Primary care diagnostic and treatment pathways in Dutch women with urinary incontinence.

OBJECTIVE: To investigate how GPs manage women with urinary incontinence (UI) in the Netherlands and to assess whether this is in line with the relevant Dutch GP guideline. Because UI has been an underreported and undertreated problem for decades despite appropriate guidelines being created for general practitioners (GPs). DESIGN: Retrospective cohort study. SETTING: Routine primary care data for 2017 in the Netherlands. SUBJECTS: We included the primary care records of women aged 18-75 years with at least one contact registered for UI, and then extracted information about baseline characteristics, diagnosis, treatment, and referral to pelvic physiotherapy or secondary care. RESULTS: In total, 374 records were included for women aged 50.3 ± 15.1 years. GPs diagnosed 31.0%, 15.2%, and 15.0% women with stress, urgency, or mixed UI, respectively; no diagnosis of type was recorded in 40.4% of women. Urinalysis was the most frequently used diagnostic test (42.5%). Education was the most common treatment, offered by 17.9% of GPs; however, no treatment or referral was reported in 15.8% of cases. As many as 28.7% and 21.7% of women were referred to pelvic physiotherapy and secondary care, respectively. CONCLUSION: Female UI is most probably not managed in line with the relevant Dutch GP guideline. It is also notable that Dutch GPs often fail to report the type of UI, to use available diagnostic approaches, and to provide appropriate education. Moreover, GPs referred to specialists too often, especially for the management of urgency UI.Key pointsUrinary incontinence (UI) has been an underreported and undertreated problem for decades. Despite various guidelines, UI often lies outside the GPs comfort zone.•According to this study: general practitioners do not treat urinary incontinence according to guidelines.•The type of incontinence is frequently not reported and diagnostic approaches are not fully used.•We believe that increased awareness will help improve treatment and avoidable suffering.

Genetic variants associated with methotrexate-induced mucositis in cancer treatment: A systematic review and meta-analysis.

Methotrexate (MTX), an important chemotherapeutic agent, is often accompanied with mucositis. The occurrence and severity are unpredictable and show large interindividual variability. In this study, we review and meta-analyze previously studied genetic variants in relation to MTX-induced mucositis. We conducted a systematic search in Medline and Embase. We included genetic association studies of MTX-induced mucositis in cancer patients. A meta-analysis was conducted for single nucleotide polymorphisms (SNPs) for which at least two studies found a statistically significant association. A total of 34 SNPs were associated with mucositis in at least one study of the 57 included studies. Two of the seven SNPs included in our meta-analysis were statistically significantly associated with mucositis: MTHFR c.677C > T (recessive, grade ≥3 vs grade 0-2, OR 2.53, 95 %CI [1.48-4.32], False Discovery Rate[FDR]-corrected p-value 0.011) and MTRR c.66A > G (overdominant, grade ≥1 vs grade 0, OR 2.08, 95 %CI [1.16-3.73], FDR-corrected p-value 0.042).

Effects of age and genetic variations in VKORC1, CYP2C9 and CYP3A4 on the phenprocoumon dose in pediatric patients.

AIM: To study the effects of clinical and genetic factors on the phenprocoumon dose requirement in pediatric patients and to develop a dosing algorithm. METHODS: Pediatric patients who used phenprocoumon were invited to participate in a retrospective follow-up study. Clinical information and genotypes of genetic variations in CYP2C9, VKORC1, CYP4F2, CYP2C18 and CYP3A4 were collected and tested with linear regression for association with phenprocoumon dose requirement. RESULTS: Of the 41 patients included in the analysis, age, VKORC1, CYP2C9*2/*3 and CYP3A4*1B were statistically significantly associated with dose requirement, and together explained 80.4% of the variability in phenprocoumon dose requirement. CONCLUSION: Our study reveals that age and genetic variations explain a significant part of the variability in phenprocoumon dose requirement in pediatric patients.

Pharmacogenomics in Pediatric Patients: Towards Personalized Medicine.

It is well known that drug responses differ among patients with regard to dose requirements, efficacy, and adverse drug reactions (ADRs). The differences in drug responses are partially explained by genetic variation. This paper highlights some examples of areas in which the different responses (dose, efficacy, and ADRs) are studied in children, including cancer (cisplatin), thrombosis (vitamin K antagonists), and asthma (long-acting ß2 agonists). For childhood cancer, the replication of data is challenging due to a high heterogeneity in study populations, which is mostly due to all the different treatment protocols. For example, the replication cohorts of the association of variants in TPMT and COMT with cisplatin-induced ototoxicity gave conflicting results, possibly as a result of this heterogeneity. For the vitamin K antagonists, the evidence of the association between variants in VKORC1 and CYP2C9 and the dose is clear. Genetic dosing models have been developed, but the implementation is held back by the impossibility of conducting a randomized controlled trial with such a small and diverse population. For the long-acting ß2 agonists, there is enough evidence for the association between variant ADRB2 Arg16 and treatment response to start clinical trials to assess clinical value and cost effectiveness of genotyping. However, further research is still needed to define the different asthma phenotypes to study associations in comparable cohorts. These examples show the challenges which are encountered in pediatric pharmacogenomic studies. They also display the importance of collaborations to obtain good quality evidence for the implementation of genetic testing in clinical practice to optimize and personalize treatment.