Randomized Trial of 2 Self-Titrated Oral Appliances for Airway Management.

The effectiveness and predictability of 2 different oral appliance (OA) designs to reduce the respiratory event index (REI) in moderate and severe obstructive sleep apnea (OSA) patients requires elucidation. The primary aim of the trial was to determine if 2 widely used midline-traction and bilateral-thrust OA designs differ in effectiveness to reduce the REI within a single test population categorized by OSA severity. Moderate and severe adult OSA patients, who were previously prescribed continuous positive airway pressure therapy (CPAP) but were dissatisfied with it (n = 56), were studied by home-polygraphy in a randomized crossover trial using either midline-traction with restricted mouth opening (MR) or bilateral thrust with opening permitted (BP) design OAs. OAs were used nightly for 4 wk (T2) followed by a 1-wk washout period, then 4 wk (T4) using the alternate OA. REI and oxygen saturation (SaO2) were primary outcomes, while predictability and efficacy comparison of the 2 OAs were secondary outcomes. Thirty-six participants had used MR and BP OAs during both 4-wk study legs. Twenty (55.6%) MR OA-using participants, 25 (69.4%) BP OA-using participants, and 16 (44.4%) participants using both OAs had significant REI reductions. Overall baseline (T0) median REI (interquartile range) of 33.7 (20.7-54.9) was reduced to 18.0 (8.5-19.4) at T2 and to 12.5 (8.2-15.9) at T4 (P < 0.001). Comparison of the 2 sequence groups' (MR-BP and BP-MR) REI showed the median differences between T0 and T2 and T4 were highly significant (P < 0.001). Regression analysis predicted about half of all users will have REIs between 8 and 16 after 2 mo. Baseline overjet measures >2.9 mm predicted greater OA advancement at T4. Mean and minimum SaO2 did not change significantly from T0 to T2 or T4. MR and BP OA designs similarly attenuated REI in moderate and severe OSA individuals who completed the 8-wk study protocol with greater REI reduction in those with severe OSA (ClinicalTrials.gov NCT03219034).

Twelve-year follow-up of conservative management of postnatal urinary and faecal incontinence and prolapse outcomes: randomised controlled trial.

OBJECTIVE: To determine the long-term (12-year) effects of a conservative nurse-led intervention for postnatal urinary incontinence. DESIGN: Follow-up of a randomised controlled trial. SETTING: Community-based intervention in three centres (in the UK and New Zealand). POPULATION: A cohort of 747 women with urinary incontinence at 3 months after childbirth, of whom 471 (63%) were followed up after 12 years. METHODS: Women were randomly allocated to active conservative treatment after delivery (pelvic floor muscle training and bladder training), or to a control group receiving standard care. MAIN OUTCOME MEASURES: Prevalence of urinary incontinence (primary outcome) and faecal incontinence, symptoms and signs of prolapse, and performance of pelvic floor muscle training at 12 years. RESULTS: The significant improvements relative to controls that had been found in urinary incontinence (60 versus 69%; risk difference, RD, -9.1%; 95% confidence interval, 95% CI, -17.3 to -1.0%) and faecal incontinence (4 versus 11%; RD -6.1%; 95% CI -10.8 to -1.6%) at 1 year did not persist for urinary incontinence (83 versus 80%; RD 2.1%; 95% CI -4.9 to 9.1%) or faecal incontinence (19 versus 15%; RD 4.3%; 95% CI -2.5 to 11.0%) at the 12-year follow up, irrespective of incontinence severity at trial entry. The prevalence of prolapse symptoms or objectively measured pelvic organ prolapse also did not differ between the groups. In the short term the intervention motivated more women to perform pelvic floor muscle training (83 versus 55%), but this fell in both groups by 12 years (52 versus 49%). CONCLUSIONS: The moderate short-term benefits of a brief nurse-led conservative treatment for postnatal urinary incontinence did not persist. About four-fifths of women with urinary incontinence 3 months after childbirth still had this problem 12 years later.

Diffusion-weighted and multiphase contrast-enhanced MRI as surrogate markers of response to neoadjuvant sunitinib in metastatic renal cell carcinoma.

BACKGROUND: Current imaging criteria for categorising disease response in metastatic renal cell carcinoma (mRCC) correlate poorly with overall survival (OS) in patients on anti-angiogenic therapies. We prospectively assess diffusion-weighted and multiphase contrast-enhanced (MCE) MR imaging (MRI) as markers of outcome. METHODS: Treatment-naive mRCC patients on a phase II trial using sunitinib completed an MRI substudy. Whole-tumour apparent diffusion coefficient (ADC) maps and histograms were generated, and mean ADC and AUC(low) (proportion of the tumour with ADC values lying below the 25th percentile of the ADC histogram) recorded. On MCE-MRI, regions of interest were drawn around the most avidly enhancing components to analyse enhancement parameters. Baseline (n=26) and treatment-related changes in surviving patients (n=20) were correlated with OS. Imaged metastases were also analysed. RESULTS: Forty-seven per cent of the patients showed significant changes in whole-tumour mean ADC following therapy, but there was no correlation with outcome. Patients with a high baseline AUC(low) and greater-than-median AUC(low) increase had reduced OS (HR=3.67 (95% confidence interval (CI)=1.23-10.9), P=0.012 and HR=3.72 (95% CI=0.98-14.21), P=0.038, respectively). There was no correlation between MCE-MRI parameters and OS. Twenty-eight metastases were analysed and showed positive correlation with primary tumour mean ADC for individual patients (r=0.607; P<0.001). CONCLUSION: Primary RCC ADC histogram analysis shows dynamic changes with sunitinib. Patients in whom the tumour ADC histogram demonstrated high baseline AUC(low) or a greater-than-median increase in AUC(low) with treatment had reduced OS.

Surveillance results of depleted uranium-exposed Gulf War I veterans: sixteen years of follow-up.

As part of a longitudinal surveillance program, 35 members of a larger cohort of 77 Gulf War I veterans who were victims of depleted uranium (DU) "friendly fire" during combat underwent a 3-day clinical assessment at the Baltimore Veterans Administration Medical Center (VAMC). The assessment included a detailed medical history, exposure history, physical examination, and laboratory studies. Spot and 24-h urine collections were obtained for renal function parameters and for urine uranium (U) measures. Blood U measures were also performed. Urine U excretion was significantly associated with DU retained shrapnel burden (8.821 mug U/g creatinine [creat.] vs. 0.005 mug U/g creat., p = .04). Blood as a U sampling matrix revealed satisfactory results for measures of total U with a high correlation with urine U results (r = .84) when urine U concentrations were >/=0.1 mug/g creatinine. However, isotopic results in blood detected DU in only half of the subcohort who had isotopic signatures for DU detectable in urine. After stratifying the cohort based on urine U concentration, the high-U group showed a trend toward higher concentrations of urine beta(2) microglobulin compared to the low-U group (81.7 v. 69.0 mug/g creat.; p = .11 respectively) and retinol binding protein (48.1 vs. 31.0 mug/g creat.; p = .07 respectively). Bone metabolism parameters showed only subtle differences between groups. Sixteen years after first exposure, this cohort continues to excrete elevated concentrations of urine U as a function of DU shrapnel burden. Although subtle trends emerge in renal proximal tubular function and bone formation, the cohort exhibits few clinically significant U-related health effects.

Health surveillance of Gulf War I veterans exposed to depleted uranium: updating the cohort.

A cohort of seventy-four 1991 Gulf War soldiers with known exposure to depleted uranium (DU) resulting from their involvement in friendly-fire incidents with DU munitions is being followed by the Baltimore Veterans Affairs Medical Center. Biennial medical surveillance visits designed to identify uranium-related changes in health have been conducted since 1993. On-going systemic exposure to DU in veterans with embedded metal fragments is indicated by elevated urine uranium (U) excretion at concentrations up to 1,000-fold higher than that seen in the normal population. Health outcome results from the subcohort of this group of veterans attending the 2005 surveillance visit were examined based on two measures of U exposure. As in previous years, current U exposure is measured by determining urine U concentration at the time of their surveillance visit. A cumulative measure of U exposure was also calculated based on each veteran's past urine U concentrations since first exposure in 1991. Using either exposure metric, results continued to show no evidence of clinically significant DU-related health effects. Urine concentrations of retinol binding protein (RBP), a biomarker of renal proximal tubule function, were not significantly different between the low vs. high U groups based on either the current or cumulative exposure metric. Continued evidence of a weak genotoxic effect from the on-going DU exposure as measured at the HPRT (hypoxanthine-guanine phosphoribosyl transferase) locus and suggested by the fluorescent in-situ hybridization (FISH) results in peripheral blood recommends the need for continued surveillance of this population.

Laparoscopic colposuspension for urinary incontinence in women.

BACKGROUND: Laparoscopic colposuspension was one of the first minimal access operations for the treatment of women with stress urinary incontinence, with the presumed advantages over traditional Burch colposuspension of avoiding major incisions, shorter hospital stay, and quicker return to normal activities. A variety of approaches and methods are used. OBJECTIVES: To determine the effects of laparoscopic colposuspension for urinary incontinence. SEARCH STRATEGY: We searched the Cochrane Incontinence Group Specialised Trials Register (searched 21 September 2005). Additional trials were sought from other sources such as reference lists, reviews and researchers and authors were contacted for unpublished data and trials. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials in women with symptomatic or urodynamic diagnosis of stress or mixed incontinence that included laparoscopic surgery in at least one arm of the study. DATA COLLECTION AND ANALYSIS: Trials were evaluated for methodological quality and appropriateness for inclusion by the reviewers. Data were extracted by two of the reviewers and cross checked by another. Trial data were analysed by intervention. Where appropriate, a summary statistic was calculated. MAIN RESULTS: Twenty-one eligible trials were identified. Nine involved the comparison of laparoscopic with open colposuspension. Whilst the women's subjective impression of cure seemed similar for both procedures in the short and medium term follow-up, there was some evidence of poorer results of laparoscopic colposuspension, within 18 months, on objective outcomes. Two poor quality trials reported conflicting long term results (after five years) for this comparison. No significant differences were observed for post-operative urgency, voiding dysfunction or de novo detrusor overactivity. Trends were shown towards a lower perioperative complication rate, longer operating time, less intraoperative blood loss, less postoperative pain, shorter hospital stay, quicker return to normal activities, and shorter duration of catheterisation for laparoscopic compared with open colposuspension. Benefits did not come without a price, as laparoscopic colposuspension in the short term is more costly.Eight studies compared laparoscopic colposuspension with newer 'self-fixing' vaginal slings. Overall there were no significant differences in the reported subjective cure rates of the two procedures, however vaginal sling procedures did have significantly higher objective cure rates at 18 months. No significant differences were observed for post-operative voiding dysfunction, de novo detrusor activity and perioperative complications. Laparoscopic colposuspension has a significantly longer operation time, longer hospital stay and slower return to normal activities when compared to the sling procedures. Significantly higher subjective and objective (dry on 'ultrashort' pad test) one year cure rates were found for women randomised to two paravaginal sutures compared with one suture in a single trial (89% versus 65% and 83% versus 58% respectively). Two small studies compared sutures with mesh and staples for laparoscopic colposuspension and the comparisons, although showing a trend towards favouring the sutures, were not significant. One study compared transperitoneal with extraperitoneal access for laparoscopic colposuspension but it was also small and of poor quality. AUTHORS' CONCLUSIONS: The long-term performance of laparoscopic colposuspension remains uncertain. Currently available evidence suggests that it may be as good as open colposuspension at two years post surgery. Like other laparoscopically performed operations, patients having laparoscopic colposuspension recovered quicker, but the operation itself took longer to perform. However, the newer vaginal sling procedures appear to offer even greater benefits of minimal access surgery and better objective outcomes in the short-term. If laparoscopic colposuspension is performed, two paravaginal sutures appear to be more effective than one. The place of laparoscopic colposuspension in clinical practice should become clearer when ongoing trials are reported and when there are more data available describing long-term cure results.

New postnatal urinary incontinence: obstetric and other risk factors in primiparae.

OBJECTIVE: To identify obstetric and other risk factors for urinary incontinence that occurs during pregnancy or after childbirth. DESIGN: Questionnaire survey of women. SETTING: Maternity units in Aberdeen (Scotland), Birmingham (England) and Dunedin (New Zealand). POPULATION: A total of 3405 primiparous women with singleton births delivered during 1 year. METHODS: Questionnaire responses and obstetric case note data were analysed using multivariate analysis to identify associations with urinary incontinence. MAIN OUTCOME MEASURES: Urinary incontinence at 3 months after delivery first starting in pregnancy or after birth. RESULTS: The prevalence of urinary incontinence was 29%. New incontinence first beginning after delivery was associated with older maternal age (oldest versus youngest group, OR 2.02, 95% CI 1.35-3.02) and method of delivery (caesarean section versus spontaneous vaginal delivery, OR 0.28, 95% CI 0.19-0.41). There were no significant associations with forceps delivery (OR 1.18, 95% CI 0.92-1.51) or vacuum delivery (OR 1.16, 95% CI 0.83-1.63). Incontinence first occurring during pregnancy and still present at 3 months was associated with higher maternal body mass index (BMI>25, OR 1.68, 95% CI 1.16-2.43) and heavier babies (birthweight in top quartile, OR 1.56, 95% CI 1.12-2.19). In these women, caesarean section was associated with less incontinence (OR 0.39, 95% CI 0.27-0.58) but incontinence was not associated with age. CONCLUSIONS: Women have less urinary incontinence after a first delivery by caesarean section whether or not that first starts during pregnancy. Older maternal age was associated with new postnatal incontinence, and higher BMI and heavier babies with incontinence first starting during pregnancy. The effect of further deliveries may modify these findings.

Childbirth and pelvic floor trauma.

The issue of traumatic damage to the pelvic floor in childbirth is attracting more and more attention amongst obstetric caregivers and laypersons alike. This is partly due to the fact that elective caesarean section as a potentially preventative intervention is increasingly available and perceived as safe. As there is a multitude of emotive issues involved, including health economics and the relative roles of healthcare providers, the discussion surrounding pelvic floor trauma in childbirth has not always been completely rational. However, after 25 years of urogynaecological research in this field it should be possible to determine whether pelvic floor trauma in childbirth is myth or reality, and, if real, whether it matters for the pathogenesis of incontinence and prolapse. On reviewing the available evidence, it appears that there are sufficient grounds to assume that vaginal delivery (or even the attempt at vaginal delivery) can cause damage to the pudendal nerve, the inferior aspects of the levator ani muscle and fascial pelvic organ supports. Risk factors for such damage have been defined and variously include operative vaginal delivery, a long second stage, and macrosomia. It is much less clear, however, whether such trauma is clinically relevant, and how important it is in the aetiology of pelvic floor morbidity later in life.

Laparoscopic colposuspension versus urethropexy: a case-control series.

Laparoscopic colposuspension (LC) was first described in the early 1990s as a technique distinct from open Burch colposuspension. Subsequently, however, LC was closely modelled along the lines of the Burch technique, and the distinct features of the original urethropexy (UP) were largely disregarded. In this case-control series the authors aimed to compare symptoms and anatomical outcomes after standard LC and urethropexy +/- paravaginal repair. The design was a clinical retrospective case-control trial. The setting was the urogynaecology and endogynaecology services of tertiary hospitals. Fifty patients after LC and 50 women after UP surgery, matched for age, body mass index, previous surgery, pre-existing urge incontinence and length of follow-up (1.01 year, range 0.02-3.54 years) for LC and 0.98 years (range 0.06-3.55 years) for UP). Intervention consisted of standardised interview and translabial ultrasound imaging. There were no significant differences for subjective cure of stress incontinence (80% for UP vs. 74% for LC), postoperative urge incontinence, frequency and nocturia. Significantly more UP patients complained of voiding dysfunction (p=0.01). Significant differences were found for urethral rotation, position of the bladder neck on Valsalva and bladder neck descent on Valsalva (all p<0.001). Both procedures were shown to be effective in curing stress incontinence. The incidence of bladder symptoms was comparable, with the exception of voiding difficulty. Significant differences were observed regarding anatomical appearances, with urethropexies showing more recurrent bladder neck hypermobility and cystocele.

Age-dependent telomere attrition as a potential indicator of racial differences in renal growth patterns.

BACKGROUND: Racial differences in the predilection to salt sensitivity may arise from different renal growth patterns. To test this idea, we monitored age-dependent telomere attrition rate, reflecting largely the replicative history of somatic cells, in the outer renal cortex and the inner renal medulla of African Americans and Caucasians. METHODS: Telomere length, determined by the mean length of the terminal restriction fragments (TRF), was measured in specimens from 58 African-American and 63 Caucasian males, ages 1 day to 71 years. RESULTS: In the outer renal cortex, TRF length attrition rate was significantly slower in African Americans (-0.021 +/- 0.0064 kb/year) than in Caucasians (-0.060 +/- 0.0094 kb/year) (p = 0.0007). In both ethnic groups the TRF length attrition rate was slower in the inner medulla than in the outer renal cortex, but without significant racial differences. CONCLUSIONS: The proximal tubule is the most abundant nephron structure in the outer renal cortex. Less proliferative growth of proximal tubular cells in kidneys from African Americans may be one factor explaining the slower age-dependent telomere attrition rate in the outer renal cortex of African Americans than in Caucasians.

Modeling the rate of attachment of Listeria monocytogenes, Pantoea agglomerans, and Pseudomonas fluorescens to, and the probability of their detachment from, potato tissue at 10 degrees C.

The rate of attachment of bacteria to, and their subsequent detachment from, the cut surface of raw potato tissue was measured and modeled by using mathematical approaches that allowed detailed objective comparisons of adhesion processes under different conditions. Attachment was rapid and reached equilibrium after contact for 60 min. A new method to measure the probability of detachment was developed and modeled, revealing that the probability of detachment for Pseudomonas fluorescens remained unchanged for contact times between less than 5 s and 60 min. Listeria monocytogenes, however, was more easily removed initially, with the probability of detachment decreasing over the first 2 min of contact but remaining constant and equivalent to that for Pseudomonas fluorescens thereafter. For all of the bacteria tested, the number of bacteria attached after 2 min of contact was proportional to the inoculum concentration raised to the power of 0.79.

TVT and Sparc suburethral slings: a case-control series.

Two midurethral slings, TVT and Sparc, are the subject of this case-control series aimed at assessing sling placement, voiding function, bladder symptoms and patient satisfaction. Thirty-seven Sparc and 69 TVT patients were matched for age, body weight, pre-existing urge incontinence, preoperative voiding, concomitant surgery and length of follow-up (mean 0.6, range 0.1-1.5 years). There were no significant differences for subjective cure/improvement, satisfaction or symptoms of incontinence. The clinical stress test was positive in 8/37 Sparc vs 4/69 TVT patients ( p=0.019). The TVT had a more negative effect ( p=0.001) on postoperative voiding. The Sparc was situated more cranially at rest and further from the symphysis pubis, and was more mobile ( p<0.001) on Valsalva. There are significant differences in medium-term outcomes after TVT and Sparc, affecting tape placement, mobility, effect on voiding function and objective stress continence. Patient satisfaction and subjective cure rates seem similar.

The 'iris effect': how two-dimensional and three-dimensional ultrasound can help us understand anti-incontinence procedures.

OBJECTIVE: The objective of this prospective, observational study in patients after tension-free vaginal tape (TVT) implantation was to describe the spatial relationship between suburethral sling implants, urethra and bony pelvis with the help of translabial two-dimensional and three-dimensional (3D) ultrasound. METHODS: A total of 141 women were examined by translabial ultrasound, supine and after voiding. The TVT sling is highly echogenic and easily identified posterior to the urethra. Tape location was described in the mid-sagittal plane relative to bladder neck and inferoposterior symphyseal margin, at rest and on Valsalva maneuver. In a subset of 83 women, 3D volume ultrasound was performed. RESULTS: The cranial tape margin was situated on average 9.3 mm above and 16.5 mm posterior to the symphyseal margin (Valsalva: 3.9 mm below and 9.6 mm behind the symphysis); the average tape movement on Valsalva was 16 (range, 2-34.2) mm. The distance between tape and inferoposterior symphyseal margin narrowed highly significantly from 20.4 +/- 4.3 mm at rest to 12.9 +/- 3.9 mm on Valsalva (P < 0.001). When a fitted line plot was placed through tape coordinates on an x-y coordinate system, it became evident that tape movement occurs in an arc around the fulcrum of the posterior symphysis pubis. The result is an increasing reduction in the gap between tape and symphysis pubis (termed the 'iris effect'), implying mechanical compression of the urethra. CONCLUSIONS: The curative effect of the TVT on stress incontinence is likely to be due to mechanical compression of the urethra between implant and symphysis pubis. A large variation in tape location and movement explains its wide margin of clinical safety and efficacy.

Batch growth of Salmonella typhimurium LT2: stoichiometry and factors leading to cessation of growth.

Salmonella typhimurium LT2 was grown in batch culture (trypticase soy broth, with 0.3%(w/v) yeast extract, 1% (w/v) glucose and 0.5% (w/v/) NaCl, 20 degrees C) at a range of initial pH (4.4, 4.8, 5.0 and 7.0). The consumption of oxygen and glucose was found to be independent of initial pH, and stoichiometric with growth. Mean yield coefficients of 6.9 x 10(-15) and 15.5 x 10(-15) mol oxygen/cell were estimated. Calculation of the instantaneous state of carbon during the cultivation showed stoichiometric conversion of glucose into biomass, carbon dioxide and organic acids. The concentration of the undissociated form of the primary acidic product (acetic acid) was shown to be the factor limiting growth.

Salmonella enterica serovar Typhimurium and Listeria monocytogenes acid tolerance response induced by organic acids at 20 degrees C: optimization and modeling.

An acid tolerance response (ATR) has been demonstrated in Listeria monocytogenes and Salmonella enterica serovar Typhimurium in response to low pH poised (i.e., adapted) with acetic or lactic acids at 20 degrees C and modeled by using dynamic differential equations. The ATR was not immediate or prolonged, and optimization occurred after exposure of L. monocytogenes for 3 h at pH 5.5 poised with acetic acid and for 2 h at pH 5.5 poised with lactic acid and after exposure of S. enterica serovar Typhimurium for 2 h at pH 5.5 poised with acetic acid and for 3 h at pH 5.5 poised with lactic acid. An objective mechanistic analysis of the acid inactivation data yielded estimates of the duration of the shoulder (t(s)), the log-linear decline (k(max)), and the magnitude of a critical component (C). The magnitude of k(max) gave the best agreement with estimates of conditions for optimum ATR induction made from the raw data.

The day of discharge after total hip arthroplasty and the achievement of rehabilitation functional milestones: 11-year trends.

This is a report on 11 years (1990-2000) of total hip arthroplasty cases and days of discharge from one large city hospital. In 1990, patients stayed an average of 9.7 days after surgery. By 2000, patients stayed only 5.3 days. In general, women stayed longer than men, but this gap had nearly disappeared by 2000. The patients discharged in 2000 achieved fewer functional milestones during their hospital stay than those discharged in 1990.

Modelling microbial growth in structured foods: towards a unified approach.

Historically, the ability of foods to support the growth of spoilage organisms and food-borne pathogens has been assessed by inoculating a food with an organism of interest, and following its growth over a period of time. Information gained from such challenge tests, together with knowledge of the organoleptic stability of the product, can then be used to determine an appropriate shelf-life for the food. Whilst this approach may be seen as the "gold-standard" of microbiological assessment of food, it is both time-consuming and costly. A major advance to complement challenge testing was the development of predictive modelling, when it was demonstrated that the growth of a wide range of organisms of interest could be quite accurately modelled as a function of only a few environmental parameters-primarily temperature, pH and water activity (a(w)), with perhaps other factors such as nitrite, organic acids and oxygen. This approach to predictive microbiology is embodied in software tools such as the UK Food MicroModel and the Pathogen Modeling Program from the USA. Whilst modelling of this form yields accurate predictions of the growth of organisms in the majority of foods, there are occasions when there are discrepancies between the model and the observed growth. These discrepancies are most often described as "fail-safe", i.e. the observed growth is slower than predicted by the model. This paper examines the role of food structure in the development of microbial populations and communities, and describes the methodologies we propose to begin to tackle some of these complex and interlinked issues.