Case-Control Study on the Routes of Transmission of SARS-CoV-2 after the Third Pandemic Wave in Tuscany, Central Italy.

The emergence of hyper-transmissible SARS-CoV-2 variants that rapidly became prevalent throughout the world in 2022 made it clear that extensive vaccination campaigns cannot represent the sole measure to stop COVID-19. However, the effectiveness of control and mitigation strategies, such as the closure of non-essential businesses and services, is debated. To assess the individual behaviours mostly associated with SARS-CoV-2 infection, a questionnaire-based case-control study was carried out in Tuscany, Central Italy, from May to October 2021. At the testing sites, individuals were invited to answer an online questionnaire after being notified regarding the test result. The questionnaire collected information about test result, general characteristics of the respondents, and behaviours and places attended in the week prior to the test/symptoms onset. We analysed 440 questionnaires. Behavioural differences between positive and negative subjects were assessed through logistic regression models, adjusting for a fixed set of confounders. A ridge regression model was also specified. Attending nightclubs, open-air bars or restaurants and crowded clubs, outdoor sporting events, crowded public transportation, and working in healthcare were associated with an increased infection risk. A negative association with infection, besides face mask use, was observed for attending open-air shows and sporting events in indoor spaces, visiting and hosting friends, attending courses in indoor spaces, performing sport activities (both indoor and outdoor), attending private parties, religious ceremonies, libraries, and indoor restaurants. These results might suggest that during the study period people maintained a particularly responsible and prudent approach when engaging in everyday activities to avoid spreading the virus.

Evaluation of the Anti-Spike (RDB) IgG Titer among Workers Employed at the University of Pisa Vaccinated with Different Types of SARS-CoV-2 Vaccines.

With the development of SARS-CoV-2 vaccines, many authors started evaluating the immunization efficacy of the available vaccines mainly through sero-positivity tests or by a quantitative assessment of the IgG against the spike protein of SARS-CoV-2 virus in vaccinated subjects. In this work, we compared the titers resulting from vaccination and tried to understand the potential factors affecting the immune response to the available SARS-CoV-2 vaccines. This study was conducted on 670 volunteers employed at the University of Pisa and undergoing a health surveillance program at the University Hospital of Pisa. For each participant, 10 mL of blood, information about contacts with confirmed cases of COVID-19, age, sex, SARS-CoV-2 vaccination status, previous SARS-CoV-2 infection and symptoms, type of vaccine and the date of administration were collected. In the multivariate analysis, the type of vaccine, the presence of symptoms in SARS-CoV-2 positive individuals, and the distance from the second dose significantly affected the antibody titer; the combined vaccination resulted in a faster decay over time compared with the other types of vaccination. No significant differences were observed between Spikevax and Comirnaty (p > 0.05), while the antibody levels remain more stable in subjects undergoing Vaxzevria vaccination (p < 0.01) compared with mRNA-based ones.

Analysis of the excess mortality and factors associated with deaths from COVID-19 versus other causes in Central Tuscany (Italy) in 2020.

OBJECTIVES: to assess the extent of the excess mortality from all causes in 2020 compared to 2015-2019 in Central Tuscany (Italy) as a proxy to estimate COVID-19-related excess mortality and to identify demographic and clinical differences between subjects who died from COVID-19 and those who died from other causes in 2020. DESIGN: descriptive analysis of the temporal trend of general mortality. SETTING AND PARTICIPANTS: the study population is represented by the 1.6 million residents living in the territory of the Central Tuscany Healthcare Authority in Central Italy, i.e., little less than half of the population of Tuscany, in an area of just over one fifth of the entire region, where the provinces of Florence, Pistoia, and Prato are comprised. MAIN OUTCOME MEASURES: using the Italian National Resident Population Registry (ANPR) as a source of mortality data, standardized mortality ratios with 95% confidence intervals were calculated to compare the number of deaths in 2020 with the number of deaths expected on the basis of mortality data from 2015 to 2019. Furthermore, after record linkage with data from the integrated surveillance of cases of SARS-CoV-2 virus infection and with the MaCro dataset of comorbidities, the characteristics of subjects who died from COVID-19 were compared with those of patients who died from other causes using a multivariate logistic regression model; odds ratios with 95% confidence intervals were calculated. RESULTS: a statistically significant excess mortality was observed during the first pandemic wave in March and April, and during the second wave in the fall; it ranged between +9% in March and +51% in November. On the contrary, in January, February, and May, all-cause mortality was significantly lower than in previous years. The male gender, dyslipidaemia, and dementia were positively associated with death from COVID-19 rather than from all other causes. On the contrary, heart failure and recent tumours were more represented among deaths from other causes. CONCLUSIONS: much of the over-mortality observed in spring is attributable to the harvesting effect COVID-19 exerted on a segment of population with serious underlying chronic conditions and who in the previous months had survived a mild winter and a flu season of medium intensity. In the second pandemic wave, in autumn, the impact of both direct and indirect effects of COVID-19 was substantially higher. Consistently with the available evidence, death from COVID-19 was related to the male gender and to clinical conditions such as dyslipidaemia and dementia.

Epidemiological, demographic and clinical data on chronic viral hepatitis C in Tuscany.

BACKGROUND: Recent introduction of direct antiviral agents (DAAs) has completely changed the scenario regarding hepatitis C virus (HCV) treatment. Certain countries' economic health programs prioritize DAAs according to specific clinical features of HCV-infected patients. The aim of this study was to define epidemiological, demographic and clinical characteristics of HCV-infected patients in the Tuscany region of central Italy. METHODS: We enrolled HCV patients with chronic viral hepatitis who were referred to the outpatient services of 16 hospitals in Tuscany from 1 January 2015 to 31 December 2015. Case report forms contained patient information including main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations (liver biopsy or transient elastometry, liver ultrasound), eligibility for DAAs, and liver transplantation or therapy already in progress. RESULTS: Of all patients considered, 2919 HCV patients were enrolled (mean age: 57.44 ± 15.15; 54% males, 46% females). All routes of transmission were well represented (intravenous drug use in 20.7%; nosocomial/dental care in 20.6%; and coagulation factors/blood transfusions in 13.3%). Diabetes was the highest represented comorbidity (20.8%), followed by metabolic syndrome (15.5%) and ischemic heart disease (6.2%). The most prevalent HCV genotypes were 1b (47.4%) and 2 (16.5%). In the whole cohort of patients, 32.8% were cirrhotic (40 patients were listed for liver transplantation). Signs of portal hypertension were present mostly in the group older than 45 years (92.3%). Extrahepatic HCV-related diseases were present in 13.3% of cases (cryoglobulinemic syndrome in 58.3% and B-cell non-Hodgkin's lymphoma in 10.5%). CONCLUSIONS: Our study provides evidence of a high prevalence of epidemiological changes in HCV infection with a major prevalence of advanced liver disease, such as portal hypertension, in this elderly cohort of patients.

Clinical epidemiology of chronic viral hepatitis B: A Tuscany real-word large-scale cohort study.

AIM: To build a regional database of chronic patients to define the clinical epidemiology of hepatitis B virus (HBV)-infected patients in the Tuscan public health care system. METHODS: This study used a cross-sectional cohort design. We evaluated chronic viral hepatitis patients with HBV referred to the outpatient services of 16 hospital units. Information in the case report forms included main demographic data, blood chemistry data, viral hepatitis markers, instrumental evaluations, and eligibility for treatment or ongoing therapy and liver transplantation. RESULTS: Of 4015 chronic viral hepatitis patients, 1096 (27.3%) were HBV infected. The case report form was correctly completed for only 833 patients (64% males, 36% females; mean age 50.1 ± 15.4). Of these HBV-infected patients, 73% were Caucasian, 21% Asian, 4% Central African, 1% North African and 1% American. Stratifying patients by age and nationality, we found that 21.7% of HBV-infected patients were aged < 34 years (only 2.8% were Italian). The most represented routes of transmission were nosocomial/dental procedures (23%), mother-to-child (17%) and sexual transmission (12%). The most represented HBV genotypes were D (72%) and A (14%). Of the patients, 24.7% of patients were HBeAg positive, and 75.3% were HBeAg negative. Of the HBV patients 7% were anti-HDV positive. In the whole cohort, 26.9% were cirrhotic (35.8% aged < 45 years), and 47% were eligible for or currently undergoing treatment, of whom 41.9 % were cirrhotic. CONCLUSION: Only 27.3% of chronic viral hepatitis patients were HBV infected. Our results provide evidence of HBV infection in people aged < 34 years, especially in the foreign population not protected by vaccination. In our cohort of patients, liver cirrhosis was also found in young adults.

Improved endothelial function after short-term therapy with evolocumab.

BACKGROUND: The reduction of cholesterol levels with cholesterol-lowering therapy may improve endothelial function. Lipid-lowering therapy has been greatly enhanced by the introduction of proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies. Less is known of the effect of PCSK9 inhibitors on endothelial function of subjects with hypercholesterolemia. OBJECTIVE: To assess whether treatment with PCSK9 inhibitors may improve endothelial function evaluated by brachial artery vasoreactivity test. METHODS: Brachial artery vasoreactivity test was performed in 14 consecutive patients with previous myocardial infarction before and after 2 months of therapy with evolocumab 140 mg twice in a month. Mean brachial artery diameter, velocity time integral, flow-mediated dilation (FMD) and low-density lipoprotein (LDL) cholesterol levels were also evaluated. RESULTS: After 2 months of treatment with evolocumab, mean total cholesterol levels decreased from 245 ± 41 to 128 ± 30 mg/dL (P < .001, -48%), and LDL levels from 176 ± 43 to 71 ± 26 mg/dL (P = .001, -59%); FMD conversely increased from 6.3 ± 4.1% to 8.8 ± 6.3% (P = .004, +40%). Improvement in FMD was proportional to reduction of LDL levels (r = 0.69, P = .006). Therapy with evolocumab increased brachial artery diameter during vasoreactivity test (peak values 0.39 ± 0.09 vs 0.36 ± 0.11 cm, P = .010; final values 0.36 ± 0.10 vs 0.34 ± 0.10 cm, P = .001), and velocity time integral (peak levels 96 ± 1 vs 85 ± 9 cm, P = .045). CONCLUSIONS: Two months of treatment with evolocumab 140 mg may improve endothelial function in subjects with increased cardiovascular risk. The improvement in endothelial function is proportional to LDL reduction.

Predictive value of very low frequency at spectral analysis among patients with unexplained syncope assessed by head-up tilt testing.

BACKGROUND: The role of heart rate variability (HRV) in the prediction of vasovagal syncope during head-up tilt testing (HUTt) is unclear. AIM: To evaluate the ability of the spectral components of HRV at rest to predict vasovagal syncope among patients with unexplained syncope referred for HUTt. METHODS: Twenty-six consecutive patients with unexplained syncope were enrolled in the study. All patients underwent HRV evaluation at rest (very low frequency [VLF], low frequency [LF], high frequency [HF] and LF/HF ratio) and during HUTt. HUTt was performed using the Westminster protocol. Continuous electrocardiogram and blood pressure monitoring were performed throughout the test. RESULTS: Eight (31%) patients developed syncope during HUTt. There were no baseline differences in terms of clinical features and HRV variables among patients who developed syncope and those who did not, except for VLF (2421 vs 896ms2; P<0.001). In the multivariable logistic regression analysis, including age and sex, VLF was the only independent variable associated with syncope during HUTt (odds ratio 1.002, 95% confidence interval 1.0003-1.0032; P=0.02). The area under the curve at rest was 0.889 for VLF, 0.674 for HF and 0.611 for LF. A value of VLF>2048ms2 was the optimal cut-off to predict syncope during HUTt (sensitivity 87.5%, specificity 72.2%). CONCLUSIONS: VLF at rest predicted the incidence of syncope during HUTt. Further studies are warranted to confirm these preliminary data.

Mortality of populations residing in geothermal areas of Tuscany during the period 2003-2012.

INTRODUCTION: The limited scientific knowledge on the relationship between exposure and health effects in relation to geothermal activity motivated an epidemiologic investigation of Tuscan geothermal area. AIM: This study aims at describing mortality of populations living in Tuscan municipalities in the period 2003-2012. METHOD: Sixteen municipalities were included in the study area: eight in the northern and eight in the southern area. Mortality data come from the Regional Mortality Registry of Tuscany. Fifty-four causes of death, considered of interest for population health status or consistent with "Project SENTIERI" criteria, are analyzed. RESULTS: Results show a worse mortality profile in the southern area, especially in males, for whom excesses of all cancers and some causes of cancer emerge, while in the northern area an excess of cerebrovascular diseases among females merits attention. Further and more appropriate studies are needed to clarify the etiology of some diseases and to better assess a potential cause-effect relationship.

Uptake of cervical cancer screening among the migrant population of Prato Province, Italy.

OBJECTIVE: To determine the level of participation in cervical cancer screening among the migrant population of Prato Province, Italy. METHODS: A retrospective cross-sectional study was conducted using data for women aged 25-64 years who were resident in one of the municipalities of Prato Province and had received at least one invitation to undergo a cervical cancer screening test. Data were extracted from both the Local Health Unit Serviceable Registry and cervical cancer screening archives for the period July 1, 2004, to June 30, 2007. RESULTS: Of the 69 459 residents eligible for cervical cancer screening, 7339 (10.6%) did not have Italian citizenship. Adherence with cervical cancer screening among the migrant population was lower than that of the Italian resident population: uptake increased from 52.4% in 2004 to 57.3% in 2007 among the Italian resident population, but decreased from 31.4% to 28.2% among migrants. CONCLUSION: The migrant population of Prato Province has decreased adherence with cervical cancer screening.

Attempt to calculate the prevalence and features of chronic hepatitis C infection in Tuscany using administrative data.

AIM: To evaluate this prevalence in Tuscan populations that was known and unknown to the Tuscan Regional Health Service in 2015. METHODS: Tuscan Health administrative data were used to evaluate hepatitis C virus (HCV) infected people known to the Regional Health Service. Residents in Tuscany with a HCV exemption code (070.54) were identified. Using the universal code attributed to each resident, these patients were matched with hospital admission codes identified by the International Classification of Diseases, Ninth Revision (ICD-9), Clinical Modification, and with codes for dispensing drugs to patients by local and hospital pharmacies. Individuals were considered only once. Capture-recapture analysis was used to evaluate the HCV-infected population unknown to the Regional Health Service. RESULTS: In total, 14526 individuals were living on 31/12/2015 with an exemption code for HCV. In total, 9524 patients were treated with pegylated interferon + ribavirin and/or direct-acting antiviral drugs during the last 10 years, and 13879 total hospital admissions were noted in the last 15 years. After data linkage, the total number was 25918. After applying the Capture-Recapture analysis, the number of unknown HCV-infected people was 23497. Therefore, the total number of chronic HCV-infected people was 38643, excluding those achieved sustained virological response to previous treatment. CONCLUSION: Our results show a prevalence of HCV infected people of 1%. Tuscan administrative data could be useful for calculating health care costs and health planning in the coming years.

[Alcohol dependence in the Italian general population: diagnostic criteria according to general practitioners and to the Composite International Diagnostic Interview (CIDI)]. / L'alcoldipendenza nella popolazione generale: i criteri di diagnosi secondo i medici di medicina generale e secondo l'intervista Composite International Diagnostic Interview (CIDI).

OBJECTIVES: to identify the criteria used by general practitioners (GPs) for the diagnosis of alcohol dependence (AD) and to compare them with the criteria of the Composite International Diagnostic Interview (CIDI). DESIGN: cross-sectional correlational study. SETTING AND PARTICIPANTS: the 55 GPs of Friuli Venezia Giulia Region (Northern Italy) and Tuscany Region (Central Italy) who took part in the research conducted a clinical evaluation of the first 40 patients who came for a medical examination. MAIN OUTCOME MEASURES: prevalence of AD diagnosed by GPs and CIDI and their association with sociodemographic variables, other diseases, and alcohol consumption. RESULTS: AD prevalence assessed by the GPs was 5.4%, while AD prevalence assessed by the CIDI was 4.4%, with an overlap of about 26%. Patients identified as AD by the GPs were older and more frequently suffering from liver disease and hypertension than patients identified by the CIDI. CONCLUSIONS: the limited overlap between diagnoses of AD made by GPs and the one made by the CIDI is problematic. GPs appear to identify mainly more severe forms of AD, in which excessive consumption of alcohol is associated with the presence of liver disease, while the CIDI could identify younger patients who have not yet developed diseases. GPs' recognition of AD could be increased by using their expertise along with standardised questionnaires which measure alcohol consumption.

[Impacts of geocoding quality in environmental epidemiology studies: two case-studies in Tuscany Region (Central Italy)]. / L'impatto della qualità della georeferenziazione negli studi di epidemiologia ambientale: due casi studio in Toscana.

OBJECTIVES: Geographical Information Systems (GIS) are widely used in environmental epidemiology studies to locate study population by geocoding addresses and to evaluate exposures and relationship with health outcomes. Despite this, Italian environmental epidemiologists poorly discuss quality of address geocoding results. DESIGN: two case-studies have been carried out in Tuscany Region (Central Italy): one in the mountain area in the Municipality of Piancastagnaio (Siena Province) and one in the urban area around the airport of Florence. Three geocoding systems have been compared: the geographical database produced by Tuscany Region and two commercial systems (Google and Bing-Microsoft); 1,549 addresses in Piancastagnaio and 2,946 addresses in Florence have been tested. RESULTS: Tuscan geographical database showed better performance than the two commercial systems, with bigger differences in Piancastagnaio. In this area, mean difference between regional system and Google service is more than 300 mt, with peaks of 7-8 km. Bing- Microsoft system does not provide any information on addresses in Piancastagnaio: all input addresses were geocoded in the centroid of the municipality or in the centre of a few principal streets. Lowest differences among the three methods were observed in the urban area of Florence: mean difference between Tuscany and Goggle systems was 150 mt, with less than 2 km peaks; between Tuscany and Bing-Microsoft mean difference was 100 mt with 3 km peaks. In both case-studies, but especially in Piancastagnaio area, these differences gave rise to great misclassification in the evaluation of individual exposure and health outcome. CONCLUSION: the study highlighted the impacts of address geocoding process in exposure assessment in environmental health research and pointed out the need of specifically evaluate the quality of cartographic data.

The epidemiological changes of HCV and HBV infections in the era of new antiviral therapies and the anti-HBV vaccine.

The World Health Organization (WHO) resolution adopted in 2010 recognized viral hepatitis as a global health problem. In April 2014, for the first time, the WHO produced guidelines for the screening, care and treatment of persons with hepatitis C infections. In May 2014, a follow-up resolution urged WHO Member States to develop and implement a national strategy for the prevention, diagnosis and treatment of viral hepatitis based on the local epidemiological context. Although blood donor screening, which began in the early 1990s, has reduced the spread of the virus in the population, the WHO estimates that 150 million people are chronically infected with hepatitis C virus (HCV) and are at an increased risk of developing liver cirrhosis and hepatocellular carcinoma. In addition, 3-4 million people are infected each year. HCV treatment is currently evolving rapidly, and several drugs are in various stages of development. With regard to the hepatitis B virus (HBV), in March 2015, the WHO published the first guidelines for the prevention, care and treatment of persons with chronic hepatitis B infection, which were designed to complement the recent guidelines on HCV. Although the introduction of an effective vaccine against the hepatitis B virus has reduced the prevalence and health and economic impact of hepatitis in industrialized countries, the WHO estimates that more than 2 billion people are HBV-infected and 350 million people are chronic carriers.

[Trends in occurrence, treatment, and outcomes of acute myocardial infarction in Tuscany Region (Central Italy), 1997-2010]. / Trend temporali di occorrenza, trattamento ed esiti dell'infarto miocardico acuto in Toscana, 1997-2010.

OBJECTIVES: to describe trends in attack rate, treatment, and outcomes of acute myocardial infarction (AMI) in Tuscany Region (Central Italy). DESIGN: population-based epidemiological study using the Tuscany Acute Myocardial Infarction Registry. SETTING AND PARTICIPANTS: cases have been identified by record linkage between the hospital discharge database and the mortality registry, and divided into hospitalised AMI (1997-2012) and out-of-hospital coronary deaths (1997-2010). Details on hospitalised cases based on the presence/absence of ST-segment elevation (STEMI / NSTEMI) can be detected for the period 2001-2012. MAIN OUTCOMEMEASURES: distribution by calendar time, gender, and type of event of absolute frequencies, age-standardised attack rates (per 100,000; standard Tuscany population, 2001) and percentages (standard: total hospitalised cases in 2011) of invasive cardiac procedures and 28-day case fatality in hospitalised cases. RESULTS: a reduction in both out-of-hospital coronary deaths and STEMI hospitalisations (attack rates, respectively, - 2.3% and -3.9% in males, -3.3% and -4.1% in females) and an increase in NSTEMI hospitalisations (+13.1% in males and +13.3% in females) were shown. The use of invasive cardiac procedures (PCI, coronary angiography) in hospitalised cases shows a considerable increase over time both in STEMI and in NSTEMI. The proportion, however, always remains lower in the whole period after the age of 70 and in women. The short term prognosis in hospitalised AMI cases shows an improvement over time, which, however, disappears when stratified by type of AMI. This trend is mainly related to the different weight that STEMI and NSTEMI have on incidence over time (increase in attack rates for NSTEMI and reduction for STEMI, with worst prognosis). CONCLUSIONS: results confirm the important changes in epidemiology, clinical presentation, and treatment of acute coronary disease in Tuscany, previously identified in the international literature. Differences in coronary reperfusion treatment of hospitalised cases still persist by age and gender. Additional efforts are needed to ensure equity in access to the best treatment for AMI.

Italy between drinking culture and control policies for alcoholic beverages.

This paper focuses on whether the on-going dramatic decrease in alcohol consumption in Italy, especially of wine, during 1961-2008, was associated with which parallel sociodemographic and economic changes and with alcohol control policies. The study, using both time series (TS) and artificial neural network (ANN)-based analyses documents that its selected sociodemographic and economic factors, and particularly urbanization, had a definite connection with wine consumption decrease, spirits decrease, and the increase in beer consumption over time. On the other hand, control policies showed no effect on the decline in alcohol consumption, since no alcohol control policy existed in Italy between 1960 and 1987. A few policies introduced since 1988 (BAC and sale restrictions during mass events) may have contributed to reducing or to maintaining the on-going reduction. Study limitations are noted and future needed research is suggested.

User-only design to assess drug effectiveness in clinical practice: application to bisphosphonates and secondary prevention of fractures.

PURPOSE: Different strategies applicable to control for confounding by indication in observational studies were compared in a large population-based study regarding the effect of bisphosphonates (BPs) for secondary prevention of fractures. METHODS: The cohort was drawn from healthcare utilization databases of 13 Italian territorial units. Patients aged 55 years or more who were hospitalized for fracture during 2003-2005 entered into the cohort. A nested case-control design was used to compare BPs use in cohort members who did (cases) and who did not experience (controls) a new fracture until 2007 (outcome). Three designs were employed: conventional-matching (D1 ), propensity score-matching (D2 ), and user-only (D3 ) designs. They differed for (i) cohort composition, restricted to patients who received BPs straight after cohort entry (D3 ); (ii) using propensity score for case-control matching (D2 ); and (iii) compared groups of BPs users versus no users (D1 and D2 ) and long-term versus short-term users (D3 ). RESULTS: Bisphosphonate users had odds ratios (95% confidence interval) of 1.20 (1.01 to 1.44) and 0.95 (0.74 to 1.24) by applying D1 and D2 designs, respectively. Statistical evidence that long-term BPs use protects the outcome onset with respect to short-term use was observed for user-only design (D3 ) being the corresponding odds ratio (95% confidence interval) 0.64 (0.44 to 0.93). CONCLUSIONS: User-only design yielded closer results to those seen in RCTs. This approach is one possible strategy to account for confounding by indication.

Effectiveness of oral bisphosphonates for primary prevention of osteoporotic fractures: evidence from the AIFA-BEST observational study.

PURPOSE: Osteoporosis is a chronic disease of the bone, whose incidence increases progressively with aging. The main consequences of osteoporosis are fragility fractures, which have considerable medical, social, and economic implications. Adequate treatment of osteoporosis must be considered as a compelling public health intervention. Bisphosphonates (BPs) represent the most significant advance in this field in the past decade, and they are widely used in the treatment of osteoporosis. However, evidence for their effectiveness is limited to secondary prevention, whereas their effect in primary prevention is uncertain and needs further investigation. METHODS: Using administrative data collected in the "Biphosphonates Efficacy-Safety Tradeoff" (BEST) study, a nested case-control study was conducted by including 56,058 participants, aged 55 years who were started on oral BPs from 2003 to 2005. Cases were the 1,710 participants who were hospitalized for osteoporotic fractures until 2007. Up to 20 controls were randomly selected for each case. Conditional logistic regression model was used to estimate odds ratio of fracture associated with categories of treatment duration. RESULTS: Compared with participants assuming BPs for less than 1 year, those who remained on therapy for at least 2 years had a 21% (95% confidence interval (CI) 7 to 33%) fracture risk reduction. CONCLUSION: This study provides evidence that BPs, dispensed for primary prevention of osteoporotic fractures, are associated with a reduced risk of osteoporotic fractures after at least 2 years of treatment.