Postmarketing active surveillance of myocarditis and pericarditis following vaccination with COVID-19 mRNA vaccines in persons aged 12 to 39 years in Italy: A multi-database, self-controlled case series study.

BACKGROUND: Myocarditis and pericarditis following the Coronavirus Disease 2019 (COVID-19) mRNA vaccines administration have been reported, but their frequency is still uncertain in the younger population. This study investigated the association between Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) mRNA vaccines, BNT162b2, and mRNA-1273 and myocarditis/pericarditis in the population of vaccinated persons aged 12 to 39 years in Italy. METHODS AND FINDINGS: We conducted a self-controlled case series study (SCCS) using national data on COVID-19 vaccination linked to emergency care/hospital discharge databases. The outcome was the first diagnosis of myocarditis/pericarditis between 27 December 2020 and 30 September 2021. Exposure risk period (0 to 21 days from the vaccination day, subdivided in 3 equal intervals) for first and second dose was compared with baseline period. The SCCS model, adapted to event-dependent exposures, was fitted using unbiased estimating equations to estimate relative incidences (RIs) and excess of cases (EC) per 100,000 vaccinated by dose, age, sex, and vaccine product. Calendar period was included as time-varying confounder in the model. During the study period 2,861,809 persons aged 12 to 39 years received mRNA vaccines (2,405,759 BNT162b2; 456,050 mRNA-1273); 441 participants developed myocarditis/pericarditis (346 BNT162b2; 95 mRNA-1273). Within the 21-day risk interval, 114 myocarditis/pericarditis events occurred, the RI was 1.99 (1.30 to 3.05) after second dose of BNT162b2 and 2.22 (1.00 to 4.91) and 2.63 (1.21 to 5.71) after first and second dose of mRNA-1273. During the [0 to 7) days risk period, an increased risk of myocarditis/pericarditis was observed after first dose of mRNA-1273, with RI of 6.55 (2.73 to 15.72), and after second dose of BNT162b2 and mRNA-1273, with RIs of 3.39 (2.02 to 5.68) and 7.59 (3.26 to 17.65). The number of EC for second dose of mRNA-1273 was 5.5 per 100,000 vaccinated (3.0 to 7.9). The highest risk was observed in males, at [0 to 7) days after first and second dose of mRNA-1273 with RI of 12.28 (4.09 to 36.83) and RI of 11.91 (3.88 to 36.53); the number of EC after the second dose of mRNA-1273 was 8.8 (4.9 to 12.9). Among those aged 12 to 17 years, the RI was of 5.74 (1.52 to 21.72) after second dose of BNT162b2; for this age group, the number of events was insufficient for estimating RIs after mRNA-1273. Among those aged 18 to 29 years, the RIs were 7.58 (2.62 to 21.94) after first dose of mRNA-1273 and 4.02 (1.81 to 8.91) and 9.58 (3.32 to 27.58) after second dose of BNT162b2 and mRNA-1273; the numbers of EC were 3.4 (1.1 to 6.0) and 8.6 (4.4 to 12.6) after first and second dose of mRNA-1273. The main study limitations were that the outcome was not validated through review of clinical records, and there was an absence of information on the length of hospitalization and, thus, the severity of the outcome. CONCLUSIONS: This population-based study of about 3 millions of residents in Italy suggested that mRNA vaccines were associated with myocarditis/pericarditis in the population younger than 40 years. According to our results, increased risk of myocarditis/pericarditis was associated with the second dose of BNT162b2 and both doses of mRNA-1273. The highest risks were observed in males of 12 to 39 years and in males and females 18 to 29 years vaccinated with mRNA-1273. The public health implication of these findings should be considered in the light of the proven mRNA vaccine effectiveness in preventing serious COVID-19 disease and death.

Colonoscopy later than 270 days in a fecal immunochemical test-based population screening program is associated with higher prevalence of colorectal cancer.

BACKGROUND : Colorectal cancer (CRC) screening programs based on fecal immunochemical testing (FIT) generate substantial pressure on colonoscopy capacity in Europe. Thus, a relevant proportion of FIT-positive patients undergo colonoscopy after the recommended 30-day interval, which may be associated with an excess CRC risk. METHODS : In a cohort of 50-69-year-old patients undergoing biennial rounds of FIT (OC-Hemodia latex agglutination test; cutoff 20 µg hemoglobin/g feces) between 2004 and 2017, we assessed the outcome at colonoscopy (low/high risk adenoma/CRC/advanced stage CRC) among FIT-positive patients, according to different time intervals. The association of each outcome with waiting time, and demographic and clinical factors, was analyzed through multivariable analysis. RESULTS : 123 138/154 213 FIT-positive patients (79.8 %) underwent post-FIT colonoscopy. Time to colonoscopy was ≤ 30 days, 31-180 days, and ≥ 181 days in 50 406 (40.9 %), 71 724 (58.3 %), and 1008 (0.8 %) patients, respectively. At colonoscopy, CRC, high risk adenoma, and low risk adenoma were diagnosed in 4813 (3.9 %), 30 500 (24.8 %), and 22 986 (18.7 %) patients, respectively. An increased CRC prevalence at colonoscopy was observed for a time to colonoscopy of ≥ 270 days (odds ratio [OR] 1.75, 95 % confidence interval [CI] 1.15-2.67), whereas it was stable for waiting times of < 180 days. The proportion of advanced CRC also increased after 270 days (OR 2.79, 95 %CI 1.03-7.57). No increase for low or high risk adenomas according to time to colonoscopy was observed. CONCLUSION : In a European FIT-based screening program, post-FIT colonoscopy after 9 months was associated with an increased risk of CRC and CRC progression.

Impact of screening programme using the faecal immunochemical test on stage of colorectal cancer: Results from the IMPATTO study.

To evaluate the impact of faecal immunochemical test (FIT) screening on stage distribution at diagnosis, and to estimate relative incidence rates by stage in screened at first and subsequent rounds vs. unscreened. We included all incident cases occurring in 2000-2008 in 50- to 71-year-olds residing in areas with an FIT-screening programme. Multinomial logistic models were computed to estimate the relative risk ratio (RRR) of stages I and IV, compared to stage II + III, adjusting for age, sex, geographical area, and incidence year. Proportions were then used to estimate incidence rate ratios (IRR) by stage for screened subjects at the first and at subsequent rounds vs. unscreened subjects, applying the expected changes in overall incidence during screening phases. 11,663 cancers were included: 5965 in not-invited and 5,698 in invited subjects, 3,425 of whom attendees. Compared to not-invited, invited subjects had RRR 2.04 (95% CI: 1.84; 2.46) of stage I and RRR 0.77 (95% CI: 0.69; 0.87) of stage IV. Differences were stronger comparing attendees vs. nonattendees. Interval cancers were more frequently stage I compared to non-invited (RRR 1.54; 95% CI: 1.15; 2.04), but there was no difference for stage IV. IRRs in screened at first round vs. unscreened were 4.6 (95% CI: 4.2; 5.1), 1.4 (95% CI: 1.3; 1.5) and 0.7 (95% CI: 0.6; 0.9) for stages I, II + III and IV, respectively; in the following rounds the IRRs of screened vs. unscreened were 1.4 (95% CI: 1.2; 1.6), 0.8 (95% CI: 0.7; 0.9) and 0.3 (95% CI: 0.1; 0.4) for stages I, II + III and IV, respectively. FIT screening reduces the incidence of metastatic cancers by about 70% after the first round.

Impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test.

OBJECTIVE: Colorectal cancer (CRC) screening programmes based on the guaiac faecal occult blood test (gFOBT) reduce CRC-specific mortality. Several studies have shown higher sensitivity with the faecal immunochemical test (FIT) compared with gFOBT. We carried out an ecological study to evaluate the impact of FIT-based screening programmes on CRC mortality. DESIGN: In the Veneto Region (Italy), biennial FIT-based screening programmes that invited 50-69-year-old residents were introduced in different areas between 2002 and 2009. We compared CRC mortality rates from 1995 to 2011 between the areas where screening started in 2002-2004 (early screening areas (ESA)) and areas that introduced the screening in 2008-2009 (late screening areas (LSA)) using Poisson regression models. We also compared available data on CRC incidence rates (1995-2007) and surgical resection rates (2001-2012). RESULTS: Before the introduction of screening, CRC mortality and incidence rates in the two areas were similar. Compared with 1995-2000, 2006-2011 mortality rates were 22% lower in the ESA than in the LSA (rate ratio (RR)=0.78; 95% CI 0.68 to 0.89). The reduction was larger in women (RR=0.64; CI 0.51 to 0.80) than in men (RR=0.87; CI 0.73 to 1.04). In the ESA, incidence and surgery rates peaked during the introduction of the screening programme and then returned to the baseline (2006-2007 incidence) or dropped below initial values (surgery after 2007). CONCLUSIONS: FIT-based screening programmes were associated with a significant reduction in CRC mortality. This effect took place much earlier than reported by gFOBT-based trials and observational studies.

Cancer incidence in immigrants by geographical area of origin: data from the Veneto Tumour Registry, Northeastern Italy.

Objective: We investigated whether there are differences in cancer incidence by geographical area of origin in North-eastern Italy. Methods: We selected all incident cases recorded in the Veneto Tumour Registry in the period 2015-2019. Subjects were classified, based on the country of birth, in six geographical areas of origin (Italy, Highly Developed Countries-HDC, Eastern Europe, Asia, Africa, South-central America). Age-standardized incidence rates and incidence rate ratio (IRR) were calculated, for all cancer sites and for colorectal, liver, breast and cervical cancer separately. Results: We recorded 159,486 all-site cancer cases; 5.2% cases occurred in subjects born outside Italy, the majority from High Migratory Pressure Countries (HMPC) (74.3%). Incidence rates were significantly lower in subjects born in HMPC in both sexes. Immigrants, in particular born in Asia and Africa, showed lower rates of all site cancer incidence. The lowest IRR for colorectal cancer was observed in males from South-Central America (IRR 0.19, 95%CI 0.09-0.44) and in females from Asia (IRR 0.32, 95%CI 0.18-0.70). The IRR of breast cancer appeared significantly lower than Italian natives in all female populations, except for those coming from HDC. Females from Eastern Europe showed a higher IRR for cervical cancer (IRR 2.02, 95%CI 1.57-2.61). Conclusion: Cancer incidence was found lower in subjects born outside Italy, with differences in incidence patterns depending on geographical area of origin and the cancer type in question. Further studies, focused on the country of birth of the immigrant population, would help to identify specific risk factors influencing cancer incidence.

Post-marketing active surveillance of Guillain Barré Syndrome following COVID-19 vaccination in persons aged ≥12 years in Italy: A multi-database self-controlled case series study.

BACKGROUND: Recently published studies have reported association of COVID-19 vaccine ChAdOx1-S (Vaxzevria) with Guillain Barré Syndrome (GBS). Less is known about the safety of other COVID-19 vaccines with respect to GBS outcome. This study investigated the association of COVID-19 vaccines with GBS in more than 15 million persons aged ≥12 years in Italy. METHODS: Study population was all individuals aged ≥12 years who received at least one dose of COVID-19 vaccines, admitted to emergency care/hospital for GBS from 27 December 2020-30 September 2021 in Italy. Identification of GBS cases and receipt of at least one dose of mRNA-1273 (Elasomeran), BNT162b2 (Tozinameran), ChAdOx1-S (Vaxzevria) and Ad26.COV2.S (Janssen) through record linkage between regional health care and vaccination registries. Relative Incidence (RI) was estimated Self-controlled case series method adapted to event-dependent exposure using in the 42-day exposure risk period after each dose compared with other observation periods. RESULTS: Increased risk of GBS was found after first (RI = 6.83; 95% CI 2.14-21.85) and second dose (RI = 7.41; 2.35-23.38) of mRNA-1273 and first dose of ChAdOx1-S (RI = 6.52; 2.88-14.77). Analysis by age found an increased risk among those aged≥60 years after first (RI = 8.03; 2.08-31.03) and second dose (RI = 7.71; 2.38-24.97) of mRNA-1273. The first dose of ChAdOx1-S was associated with GBS in those aged 40-59 (RI = 4.50; 1.37-14.79) and in those aged ≥ 60 years (RI = 6.84; 2.56-18.28). CONCLUSIONS: mRNA-1273 and ChAdOx1-S vaccines were associated with an increased risk of GBS however this risk resulted in a small number of excess cases. Limitations were loss of GBS outpatient cases and imprecision of the estimates in the subgroup analysis due to a low number of events.

Thirty-two-year trends of cancer incidence by sex and cancer site in the Veneto Region from 1987 to 2019.

Background: This observational study considers the sex-specific incidence of the most incident cancers as recorded in the population-based Veneto Regional Cancer Registry over a period of more than 30 years (1987-2019). Methods: The Veneto Regional Cancer Registry collected data for the time interval 1987-2019. Significant changes in incidence trends calculated on age-standardized incidence rates (Annual Percent Change-APC) were identified by join point regression analysis. Results: Overall, the incidence trend for all cancers decreased in males and remained stable in females. In nine cancer sites, the incidence trends showed consistent differences by sex (oral cavity, esophagus, colon rectum and anus, liver, larynx, lung, cutaneous malignant melanoma, bladder, and thyroid gland). Other malignancies did not show significant sex-related differences (stomach, pancreas, biliary tract, kidney/urinary tract, central nervous system, multiple myeloma, non-Hodgkin lymphoma, and leukemia). Conclusion: In the period 1987-2019, this study revealed sex-related differences in cancer incidence trends. Over time, cancer incidence remained higher in males, with a decreasing epidemiological impact, plausibly resulting from prevention campaigns against environmental cancer risk factors, as tobacco and alcohol. Conversely, a significant decrease was not observed in the incidence trend in females. These findings contribute essential insights for profiling the epidemiological map of cancer in a large Italian population, allowing comparison with other European cancer epidemiology studies and providing updated data supporting sex-related primary and secondary cancer prevention strategies.

Cost items in melanoma patients by clinical characteristics and time from diagnosis.

Background: Costs related to the care of melanoma patients have been rising over the past few years due to increased disease incidence as well as the introduction of innovative treatments. The aim of this study is to analyse CMM cost items based on stage at diagnosis, together with other diagnostic and prognostic characteristics of the melanoma. Methods: Analyses were performed on 2,647 incident cases of invasive CMM that were registered in 2015 and 2017 in the Veneto Cancer Registry (RTV). Direct melanoma-related costs per patient were calculated for each year ranging from 2 years before diagnosis to 4 years after, and were stratified by cost items such as outpatient services, inpatient drug prescriptions, hospital admissions, hospice admissions, and emergency room treatment. Average yearly costs per patient were compared according to available clinical-pathological characteristics. Lastly, log-linear multivariable analysis was performed to investigate potential cost drivers among these clinical-pathological characteristics. Findings: Overall, the average direct costs related to melanoma are highest in the first year after diagnosis (€2,903) and then decrease over time. Hospitalization costs are 8 to 16 times higher in the first year than in subsequent years, while the costs of outpatient services and inpatient drugs decrease gradually over time. When stratified by stage it is observed that the higher expenditure associated with more advanced stages of CMM is mainly due to inpatient drug use. Conclusion: The results of the present study show that grouping patients according to tumour characteristics can improve our understanding of the different cost items associated with cutaneous malignant melanoma. CMM patients experience higher costs in the first year after diagnosis due to higher hospitalization and outpatient services. Policy makers should consider overall and stage-specific annual costs when allocating resources for the management of CMM patients.

Cutaneous Melanoma in Alpine Population: Incidence Trends and Clinicopathological Profile.

Previous studies associated high-level exposure to ultraviolet radiation with a greater risk of cutaneous malignant melanoma (CMM). This study focuses on the changing incidence of CMM over time (from 1990 to 2017) in the Veneto region of Northeast Italy, and its Alpine area (the province of Belluno). The clinicopathological profile of CMM by residence is also considered. A joinpoint regression analysis was performed to identify significant changes in the yearly incidence of CMM by sex and age. For each trend, the average annual percent change (AAPC) was also calculated. In the 2017 CMM cohort, the study includes a descriptive analysis of the disease's categorical clinicopathological variables. In the population investigated, the incidence of CMM has increased significantly over the last 30 years. The AAPC in the incidence of CMM was significantly higher among Alpine residents aged 0-49 than for the rest of the region's population (males: 6.9 versus 2.4; females 7.7 versus 2.7, respectively). Among the Alpine residents, the AAPC was 3.35 times greater for females aged 0-49 than for people aged 50+. The clinicopathological profile of CMM was significantly associated with the place of residence. Over three decades, the Veneto population has observed a significant increase in the incidence of CMM, and its AAPC. Both trends have been markedly more pronounced among Alpine residents, particularly younger females. While epidemiology and clinicopathological profiles support the role of UV radiation in CMM, the young age of this CMM-affected female population points to other possible host-related etiological factors. These findings also confirm the importance of primary and secondary prevention strategies.

Quality control on digital cancer registration.

Population-based cancer registration methods are subject to internationally-established rules. To ensure efficient and effective case recording, population-based cancer registries widely adopt digital processing (DP) methods. At the Veneto Tumor Registry (RTV), about 50% of all digitally-identified (putative) cases of cancer are further profiled by means of registrars' assessments (RAs). Taking these RAs for reference, the present study examines how well the registry's DP performs. A series of 1,801 (putative) incident and prevalent cancers identified using DP methods were randomly assigned to two experienced registrars (blinded to the DP output), who independently re-assessed every case. This study focuses on the concordance between the DP output and the RAs as concerns cancer status (incident versus prevalent), topography, and morphology. The RAs confirmed the cancer status emerging from DP for 1,266/1,317 incident cancers (positive predictive value [PPV] = 96.1%) and 460/472 prevalent cancers (PPV = 97.5%). This level of concordance ranks as "optimal", with a Cohen's K value of 0.91. The overall prevalence of false-positive cancer cases identified by DP was 2.9%, and was affected by the number of digital variables available. DP and the RAs were consistent in identifying cancer topography in 88.7% of cases; differences concerned different sites within the same anatomo-functional district (according to the International Agency for Research on Cancer [IARC]) in 9.6% of cases. In short, using DP for cancer case registration suffers from only trivial inconsistencies. The efficiency and reliability of digital cancer registration is influenced by the availability of good-quality clinical information, and the regular interdisciplinary monitoring of a registry's DP performance.

Renin-Angiotensin-Aldosterone System Inhibitors and Risk of Death in Patients Hospitalised with COVID-19: A Retrospective Italian Cohort Study of 43,000 Patients.

INTRODUCTION: The epidemic due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been spreading globally, raising increasing concerns. There are several controversial hypotheses on the potentially harmful or beneficial effects of antihypertensive drugs acting on the renin-angiotensin-aldosterone system (RAAS) in coronavirus disease 2019 (COVID-19). Furthermore, there is accumulating evidence, based on several observational studies, that angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) do not increase the risk of contracting SARS-CoV-2 infection. On the other hand, conflicting findings regarding the role of ACEIs/ARBs as prognosis modifiers in COVID-19 hospitalised patients have been reported. OBJECTIVE: The aim of this large-scale, retrospective cohort study was to investigate whether prior exposure to ACEIs and/or ARBs was associated with all-cause mortality among over 40,000 hospitalised COVID-19 patients compared with calcium channel blockers (CCBs), a potential therapeutic alternative. METHODS: This study was conducted using COVID-19 registries linked to claims databases from Lombardy, Veneto and Reggio Emilia (overall, 25% of Italian population). Overall, 42,926 patients hospitalised between 21 February and 21 April 2020 with a diagnosis of COVID-19 confirmed by real-time polymerase chain reaction tests were included in this study. All-cause mortality occurring in or out of hospital, as reported in the COVID-19 registry, was estimated. Using Cox models, adjusted hazard ratios (HRs) of all-cause mortality (along with 95% confidence intervals [CIs]) were estimated separately for ACEIs/ARBs and other antihypertensives versus CCBs and non-use. RESULTS: Overall, 11,205 in- and out-of-hospital deaths occurred over a median of 24 days of follow-up after hospital admission due to COVID-19. Compared with CCBs, adjusted analyses showed no difference in the risk of death among ACEI (HR 0.97, 95% CI 0.89-1.06) or ARB (HR 0.98, 95% CI 0.89-1.06) users. When non-use of antihypertensives was considered as a comparator, a modest statistically significant increase in mortality risk was observed for any antihypertensive use. However, when restricting to drugs with antihypertensive indications only, these marginal increases disappeared. Sensitivity and subgroup analyses confirmed our main findings. CONCLUSIONS: ACEI/ARB use is not associated with either an increased or decreased risk of all-cause mortality, compared with CCB use, in the largest cohort of hospitalised COVID-19 patients exposed to these drugs studied to date. The use of these drugs therefore does not affect the prognosis of COVID-19. This finding strengthens recommendations of international regulatory agencies about not withdrawing/switching ACEI/ARB treatments to modify COVID-19 prognosis.

Sarcoma risk and dioxin emissions from incinerators and industrial plants: a population-based case-control study (Italy).

BACKGROUND: It is not clear whether environmental exposure to dioxin affects the general population. The aim of this research is to evaluate sarcoma risk in relation to the environmental pollution caused by dioxin emitted by waste incinerators and industrial sources of airborne dioxin. The study population lives in a part of the Province of Venice (Italy), where a population-based cancer registry (Veneto Tumour Registry--RTV) has been active since 1987. METHODS: Two hundred and five cases of visceral and extravisceral sarcoma, confirmed by microscopic examination, diagnosed from 01.01.1990 to 31.12.1996, were extracted from the RTV database. Diagnoses were revised using the actual pathology reports and clinical records. For each sarcoma case, three controls of the same age and sex were randomly selected from the population files of the Local Health Units (LHUs). The residential history of each subject, whether case or control, was reconstructed, address by address, from 1960 to the date of diagnosis. All waste incinerators and industrial sources of airborne dioxin in the Province of Venice were taken into account, as was one very large municipal waste incinerator outside the area but close to its boundaries. The Industrial Source Complex Model in Long Term mode, version 3 (ISCLT3), was used to assess the level of atmospheric dispersion. A specific value for exposure was calculated for each point (geo-referenced address) and for each calendar year; the exposure value for each subject is expressed as the average of specific time-weighted values. The analysis takes into account 172 cases and 405 controls, aged more than 14 years. RESULTS: The risk of developing a sarcoma is 3.3 times higher (95% Confidence Interval--95% CI: 1.24-8.76) among subjects, both sexes, with the longest exposure period and the highest exposure level ; a significant excess of risk was also observed in women (Odds Ratio OR = 2.41, 95% CI: 1.04-5.59) and for cancers of the connective and other soft tissue (International Classification of Diseases, ninth Revision--ICD-IX 171), both sexes (OR = 3.27, 95% CI: 1.35-7.93). CONCLUSION: Our study supports the association between modelled dioxin exposure and sarcoma risk.

Trends in mortality from chronic liver disease.

PURPOSE: Mortality from liver cirrhosis has sharply declined in most countries in the last few decades, but includes only a fraction of deaths due to chronic liver disease. METHODS: Mortality records for liver cirrhosis, liver cancer, viral hepatitis, and the three disease categories combined were extracted for the period 1995 to 2010 in the Veneto Region (northeastern Italy). The presence of a birth cohort effect was assessed by fitting Poisson regression models. The alcoholic or viral etiology was retrieved through multiple causes of death analysis for the years 2008 to 2010. RESULTS: Liver cirrhosis mortality represented only one-third of all liver disease deaths; this proportion was even smaller for deaths with a viral etiology and among elderly people. Through the study period, age-standardized rates declined by 50% for liver cirrhosis, and by 30% (world standard) or by 25% (regional standard) for all liver diseases; the reduction in proportional mortality was limited to 11%. Mortality rates started to decline in subjects born after the early 1920s. CONCLUSIONS: The decline in mortality was smaller than that reported by standard statistics for chronic liver disease; these statistics should routinely include viral hepatitis and liver cancer deaths. When available, multiple causes of death data should be analyzed.

Effect of implementation of a dyspepsia and Helicobacter pylori eradication guideline in primary care.

BACKGROUND: Many international guidelines address appropriateness, prescribing variability and drug-related expenditure in primary dyspepsia management. AIMS: To evaluate the impact on general practitioner (GP) practice and healthcare costs of a participatory intervention to modify primary dyspepsia and Helicobacter pylori (Hp) infection management, by standardised implementation of an international guideline in the local setting, through a prospective, controlled before-and-after study. METHODS: Primary dyspepsia management was monitored in the Local Health District of Padua; 63 of all 354 local GPs (total patient population: 82,284) took part in a primary-care improvement programme. Measured variables were: mean prescribed gastroscopies/1,000 registered patients, mean expenditure/1,000 registered patients for antisecretories (H(2) blockers) and proton pump inhibitors (PPIs), inter-GP prescribing variability and adherence to guidelines, analysed through prospectively filled-out reports on GP consultations for dyspepsia. A 3-month pre-survey period was compared with a 6-month intervention period following implementation of an agreed guideline. RESULTS: Compared to non-participating GPs, intervention yielded a 30 and 26.4% reduction in H(2)-blocker and PPI expenditure, respectively. Application of the guideline led to an upward trend in endoscopy prescriptions, coupled with a 7% increase in appropriate referrals. Intra-group variability marginally decreased; guideline compliance rose slightly. CONCLUSIONS: Participatory intervention can reduce prescribing variability among GPs and inappropriate esophagogastroduodenoscopies, lowering related costs. Results may not have been spectacular, but in view of the number of patients involved, they may have an important impact on Local Health District expenditure.