the authors estimated the prevalence and incidence of cluster headache (CH) in the Republic of San Marino (26,628 inhabitants at 31 December 1999). All cases were diagnosed by direct interview according to International Headache Society criteria. The prevalence rate was 56/100,000 (95% CI 31.3 to 92.4), and the incidence rate was 2.5/100,000/year (95% CI 1.14 to 4.75). Most cases showed rare clusters. This is the first prospective study on the incidence of CH.

Seroprevalence and anti-HEV persistence in the general population of the Republic of San Marino.

The prevalence of anti-HEV was assessed in 2,233 subjects aged 20-79 years in the Republic of San Marino in the years 1990-1991. The sera were tested by ELISA and further confirmed by Western blot (WB) analysis. The overall anti-HEV prevalence was 1.5%. A significant trend by age was observed. Anti-HEV prevalence was 0.6% in subjects <30 years and 3.3% in those older than 70 years of age. Family size larger than four persons (OR = 3.8; 95% CI = 1.8-13.2) was the sole independent predictor of anti-HEV positivity in the multivariate analysis. Anti-HAV and anti-HEV prevalences did not show a parallel trend by age. No association was found either between hepatitis E virus (HEV) or hepatitis C virus (HCV) infections. Follow-up samples 5 years apart were available for 38 out of 54 (70%) anti-HEV ELISA-positive subjects. Eight out of 22 (37%) WB-confirmed anti-HEV-positive subjects were still anti-HEV-positive after 5 years. However, anti-HEV remained positive in all but two (75%) of the subjects with WB-confirmed ELISA positivity value of S/CO > or = 2 (cutoff 1.2), but in only 2 out of the 14 subjects (14%) with a WB-confirmed ELISA positivity value of S/CO < 2 (P < 0.005). None of the 16 subjects ELISA-positive but not WB-confirmed was anti-HEV-positive 5 years apart. Therefore, only a relative proportion of subjects once infected with HEV maintain for at least 5 years anti-HEV antibodies.

Population-based survey of hepatitis A virus infection in the Republic of San Marino.

In 1990-1991, the prevalence of antibodies to hepatitis A virus infection (anti-HAV) was assayed by the ELISA method among 1528 apparently healthy subjects, 20-85 years old in the Republic of San Marino. Subjects were selected from the list of residents by a random stratified sampling procedure with a proportional allocation by age, sex and district of residence. The overall anti-HAV prevalence was 64.7%; it increased from 28.6% in subjects 20-30 years old to 97% in those > 60 years (p < 0.01). No gender difference was observed. At the multivariate analysis age > 40 years (OR: 39.5; 95% CI: 12.4-126) and lowest level of schooling (OR: 1.8; 95% CI: 1.1-2.9), which is a good indirect indicator of socio-economic status, resulted both independent predictors of anti-HAV seropositivity. These findings reflect the improved sanitation standards in this area and indicate that the proportion of non-immune adults is increasing with a higher risk of symptomatic infection in the near future.

A population based study of Helicobacter pylori infection in a European country: the San Marino Study. Relations with gastrointestinal diseases.

Helicobacter pylori is present worldwide but few large population studies exist on the epidemiology of the infection. A random cross sectional study was performed of H pylori infection in the adult population of San Marino, a European country with high gastric cancer rate, to assess its prevalence and to evaluate its relations with gastrointestinal disease. In 2237 subjects (77% of the initial sample) H pylori IgG antibodies were detected with enzyme linked immunosorbent assay (ELISA) and immunoblotting. A questionnaire including questions about occupation, place of birth, and smoking was given to all subjects. Dyspepsia, peptic ulcer, and gastric cancer in the subjects, relatives, and partners as well as use of drug, dental treatment/prostheses, and gastrointestinal endoscopies, were evaluated by multivariate analysis. H pylori prevalence was of 51%, increased with age from 23% (20-29 years) to 68% (> or = 70 years), and was higher among manual workers. H pylori was independently associated with ulcer (OR = 1.63, 95% confidence intervals (CI) = 1.16 to 2.27), H2 antagonists (OR = 1.94, 95% CI = 1.21 to 3.10), and benzodiazepines (OR = 1.57, 95% CI = 1.02 to 2.42), dental prostheses (OR = 1.25, 95% CI = 1.05 to 1.49), gastroscopy in the past five years (OR = 1.50, 95% CI = 1.05 to 2.14), peptic ulcer in siblings (OR = 1.52, 95% CI = 1.09 to 2.12), gastric cancer in father (OR = 1.61, 95% CI = 1.02 to 2.52). The association of seropositivity with history of ulcer, gastric cancer in family, gastroscopy, and H2 antagonists suggests that H pylori is an epidemiological key factor in the pathogenesis of gastroduodenal diseases in this area.