Trends in Antibiotic Prescribing in Adults in Dutch General Practice

Background: Antibiotic consumption is associated with adverse drug events (ADE) and increasing antibiotic resistance. Detailed information of antibiotic prescribing in different age categories is scarce, but necessary to develop strategies for prudent antibiotic use. The aim of this study was to determine the antibiotic prescriptions of different antibiotic classes in general practice in relation to age. Methodology: Retrospective study of 22 rural and urban general practices from the Dutch Registration Network Family Practices (RNH). Antibiotic prescribing data were extracted from the RNH database from 2000-2009. Trends over time in antibiotic prescriptions were assessed with multivariate logistic regression including interaction terms with age. Registered ADEs as a result of antibiotic prescriptions were also analyzed. Principal Findings: In total 658,940 patients years were analyzed. In 11.5% (n = 75,796) of the patient years at least one antibiotic was prescribed. Antibiotic prescriptions increased for all age categories during 2000-2009, but the increase in elderly patients (>80 years) was most prominent. In 2000 9% of the patients >80 years was prescribed at least one antibiotic to 22% in 2009 (P<0.001). Elderly patients had more ADEs with antibiotics and co-medication was identified as the only independent determinant for ADEs. Conclusion/Discussion: The rate of antibiotic prescribing for patients who made a visit to the GP is increasing in the Netherlands with the most evident increase in the elderly patients. This may lead to more ADEs, which might lead to higher consumption of health care and more antibiotic resistance

Oropharyngeal Chlamydia trachomatis in women; Spontaneous clearance and cure after treatment (FemCure)

Objectives: Women attending STI clinics are not routinely tested for oropharyngeal Chlamydia trachomatis (CT) infections. We aimed to assess spontaneous clearance of oropharyngeal CT and cure after antibiotic treatment in women. Methods: Women with vaginal or rectal CT (n=560) were recruited at STI clinics in 2016-2017, as part of the FemCure study (prospective cohort study). We included participants' data from week -1, that is, the diagnosis at initial visit, when clinics applied selective oropharyngeal testing. At week -1, a total of 241 women were oropharyngeally tested (30 positive) and 319 were untested. All FemCure participants provided nurse-collected oropharyngeal samples at study enrolment, that is, week 0, just prior to treatment (n=560), and after treatment at weeks 4 (n=449), 8 (n=433) and 12 (n=427). Samples were tested by nucleic acid amplification test, and at week 0 also by viability testing by viability PCR. Proportions of oropharyngeal CT test results were presented to represent spontaneous clearance and cure. Results: Of 30 women diagnosed with oropharyngeal CT at week -1, fifteen (50%) were negative at week 0 after a median of 9 days, that is, € spontaneous clearance'. At week 0, a total of 560 participants were tested, and 46 (8.8%) were oropharyngeal CT positive; 12 of them (26.1%) had viable CT. Of the 46 positive, 36 women had an oropharyngeal test after treatment; 97.2% (35/36) were negative at week 4, that is, € cure'. Of all women with follow-up visits, the proportion of oropharyngeal CT positive was between 0.5% and 1.6% between weeks 4 and 12. Of those not tested at week -1 (n=319), 8.5% (n=27) were oropharyngeal positive at week 0. Conclusions: The clinical importance of oropharyngeal CT in women is debated. We demonstrated that spontaneous clearance of oropharyngeal CT among women is common; of those who did not clear for CT, three-quarters had non-viable CT. After regular treatment with azithromycin or doxycycline, cure rate (97%) of oropharyngeal CT is excellent. Trial registration number: NCT02694497

Spontaneous clearance of Chlamydia trachomatis accounting for bacterial viability in vaginally or rectally infected women (FemCure)

Objectives: Spontaneous clearance of Chlamydia trachomatis (CT) infections can occur between diagnosis and treatment. We followed CT patien

Association of cytomegalovirus and other pathogens with frailty and diabetes mellitus, but not with cardiovascular disease and mortality in psycho-geriatric patients; a prospective cohort study

Background: Studies about associations of infections with herpes viruses and other pathogens, such as Chlamydia pneumoniae (CP) and Helicobacter pylori (HP) with cardiovascular disease (CVD), diabetes mellitus (DM), frailty and/or mortality are conflicting. Since high levels of antibodies against these pathogens occur in the elderly, the role of these pathogens in morbidity and mortality of vulnerable elderly was explored.Results: Blood samples of 295 community dwelling psycho-geriatric patients were tested for IgG antibodies to herpes simplex virus type 1 and 2, varicella zoster virus, Epstein Barr virus (EBV), cytomegalovirus (CMV), human herpes virus type 6 (HHV6), CP and HP. Frailty was defined with an easy-to-use previously described frailty risk score. Relative risks (RR) with 95% confidence intervals were calculated to evaluate associations between CVD, DM, frailty and pathogens. Pathogens as a predictor for subsequent mortality were tested using Kaplan Meier analyses and Cox proportional hazard models. The mean age was 78 (SD: 6.7) years, 20% died, 44% were defined as frail, 20% had DM and 49% had CVD. Presence of CMV antibody titers was associated with frailty, as shown by using both qualitative and quantitative tests, RR ratio 1.4 (95% CI: 1.003-2.16) and RR ratio 1.5 (95% CI: 1.06-2.30), respectively. High IgG antibody titers of HHV6 and EBV were associated with DM, RR ratio 3.3 (95% CI: 1.57-6.49). None of the single or combined pathogens were significantly associated with mortality and/or CVD.Conclusions: Prior CMV infection is associated with frailty, which could be in line with the concept that CMV might have an important role in immunosenescence, while high IgG titers of HHV6 and EBV are associated with DM. No association between a high pathogen burden and morbidity and/or mortality could be demonstrated

Antibody testing in estimating past exposure to chlamydia trachomatis in the Netherlands chlamydia cohort study

The asymptomatic course of Chlamydia trachomatis (CT) infections can result in underestimated CT lifetime prevalence. Antibody testing might improve this estimate. We assessed CT antibody positivity and predictive factors thereof in the Netherlands Chlamydia Cohort Study. Women who had >1 CT Nucleic Acid Amplification Test (NAAT) in the study (2008–2011) and who provided self-reported information on NAATs were tested for CT major outer membrane protein specific IgG in serum (2016). CT antibody positivity was assessed and predictive factors were identified using multivariable logistic regressions, separately for CT-positive women (>1 positive NAAT or >1 self-reported positive CT test) and CT-negative women (negative by study NAAT and self

Mpox vaccination willingness, determinants, and communication needs in gay, bisexual, and other men who have sex with men, in the context of limited vaccine availability in the Netherlands (Dutch Mpox-survey)

IntroductionIn the 2022 multicountry mpox (formerly named monkeypox) outbreak, several countries offered primary preventive vaccination (PPV) to people at higher risk for infection. We study vaccine acceptance and its determinants, to target and tailor public health (communication-) strategies in the context of limited vaccine supply in the Netherlands. MethodsOnline survey in a convenience sample of gay, bisexual and other men who have sex with men, including transgender persons (22/07-05/09/2022, the Netherlands). We assessed determinants for being (un)willing to accept vaccination. We used multivariable multinominal regression and logistic regression analyses, calculating adjusted odds ratios (aOR) and 95 percent confidence-intervals. An open question asked for campaigning and procedural recommendations. ResultsOf respondents, 81.5% (n = 1,512/1,856) were willing to accept vaccination; this was 85.2% (799/938) in vaccination-eligible people and 77.7% (713/918) in those non-eligible. Determinants for non-acceptance included: urbanization (rural: aOR:2.2;1.2-3.7; low-urban: aOR:2.4;1.4-3.9; vs. high-urban), not knowing mpox-vaccinated persons (aOR:2.4;1.6-3.4), and lack of connection to gay/queer-community (aOR:2.0;1.5-2.7). Beliefs associated with acceptance were: perception of higher risk/severity of mpox, higher protection motivation, positive outcome expectations post vaccination, and perceived positive social norms regarding vaccination. Respondents recommended better accessible communication, delivered regularly and stigma-free, with facts on mpox, vaccination and procedures, and other preventive options. Also, they recommended, "vaccine provision also at non-clinic settings, discrete/anonymous options, self-registration" to be vaccinated and other inclusive vaccine-offers (e.g., also accessible to people not in existing patient-registries). ConclusionIn the public health response to the mpox outbreak, key is a broad and equitable access to information, and to low-threshold vaccination options for those at highest risk. Communication should be uniform and transparent and tailored to beliefs, and include other preventive options. Mpox vaccine willingness was high. Public health efforts may be strengthened in less urbanized areas and reach out to those who lack relevant (community) social network influences

Participation, retention, and associated factors of women in a prospective multicenter study on Chlamydia trachomatis infections (FemCure)

Prospective studies are key study designs when attempting to unravel health mechanisms that are widely applicable. Understanding the internal validity of a prospective study is essential to judge a study's quality. Moreover, insights in possible sampling bias and the external validity of a prospective study are useful to judge the applicability of a study's findings. We evaluated participation, retention, and associated factors of women in a multicenter prospective cohort (FemCure) to understand the study's validity.Chlamydia trachomatis (CT) infected adult women, negative for HIV, syphilis, and Neisseria gonorrhoeae were eligible to be preselected and included at three sexually transmitted infection (STI) clinics in the Netherlands (2016-2017). The planned follow-up for participants was 3 months, with two weekly rectal and vaginal CT self-sampling and online questionnaires administered at home and at the clinic. We calculated the proportions of preselected, included, and retained (completed follow-up) women. Associations with non-preselection, noninclusion, and non-retention (called attrition) were assessed (logistic and Cox regression).Among the 4,916 women, 1,763 (35.9%) were preselected, of whom 560 (31.8%) were included. The study population had diverse baseline characteristics: study site, migration background, high education, and no STI history were associated with non-preselection and noninclusion. Retention was 76.3% (n = 427). Attrition was 10.71/100 person/month (95% confidence interval 9.97, 12.69) and was associated with young age and low education. In an outpatient clinical setting, it proved feasible to include and retain women in an intensive prospective cohort. External validity was limited as the study population was not representative (sampling bias), but this did not affect the internal validity. Selective attrition, however (potential selection bias), should be accounted for when interpreting the study results

Design of the FemCure study: Prospective multicentre study on the transmission of genital and extra-genital Chlamydia trachomatis infections in women receiving routine care

Background: In women, anorectal infections with Chlamydia trachomatis (CT) are about as common as genital CT, yet the anorectal site remains largely untested in routine care. Anorectal CT frequently co-occurs with genital CT and may thus often be treated co-incidentally. Nevertheless, post-treatment detection of CT at both anatomic sites has been demonstrated. It is unknown whether anorectal CT may play a role in post-treatment transmission. This study, called FemCure, in women who receive routine treatment (either azithromycin or doxycycline) aims to understand the post-treatment transmission of anorectal CT infections, i.e., from their male sexual partner(s) and from and to the genital region of the same woman. The secondary objective is to evaluate other reasons for CT detection by nucleic acid amplification techniques (NAAT) such as treatment failure, in order to inform guidelines to optimize CT control. Methods: A multicentre prospective cohort study (FemCure) is set up in which genital and/or anorectal CT positive women (n=400) will be recruited at three large Dutch STI clinics located in South Limburg, Amsterdam and Rotterdam. The women self-collect anorectal and vaginal swabs before treatment, and at the end of weeks 1, 2, 4, 6, 8, 10, and 12. Samples are tested for presence of CT-DNA (by NAAT), load (by quantitative polymerase chain reaction -PCR), viability (by culture and viability PCR) and CT type (by multilocus sequence typing). Sexual exposure is assessed by online self-administered questionnaires and by testing samples for Y chromosomal DNA. Using logistic regression models, the impact of two key factors (i.e., sexual exposure and alternate anatomic site of infection) on detection of anorectal and genital CT will be assessed. Discussion: The FemCure study will provide insight in the role of anorectal chlamydia infection in maintaining the CT burden in the context of treatment, and it will provide practical recommendations to reduce avoidable transmission. Implications will improve care strategies that take account of anorectal CT