The impact of short-selling in financial markets

This dissertation empirically examines the impact of short-selling in financial markets. Given the increasing participation of short-sellers in financial markets, this research provides empirical evidence on an increasingly important issue. Each chapter addresses a research question with scarce or conflicting prior research findings to provide evidence which can assist researchers, investors and regulators to understand and manage the impact of short-selling in financial markets

Do we need a core outcome set for childbirth perineal trauma research? A systematic review of outcome reporting in randomised trials evaluating the management of childbirth trauma.

BACKGROUND: Selecting appropriate outcomes to reflect both beneficial and harmful effects is a critical step in designing childbirth trauma trials. OBJECTIVE: To evaluate the outcomes and outcome measures reported in randomised controlled trials evaluating interventions for childbirth trauma. SEARCH STRATEGY: Randomised trials were identified by searching bibliographical databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE. SELECTION CRITERIA: Randomised trials evaluating the efficacy and safety of different techniques in the management of perineal lacerations. DATA COLLECTION AND ANALYSIS: Two researchers independently assessed studies for inclusion, evaluated methodological quality, and extracted the relevant data. Spearman's ρ correlation and multivariate linear regression analysis using the backward stepwise model were used for analysis. MAIN RESULTS: Forty-eight randomised trials, reporting data from 20 308 women, were included. Seventeen different interventions were evaluated. Included trials reported 77 different outcomes and 50 different outcome measures. Commonly reported outcomes included pain (34 trials; 70%), wound healing (20 trials; 42%), and anorectal dysfunction (16 trials, 33%). In the multivariate analysis, no relationship was demonstrated between the quality of outcome reporting and year of publication (P = 0.31), journal impact factor (P = 0.49), and methodological quality (P = 0.13). CONCLUSION: Outcome reporting in childbirth trauma research is heterogeneous. Developing, disseminating, and implementing a core outcome set in future childbirth trauma research could help address these issues. TWEETABLE ABSTRACT: Developing @coreoutcomes for childbirth trauma research could help to reduce #research waste

Do predictive parameters for a successful therapy with duloxetine in stress urinary incontinent women exist?

Methodik: Sekundäranalyse der SUIT, einer 12 monatigen, prospektiven Beobachtungsstudie zur Evaluation der Therapieresultate der Belastungsharninkontinenz sowie deren Kosten Von 4002 inkludierten SUIT Patientinnen erhielten 1714 Patientinnen Duloxetin, die Daten von 1222 Frauen konnten für die Sekundäranalyse berücksichtigt und bezogen auf unsere Fragestellung Daten von 1087 Frauen ausgewertet werden. Univariable und multivariable Analysen wurden mithilfe der Statistikprogramme SAS (Version 9.2) und SPSS (PASW Statistics 18.0) durchgeführt, binäre Parameter wurden mittels Fishers exaktem Test und Parameter mit mehr als 2 Ausprägungen mit dem Chi-Quadrat-Test untersucht und entsprechende p-Werte angegeben. Eine schrittweise vorwärts gerichtete logistische Regressionsanalyse wurde durchgeführt. Ergebnisse: Während in der univariablen Analyse Rauchen (p = 0,019) sowie ein BMI <20 (p= 0,024) mit weniger Therapieabbrüchen assoziiert waren, ein BMI > 30 jedoch mit einer gestiegenen Abbruchwahrscheinlichkeit (p= 0,024), ließen sich diese Ergebnisse in der multivariablen Analyse so nicht bestätigen. Ohne Einfluß auf die Therapieadhärenz war der Operationsstatus der Patientin (p = 0,382). In der multivariablen Analyse waren das Land der Behandlung relevant (p < 0,001) mit den geringsten Therapieabbrüchen innerhalb Deutschlands, ein Patientinnenalter >65 Jahre (p= 0,016) sowie 7 bis 13 Harninkontinenzepisoden / Woche (p < 0,001) und der Schweregrad der HIK (OR bei moderater HIK 3,16; bei schwerer HIK 5,39 bei p < 0,001), mit einer reduzierten Wahrscheinlichkeit für ein vorzeitiges Therapieende assoziiert. Eine Komedikation von Duloxetin mit anderen Medikamenten erhöht die Probabilität eines frühzeitigen Therapieabbruches (OR=4,32; p<0,001), insbesondere Anticholinergika erhöhen diese Wahrscheinlichkeit (OR =18,72; p<0,001). Diskussion: Prädiktive Parameter für den Therapieerfolg von Duloxetin sind für eine resourcenorientierte Behandlungsinitiierung belastungsharninkontinenter Frauen wünschenswert, aber rar. Gründe für hohe Abbruchraten im klinischen Alltag sind wahrscheinlich der gemeinsame Metabolisierungsweg vieler Pharmaka via Cytochrom P450 Isoenzymen (CYP 1A2 und CYP 2D6) und dem damit einhergehendem Interaktionspotential. Insbesondere für die bis zu 10% Kaukasierinnen mit einer defizitären CYP 2D6-Enzymausstattung sowie die bis zu 5% extrem schnellen Metaboliserinnen ist dies von klinischer Relevanz. Der Einfluß von Nikotinkonsum via 1A2 konnte nicht abschließend geklärt werden, Hinweise auf eine reduzierte Abbruchwahrscheinlichkeit bestehen (insbesondere bei Duloxetinmonotherapie). Potenzielle Zusammenhänge mögen nicht aufgedeckt worden sein, da die Enzymausstattung der Patientinnen unbekannt und mögliche Interaktionen unerkannt stattgefunden haben können. Die deutlich höhere Bereitschaft von Frauen, eine (durchaus effiziente) Behandlung der Belastungsharninkontinenz zu beenden, wenn zeitgleich andere Medikamente eingenommen werden, beruht sehr wahrscheinlich auf CYP 450 - bedingten Arzneimittelinteraktionen. Vor diesem Hintergrund sollten Komedikationen kritisch bedacht werden.Methods: Secondary analysis of the SUIT study, a 12 month longitudinal observational study to evaluate results and direct costs of stress urinary incontinence treatment Out of 4002 women included into SUIT 1714 received duloxetine. Data of 1222 women were verified for meeting inclusion and exclusion criteria for the secondary analysis, hence data of 1087 women could be analyzed. Univariate and multivariate analyses with the aid of the statistical programs SAS version 9.2 and SPSS (PASW statistics 18.0) were performed. Binary parameters have been tested with Fisher`s exact test, parameters with more than two characteristics were analysed with chi-square- test and accordingly p-value indicated. A stepwise forward logistic regression analysis was performed. Results: A reduced probability for a premature termination of treatment was found for smoking (p = 0.019) as well as for a BMI 30 was associated with an increased probability of treatment discontinuation (p= 0.024). These results were not confirmed in the multivariate analysis. Without any effect was the fact whether a woman has undergone stress urinary incontinence surgery in the past (p = 0.382). Parameters associated with a reduced likelihood of a preterm duloxetine treatment termination in the multivariate analysis were the country in which treatment took place (p< 0.001) with the least terminations in Germany, age >65 years (p=0.016) as well as 7-13 incontinence episodes/week (p<0.001) and the grade of incontinence (OR= 3.16 with moderate incontinence, OR= 5.39 with severe incontinence). A co-administration of duloxetine with other medication was associated with an increment of therapy quit (OR= 4.32, p<0.001), particularly anticholinergics (OR=18.72, p<0.001). Discussion: Predictive parameters for a successful therapy with duloxetine in women suffering stress urinary incontinence are desirable- but rare. High discontinuation rates in the clinical practice are most probably the results of a similar metabolism of frequently used pharmaceutics and duloxetine via cytochtome p450 isoenzymes (1A2 and 2D6) and the along going interaction potential. This is of special relevance for the up to 10% Caucasian with deficient 2D6 enzymes and the up to 5% ultrarapid metabolizer. The influence of nicotine usus via 1A2 is not concluding clarified, as there are hints of reduced likelihood of therapy discontinuation among smoking women, notably under duloxetine monotherapy. It is possible that potential relationships were not revealed, as the enzyme status of the participants was unknown and feasible interactions may have occured unrecognized. Against the backdrop of an increased chance to terminate an efficient stress urinary incontinence treatment if women ingest other medication - most probably due to CYP 450 interactions- co-medications should be considered critically

A Critical Review Of The Literature On Functional Anatomy Of The Muscles Of Mastication

OBJECTIVE: To establish the relationship between postpartum levator ani muscle (LAM) avulsion and signs and/or symptoms of pelvic floor dysfunction (PFD). DESIGN: Observational longitudinal cohort study. SETTING: District General University Hospital, UK. POPULATION OR SAMPLE: Primigravida at 36 weeks' gestation and 3 months postpartum. METHODS: Pelvic floor muscle strength (PFMS) and pelvic organ prolapse were assessed clinically using validated methods. Transperineal ultrasound was performed to identify LAM avulsion and measure hiatus dimensions. Validated questionnaires evaluated sexual function, urinary and faecal incontinence. MAIN OUTCOME MEASURES: PFD signs and symptoms related to LAM avulsion. RESULTS: Two hundred and sixty nine primigravida without LAM avulsion participated and 71% (n = 191) returned postpartum. LAM avulsion was found in 21% of vaginal deliveries (n = 30, 95%CI 15.1-28.4%). Women with minor and major avulsion had worse PFMS (P < 0.038) and more anterior compartment prolapse (maximum stage 2; P < 0.024). Antenatal hiatus antero-posterior diameter on ultrasound was significantly smaller in women sustaining avulsion (P = 0.011). Postnatal measurements were significantly increased following avulsion. Women with major avulsion were less sexually active at both antenatal and postnatal periods (P < 0.030). These women had more postnatal urinary incontinence and symptoms such as reduced vaginal sensation and 'too loose vagina'. No postnatal differences were found for faecal incontinence, prolapse symptoms or quality of life. The correlation of differences in variables was only slight-fair with avulsion severity. CONCLUSIONS: Twenty one percent of women sustain LAM avulsion during their first vaginal delivery with significant impact on signs and symptoms of PFD. As avulsion has been described as the missing link in the development of prolapse; longer term follow-up is vital