Chronic cough in postmenopausal women and its associations to climacteric symptoms.

BACKGROUND: Postmenopausal women often have chronic cough. Hormonal changes might be affecting lung function and the mucous membrane of the airways, causing hypersensitivity of the cough reflex. Therefore, postmenopausal hormonal changes could play a key role in the association between increased cough and menopause. The aim of this study is to evaluate the relation of chronic cough and postmenopausal symptoms. METHODS: We performed a questionnaire-based cohort study in generally healthy postmenopausal women (age 45-65 years). Women with cough explained by a pre-existing diagnosis were excluded. Comorbidities, medication and baseline data were collected. The Menopause Rating Scale II (MRS II) was combined with the Leicester Cough Questionnaire. Groups were divided in chronic cough versus non-coughing participants, chronic cough was defined as symptoms over 8 weeks. We performed correlations and logistic regression for predicting cough based on postmenopausal symptoms. RESULTS: Sixty-six of 200 women (33%) reported symptoms of chronic cough over 8 weeks. No significant differences in baseline data (age, BMI, onset of menopause, years since menopause, concomitant diseases, and medication) were found between coughing and non-coughing women. The MRS II showed higher menopausal symptoms in patients with cough, with significant differences in 2 of the 3 MRS-domains (urogenital (p < 0.001) and somato-vegetative (p < 0.001)). Climacteric symptoms correlated strongly with parameters of cough (p < 0.001). On the basis of the MRS total score (p < 0.001) and the somato-vegetative and urogenital domains (p < 0.05), the prediction for respiratory complaints could be shown. DISCUSSION: Chronic cough was significantly associated with menopausal symptoms. Therefore chronic cough as a possible climacteric symptom and its underlying mechanisms should be further explored.

Internet-based cognitive behavioral therapy for improving health-related quality of life in patients with endometriosis: study protocol for a randomized controlled trial.

BACKGROUND: The trial investigates the efficacy of internet-based cognitive behavioral therapy (iCBT) in improving health-related QoL in patients with endometriosis, which is a chronic gynecological condition affecting up to 15% of people with female-assigned reproductive organs. Endometriosis is stress-related and comes with various physical symptoms such as pelvic pain and infertility. It has a substantial impact on health-related quality of life (QoL), and mind-body interventions seem promising in reducing the psychological burden. METHODS: This is a monocentric randomized-controlled trial recruiting 120 patients with endometriosis. The intervention consists of eight iCBT modules focusing on psychoeducation, cognitive restructuring, pacing, and emotion regulation. Participants will receive written feedback from a trained therapist weekly. The comparator is a waitlist control group. All participants will be followed up 3 months after the intervention, and the intervention group will additionally be followed up 12 months after the intervention. Trial participants will not be blinded to the allocated trial arm. Primary outcome measures are endometriosis-related QoL, pain, and pain-related disability. Secondary outcomes include coping, illness representations, and psychological flexibility. Statistical analyses will be performed following intention-to-treat principles. DISCUSSION: This randomized-controlled trial is the first trial to test the efficacy of iCBT for improving endometriosis-related QoL. Potential predictor variables and key mechanisms in treatment will be investigated to enable further progression in medical and psychological care for patients with endometriosis. TRIAL REGISTRATION: ClinicalTrials.gov , NCT05098444 Registered on October 28, 2021.

Subcutaneous progesterone versus vaginal progesterone for luteal phase support in in vitro fertilization: A retrospective analysis from daily clinical practice.

OBJECTIVE: Progesterone application for luteal phase support is a well-established concept in in vitro fertilization (IVF) treatment. Water-soluble subcutaneous progesterone injections have shown pregnancy rates equivalent to those observed in patients receiving vaginal administration in randomized controlled trials. Our study aimed to investigate whether the results from those pivotal trials could be reproduced in daily clinical practice in an unselected patient population. METHODS: In this retrospective cohort study in non-standardized daily clinical practice, we compared 273 IVF cycles from 195 women undergoing IVF at our center for luteal phase support with vaginal administration of 200 mg of micronized progesterone three times daily or subcutaneous injection of 25 mg of progesterone per day. RESULTS: Various patient characteristics including age, weight, height, number of oocytes, and body mass index were similar between both groups. We observed no significant differences in the clinical pregnancy rate (CPR) per treatment cycle between the subcutaneous (39.9%) and vaginal group (36.5%) (p=0.630). Covariate analysis showed significant correlations of the number of transferred embryos and the total dosage of stimulation medication with the CPR. However, after adjustment of the CPR for these covariates using a regression model, no significant difference was observed between the two groups (odds ratio, 0.956; 95% confidence interval, 0.152-1.786; p=0.888). CONCLUSION: In agreement with randomized controlled trials in study populations with strict selection criteria, our study determined that subcutaneous progesterone was equally effective as vaginally applied progesterone in daily clinical practice in an unselected patient population.

Term cesarean breech delivery in the first pregnancy is associated with an increased risk for maternal and neonatal morbidity in the subsequent delivery: a national cohort study.

PURPOSE: To determine whether there is an association between term cesarean breech delivery in the first pregnancy and maternal and neonatal morbidities in the subsequent pregnancy and delivery. METHODS: We conducted a retrospective, nationwide Finnish population-based cohort study, including all deliveries from January 2000 to December 2017. We included all women with the first two consecutive singleton deliveries of which the first one was a breech delivery regardless of mode of delivery (n = 11,953), and constructed a data set in which the first two deliveries for these women were connected. The outcomes of the second delivery of the women with a first pregnancy that resulted in cesarean breech delivery at term were compared with women whose first pregnancy resulted in a vaginal breech delivery at term. P-value, odds ratio, and adjusted odds ratio were calculated. RESULTS: Neonates of a subsequent delivery after cesarean breech delivery had an increased risk for arterial umbilical cord pH below seven, a higher rate of a 5 min APGAR score < 7 and a higher rate of neonatal intensive care unit admission. The women with a history of cesarean section with the fetus in breech presentation were more often in need of a blood transfusion and suffered more often a uterus rupture. In this group, the second delivery was more often a planned cesarean section, an emergency cesarean section, or an instrumental vaginal delivery. CONCLUSIONS: Primary cesarean breech section in the first pregnancy is associated with adverse neonatal and maternal outcomes in the subsequent delivery.

Mouse embryos exposed to oxygen concentrations that mimic changes in the oviduct and uterus show improvement in blastocyst rate, blastocyst size, and accelerated cell division.

After in vivo fertilisation, the preimplantation embryo goes through cleavage during migration along the oviduct in mammals or the fallopian tube in a woman and ends up inside the uterus. This study investigates the effect of a protocol aimed at closely reproducing that natural oxygen concentration in the oviduct (7 % O2 from day 1 to day 3 and 2 % from day 3 to day 5), in contrast to the concentrations (5 % or 20 %) widely used in practice in ART using morphokinetic. Female mice (BI6/CBAca) were sacrificed, and zygotes were isolated 20 h after mating and randomly allocated to three parallel groups, which were grown under high atmospheric, low, or sequential oxygen concentrations. Zygotes were cultured in GTL medium (Vitrolife) and observed by the Primovision time-lapse system. Blastocyst rate at 120 h in the sequential group (91.3 %) was significantly increased over the high (76.3 %) and low (74.4 %) groups. Blastocyst size was also enlarged in the sequential group compared to the high and low groups. Moreover, cell division in the sequential group was significantly faster at almost every cleavage stage than it was in the other groups. Notably, the duration of the interims between stages also differed significantly between the groups. This study demonstrated that, in comparison to routinely used high or low oxygen conditions, oxygen concentrations mimicking changes in the oviduct and uterus significantly improve the blastocyst rate and size and accelerate cell division at several stages as well as the interims between cleavage events.

Effects of opening the incubator on morphokinetics in mouse embryos.

OBJECTIVE: To evaluate the effects of incubator door openings by the sensitive measurement of morphokinetics using time-lapse imaging. STUDY DESIGN: To mimic lab practice and to evaluate minimal changes in culture conditions a randomized parallel group study with mouse embryos was designed. 249 murine zygotes derived from 31 mice were randomly distributed into two groups. Embryos of the control group were non-invasively monitored with a Primovision time-lapse system (Vitrolife) in the incubator that was completely closed for 5 days, while the conditions for the embryos in the treatment group were interrupted by two door openings per day of 10 s each. RESULTS: Door opening twice per day did not lead to significant differences in blastocyst formation rate (p = 0.820), however significantly more embryos hatched in a shorter duration (p = 0.011), and the embryos transitioned more quickly from 2C to 3C, from 3C to 4C, from 2C to 5C and from 5C to blastocyst stage (p < 0.001 in cc2, p = 0.037 in cc3, p = 0.002 in t2 to t5, and p = 0.015 in t5 to blastocyst). Size of the blastocysts from the treatment group was 1.562 µm smaller compared to that of control embryos (p = 0.016). CONCLUSIONS: Even disruptions in culture conditions as simple as incubator door openings lead to measurable, significant changes in morphokinetics that would have been missed with standard parameters such as blastocyst rate. This underlines the relevance of undisturbed and stable culture conditions and emphasizes the need for further research in this field.

Caesarean section and its impact on fertility and time to a subsequent pregnancy in Germany: a database analysis in gynecological practices.

PURPOSE: To analyze the impact of caesarean section (CS) on fertility and time to pregnancy in German gynecological practices. METHODS: Women initially diagnosed for the first time with a vaginal delivery (VD) or CS between 2000 and 2013 were identified by 227 gynecologists in the IMS Disease Analyzer database. They were included if they were aged between 16 and 40 years, and were not previously diagnosed with female sterility. The two main outcomes were the first-time diagnosis of female sterility and the time between the first delivery and the next pregnancy within 10 years. A multivariate Cox regression model was used to predict these outcomes on the basis of patient characteristics. RESULTS: 6483 patients were included in the CS group and 6483 in the VD group. Mean age was 30.6 years and the proportion of individuals with private health insurance amounted to 9.0 %. Within 10 years of the index date, 19.5 % of women who delivered by CS and 18.3 % of women who delivered vaginally were diagnosed with sterility (p value = 0.0148). CS and polycystic ovary syndrome significantly increased the risk of sterility. Within 10 years of the index date, 57.9 % of women who underwent a CS and 64.0 % of women who delivered vaginally were pregnant for the second time (p value <0.001). CS, polycystic ovary syndrome, and the deterioration of menstrual cycle significantly decreased the chance of becoming pregnant a second time. CONCLUSIONS: CS is associated with an increased risk of sterility and a decreased number of subsequent pregnancies in Germany.

Impact of caesarean section on mode of delivery, pregnancy-induced and pregnancy-associated disorders, and complications in the subsequent pregnancy in Germany.

OBJECTIVES: To analyze the impact of caesarean section (CS) on mode of delivery, pregnancy-induced and pregnancy-associated disorders, as well as complications in the subsequent pregnancy within German gynecological practices. METHODS: 1,801 women with CS and 1,801 matched women with vaginal delivery (VD) from the IMS Disease Analyzer database were included. The impact of previous CS on the mode of delivery and pregnancy-associated disorders as well as complications prior to or during birth in the subsequent pregnancy were analyzed. Cox regressions were used to determine the influence of CS with regard to these outcomes. RESULTS: Medical abortion and single spontaneous delivery were significantly less frequent in women with a history of CS compared to VD (OR equal to 0.52 and 0.04 respectively), whereas CS after CS was the significantly more common mode of delivery (79.0% versus 9.3%, OR=36.47). Gestational hypertension without significant proteinuria, gestational hypertension with significant proteinuria, and polyhydramnios were more frequent in women with CS than in women with VD (OR equal to 6.80, 1.71, and 2.29). Hemorrhage and maternal care for known or suspected disproportion were more common in the CS group than in the VD group (OR equal to 1.34 and 3.75). Prolonged pregnancy, preterm labor, abnormalities arising from forces of labor, and perineal laceration during delivery were significantly less frequent in women with CS than in women with VD (OR between 0.32 and 0.75), whereas long labor was more common (OR=2.09). CONCLUSION: Women with CS were more likely to undergo further CS and to develop major pregnancy-associated diseases in the following pregnancy compared to women with VD.

Emergency peripartum hysterectomy and risk factors by mode of delivery and obstetric history: a 10-year review from Helsinki University Central Hospital.

OBJECTIVE: This study aims to estimate the occurrence of emergency peripartum hysterectomy (EPH) and to quantify its risk factors in connection with the mode of delivery and the obstetric history of patients at the Helsinki University Central Hospital, Finland. METHODS: In a retrospective, matched case-control study we identified 124 cases of EPH from 2000 to 2010 at our hospital. These were matched with 248 control patients. RESULTS: The incidence rate of EPH was 9.9/10,000. Patients whose current delivery was vaginal, and had a cesarean section (CS) in their history had a six-fold risk for EPH. Women who underwent their first CS had a nine times higher risk, while patients who currently underwent CS and had a history of previous CS, had a 22 times higher risk. Those who experienced prostaglandin-E1 induction had a five-fold risk. Maternal age >35 years, previous curettage, and twin pregnancy were identified as significant risk factors. In 41 cases, interventions to reduce bleeding were performed. CONCLUSION: Obstetric emergency training and guidelines for massive hemorrhage should be established in any delivery department. Moreover, all possible precautions should be taken to avoid the first CS if it is obstetrically unnecessary. Induction with prostaglandin-E1, maternal age >35 years, previous curettage, twin pregnancies, and early gestation were identified as risk factors for EPH.

Influence of a patient information program on adherence and persistence with an aromatase inhibitor in breast cancer treatment--the COMPAS study.

BACKGROUND: It is known that suboptimal adherence rates may affect endocrine treatments for breast cancer, but little information has been reported whether any efforts to improve treatment adherence have been successful. We designed a randomized, controlled study to investigate the effect of oral or written patient information program on adherence and persistence when receiving an aromatase inhibitor (AI). METHODS: The study cohort included 181 female patients receiving an adjuvant AI treatment randomly assigned to one of three groups. The first group received reminder letters and information booklets, the second group was reminded and informed through telephone calls and the control group received neither. The primary endpoint was the rate at which patients were classified as adhering to treatment after twelve months. RESULTS: Baseline results showed a well-balanced randomization with no significant differences between groups. After 12 months, 48% (CI 35-62) of the control group, 62.7% (CI 49-75) in the telephone group and 64.7% (CI 51-77) in the letter group were adhering to therapy. A post hoc pooled analysis with a one-way hypothesis for both interventions versus control indicated a significant difference between the groups favouring the intervention (p = 0.039). CONCLUSION: The aim of this study was to investigate the efficacy of a simple and practical interventional program in enhancing adherence to breast cancer treatment. Patients receiving additional/supplemental information appeared to have an improved adherence rate even though the differences between groups were not statistically significant for the primary endpoint.

The effect of age, sex hormones, and bone turnover markers on calcaneal quantitative ultrasonometry in healthy German men.

The aim of this cross-sectional study was to determine the age-dependent variations of calcaneal quantitative ultrasonometry (QUS) and the association with sex hormones and biochemical bone turnover markers in a large sample of unselected healthy German men. Bone measurements are expected to behave differently among men and women. The speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness index (SI) of the os calcaneus were measured in 506 German men aged 20-79 yr (mean age: 45.7 yr). Additionally, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, testosterone, dehydroepiandrosterone sulfate (DHEA-S), sex hormone-binding globulin (SHBG) as well as N-terminal propeptide of human procollagen type I (PINP), C-terminal telopeptide of type I collagen (ICTP), osteocalcin, bone-specific alkaline phosphatase, and CrossLaps were measured with standardized essays and correlated with the QUS results. The QUS results comprised an overall change of 12.4%, 3.2%, and 23.2% for BUA, SOS, and SI, respectively, between the 20-29 and 70-79 yr age groups (p ≤ 0.001). The annual rate of the age-related differences was 0.33% (standard deviation [SD]: 0.31), 0.06% (SD: 0.08), and 0.53% (SD: 0.56) for BUA, SOS, and SI, respectively. Testosterone and DHEA-S were significantly associated with QUS parameters and increasing age, whereas SHBG showed an age-related increase and was inversely related with QUS values (p < 0.05). Bone turnover markers present lower values gradually, and we found a significant correlation between carboxy-terminal collagen crosslinks (CTX), osteocalcin (OC), bone alkaline phosphatase (BAP), and QUS variables (p < 0.05).

Influence of compliance on bone mineral density changes in postmenopausal women with early breast cancer on Anastrozole.

PURPOSE: Adjuvant treatment for hormone receptor-positive breast cancer in postmenopausal women with aromatase inhibitors is associated with increased bone loss depending on the compliance to treatment. METHODS: In this bone substudy, bone mineral density (BMD) was assessed by dual energy X-ray absorptiometry at baseline and after 12- and 24-month treatment in 63 patients receiving Anastrozole as adjuvant treatment for hormone receptor-positive early breast cancer. To minimize the effects of confounders, a matched pair analysis (compliant N = 21, non-compliant N = 21) was performed. RESULTS: Anastrozole treatment in compliant patients leads to a decrease in BMD (g/cm(2)) at lumbar spine and total hip from baseline to 12 and 24 months (-2.57 % P = 0.004; -2.02 % P = 0.05; -2.57 % P = 0.001 and -4.18 % P = 0.003, respectively) compared to non-compliant patients (-1.71 % P = 0.050; -2.00 % P = 0.085; -1.65 % P = 0.055 and -3.20 % P = 0.005, respectively). CONCLUSIONS: Anastrozole treatment in compliant patients with breast cancer resulted in a larger, increase in bone loss at 12 and 24 months compared to non-compliant patients. Bone loss stabilized in both groups at the spine from 12- to 24-month treatment, whereas maintained at the total hip.

Effects of a low-dose oral estrogen only treatment on bone mineral density and quantitative ultrasonometry in postmenopausal women.

INTRODUCTION: The aim of this study was to evaluate an oral low-dose estrogen therapy on bone mineral density (BMD) and quantitative ultrasonometry (QUS) in osteopenic postmenopausal women. MATERIAL AND METHODS: This prospective, open-label cohort study investigated 120 postmenopausal hysterectomized women. Forty-seven women had been treated with 0.3 mg conjugated equine estrogen daily (ET). Primary end point was the change in BMD at the spine after 24 months. Secondary end points were among other changes in QUS at the os calcis and phalanges. RESULTS: After matching 42 participants in the ET group, 42 controls were analyzed. The change in BMD differed significantly after 24 months (p = 0.019). Women on ET showed significant increase of spine and hip Z-score, whereas controls showed significant decreases in spine and total hip BMD. In QUS of the os calcis and the phalanges, a number of variables showed a significant improvements with ET. CONCLUSION: Our results comprised a positive effect of an oral low-dose estrogen therapy on BMD. Limitations of the study are the small sample size and the open-label, non-randomized cohort study design. The findings are in accordance to the common literature and support the use of ET in the primary prevention of postmenopausal bone loss.

Persistence and compliance of medications used in the treatment of osteoporosis--analysis using a large scale, representative, longitudinal German database.

OBJECTIVE: Osteoporosis can be effectively treated with a number of medications. However, high persistence and compliance are required to assure efficacy. This study analyses persistence and compliance with a variety of medical interventions including p.o., i.v. and s.c. administrations in Germany. METHODS: This retrospective cohort study used a representative longitudinal database (IMS® LRx) comprising longitudinal prescription data for Germany from almost 80% of all German prescriptions of members of the German statutory health insurance system. Persistence is defined as the proportion of patients who remained on their initially prescribed therapy at 1 year. Compliance is measured indirectly based on the medication possession ratio (MPR). RESULTS: A total of more than 1 million patients (1,107,482) for the period 07/2007 - 06/2009 was identified in the database who received a prescription for a bisphosphonate, strontium or PTH. Of these, 268,568 patients fulfilled further inclusion criteria and were included in the persistence and compliance analysis. At 12 months the proportion of patients that remained on treatment were 65.6% for zoledronate 5 mg; 56.6% for ibandronate i.v. 3 mg; 54.7% for PTH (teriparatide and 1-84 PTH), 51.0% for ibandronate 150 mg p.o.; 44.8% for alendronate 70 mg; 43.4% for etidronate. Other values were risedronate plus calcium 42.3%; alendronate plus vitamin D 37.8%; risedronate 35 mg 35.2%; risedronate 5 mg 30.6%; strontium ranelate 31.4% and alendronate 10 mg 17.3%. CONCLUSION: Persistence and compliance during the treatment of osteoporosis were found to be insufficient. Treatment using the intravenous route and PTH showed the highest persistence and compliance rates and daily oral bisphosphonates the lowest. More effort to improve treatment compliance and persistence is needed to assure clinical efficacy.

Cost comparison of outpatient treatment with granulocyte colony-stimulating factors (G-CSF) in Germany.

BACKGROUND: Granulocyte colony-stimulating factors (G-CSF), are available for prevention of neutropenia and reduction of its complications in cytostatic chemotherapy. The purpose of this analysis was to determine the consumption rates for various G-CSF and to compare outpatient medication costs per patient and treatment cycle. METHODS: Prescription data of statutory health insurance members in Germany (IMS®LRx database) with G-CSF prescriptions between January 2008 and July 2010 were evaluated. A period of observation of at least 6 months prior to and after the G-CSF prescription was required. RESULTS: Prescription data of 8,726 patients treated with original filgrastim, 4,240 with biosimilar filgrastim, 6,456 with lenograstim, and 9,939 with pegfilgrastim were analyzed. The regression model showed statistically significant costreducing effects per cycle for treatment with lenograstim compared with non-lenograstim (-0.47 vs. original filgrastim; -0.15 vs. biosimilar filgrastim; -1.04 vs. pegfilgrastim; each p < 0.0001). This result has been adjusted for patient age, gender, number of injections, and prescribing specialist group. CONCLUSIONS: Treatment with the original preparation lenograstim is significantly cheaper compared to the other two original drugs and biosimilar. The costs of G-CSF treatment with the original preparation lenograstim and the filgrastim biosimilars are in a similar range, but with a significantly lower cost for lenograstim. Compared to their reference product the biosimilars thus show a cost advantage.

The Impact of Breast Care Nurses on Patients' Satisfaction, Understanding of the Disease, and Adherence to Adjuvant Endocrine Therapy.

BACKGROUND: Breast care nurses (BCNs) are specialized caregivers in certified breast cancer center teams. The impact of a BCN's work remains unknown. PATIENTS AND METHODS: The role of BCN care was evaluated in a post-discharge mail survey of 360 patients. RESULTS: A total of 207 (87%) of 237 (66%) returned questionnaires were analyzed; 171 (83%) patients had BCN contact, 36 (17%) did not. The mean global quality of life scores (EORTC-QLQ-C30) were 66.3 for women with contact to a BCN versus 62.5 for women without such contact (p < 0.05). Women with a BCN contact had better results than women without (p < 0.001) for the following parameters: receipt of information material (84 vs. 64%), information about hospital procedures (93 vs. 72%) and treatment plan (91 vs. 63%), and knowledge of own tumor hormone receptor status (83 vs. 53%). Medication adherence correlated with the knowledge about the tumor hormone receptor status and was significantly higher in women having contact with a BCN (79 vs. 56%). The high recommendation rate (81%) reflects the high level of satisfaction with BCNs. A qualitative analysis of comments and suggestions identified aspects to improve BCN services. CONCLUSIONS: BCN improve satisfaction and treatment adherence in breast cancer patients.