GP consultations for menstrual disorders after COVID-19 vaccination - A self-controlled cohort study based on routine healthcare data from the Netherlands.

INTRODUCTION: Several studies described that COVID-19 vaccinations can cause menstrual disorders. Our study aimed to describe whether this also resulted in more general practitioner (GP) consultations for menstrual disorders after COVID-19 vaccination, based on a large cohort study. METHODS: A retrospective self-controlled cohort study was performed including vaccinated women in 2021 aged 12-49 years from two large, representative GP databases in the Netherlands. Incidence rates and incidence rate ratio's (IRR) were calculated using Poisson regression, adjusting for SARS-CoV-2 infection as time-varying confounder. The exposed period was set at maximum six months after each COVID-19 vaccination and the non-exposed period was defined as all-time outside the exposed period. RESULTS: The cohort included 631,802 women, of which 18,986 (3 %) consulted the GP for a menstrual disorder during 2021. Increased GP consultations were observed among 12-14 year olds for amenorrhea/hypomenorrhea/oligomenorrhea (IRR: 1.85, 95 % CI: 1.30-2.65) and irregular/frequent menstruation (IRR: 1.33, 95 % CI: 1.06-1.69) after COVID-19 vaccination in general, and after Pfizer/BioNTech vaccination (IRR: 1.87, 95 % CI: 1.31-2.67 for amenorrhea/hypomenorrhea/oligomenorrhea and IRR: 1.35, 95 % CI: 1.06-1.70 for irregular/frequent menstruation). Persons from this age group were in general also vaccinated with Pfizer/BioNTech. No increase in the frequency of GP consultations were observed for older age groups, other vaccine brands, and potential risk groups. CONCLUSION: For the majority of women, no increased GP consultations for menstrual disorders was found. Solely for the youngest age group (12-14 year olds) increased GP consultations for specific types of menstrual disorders was found after Pfizer/BioNTech vaccination.

[Persistent subjective cognitive decline in middle age: diagnosis and treatment]. / Persisterende subjectieve geheugen-klachten op middelbare leeftijd: diagnostiek en behandeling.

A 47-year-old highly educated man without psychiatric history was referred for psychiatric evaluation because of persistent subjective cognitive decline after repeated and extensive diagnostic evaluation in an outpatient memory clinic. The patient developed increasing preoccupation and anxiety with memory complaints and concerns, despite repetitive negative findings from clinical investigations. This clinical case is coined as ‘neurocognitive hypochondria’, a syndrome interfacing with cogniform and illness anxiety disorders, in which obsessions and concerns about progression of unexplained memory deficits are indicated for specialized treatment. This case study provides more insight into differential diagnosis, classification according to the current DSM-5 criteria and discussion on potential treatment approaches.

All-cause mortality with current and past use of antidepressants or benzodiazepines after major osteoporotic and hip fracture.

In the first year, after an osteoporotic fracture of a hip, forearm, upper arm, or spine, the dispensing rates of antidepressants and benzodiazepines increased significantly. After those fractures, recent and past use of antidepressants and benzodiazepines was associated with increased all-cause mortality; current use was not associated with mortality risk. INTRODUCTION: It remains unclear to what extent use of antidepressants and benzodiazepines is associated with mortality risk after a major osteoporotic fracture (MOF). We aimed to study the cumulative use of antidepressants and benzodiazepines during the year after MOF or hip fracture (HF) and whether the use was associated with mortality. METHODS: A cohort study was performed within the Dutch PHARMO Database Network including all patients aged 65+ with a first record of MOF (hip, humerus, forearm, and clinical vertebral fracture) between 2002 and 2011. Data were analyzed using Cox regression models, adjusted for comorbidities, and concomitant medication use and broken down to index fracture type. RESULTS: A total of 4854 patients sustained a first MOF, of whom 1766 patients sustained a HF. Mean follow-up was 4.6 years, divided in 30-day periods. The cumulative antidepressant and benzodiazepine use during the first year after MOF increased from 10.6 to 14.7% and from 24.0 to 31.4%, respectively. Recent (31-92 days before each follow-up period) and past use (> 92 days before) of antidepressants and benzodiazepines after MOF or HF was associated with an increased all-cause mortality risk but current use (< 30 days before) was not. CONCLUSION: There is a considerable increase in dispensing rate of antidepressants and benzodiazepines in the first year after a MOF. Recent and past use of these medications was associated with all-cause mortality. The finding that current use was not associated with mortality should be further explored and may probably be explained by the healthy survivor's bias.

Association between use of antidepressants or benzodiazepines and the risk of subsequent fracture among those aged 65+ in the Netherlands.

This is the first study to examine the association between antidepressant and benzodiazepine use following a MOF and risk of subsequent fracture in those 65+. Using national data, drug use following MOF showed that the 1-year fully adjusted risk of subsequent MOF in those on antidepressants was more than doubled. INTRODUCTION: We evaluated the association between the use of antidepressants or benzodiazepines and the risk of a subsequent major osteoporotic fracture. METHODS: A cohort study was performed using the Dutch PHARMO Database Network. Between 2002 and 2011, a total of 4854 patients sustained a first major osteoporotic fracture after the age of 65 years, of which 1766 sustained a hip fracture. Incidence rates and adjusted hazard ratios were calculated using Cox proportional hazards models. RESULTS: Within 1 year following a major osteoporotic fracture, 15% (95% CI 13.7-15.7) and 31% (95% CI 30.1-32.8) of patients were dispensed an antidepressant or benzodiazepine, respectively. Current use of antidepressants in the first year following a major osteoporotic fracture was associated with subsequent fracture (adjusted HR 2.17 (95% CI 1.37-3.43)). Recent and past use of antidepressants were also associated with an increased risk of subsequent fracture. When the complete follow-up period was included, only the current use of antidepressants was associated with subsequent fracture following a major osteoporotic fracture (adjusted HR 1.48; 95% CI 1.06-2.06). Current benzodiazepine use was not associated with an increased risk of fracture within 1 year following a major osteoporotic fracture (adjusted HR 1.18; 95% CI 0.76-1.81) or during the complete follow-up period (adjusted HR 1.18; 95% CI 0.90-1.55). CONCLUSION: This study provides evidence that antidepressants should be used with caution following a major osteoporotic fracture. It provides needed insights that can be used to inform clinicians when assessing subsequent fracture risk in patients.

Chemotherapy for ovarian cancer in the Netherlands: a population-based study on treatment patterns and outcomes.

Information on treatment patterns for ovarian cancer (OC) is limited. The aim of this study was to describe current patterns of chemotherapy and other systemic treatments for OC in the Netherlands and evaluate survival outcomes following subsequent lines of treatment. Data from the Eindhoven Cancer Registry, including on newly diagnosed cancer patients, were linked to the PHARMO Database Network, including information on in- and out-patient drug use. Patients diagnosed with OC between January 2000 and December 2010 were selected. An algorithm was used to identify separate lines of treatment. Data were studied descriptively. Detailed data on systemic drug use were available for 261 patients (17%) with OC. In first-line treatment, 87% of the patients (227/261) received platinum-based chemotherapy. Of the 161 patients receiving second-line treatment, 101 patients (63%) received platinum-based chemotherapy. In third line, this was 51% (53/103). The median number of treatment lines received by patients was two (interquartile range 1-3), and eight or more lines of chemotherapy were identified for 12 patients. Median survival from diagnosis onwards was 47 months from the end of first-line treatment, median survival was 32 months, and from the end of second-line treatment, it was 14 months. Predominantly beyond second-line treatment, there is much variety in treatment patterns with chemotherapy for OC. Although uncertainty remains regarding the desirability of this observed treatment variation, there seems a need for detailed clinical guidance, assuring that physicians can properly choose the most suitable treatment for each patient.

[Prevalence of diabetes mellitus in the Netherlands more than doubled in the period 1999-2014]. / Meer dan verdubbeling van de prevalentie van diabetes.

OBJECTIVE: To study the trend in the prevalence of diabetes in the Netherlands during the period 1999-2014. DESIGN: Descriptive study of prevalence. METHODS: The prevalence of diabetes during the period 1999-2014 was calculated on the basis of data from the PHARMO Database Network, a network of electronic databases that includes data from public pharmacies for 3.8 million residents of the Netherlands. A person with diabetes was defined as someone with at least two dispensings for a glucose lowering-drug within six months. Prevalence was adjusted for variation in age demographics per sex to investigate the influence of these variations on population demographics. RESULTS: The prevalence of diabetes in the Netherlands increased from 1.8% in 1999 to 4.9% in 2014. The increase was more pronounced among men as age increased. Only half of the increase was explained by changes in age demographics per sex. CONCLUSION: The study showed that the prevalence of diabetes more than doubled during the period 1999-2014. This trend can only be partly explained by changes in age demographics per sex.

Long-term persistence with anti-osteoporosis drugs after fracture.

UNLABELLED: Long-term persistence with anti-osteoporosis drugs and determinants for discontinuation among fracture patients were examined. Persistence was 75.0 and 45.3 % after 1 and 5 years, respectively. Those aged ≥80 years were at increased risk of early discontinuation. Within 1 year after discontinuation, 24.3 % restarted therapy, yet 47.0 % persisted for 1 year. INTRODUCTION: The risk of osteoporotic fracture can effectively be reduced with use of anti-osteoporosis drugs. However, little is known about persistence with these drugs after fracture where subsequent fracture risk is high. The aims were to determine long-term persistence with anti-osteoporosis drugs among fracture patients, including its determinants, and to describe restart and subsequent persistence. METHODS: A cohort study was conducted within the Dutch PHARMO Database Network. Patients aged ≥50 years (n = 961) who received anti-osteoporosis drugs within 1 year after fracture, but not in the preceding year, were included (2002-2011). Persistence (defined as the proportion on treatment) and the proportion restarting after discontinuation were estimated using Kaplan-Meier analyses. Time-dependent Cox regression was used to identify determinants of non-persistence including age, sex, initial dosage regime, fracture type, comorbidities, and drug use. RESULTS: Persistence with anti-osteoporosis drugs was 75.0 % (95 % confidence interval (CI) 72.0-77.7) and 45.3 % (95 % CI 40.4-50.0) after 1 and 5 years, respectively. A significant determinant of non-persistence was age ≥80 years (reference 50-59 years: adjusted hazard ratio [adj. HR] 1.65; 95 % CI 1.15-2.38). This effect was not constant over time (≤360 days following initiation: adj. HR 2.07; 95 % CI 1.27-3.37; >360 days: adj. HR 1.08; 95 % CI 0.62-1.88). Within 1 year after discontinuation, 24.3 % (95 % CI 20.1-29.2) restarted therapy, yet 47.0 % persisted for 1 year. CONCLUSIONS: This study identified suboptimal persistence with anti-osteoporosis drugs among fracture patients. Major target groups for measures aimed to improve persistence may be those aged >80 years and those restarting therapy.

Long term trends in oral antidiabetic drug use among children and adolescents in the Netherlands.

AIM: The aim of the study was to document long term trends in oral antidiabetic drug (OAD) use among children and adolescents in the Netherlands. METHODS: A population-based cohort study was conducted using the Dutch PHARMO Database Network. All patients younger than 20 years old with at least one OAD dispensing were identified. Age-adjusted and age-specific incidence (1999-2011) and prevalence (1998-2011) rates of OAD use were calculated. Trends over time were assessed using joinpoint regression software. A subset of PHARMO Database Network (including community pharmacy dispensing records linked to general practitioner data (OPD-GP database)) was used to assess indications for OADs. RESULTS: In 2011, the overall age-adjusted incidence and prevalence rates of OAD use were 20.7/100 000 (95% CI 19.2, 22.1) person-years (PY) and 53.8/100 000 (95% CI 51.5, 56.1) persons, respectively. The average annual percentage change (AAPC) in the overall age-adjusted incidence rates from 1999 to 2011 was 18.9% (95% CI 4.5, 35.2). The incidence and prevalence rates of OAD use were higher among females and older age categories. The increases in rates of OAD use were mainly driven by metformin. For only 50% of the 98 patients in the OPD-GP database, indications for OAD prescriptions were reported with type 1 diabetes (n = 20), type 2 diabetes (n = 16), and overweight/obesity (n = 10). CONCLUSIONS: Incidence and prevalence rates of OAD use in children and adolescents substantially increased in the Netherlands, especially among older age categories (10-14 and 15-19 years) and females. The main indications for use of OADs were type 1 and 2 diabetes and overweight/obesity.

Which long-acting bronchodilator is most cost-effective for the treatment of COPD?

BACKGROUND: The aim of this study was to estimate the cost-effectiveness of tiotropium versus salmeterol to inform decision making within the Dutch healthcare setting. METHODS: A previously published, validated COPD progression model was updated with new exacerbation data and adapted to the Dutch setting by including Dutch estimates of healthcare use for COPD maintenance treatment and Dutch unit costs. Exacerbation data from the POET-COPD trial were combined with evidence from earlier tiotropium studies using Bayesian meta-analysis. The model-based analysis was performed using a one- and five-year time horizon. Main health outcomes were the number of exacerbations and quality-adjusted life years (QALYs). RESULTS: One-year costs per patient from the healthcare perspective were v1370 for tiotropium and v1359 for salmeterol; a difference of v11 (95% uncertainty interval (UI): -198-212). The annual number of exacerbations was 0.068 (-0.005-0.140) lower in the tiotropium group. The number of QALYs in the tiotropium group was 0.011 (-0.019-0.049) higher, resulting in an incremental cost-effectiveness ratio (ICER) of v1015 per QALY. After five years, the difference in exacerbations, QALYs and costs between the tiotropium and salmeterol group were -0.435 (-0.915-0.107), 0.079 (-0.272-0.520) and v-277 (-1586-1074), respectively, indicating that tiotropium was more effective and less costly. Using a societal perspective, tiotropium dominated salmeterol both after one and five years. CONCLUSION: Tiotropium reduced exacerbations and exacerbation-related costs. After one year the cost per QALY of tiotropium compared with salmeterol was very low, while after five years tiotropium was found to dominate salmeterol.

Meditation on the pathogenesis of hypopharyngeal (Zenker's) diverticulum and a report of endoscopic treatment in 545 patients.

Much discussion in the literature concerning Zenker's diverticulum is related to etiology. Various theories have been propounded, but no single conclusion is generally accepted. We believe that an anatomic predisposition plays a prominent role. Considerations for this conclusion will be discussed. In the otorhinolaryngology departments of University Hospital and Martini Hospital (Groningen, the Netherlands) 545 patients with a diverticulum were treated endoscopically since 1964. Initially we used the procedure described by Dohlman. With the increase in the number of patients, the technique and instruments used have improved. In 1981 we started to apply a microendoscopic procedure with a special double-lipped scope and the carbon dioxide laser. The rate of complications was very low, and 91% of the patients are highly satisfied. In view of our results, we feel justified in maintaining that endoscopic treatment is a relatively safe and effective method.

Endoscopic treatment of the hypopharyngeal (Zenker's) diverticulum.

Over the years the techniques for endoscopic treatment of Zenker's diverticulum have been improved. Initially, in 1964, we used the electrocoagulation technique as described by Dohlman, but currently we prefer to sever the tissue bridge between the diverticulum and esophagus with the CO2 laser under microscopic control. The results of endoscopic treatment in 507 patients with a diverticulum are discussed. It is concluded that endoscopic treatment can readily be performed with good results, especially in the case of elderly patients in a poor general condition.

Upper esophageal sphincterotomy in dysphagic patients with and without a diverticulum.

Symptoms of high dysphagia are sometimes too readily interpreted as symptoms of globus. When patients have unmistakable difficulties during meals, focused diagnostic procedures are indicated. The upper esophageal sphincter (UES) is the key structure at the transition from hypopharynx to esophagus. In many disorders presenting with dysphagia, the UES mechanism remains intact and can cause the symptoms. Especially in patients with a hypopharyngeal (Zenker's) diverticulum and in patients with a hypopharyngeal paralysis due to a neurologic disorder, sphincterotomy may be indicated. In the microendoscopic treatment of Zenker's diverticulum, a transmucosal sphincterotomy is created and at the same time a more ample overflow from diverticulum to esophagus is effected. In view of our results in 507 patients we are justified in maintaining that this procedure can be regarded as a safe and effective treatment. In patients with neurologic dysphagia, sphincterotomy by an external approach can ensure adequate passage of food from the hypopharynx to the esophagus, resulting in marked improvement of the dysphagic symptoms. Our technique and results of external approach sphincterotomy are described here.