Hysterectomy is not associated with increased risk of urinary incontinence-a northern Finland birth cohort 1966 study.

Introduction: Hysterectomy has been suggested to increase the risk of urinary incontinence (UI), although evidence is controversial. In our population-based cohort study, we aimed to assess the independent effect of hysterectomy on the risk of de novo UI.

Material And Methods: This is a population-based cohort study on the women of the Northern Finland Birth Cohort 1966 (n = 5889).

Urinary incontinence associates with poor work ability in middle-aged women: A Northern Finland Birth cohort 1966 study.

Introduction: Urinary incontinence is a common ailment in women and is likely to affect their work ability. We investigated the associations between the different subtypes of urinary incontinence and several dimensions of perceived work ability in middle-aged general population.

Material And Methods: Cross-sectional survey at age 46 among participants of the Northern Finland Birth Cohort 1966 study (n = 3706, response rate 72%).

Low testosterone at age 31 associates with maternal obesity and higher body mass index from childhood until age 46: A birth cohort study.

Background: Low testosterone (T) levels in men associate with increased risks of obesity, type 2 diabetes, metabolic syndrome, and cardiovascular diseases. However, most studies are cross-sectional with follow-up-time < 10 years, and data on early growth are limited.

Objective: To compare prenatal factors and body mass index (BMI) development from birth to age 46 in relation to low T at age 31.

Long-term results of a prospective randomized trial comparing tension-free vaginal tape versus transobturator tape in stress urinary incontinence.

Introduction And Hypothesis: This study was aimed at investigating the long-term effectiveness of minimally invasive mid-urethral sling (MUS) surgery and at comparing the outcomes between retropubic (tension-free vaginal tape, TVT) and transobturator tape (TOT) methods in the treatment of stress urinary incontinence (SUI) and mixed urinary incontinence (MUI) with a predominant stress component in a long-term follow-up of a randomized controlled trial.

Methods: This work is a long-term follow-up study of a previous prospective randomized trial conducted in the Department of Obstetrics and Gynecology at Oulu University Hospital between January 2004 and November 2006. The original 100 patients were randomized into the TVT (n=50) or TOT (n=50) group.

An optimal growth pattern during pregnancy and early childhood associates with better fertility in men.

Objective: This study aimed to evaluate the association between birth weight (BW), childhood and adolescent BMI, with reproductive capacity in men.

Design: A prospective, population-based cohort study (Northern Finland birth cohort 1966).

Methods: Around 6196 men born in 1966 were followed from birth to age 50 years.

Laparoscopically guided transversus abdominis plane block versus local wound analgesia in laparoscopic surgery for peritoneal endometriosis: study protocol for a prospective randomized controlled double-blinded LTAP-trial.

Background: Ultrasound-guided transversus abdominis plane block (TAP) performed by anesthesiologist has been shown to be an effective and safe analgesia method in abdominal surgery, reducing postoperative opioid consumption. Recently, there has been growing interest to insert TAP under laparoscopic vision (LTAP) by surgeon. LTAP has been used in laparoscopic gastrointestinal surgery, but studies on LTAP in gynecologic laparoscopic surgery are sparse and inconsistent.

In vivo effects of AZD4547, a novel fibroblast growth factor receptor inhibitor, in a mouse model of endometriosis.

Endometriosis is a chronic disease, characterized by the growth of endometrial-like cells outside the uterine cavity. Due to its complex pathophysiology, a totally resolving cure is yet to be found. The aim of this study was to compare the therapeutic efficacy of AZD4547, a novel fibroblast growth factor receptor inhibitor (FGFRI), with a well-characterized progestin, etonogestrel (ENG) using a validated in vivo mouse model of endometriosis.

IMI - Oral biopharmaceutics tools project - Evaluation of bottom-up PBPK prediction success part 4: Prediction accuracy and software comparisons with improved data and modelling strategies.

Oral drug absorption is a complex process depending on many factors, including the physicochemical properties of the drug, formulation characteristics and their interplay with gastrointestinal physiology and biology. Physiological-based pharmacokinetic (PBPK) models integrate all available information on gastro-intestinal system with drug and formulation data to predict oral drug absorption. The latter together with in vitro-in vivo extrapolation and other preclinical data on drug disposition can be used to predict plasma concentration-time profiles in silico.

An industrial approach towards solid dosage development for first-in-human studies: Application of predictive science and lean principles.

Tablet development is challenging during early clinical phases of drug discovery because of dose uncertainty, limited active pharmaceutical ingredient availability, and short lead times. Here, we introduce a new framework to expedite product development using a suite of in-house and commercially available predictive tools developed through the integration of computer modelling and material-sparing characterisation methods. The strategy underpins the use of dry granulation for formulation development with guidance on scale-up and manufacturability to achieve 'First Time Right'.

Women with polycystic ovary syndrome present with altered endometrial expression of stanniocalcin-1†.

Stanniocalcin-1 (STC-1) is a pro-survival factor that protects tissues against stressors, such as hypoxia and inflammation. STC-1 is co-expressed with the endometrial receptivity markers, and recently endometrial STC-1 was reported to be dysregulated in endometriosis, a condition linked with endometrial progesterone resistance and inflammation. These features are also common in the endometrium in women with polycystic ovary syndrome (PCOS), the most common endocrine disorder in women.

IMI - Oral biopharmaceutics tools project - Evaluation of bottom-up PBPK prediction success part 2: An introduction to the simulation exercise and overview of results.

Orally administered drugs are subject to a number of barriers impacting bioavailability (F), causing challenges during drug and formulation development. Physiologically-based pharmacokinetic (PBPK) modelling can help during drug and formulation development by providing quantitative predictions through a systems approach. The performance of three available PBPK software packages (GI-Sim, Simcyp®, and GastroPlus™) were evaluated by comparing simulated and observed pharmacokinetic (PK) parameters.

Solid formulations by a nanocrystal approach: critical process parameters regarding scale-ability of nanocrystals for tableting applications.

Nanocrystallization is among the foremost drug delivery platform approaches for the commercial development of poorly soluble drugs. There exists an urge to enable a universal shift of the production of the solid nanocrystal formulations from laboratory scale to industrially feasible scale. The success of any formulation development depends on its transferability to large scale manufacture.

Brinzolamide nanocrystal formulations for ophthalmic delivery: reduction of elevated intraocular pressure in vivo.

Nanocrystal-based drug delivery systems provide important tools for ocular formulation development, especially when considering poorly soluble drugs. The objective of the study was to formulate ophthalmic, intraocular pressure (IOP) reducing, nanocrystal suspensions from a poorly soluble drug, brinzolamide (BRA), using a rapid wet milling technique, and to investigate their IOP reducing effect in vivo. Different stabilizers for the nanocrystals were screened (hydroxypropyl methylcellulose (HPMC), poloxamer F127 and F68, polysorbate 80) and HPMC was found to be the only successful stabilizer.

Nanocrystal-based per-oral itraconazole delivery: superior in vitro dissolution enhancement versus Sporanox® is not realized in in vivo drug absorption.

Nanoscience holds true promise in enabling efficient formulation development and in vivo delivery of poorly water soluble drugs. The objective of this study was to formulate solid oral nanocrystal delivery systems of itraconazole, and thus enhance the oral bioavailability of the very poorly soluble drug. Nanocrystal suspensions were prepared by a rapid wet milling technique, after which the suspensions were transformed into solid dosage forms by both freeze drying and granulating.

Dissolution studies of poorly soluble drug nanosuspensions in non-sink conditions.

Sink conditions used in dissolution tests lead to rapid dissolution rates for nanosuspensions, causing difficulties in discriminating dissolution profiles between different formulations. Here, non-sink conditions were studied for the dissolution testing of poorly water-soluble drug nanosuspensions. A mathematical model for polydispersed particles was established to clarify dissolution mechanisms.

Nanosuspensions of poorly soluble drugs: preparation and development by wet milling.

Nanosizing techniques are important tools for improving the bioavailability of water insoluble drugs. Here, a rapid wet milling method was employed to prepare nanosuspensions: 4 types of stabilizers at 4 different concentrations were tested on 2 structurally different drug compounds: indomethacin and itraconazole. Photon correlation spectroscopy (PCS) results showed that the finest nanosuspensions were obtained when 80 wt% (to drug amount) pluronic F68 was the stabilizer for indomethacin and 60 wt% pluronic F127 for itraconazole.