The association among cytochrome P450 3A, progesterone receptor polymorphisms, plasma 17-alpha hydroxyprogesterone caproate concentrations, and spontaneous preterm birth

Background Infants born <37 weeks’ gestation are of public health concern since complications associated with preterm birth are the leading cause of mortality in children <5 years of age and a major cause of morbidity and lifelong disability. The administration of 17-alpha hydroxyprogesterone caproate reduces preterm birth by 33% in women with history of spontaneous preterm birth. We demonstrated previously that plasma concentrations of 17-alpha hydroxyprogesterone caproate vary widely among pregnant women and that women with 17-alpha hydroxyprogesterone caproate plasma concentrations in the lowest quartile had spontaneous preterm birth rates of 40% vs rates of 25% in those women with higher concentrations. Thus, plasma concentrations are an important factor in determining drug efficacy but the reason 17-alpha hydroxyprogesterone caproate plasma concentrations vary so much is unclear. Predominantly, 17-alpha hydroxyprogesterone caproate is metabolized by CYP3A4 and CYP3A5 enzymes. Objective We sought to: (1) determine the relation between 17-alpha hydroxyprogesterone caproate plasma concentrations and single nucleotide polymorphisms in CYP3A4 and CYP3A5; (2) test the association between progesterone receptor single nucleotide polymorphisms and spontaneous preterm birth; and (3) test whether the association between plasma concentrations of 17-alpha hydroxyprogesterone caproate and spontaneous preterm birth varied by progesterone receptor single nucleotide polymorphisms. Study Design In this secondary analysis, we evaluated genetic polymorphism in 268 pregnant women treated with 17-alpha hydroxyprogesterone caproate, who participated in a placebo-controlled trial to evaluate the benefit of omega-3 supplementation in women with history of spontaneous preterm birth. Trough plasma concentrations of 17-alpha hydroxyprogesterone caproate were measured between 25-28 weeks of gestation after a minimum of 5 injections of 17-alpha hydroxyprogesterone caproate. We extracted DNA from maternal blood samples and genotyped the samples using TaqMan (Applied Biosystems, Foster City, CA) single nucleotide polymorphism genotyping assays for the following single nucleotide polymorphisms: CYP3A4*1B, CYP3A4*1G, CYP3A4*22, and CYP3A5*3; and rs578029, rs471767, rs666553, rs503362, and rs500760 for progesterone receptor. We adjusted for prepregnancy body mass index, race, and treatment group in a multivariable analysis. Differences in the plasma concentrations of 17-alpha hydroxyprogesterone caproate by genotype were evaluated for each CYP single nucleotide polymorphism using general linear models. The association between progesterone receptor single nucleotide polymorphisms and frequency of spontaneous preterm birth was tested using logistic regression. A logistic model also tested interaction between 17-alpha hydroxyprogesterone caproate concentrations with each progesterone receptor single nucleotide polymorphism for the outcome of spontaneous preterm birth. Results The association between CYP single nucleotide polymorphisms *22, *1G, *1B, and *3 and trough plasma concentrations of 17-alpha hydroxyprogesterone caproate was not statistically significant (P =.68,.44,.08, and.44, respectively). In an adjusted logistic regression model, progesterone receptor single nucleotide polymorphisms rs578029, rs471767, rs666553, rs503362, and rs500760 were not associated with the frequency of spontaneous preterm birth (P =.29,.10,.76,.09, and.43, respectively). Low trough plasma concentrations of 17-alpha hydroxyprogesterone caproate were statistically associated with a higher frequency of spontaneous preterm birth (odds ratio, 0.78; 95% confidence ratio, 0.61–0.99; P =.04 for trend across quartiles), however no significant interaction with the progesterone receptor single nucleotide polymorphisms rs578029, rs471767, rs666553, rs503362, and rs500760 was observed (P =.13,.08,.10,.08, and.13, respectively). Conclusion The frequency of recurrent spontaneous preterm birth appears to be associated with trough 17-alpha hydroxyprogesterone caproate plasma concentrations. However, the wide variation in trough 17-alpha hydroxyprogesterone caproate plasma concentrations is not attributable to polymorphisms in CYP3A4 and CYP3A5 genes. Progesterone receptor polymorphisms do not predict efficacy of 17-alpha hydroxyprogesterone caproate. The limitations of this secondary analysis include that we had a relative small sample size (n = 268) and race was self-reported by the patients

Erysipelas-like skin lesions associated with Campylobacter jejuni septicemia in patients with hypogammaglobulinemia

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The contribution of lifestyle coaching of overweight patients in primary care to more autonomous motivation for physical activity and healthy dietary behaviour: results of a longitudinal study

Background: Combined lifestyle interventions (CLIs) have been advocated as an effective instrument in efforts to reduce overweight and obesity. The odds of maintaining higher levels of physical activity (PA) and healthier dietary behaviour improve when people are more intrinsically motivated to change their behaviour. To promote the shift towards more autonomous types of motivation, facilitator led CLIs have been developed including lifestyle coaching as key element. The present study examined the shift in types of motivation to increase PA and healthy dieting among participants of a primary care CLI, and the contribution of lifestyle coaching to potential changes in motivational quality. Methods: This prospective cohort study included participants of 29 general practices in the Netherlands that implemented a CLI named ‘BeweegKuur’. Questionnaires including items on demographics, lifestyle coaching and motivation were sent at baseline and after 4 months. Aspects of motivation were assessed with the Behavioural Regulation and Exercise Questionnaire (BREQ-2) and the Regulation of Eating Behaviour Questionnaire (REBS). We performed a drop out analysis to identify selective drop-out. Changes in motivation were analysed with t-tests and effect size interpretations (Cohen’s d), and multivariate regression analysis was used to identify predictors of motivational change. Results: For physical activity, changes in motivational regulation were fully in line with the tenets of Self Determination Theory and Motivational Interviewing: participants made a shift towards a more autonomous type of motivation (i.e. controlled types of motivation decreased and autonomous types increased). Moreover, an autonomy supportive coaching style was generally found to predict a larger shift in autonomous types of motivation. For healthy dietary behaviour, however, except for a small decrease in external motivation, no favourable changes in different types of motivation were observed. The relation between coaching and motivation appeared to be influenced by the presence of physical activity guidance in the programme. Conclusions: Motivation of participants of a real life primary care CLI had changed towards a more autonomous motivation after 4 months of intervention. Autonomy-supportive lifestyle coaching contributed to this change with respect to physical activity. Lifestyle coaching for healthy diet requires thorough knowledge about the problem of unhealthy dieting and solid coaching skills. (aut. ref.

Motivational regulations and lifestyle in muscle-wasted COPD patients undergoing pulmonary rehabilitation

Background &amp; Aims: Low physical activity (PA) levels and a poor-quality diet are common in chronic obstructive pulmonary disease (COPD) patients eligible for pulmonary rehabilitation (PR). PR may improve short-term nutritional status and exercise capacity but generally not long-term lifestyle outcomes. We hypothesized that healthy lifestyle motivation is related to PA levels and dietary quality before PR and the responsiveness thereof after PR. Methods: Before and after standardized outpatient PR, 81 COPD patients with low muscle mass completed validated motivational regulation self-reports. Physical (in)activity was assessed before and after PR through 7-day accelerometry (GT3X Actigraph). Dietary quality was assessed using a validated cross-check dietary history before and after PR and quantified as the Mean Adequacy Ratio (MAR). Results: Patients' baseline motivational profile was unrelated to dietary quality or PA. Baseline integrated motivation and its change during PR significantly predicted MAR change during PR and its levels after PR. Baseline introjected motivation and its change during PR significantly predicted PA change during PR and its levels after PR. Conclusions: Specific motivational regulations predict dietary quality and PA improvements of patients with COPD admitted to PR. Therefore, targeting integrated and introjected motivation may be key to achieving lasting behavior change after PR. Registry site: Maastricht University Medical Centre+. Clinical trial identifier number: NCT01344135

Prevalence and diversity of filamentous fungi in the airways of cystic fibrosis patients - A Dutch, multicentre study

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A qualitative assessment of COPD patients' experiences of pulmonary rehabilitation and guidance by healthcare professionals

BACKGROUND: The present study aimed to assess COPD patients' experiences during an in-patient pulmonary rehabilitation program and the guidance provided by healthcare professionals. A third aim regarded examining ways to anticipate the transfer to the home environment after completion of the program. METHODS: Focus groups and semi-structured interviews were used to collect data from seven COPD patients at the beginning and six other COPD patients at the end of an in-patient pulmonary rehabilitation program, supplemented by a focus group and semi-structured interviews with 14 healthcare professionals of the involved disciplines. Data were analyzed using a phenomenological approach. RESULTS: Starting out, patients displayed trouble with acceptance of their disease, they had insufficient knowledge, and showed difficulties in setting specific realistic goals. Seeing fellow patients struggle with similar problems and tailored counseling by healthcare professionals helped them to overcome these barriers. During rehabilitation, patients became more confident in exercising and managing their daily life activities. Many patients evolved a desire to self-regulate their lives. Incorporating health-enhancing behaviors after returning home into their usual daily routines was anticipated to be tough. CONCLUSION: Patients undergoing pulmonary rehabilitation experience a complex health behavior change process, in which healthcare professionals fulfill a major contributing role. Therefore, guiding patients through this health behavior change process is a vital component of healthcare professionals' work, regarding which the present study made practical implications such as applying a personalized approach by giving tailored advices, applying an autonomy-supportive counseling style, teaching self-management skills, and referring patients to local exercise facilities