Revised Protocol for Secondary Prevention of Congenital Cytomegalovirus Infection With Valaciclovir Following Infection in Early Pregnancy.

BACKGROUND: A previous randomized placebo-controlled study found valaciclovir to be effective in reducing the rate of vertical cytomegalovirus transmission from mother to fetus. The better results in women infected in the first trimester compared to the periconception period were attributed to the timing of treatment. The aim of the present study was to evaluate valaciclovir efficacy in this setting using a revised protocol. METHODS: All pregnant women treated with valaciclovir in 2020-2022 who met the same criteria as in the original study were identified retrospectively from the database of the same medical center. Treatment, however, was initiated earlier: up to 9 weeks or 8 weeks from the presumed time of infection in women infected in the periconception period or the first trimester, respectively. The primary endpoint was rate of vertical cytomegalovirus transmission. Results were compared with the placebo arm in the previous study. RESULTS: Among 178 women who completed valaciclovir treatment, amniocentesis was positive for cytomegalovirus in 14 women (7.9%), significantly (P < .001) lower compared with 14 of 47 (30%) in the placebo arm in the previous study. The proportion of positive amniocentesis in the valaciclovir was significantly lower than the placebo arm both among women infected in the first trimester (14/119 vs 11/23; odds ratio [OR] = 0.15; 95% confidence interval [CI]: .05-.45, P < .001), as well as among those infected in the periconception period (0/59 vs 3/24, OR = 0; 95% CI 0-.97, P = .02). CONCLUSIONS: This study provides further evidence of the efficacy of valaciclovir in preventing vertical transmission of cytomegalovirus after primary maternal infection. Efficacy is improved with earlier treatment.

Ovarian stimulation for fertility treatments and risk of breast cancer: a matched cohort study.

STUDY QUESTION: Is there a difference in the breast cancer risk among women who underwent ART treatments compared to those who underwent medically assisted reproduction (MAR) infertility treatments or women of reproductive age in the general population? SUMMARY ANSWER: The risk of breast cancer among women treated by ART was similar to the risk among women treated by MAR and women who did not undergo fertility treatments. WHAT IS KNOWN ALREADY: Studies investigating breast cancer risk in women who have undergone fertility treatments have provided conflicting results. STUDY DESIGN, SIZE, DURATION: A retrospective, population-based cohort study included women who underwent ART or MAR treatments and women who did not undergo fertility treatments from 1994 to 2019. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women who underwent ART were matched one to one with women who underwent MAR treatments and one to one with woman from the general population of reproductive age, by year of birth and year of first delivery or nulliparity status. MAR women were also matched to ART women by treatment initiation calendar year. All included women were members of Maccabi Healthcare Services. Data regarding demographics, fertility treatments, BRCA mutation and possible confounders were obtained from the computerized database of electronic health records. The incidence of breast cancer after fertility treatments was compared to the matched controls. MAIN RESULTS AND THE ROLE OF CHANCE: Of 8 25 721 women of reproductive age, 32 366 women who underwent ART were matched with patients treated by MAR (n = 32 366) and 32 366 women of reproductive age. A total of 984 women (1.0%) were diagnosed with breast cancer (mean follow-up period, 9.1 ± 6.3 years; interquartile range [IQR], 3.8-13.7 years). The incidence rates of breast cancer per 10 000 person-years were 11.9 (95% CI, 10.7-13.3), 10.7 (95% CI, 9.6-11.9) and 10.7 (95% CI, 9.6-12.0) in the ART group, MAR group and general population, respectively. The crude risk for breast cancer was similar in the ART group compared with the general population (hazard ratio (HR) = 1.10, 95% CI, 0.94-1.28) and in the ART group compared with the MAR group (HR = 1.00, 95% CI, 0.86-1.16). Further adjustment for age, BMI, smoking, socioeconomic status and parity did not substantially impact the hazard rates for breast cancer (ART vs general population: HR = 1.10, 95% CI, 0.94-1.28; ART vs MAR: HR = 0.99, 95% CI, 0.85-1.16). Among women diagnosed with breast cancer, the prevalence of BRCA1/2 mutations and tumour staging did not differ between the ART, MAR and general population groups. Among women who underwent ART, no correlation was found between breast cancer and the number of ART cycles or the use of recombinant medications or urine-derived medications. LIMITATIONS, REASONS FOR CAUTION: The mean age of women at the end of follow-up was only 42 years thus the study was not powered to detect potential differences in the risk of postmenopausal breast cancer. In addition, we did not sub-classify the exposed patients by the reason for infertility. WIDER IMPLICATIONS OF THE FINDINGS: Breast cancer incidence following ART was comparable to that in the general population or following MAR. Women undergoing fertility treatments and their clinicians may be reassured about the safety of assisted reproduction technologies in terms of premenopausal breast cancer risk. STUDY FUNDING/COMPETING INTEREST(S): No specific funding was used and there are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Use of antibiotics and factors associated with treatment failure among 152,245 patients with pneumonia treated in the community - a retrospective cohort study.

This study aims to evaluate risk factors associated with treatment failure and the antibiotics prescribed by primary care physicians in a large patient cohort treated for pneumonia in the community. A retrospective cohort study based on the databases of Maccabi Healthcare Services that provide healthcare to a quarter of the Israeli population. Included patients were > 12 years and diagnosed with pneumonia in the outpatient setting. Cohort 1 included patients with community-acquired pneumonia (CAP), whereas cohort 2 included patients with a documented pneumonia diagnosis following hospital discharge. Treatment failure (TF) was defined as either the use of a second line antibiotic OR hospital admission within 3-14 days OR death within 30 days of diagnosis. Risk factors for TF in the study cohorts were analyzed using multivariable logistic regression. During the study period, 148,376 patients were included in cohort 1 and 3,869 patients in cohort 2, with mean ages of 46.5 ± 20.3 and 63.8 ± 19.5 years, respectively. The most commonly used antibiotics were cephalosporins (36%) and macrolides (35.5%). TF occurred in 12% of cohort 1 and was associated with older age, comorbid conditions, use of non-respiratory fluoroquinolones, and penicillin. Atypical coverage (either macrolides or tetracyclines) was associated with a lower risk of failure. Among cohort 2, TF was higher (16.4%, p < 0.001) and was associated with older age, prior cancer, and congestive heart failure. Treatment failure was associated with comorbid conditions and increasing age. Among young patients with CAP and no comorbid conditions, macrolides or tetracyclines may suffice.

Associations between breast implants and postpartum lactational mastitis in breastfeeding women: retrospective study.

OBJECTIVE: To examine the putative associations between breast implants and postpartum lactational mastitis. DESIGN: Observational retrospective study. SETTING: Digital database of Maccabi Healthcare Services, integrated health maintenance organisation in Israel. POPULATION: Breastfeeding mothers from 2003 to 2016 based on an initial health maintenance organisation data set of 28 383 singleton live births in Israel. METHODS: Multivariate analysis and propensity score matching were used to test the extent to which breast implants were associated with lactational mastitis during the 6-month postpartum period in breastfeeding mothers. Analyses for potential confounders were adjusted for socio-economic status, smoking and parity. MAIN OUTCOME MEASURE: Lactational mastitis among breastfeeding women with breast implants compared with women without breast implants. RESULTS: Mothers with breast implants (n = 6099) were significantly (P < 0.001) more likely to be diagnosed with postpartum mastitis (8.3%) than mothers with no breast implants(n = 22 284) (6.6%) at an odds ratio of 1.22 (95% CI 1.09-1.35) after adjusting for confounders. CONCLUSION: Breast augmentation is associated with an increased risk of postpartum lactational mastitis in the 6-month postpartum period. In light of these findings, it is important for health professionals to instruct women who have undergone breast augmentation on correct breastfeeding techniques, ways to avoid risk factors, and to be alert to signs permitting the early detection of lactational mastitis. TWEETABLE ABSTRACT: A study of over 28,000 breastfeeding women has shown that breast augmentation is associated with an increased risk of postpartum lactational mastitis in the six-month postpartum period.

Adherence to metformin and the onset of rheumatoid arthritis: a population-based cohort study.

Objective: The aim of this retrospective cohort study was to examine whether adherence to metformin treatment may be associated with lower onset of rheumatoid arthritis (RA).Method: Using the computerized databases of a 2.3-million state-mandated health services organization in Israel, we identified incident RA cases among a cohort of 113 749 adult patients who initiated metformin therapy between 1998 and 2014. Adherence was assessed by calculating the mean proportion of follow-up days covered (PDC) with metformin.Results: During the 18 year study period, there were 558 incident RA cases (61 per 100 000 person-years). Adherence to metformin treatment was associated with a lower risk of developing RA, with the lowest risk recorded among patients with a PDC of 40-59% [adjusted hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.45-0.84] compared with non-adherent patients (PDC < 20%). A mean daily metformin dose of 2550 mg or more was also associated with a lower risk of developing RA (adjusted HR 0.62, 95% CI 0.46-0.84) compared to a daily dose of 850 mg or less. In stratified analyses by gender, the negative association between adherence and the risk of RA was limited to women alone.Conclusions: Adherence to metformin treatment is associated with a reduced risk of developing RA in women. Further studies are needed to assess the effect of metformin on RA development in other patient populations.

Sustained virological response to ombitasvir/paritaprevir/ritonavir and dasabuvir treatment for hepatitis C: Real-world data from a large healthcare provider.

Treatment with ombitasvir/paritaprevir/ritonavir and dasabuvir, with or without ribavirin (OPrD ± RBV), was the first interferon-free direct-acting antiviral for hepatitis C virus (HCV) introduced to Israel's national basket of health services in February 2015. Patients with HCV genotype 1 (GT1) and advanced fibrosis (F3-F4) were eligible for treatment in 2015. This study aimed to characterize patients initiating OPrD ± RBV and assess sustained virological response (SVR). A retrospective cohort study was performed using the database of Maccabi Healthcare Services (MHS), a 2-million-member health plan in Israel. The study population included adults who initiated OPrD ± RBV through December 2015 per health basket criteria. A gap in medication fills (>14 days between a fill's run-out and the next fill) was used to estimate adherence. SVR was defined by the viral tests at least 12-week post-treatment. The study population consisted of 403 patients (56.3% male), with a mean age of 60.7 years (SD 11.0). Overall, 71.0% were naïve to prior HCV treatment, and 95.6% were treated with a 12-week regimen. A total of 348 patients (86.4%) completed the regimen in the usual time frame (highly adherent), whereas 8.2% completed with a gap, and 4.7% purchased less than the recommended dose. SVR rates overall and among highly adherent patients were 395/403 (98.0%; 95% CI 96.1-99.1) and 346/348 (99.4%; 95% CI 97.9-99.9), respectively. GT1b patients on 12-week regimens attained SVR rates of 194/196 (fibrosis F3) and 170/176 (cirrhosis). After a first year of provision of OPrD ± RBV with good adherence, high SVR rates were achieved in various patient subgroups and comorbidities.

Epidemiology of endometriosis: a large population-based database study from a healthcare provider with 2 million members.

OBJECTIVE: Endometriosis constitutes a significant burden on the quality of life of women, their families and healthcare systems. The objective of this study is to describe the real-world epidemiology of endometriosis in an unselected low-risk population in Israel. DESIGN: Retrospective population-based study. SETTING AND SAMPLE: The computerised databases of Maccabi Healthcare Services (MHS), a 2-million-member healthcare provider representing a quarter of the Israeli population. METHODS: The crude point prevalence (31 December 2015; diagnosed since 1998) and annual incidence (2000-2015) rates of diagnosed endometriosis (ICD-9-CM 617.xx) were assessed among women aged 15-55 years. Prevalent patients were characterised in terms of sociodemographic and clinical characteristics, including validated MHS infertility and chronic disease registries. MAIN OUTCOME MEASURES: Prevalence and incidence of diagnosed endometriosis in MHS. RESULTS: The point prevalence of endometriosis [n = 6146, mean age 40.4 ± 8.0 years (SD)] was 10.8 per 1000 (95% CI 10.5-11.0). Women aged 40-44 years had the highest prevalence rate of 18.6 per 1000 (95% CI 17.7-19.5). Infertility was documented in 37% of patients. A total of 6045 patients were included in the cohort of newly-diagnosed endometriosis (mean age 34.0 ± 8.1 years), corresponding to an average annual incidence rate of 7.2 per 10 000 (95% CI 6.5-8.0). CONCLUSIONS: We observed a substantially lower prevalence of diagnosed endometriosis compared with previous reports in high-risk populations, in line with population-based estimates from European databases (range 0.8-1.8%). Further characterisation of this cohort may help to understand what affects the prevalence of endometriosis in Israel, and to promote earlier diagnosis and improve management in clinical practice. TWEETABLE ABSTRACT: Endometriosis diagnosed in 1% of women, according to a large population-based study in a community setting.

Adherence to statins and the risk of psoriasis: a population-based cohort study.

BACKGROUND: Statins have been shown to downregulate immune mechanisms activated in psoriasis. However, previous studies on their potential role in preventing psoriasis have yielded conflicting results. OBJECTIVES: To assess the relationship between adherence to statins and the risk of psoriasis. METHODS: This retrospective cohort study included 205,820 health plan enrollees in Israel (mean age 55 years; 54·1% women) who initiated statin treatment from January 1998 through to September 2009. Adherence to statins, measured by the proportion of days covered (PDC), throughout the entire follow-up period (mean 6·2 years) was recorded. Diagnosis codes of psoriasis were assigned by a dermatologist or rheumatologist, or at discharge from hospital. RESULTS: During 1·28 million person-years (PY) of follow-up (median 5·74 years per person; interquartile range 3·78-8·36), 5615 cases of psoriasis (incidence density rate 4·4 per 1000 PY) were recorded. Compared with patients who did not adhere to statins (PDC < 20%), patients covered by statins for 40-59% of the time had a significantly lower risk of psoriasis (P < 0·05), with hazard ratios (HRs) of 0·84 and 0·74 among men and women, respectively. Among patients who adhered better to statins (PDC ≥ 80%), HRs were 0·88 (95% CI 0·79-0·98) and 1·00 (95% CI 0·90-1·11) among men and women, respectively. CONCLUSIONS: The results of the current study suggest that high and long-term adherence to statins is not associated with a meaningful reduction in the risk of developing psoriasis.

Incidence trends of keratinocytic skin cancers and melanoma in Israel 2006-11.

BACKGROUND: The incidence of melanoma and keratinocyte cancers (KCs) is rising worldwide. Squamous cell carcinomas (SCCs) and basal cell carcinoma (BCCs) are the most common of all cancers. OBJECTIVES: To determine trends in the incidence of melanoma, BCC and SCC among 1·7 million members of Maccabi Healthcare Services (MHS) from 2006 to 2011. METHODS: Data on patients newly diagnosed with melanoma, SCC and BCC were collected from the MHS Cancer Registry and based on histology reports from the centralized pathology laboratory. Age-specific and overall age-adjusted European standardized rates were computed. Trends were estimated by calculating average annual percentage change (AAPC). RESULTS: During the 6-year study period, 16,079 patients were diagnosed with at least one BCC, 4767 with SCC and 1264 with invasive melanoma. Age-standardized incidence rates were 188, 58 and 17 per 100,000 person years for BCC, SCC and melanoma, respectively. All lesions were more common among men and primarily affected the elderly. BCC rates were stable throughout the study period [AAPC -0·7%, 95% confidence interval (CI) -4·5 to 3·2], while the incidence of SCC increased significantly (AAPC 15·5%, 95% CI 2·6-30·0). In contrast, melanoma rates continuously decreased (AAPC -3·0%, 95%CI -4·5 to -0·1). CONCLUSIONS: The incidence of KC in Israel is high. The disparities in incidence trends between SCC, BCC and melanoma allude to their different aetiologies. These findings underscore the importance of continuous monitoring, education and prevention programmes in a growing high-risk population.

Association of gastrointestinal events and osteoporosis treatment initiation in newly diagnosed osteoporotic Israeli women.

BACKGROUND: The objective was to examine the association of gastrointestinal (GI) events and osteoporosis treatment initiation patterns among postmenopausal women following an osteoporosis diagnosis from an Israeli health plan. METHODS: This retrospective analysis of claims records included women aged ≥ 55 years with ≥ 1 osteoporosis diagnosis (date of first diagnosis was index date). Osteoporosis treatment initiation was defined as use of osteoporosis therapy (oral bisphosphonates or other) during 12 months postindex. GI events (diagnosis of GI conditions) were reported for 12 months preindex and postindex (from index to treatment initiation or 1 year postindex, whichever occurred first). The association of postindex GI events (yes/no) with the initiation of osteoporosis treatment (yes/no) and with type of therapy initiated (oral bisphosphonate vs. other) were examined with logistic regression and Cox proportional hazard regression (as sensitivity analysis). RESULTS: Among 30,788 eligible patients, 17.5% had preindex GI events and 13.0% had postindex GI events. About 70.6% of patients received no osteoporosis therapy within 1 year of diagnosis, 24.9% received oral bisphosphonates and 4.5% received other medications. Postindex GI events were associated with lower odds of osteoporosis medication initiation (85-86% reduced likelihood; p < 0.01). Upon treatment initiation, postindex GI was not significantly associated with the type of osteoporosis therapy initiated, controlling for baseline GI events and patient characteristics. CONCLUSIONS: Among newly diagnosed osteoporotic women from a large Israeli health plan, 70.6% did not receive osteoporosis treatment within 1 year of diagnosis. The presence of GI events was associated with reduced likelihood of osteoporosis treatment initiation.

Predictors of return to work with upper limb disorders.

BACKGROUND: Return to work (RTW) is a key goal in the proper management of upper limb disorders (ULDs). ULDs stem from diverse medical aetiologies and numerous variables can affect RTW. The abundance of factors, their complex interactions and the diversity of human behaviour make it difficult to pinpoint those at risk of not returning to work (NRTW) and to intervene effectively. AIMS: To weigh various clinical, functional and occupational parameters that influence RTW in ULD sufferers and to identify significant predictors. METHODS: A retrospective analysis of workers with ULD referred to an occupational health clinic and further examined by an occupational therapist. Functional assessment included objective and subject ive [Disability of the Arm, Shoulder and Hand (DASH) score] parameters. Quantification of work requirements was based on definitions from the Dictionary of Occupational Titles web site. RTW status was confirmed by a follow-up telephone questionnaire. RESULTS: Among the 52 subjects, the RTW rate was 42%. The DASH score for the RTW group was 27 compared with 56 in the NRTW group (P < 0.001). In multivariate analyses, only the DASH score was found to be a significant independent predictor of RTW (P < 0.05). CONCLUSIONS: Physicians and rehabilitation staff should regard a high DASH score as a warning sign when assessing RTW prospects in ULD cases. It may be advisable to focus on workers with a large discrepancy between high DASH scores and low objective disability and to concentrate efforts appropriately.

Childhood overweight or obesity increases the risk of IIH recurrence fivefold.

Overweight and obesity are less closely associated with idiopathic intracranial hypertension (IIH) in young children than in post-pubescent children and adults. We examined the hypothesis that being overweight or obese (body mass index (BMI) ⩾ 85th percentile) in children is a risk factor for IIH recurrence. A total of 43 children with IIH who were followed up for an average of 9 ± 3.4 years were evaluated in a retrospective case-control series. The rate of IIH recurrence was compared between children of healthy weight and children presenting with overweight or obesity, using survival curve analysis. The overall risk for long-term IIH recurrence in children is ~20%. Following weight stratification, the risk for IIH recurrence in our cohort was fivefold higher in children with a BMI ⩾ 85th percentile (57%) than in healthy weight children (11%; log-rank test P = 0.04). Pediatricians may consider counseling families that weight control may be a means of decreasing the risk of IIH recurrence.

Uptake of Pap smears among women in a large Israeli HMO between 2006 and 2008.

OBJECTIVES: The Papanicolaou (Pap) smear test is used in many countries as a screening procedure for cervical cancer and precancerous lesions. The actual uptake of this screening test among women at risk for cervical cancer is unknown. The aim of this study was to estimate the percentage of women who are screened by Pap smears from the relevant population at risk, and to detect factors that are independently associated with uptake of cervical screening. STUDY DESIGN: Retrospective database study. METHODS: This study was undertaken at Maccabi Healthcare Services (MHS), the second largest publicly funded health maintenance organization in Israel. The study population consisted of Israeli women aged 21-59 years who were insured by MHS between 2006 and 2008. Logistic regression analyses were used to determine the independent relationships between immigration and socio-economic status and cervical screening. RESULTS: The study population included 489,663 women who had a total of 313,602 Pap smears between 2006 and 2008. Fifty-four percent of the women did not have a Pap smear during the study period, 32% had at least one smear, and 14% had at least two smears. Living in a low socio-economic neighbourhood and recent immigration were independently and negatively associated with screening uptake. CONCLUSION: Despite the clinical guidelines and the low costs, many Israeli women who are at risk for cervical cancer are not screened.

A retrospective study of the incidence of diagnosed Type 1 diabetes among children and adolescents in a large health organization in Israel, 2000-2008.

AIMS: To determine the incidence and examine temporal trends of Type 1 diabetes among children aged < 18 years, in a large Israeli health organization. METHODS: All incident Type 1 diabetes cases diagnosed between 2000 and 2008 were ascertained from an automated diabetes registry based on members' electronic records and validated by comparison with the Israel Juvenile Diabetes Register. RESULTS: During the study period, a total of 648 incident cases of Type 1 diabetes were identified. The average annual age-and-sex-standardized incidence was 11.09 per 100,000 person-years. There was an annual 5.82% (95% CI 1.80-9.98%) rise in incidence, with a greater relative increase in toddlers under 5 years of age. Incidence increased with age and demonstrated seasonal variation. Mean age at onset of diabetes significantly (P = 0.07) decreased from 10.21 years (SD = 4.48) in 2000-2002 to 9.25 years (SD = 4.54) in 2006-2008. Among very young patients (< 5 years), average blood glucose values at diagnosis dropped from 32.4 mmol/l (SD = 9.5) to 19.5 mmol/l (SD = 11.0) over the study period, with little change in average glucose for older children. CONCLUSIONS: Incidence of diagnosed Type 1 diabetes continues to increase in Israel at a rate that is high compared with similar American and European populations. At the same time, the clinical presentation of children is changing.

The risk of overt diabetes mellitus among women with gestational diabetes: a population-based study.

AIMS: To determine the incidence of postpartum diabetes mellitus in the years following a diagnosis of gestational diabetes mellitus (GDM) and to determine whether the severity of GDM, represented by the magnitude of the deviation of diagnostic tests from the normal values or requirement for medications, is associated with the development of diabetes. METHODS: A retrospective cohort study was performed among 185 416 pregnant women who had glucose challenge test or 3 h oral glucose tolerance test (OGTT) in a large health maintenance organization in Israel. Subsequent diagnosis of diabetes was ascertained by using an automated patient registry. RESULTS: A total of 11 270 subjects were diagnosed with GDM, comprising 6.07% of the cohort. During a total follow-up period of 1 049 334 person-years there were 1067 (16.9 per 1000 person-years) and 1125 (1.1 per 1000 person-years) diagnoses of postpartum diabetes among GDM and non-GDM women, respectively. The cumulative risk of incident diabetes in GDM patients with up to 10 years of follow-up was 15.7%, compared with 1% among the non-GDM population. Gestational diabetes mellitus was associated with nearly an eightfold higher risk of postpartum diabetes after adjusting for important confounders, such as socioeconomic status and body mass index. Among women with a history of GDM, the number of abnormal OGTT values and use of insulin were associated with a substantially higher risk for developing diabetes. CONCLUSIONS: Three or four abnormal OGTT values and GDM requiring insulin or oral hypoglycaemic medications are important predictors of postpartum diabetes risk in women with a history of GDM.

Long-term trends in hepatitis A incidence following the inclusion of Hepatitis A vaccine in the routine nationwide immunization program.

For many years hepatitis A was one of the most common vaccine preventable diseases in Israel. In 1999, Israel became the first country to introduce an inactivated hepatitis A vaccine into its national childhood vaccination program. The objectives of the present study were to study trends in disease incidence after the implementation of the new vaccination policy and to assess vaccination coverage among children and adults in Israel. We used the databases of the second largest HMO in Israel (1.7 million members) to identify patients who had evidence of hepatitis A in 1998 and 2007 and to collect information on all subjects who received at least one dose of hepatitis A vaccine during the study period. Hepatitis A vaccination coverage in children <5 years and 5-14 years of age increased from 9% and 15% in 1998 to 89% and 68% in 2007, respectively. During this period the annual incidence of hepatitis A dropped from 142.4 per to 7.6 per 100 000. The most prominent reduction in the age-specific annual incidence rates was calculated in children <5 years from 239.4 per 100 000 in 1998 to 2.2 per 100 000 in 2007 and from 310.3 per 100 000 to 3.0 per 100 000 in children aged 5-14 years. In endemic areas, vaccination of infants and children against hepatitis A can greatly reduce the total burden of the disease.