Obesity and Native Tissue Repairs: A Secondary Analysis of the OPTIMAL Trial.

IMPORTANCE: The Operations and Pelvic Muscle Training in the Management of Apical Support Loss (OPTIMAL) Trial compared sacrospinous ligament fixation (SSLF) and uterosacral ligament suspension (ULS) surgical outcomes. Increasing body mass index (BMI) is associated with an increased risk of pelvic organ prolapse, and the prevalence of obesity is increasing worldwide. OBJECTIVE: The purpose of this study was to better understand the effect of obesity on the results of native tissue vaginal apical suspension procedures. STUDY DESIGN: This was a secondary analysis of the OPTIMAL Trial data set. Subgroup analysis was performed to compare surgical failure rates between SSLF and ULS across BMI subgroups after 2 years. RESULTS: There were 75, 120, 63, and 39 patients in the normal, overweight, class 1 obesity, and class 2 obesity or greater BMI subgroups, respectively. There were no statistically significant differences in surgical failure rates between SSLF and ULS within BMI subgroups; however, failure rates increased in the ULS group between the nonobese and obese groups (normal, 35.9% SSLF vs 30.6% ULS [P = 0.81]; overweight, 38.6% vs 30.2% [P = 0.44]; class 1 obesity, 38.7% vs 40.6% [P = 0.92]; class 2 obesity or greater, 21.1% vs 45% [P = 0.21]). CONCLUSIONS: The risk of surgical failure between SSLF and ULS was not significant across BMI subgroups. Additional investigation is required to further elucidate whether SSLF or ULS is a more reliable option for obese patients.

The ELFIN Mission.

The Electron Loss and Fields Investigation with a Spatio-Temporal Ambiguity-Resolving option (ELFIN-STAR, or heretoforth simply: ELFIN) mission comprises two identical 3-Unit (3U) CubeSats on a polar (∼93∘ inclination), nearly circular, low-Earth (∼450 km altitude) orbit. Launched on September 15, 2018, ELFIN is expected to have a >2.5 year lifetime. Its primary science objective is to resolve the mechanism of storm-time relativistic electron precipitation, for which electromagnetic ion cyclotron (EMIC) waves are a prime candidate. From its ionospheric vantage point, ELFIN uses its unique pitch-angle-resolving capability to determine whether measured relativistic electron pitch-angle and energy spectra within the loss cone bear the characteristic signatures of scattering by EMIC waves or whether such scattering may be due to other processes. Pairing identical ELFIN satellites with slowly-variable along-track separation allows disambiguation of spatial and temporal evolution of the precipitation over minutes-to-tens-of-minutes timescales, faster than the orbit period of a single low-altitude satellite (Torbit ∼ 90 min). Each satellite carries an energetic particle detector for electrons (EPDE) that measures 50 keV to 5 MeV electrons with Δ E/E < 40% and a fluxgate magnetometer (FGM) on a ∼72 cm boom that measures magnetic field waves (e.g., EMIC waves) in the range from DC to 5 Hz Nyquist (nominally) with <0.3 nT/sqrt(Hz) noise at 1 Hz. The spinning satellites (Tspin ∼ 3 s) are equipped with magnetorquers (air coils) that permit spin-up or -down and reorientation maneuvers. Using those, the spin axis is placed normal to the orbit plane (nominally), allowing full pitch-angle resolution twice per spin. An energetic particle detector for ions (EPDI) measures 250 keV - 5 MeV ions, addressing secondary science. Funded initially by CalSpace and the University Nanosat Program, ELFIN was selected for flight with joint support from NSF and NASA between 2014 and 2018 and launched by the ELaNa XVIII program on a Delta II rocket (with IceSatII as the primary). Mission operations are currently funded by NASA. Working under experienced UCLA mentors, with advice from The Aerospace Corporation and NASA personnel, more than 250 undergraduates have matured the ELFIN implementation strategy; developed the instruments, satellite, and ground systems and operate the two satellites. ELFIN's already high potential for cutting-edge science return is compounded by concurrent equatorial Heliophysics missions (THEMIS, Arase, Van Allen Probes, MMS) and ground stations. ELFIN's integrated data analysis approach, rapid dissemination strategies via the SPace Environment Data Analysis System (SPEDAS), and data coordination with the Heliophysics/Geospace System Observatory (H/GSO) optimize science yield, enabling the widest community benefits. Several storm-time events have already been captured and are presented herein to demonstrate ELFIN's data analysis methods and potential. These form the basis of on-going studies to resolve the primary mission science objective. Broad energy precipitation events, precipitation bands, and microbursts, clearly seen both at dawn and dusk, extend from tens of keV to >1 MeV. This broad energy range of precipitation indicates that multiple waves are providing scattering concurrently. Many observed events show significant backscattered fluxes, which in the past were hard to resolve by equatorial spacecraft or non-pitch-angle-resolving ionospheric missions. These observations suggest that the ionosphere plays a significant role in modifying magnetospheric electron fluxes and wave-particle interactions. Routine data captures starting in February 2020 and lasting for at least another year, approximately the remainder of the mission lifetime, are expected to provide a very rich dataset to address questions even beyond the primary mission science objective.

Medication effects on periurethral sensation and urethral sphincter activity.

AIM: The aim of this study was to characterize urethral neuromuscular function before and 2 weeks after medication therapy. METHODS: Premenopausal women without lower urinary tract symptoms were randomly allocated to 1 of the 6 medications for 2 weeks (pseudoephedrine ER of 120 mg, imipramine of 25 mg, cyclobenzaprine of 10 mg, tamsulosin of 0.4 mg, solifenacin of 5 mg, or placebo). At baseline and after medication, participants underwent testing: quantitative concentric needle electromyography (CNE) of the urethral sphincter using automated multimotor unit action potential software, current perception threshold (CPT) testing to measure periurethral sensation, and standard urodynamic pressure flow studies (PFS). Nonparametric tests were used to compare pre-post differences. RESULTS: Fifty-six women had baseline testing, 48 (85.7%) completed follow-up CNE, and 49 (87.5%) completed follow-up CPT and PFS testing. Demographics showed no significant differences among medication groups with respect to age (mean, 34.3; SD, 10.1), body mass index (mean, 31.8; SD, 7.5), parity (median, 1; range, 0-7), or race (14% Caucasian, 80% African American). The PFS parameters were not significantly different within medication groups. No significant pre-post changes in CNE values were noted; however, trends in amplitudes were in a direction consistent with the expected physiologic effect of the medications. With CPT testing, a trend toward increased urethral sensation at the 5-Hz stimulation level was observed after treatment with pseudoephedrine (0.15-0.09 mA at 5 Hz, P = 0.03). CONCLUSIONS: In women without lower urinary tract symptoms, pseudoephedrine improved urethral sensation but not urethral neuromuscular function on CNE or PFS. Imipramine, cyclobenzaprine, tamsulosin, solifenacin, and placebo did not change urethral sensation or neuromuscular function.

Findings of universal cystoscopy at incontinence surgery and their sequelae.

OBJECTIVE: The purpose of this study was to report the frequency of abnormal cystoscopy at incontinence surgery and to identify risk factors and sequelae of injury. STUDY DESIGN: Findings of cystoscopy were collected prospectively in 3 multicenter surgical trials. Clinical, demographic, and procedure characteristics and surgeon experience were analyzed for association with iatrogenic injury and noninjury abnormalities. Impact of abnormalities on continence outcomes and adverse events during 12 months after the procedure were assessed. RESULTS: Abnormal findings in the bladder or urethra were identified in 95 of 1830 women (5.2%). Most injuries (75.8%) were iatrogenic. Lower urinary tract (LUT) injury was most common at retropubic urethropexy and retropubic midurethral sling (MUS) procedures (6.4% each), followed by autologous pubovaginal sling procedures (1.7%) and transobturator MUS (0.4%). Increasing age (56.9 vs 51.9 years; P = .04), vaginal deliveries (3.2 vs 2.6; P = .04), and blood loss (393 vs 218 mL; P = .01) were associated with LUT injury during retropubic urethropexy; however, only age (62.9 vs 51.4 years; P = .02) and smoking history (P = .04) were associated for pubovaginal sling procedures. No factors correlated with increased risk of injury at retropubic and transobturator MUS. Notably, previous incontinence surgery, concomitant procedures, anesthesia type, and trainee participation did not increase LUT injury frequency. Although discharge with an indwelling catheter was more common after trocar perforation compared with the noninjury group (55.6% vs 18.5%; P < .001), they did not differ in overall success, voiding dysfunction, recurrent urinary tract infections, or urge urinary incontinence. CONCLUSION: Universal cystoscopy at incontinence surgery detects abnormalities in 1 in 20 women. Urinary trocar perforations that are addressed intraoperatively have no long-term adverse sequelae.

Technical and operational users' opinions of a handheld device to detect directed energy.

INTRODUCTION: Lasers, a form of directed energy (DE), are a threat to pilots and Air Force personnel. In light of this threat, a handheld medical device called the "Tricorder" is under development to improve situational awareness of DE. Current operational procedures do not include methods for recording or handling new information regarding DE. The purpose of this study was to understand Air Force personnel opinions and beliefs about desired features and operational use to enhance user acceptance of the Tricorder. METHOD: Q-methodology was implemented to study opinions and beliefs related to DE. Two groups were approached, medical personnel in the Illinois Air National Guard and four active duty members of an Air Force Rescue Squadron. Both groups completed the same Q-sort of both operational and equipment concerns. RESULTS: Six opinion sets regarding operational concerns described 61% of the total variation in perceptions among participants. The factors were: concern over health effects, implications to individuals, combat/tactical concerns, force health protection, and theater/tactical concerns. Five opinion sets described 68% of the variation in the equipment functions perceived as most important. The participants indicated that ideally the device should measure exposure, enhance laser detection/response, support night vision and ease of use, detect threats, and enhance combat medicine. CONCLUSION: This survey revealed the complexity of equipment and the operational implications of detecting DE. Q-methodology is a unique strategy to both evaluate technology and explore users' concerns.

Sacral neuromodulation effects on periurethral sensation and urethral sphincter activity.

AIMS: To characterize the effect of sacral neuromodulation (SNM) on urethral neuromuscular function. METHODS: Following IRB approval, women with refractory overactive bladder (OAB) underwent standardized urethral testing prior to and after Stage 1 SNM implantation. Periurethral sensation was measured using current perception thresholds (CPT). Striated urethral sphincter activity was quantified using concentric needle electromyography (CNE) and Multi-Motor Unit Action Potential (MUP) analysis software. Nonparametric analyses were used to characterize pre/post changes with intervention. Baseline CPT and CNE findings were compared between SNM responders and non-responders. RESULTS: Twenty-seven women were enrolled in this pilot study with a mean age of 61 ± 13 years. Twenty of 26 women (76.9%) responded to SNM and went to Stage 2 permanent implantation. Four (14.8%) withdrew after Stage 1 implantation; three of the four withdrawals had not had therapeutic responses to SNM. CPT and CNE parameters did not significantly differ from baseline 2 weeks after SNM. Pre-SNM urethral sensation was not significantly different between responders and non-responders. However, responders had larger amplitude, longer duration and more turns and phases at baseline approaching significance, reflecting more successful urethral reinnervation, than non-responders. CONCLUSIONS: SNM does not alter urethral neuromuscular function 2 weeks post Stage 1 implantation.

Validation of the surgical pain scales in women undergoing pelvic reconstructive surgery.

OBJECTIVE: Surgical pain scales (SPS) consist of 4 items that measure pain at rest, during normal activities, and during work/exercise and quantify unpleasantness of worst pain, which are valid and responsive in men undergoing hernia repair. Our objective was to evaluate the psychometric properties of SPS in women undergoing vaginal surgery for pelvic organ prolapse and stress urinary incontinence. METHODS: We modified SPS by converting original response scales from a visual analog scale to numerical rating scales. Numerical rating scales have lower error rates and higher validity than visual analog scale. The sample included 169 women with stage II to IV pelvic organ prolapse and stress urinary incontinence in a randomized trial comparing sacrospinous ligament fixation to uterosacral vault suspension with and without pelvic floor muscle training. Participants completed SPS and SF-36 at baseline, and 2 weeks and 6 months after surgery. Construct validity and responsiveness were examined in cross-sectional and longitudinal data using Pearson correlation and analysis of variance. RESULTS: Pain at rest, during normal activities, and during work/exercise worsened at 2 weeks (P<0.05); and all measures of pain improved from baseline to 6 months (P<0.0001). Construct validity was demonstrated by correlations of 0.51 to 0.74 between SPS and the SF-36 Bodily Pain Scale (P<0.0001). Pain worsened on SF-36 between baseline and 2 weeks in 63% of the participants, and this group demonstrated a mean (SD) increase in pain of 1.9 (2.8) on the SPS (effect size, 0.99), confirming responsiveness of the scale. CONCLUSIONS: The modified SPS are valid and responsive in women after pelvic reconstructive surgery.

Validation of the activities assessment scale in women undergoing pelvic reconstructive surgery.

OBJECTIVE: The Activities Assessment Scale (AAS) is a 13-item postoperative functional activity scale validated in men who underwent hernia surgery. We evaluated the psychometric characteristics of the AAS in women who underwent vaginal surgery for pelvic organ prolapse (POP) and stress urinary incontinence (SUI). METHODS: Participants included 163 women with POP and SUI enrolled in a randomized trial comparing sacrospinous ligament fixation to uterosacral vault suspension with and without perioperative pelvic floor muscle training. Participants completed the AAS and SF-36 at baseline and 2 weeks and 6 months postoperatively. Internal reliability of the AAS was evaluated using Cronbach α. Construct validity and responsiveness were examined in cross-sectional and longitudinal data using Pearson correlation coefficient and analysis of variance. The AAS is scored from zero to 100 (higher scores=better function). RESULTS: Mean (SD) baseline AAS score was 87 (17.3) (range, 25-100). Functional activity declined from baseline to 2 weeks postoperatively (mean change, -4.5; 95% confidence interval, -7.6 to -1.42) but improved above baseline at 6 months (mean change, +10.9; 95% confidence interval, 7.8-14.0). Internal reliability of the AAS was excellent (Cronbach α=0.93). Construct validity was demonstrated by a correlation of 0.59 to 0.60 between the AAS and SF-36 physical functioning scale (P<0.0001) and lower correlations between the AAS and other SF-36 scales. Patients who improved in physical functioning based on the SF-36 between 2 weeks and 6 months postoperatively showed an effect size of 0.86 for change in the AAS over the same period. CONCLUSIONS: The AAS is a valid, reliable, and responsive measure for evaluation of physical function in women after pelvic reconstructive surgery.

Qualitative assessment of the emotional and behavioural responses of haemophilia A carriers to negative experiences in their medical care.

Previous discussions with haemophilia A (HA) carriers suggested that carriers may experience inappropriate care, resulting in poor relationships with healthcare providers (HCPs; principally physicians and nurses), and unfortunate and extreme emotional and behavioural responses. This was a qualitative study to explore medical experiences of HA carriers and their emotional and behavioural responses. Eleven HA carriers and five Haemophilia Treatment Centre nurses were interviewed. Themes were identified using QSR NVivo 8.0. Carriers and nurses reported HA-related bleeding symptoms in carriers, including life-threatening haemorrhage following injury or medical intervention. Menorrhagia was common and distressing. Negative carrier experiences were related in the determination of genotypic and phenotypic status, management, precautions and HCP attitude, including dismissing carriers' symptoms, concerns or requests for care. Carriers responded with mistrust, lost confidence, disappointment, fear, anxiety, doubt of self or child, discussing experiences, avoidance of healthcare and self-treatment. Dismissive HCP attitudes, ignorance about bleeding disorders in women and unique aspects of the carrier population appear to make errors more likely. This study indicates that carriers experience inappropriate care and encounter dismissive attitudes, and respond emotionally and behaviourally. Our model suggests that systematic medical errors aggravate a negative feedback loop leading to negative emotional and behavioural responses and worsening carrier care. Improved carrier care policies and increased awareness of women's bleeding disorders may improve this situation. Further research is needed to determine whether the themes identified in this study accurately reflect the experiences of carriers in general.

KRAS mutation testing in the treatment of metastatic colorectal cancer with anti-EGFR therapies.

Survival of patients with metastatic CRC (mCRC) has improved steadily over the past several decades, due largely to the development of new combinations of standard chemotherapy, as well as to the introduction of new targeted therapies. Among the available targeted therapies are two monoclonal antibodies that target the epidermal growth factor receptor (EGFR) - cetuximab and panitumumab - which have demonstrated efficacy in the treatment of mCRC. These therapies are associated with a unique set of toxicities and costs, prompting the need for tools to select patients who are most likely to derive a benefit from them. Mutations in the KRAS oncogene have consistently been shown to predict non-response to cetuximab and panitumumab. The role of KRAS as a marker of efficacy of anti-EGFR therapies is reviewed.

Factors impacting quality of life in women with fecal incontinence.

PURPOSE: The aim of this study was to characterize differences in health-related quality of life among women presenting for treatment of fecal incontinence. METHODS: Among 155 women presenting for treatment of fecal incontinence in a specialty clinic, validated questionnaires measured impact on quality of life (Modified Manchester Health Questionnaire) and severity (the Fecal Incontinence Severity Index). Bowel symptoms, including frequency, urgency, and stool consistency, were ascertained. Comorbid diseases were self-reported. Linear regression models were constructed from significant univariate variables to examine differences observed in quality of life scores. RESULTS: The average age was 58.7 +/- 11.5 years, with no differences found in quality of life scores according to race, body mass index, or number of vaginal deliveries (P > .05). Younger age, increased urinary incontinence symptoms, prior cholecystectomy, prior hysterectomy, and severity of bowel symptoms correlated with a negative impact on quality of life in univariate analysis (P < .05). Average severity scores were 30.5 +/- 13.7, with moderate correlation seen with increasing severity and quality of life scores (R2 = 0.60). After controlling for severity, women had increased quality of life scores with more bowel urgency (15 points; 95% CI, 8.1-21.2), harder stool consistency (10 points; 95% CI, 3.8-16.3), and prior hysterectomy (9 points; 95% CI, 2.7-15.4). CONCLUSION: Bowel symptoms and having undergone a hysterectomy had the greatest negative impact on quality of life in women seeking treatment for fecal incontinence. Targeting individualized treatments to improve bowel symptoms may improve quality of life for women with fecal incontinence.

Testing and validation of a low-cost cystoscopy teaching model: a randomized controlled trial.

OBJECTIVE: To estimate whether the use of a low-cost cystoscopy model effectively trains residents in cystourethroscopy and to validate the model as a teaching tool. METHODS: A randomized, controlled, and evaluator-blinded study was performed. Twenty-nine obstetrician-gynecologist residents had access to fresh-frozen cadavers on which baseline cystoscopic skills were assessed using the validated Objective Structured Assessment of Technical Skills checklists for cystourethroscopy. Subsequently, residents were randomized to one of two arms, a didactic study arm using the cystoscopy model and a control arm. Repeated technical skills testing was performed. RESULTS: The study group demonstrated statistically significant decreases in cystoscope assembly time (128.8 seconds at baseline to 54.9 seconds postintervention; P=.005), and increases in task-specific checklist scores (from 59.3 at baseline to 92.9 postintervention; P<.001) and in global rating scale scores (from 61.0 at baseline to 87.8 postintervention; P<.001). Further, there was a significant improvement in task-specific checklist (P<.001), global rating scale (P=.002), and knowledge quiz scores (P=.011) in the study arm compared with the control arm. CONCLUSION: Use of the bladder model exhibited validity in enhancing performance and knowledge of cystourethroscopy among ob-gyn residents. LEVEL OF EVIDENCE: I.

Fondaparinux therapy in a hemodialysis patient with heparin-induced thrombocytopenia type II.

PURPOSE: The successful use of fondaparinux in a hemodialysis patient with heparin-induced thrombocytopenia type II (HIT II) is reported. SUMMARY: An 85-year-old, 68-kg Caucasian woman came to the emergency department with shortness of breath and exertional chest pain radiating to the neck. Testing revealed non-ST-segment elevation myocardial infarction, severe coronary artery disease, mitral regurgitation, left ventricular dysfunction, an ejection fraction of 25-30%, and pulmonary arterial hypertension. I.V. unfractionated heparin was given for therapeutic anticoagulation per hospital protocol and discontinued on hospital day 3 before mitral valve repair and coronary bypass procedure. Postoperatively unfractionated heparin and low-molecular-weight heparin were avoided because of a reduction in the platelet count and suspicion of HIT. Instead, the patient was placed on sequential compression devices in addition to aspirin for prophylaxis of deep venous thrombosis. By postoperative day 6, the patient's platelet count dropped 76% from baseline, and the patient was found to have heparin-dependent platelet factor 4 antibodies. Argatroban infusion was initiated but discontinued after 2 days due to bleeding. Fondaparinux was ordered for anticoagulation therapy. By hospital day 8, the patient developed renal insufficiency requiring hemodialysis and adjustment of the fondaparinux regimen. During the 30-day course of fondaparinux, the patient did not experience thromboembolic events or bleeding and did not require transfusions. There was no clotting within hemodialysis membranes, and her hepatic function improved by the time of her discharge. CONCLUSION: Fondaparinux was used in a hemodialysis patient with HIT II without the development of thromboembolic, hemodialysis-clotting, thrombocytopenic, or hemorrhagic complications. The patient's platelet count remained in the normal range during the 30-day course of fondaparinux.

Long-Term Outcomes of the Total or Supracervical Hysterectomy (TOSH) Trial.

BACKGROUND: Participants in the multi-center, randomized Total or Supracervical Hysterectomy (TOSH) trial showed within-group improvement in pelvic floor symptoms 2 years post-surgery and no differences between supracervical (SCH) versus total hysterectomy (TAH). This study describes longer term outcomes from the largest recruiting site. STUDY DESIGN: Questionnaires addressing pelvic symptoms, sexual function, and health-related quality of life were administered. Linear models and McNemar's test were utilized. RESULTS: Thirty-seven participants (69%) responded (19 TAH, 18 SCH); mean follow up was 9.1±0.7 years. No between-group differences emerged in urinary incontinence, voiding dysfunction, pelvic prolapse symptoms and overall health related quality of life (HRQOL). Within-group analysis showed significant improvement in the ability to have and enjoy sex (P = 0.002) and in the SF-36 physical component summary score (P = 0.03) among women randomized to TAH. CONCLUSION: 9 years after surgery, TOSH participants continue to experience improvement and show no major between-group differences in lower urinary tract or pelvic floor symptoms conferring no major benefit of SCH over TAH.

Securing ePHI--can clinicians and IT ever agree?

The Health Insurance Portability and Accountability Act (HIPAA) affects patients, IT professionals and providers. Implementation requires cooperation among clinical and staff, presuming an equal understanding of the law and its implementation. Two Q-sort sessions with different Conditions of Instruction (COI) were attended by each study participant: one COI focused on a personal perspective about the effectiveness of security standards in preventing or mitigating security problems with EPHI. The second COI examined the participant's perception of how a co-worker would see aspects of security problems. The first Q-sort resulted in four distinct factors, two of which, administratively minded and patient centric, suggest divergence in opinion. The second sort's results reveal the inability of participants to forecast what their co-workers will perceive as salient to a security situation. Results suggest that people might adapt to changes required by security applications if the changes in workflow are described in role-based situations.

Obesity and pelvic floor disorders: a systematic review.

OBJECTIVE: To review the current literature and summarize the effect of obesity on outcomes of surgical treatment of pelvic floor disorders as well as the effect of weight loss on pelvic floor disorder symptoms. DATA SOURCES: Relevant sources were identified by a MEDLINE search from 1966 to 2007 using the key words obesity, pelvic floor disorders, urinary incontinence (UI), fecal incontinence, and pelvic organ prolapse (POP). References of relevant studies were hand searched. METHODS OF STUDY SELECTION: Relevant human observational studies, randomized trials, and review articles were included. A total of 246 articles were identified; 20 were used in reporting and analyzing the data. Meta-analyses were performed for topics meeting the appropriate criteria. TABULATION, INTEGRATION, AND RESULTS: There is good evidence that surgery for stress UI in obese women is as safe as in their nonobese counterparts, but cure rates may be lower in the obese patient. Meta-analysis revealed cure rates of 81% and 85% for the obese and nonobese groups, respectively (P<.001; odds ratio [OR] 0.576, 95% confidence interval [CI] 0.426-0.779). Combined bladder perforation rates were 1.2% in the obese and 6.6% in the nonobese (P=.015; OR 0.277, 95% CI 0.098-0.782). There is little evidence on which to base clinical decisions regarding the treatment of fecal incontinence and POP in obese women, because few comparative studies were identified addressing the outcomes of prolapse surgery in obese patients compared with healthy-weight patients. Weight loss studies indicate that both bariatric and nonsurgical weight loss lead to significant improvements in pelvic floor disorder symptoms. CONCLUSION: Surgery for UI in obese women is safe, but more trials are needed to evaluate its long-term effectiveness as well as treatments for both fecal incontinence and POP. Weight loss, both surgical and nonsurgical, should be considered in the treatment of pelvic floor disorders in the obese woman.

Familial essential thrombocythemia with spontaneous megakaryocyte colony formation and acquired JAK2 mutations.

Essential thrombocythemia (ET) is a chronic myeloproliferative disorder, characterized by increased proliferation of megakaryocytes and elevated platelet count that usually occurs sporadically. We report a family with seven affected individuals in three generations, including one individual with a phenotype resembling polycythemia vera, a related disorder. Megakaryocyte (CFU-MK) colony formation occurred in the absence of added cytokines in cultures of peripheral blood from affected family members. Some reports of familial ET have identified mutations in THPO and MPL, the genes for a cytokine (thrombopoietin, TPO) that regulates platelet production and its receptor (c-MPL), respectively. In this family, the MPL gene was excluded by linkage analysis. Although TPO levels were elevated in most affected family members and evidence for linkage was found between the disease and THPO (theta=0.0, Z(max)=3.0), a THPO mutation was not identified by DNA sequencing. The JAK2 V617F mutation that has been associated with 50% of sporadic cases of ET was identified as a somatic mutation, an acquired defect, in peripheral blood of the two most severely affected family members. These patients also had elevated TPO levels. Further study of familial myeloproliferative diseases will help elucidate the initiating genetic events underlying ET.

Predictors of success with postoperative voiding trials after a mid urethral sling procedure.

PURPOSE: We identified predictors of passing a voiding trial after incontinence surgery with a mid urethral sling and examined if successful performance on a voiding trial was maintained. MATERIALS AND METHODS: A total of 89 women scheduled for incontinence surgery were enrolled from July 2005 until April 2006. Voiding trials were performed the day of discharge from the hospital, with a two-thirds volume void after a 300 ml fill considered passing. Those who passed underwent a second voiding trial 3 hours later. RESULTS: Of the participants 60 (67.4%) underwent tension-free vaginal tape surgery, 29 underwent transobturator tape (32.6%) and 64 (71.9%) underwent concurrent vaginal repairs. A total of 59 (67.0%) participants passed the first voiding trial. Univariate analysis identified 12 potential predicting variables for passing the first voiding trial. From these 12, model building via backward stepwise logistic regression found maximum flow on preoperative uroflowmetry to be the only significant predictive variable (p = 0.0002). Of the 59 women who passed the initial voiding trial 9 (16.4%) failed the second voiding trial. None of the 11 participants who had maximal flow rates greater than 30 cc per second failed the first or second voiding trial, whereas 17 of 22 subjects (77.3%) who had maximal flow rates less than 15 cc per second failed either of these trials. CONCLUSIONS: Maximum flow rates on preoperative uroflowmetry were the best predictor of passing an initial voiding trial after undergoing a mid urethral sling procedure for incontinence. However, the ability to maintain performance on a second voiding trial, even only 3 hours after passing an initial trial, is not assured.

MDR1 C3435T polymorphisms correlate with cyclosporine levels in de novo renal recipients.

BACKGROUND: Single nucleotide polymorphisms (SNPs) in the multidrug resistance (MDR1) gene correlate with the intestinal function of P-glycoprotein (PGP). PGP serves as a hydrophobic export pump that extrudes cyclosporine (CsA) across the luminal membrane thus preventing CsA absorption. These genetic variants may predict CsA exposure levels in the early posttransplantation period. METHODS: CsA absorption profiles were established in 75 renal transplant patients using total daily dose and body weight adjusted 4-hour area under the time-concentration curve, AUC(0-4)/mg dose/kg body weight, on posttransplant day 3. These patients were subsequently genotyped for C3435T and G2677T polymorphisms using real-time polymerase chain reaction. An analysis was conducted to assess the independent impact of C3435T and G2677T SNPs on CsA bioavailability. RESULTS: C3435T polymorphisms were found to be an independent predictor of CsA AUC(0-4)/mg dose/kg levels on postoperative day 3. An inverse correlation was found between the number of T alleles and AUC values such that every T allele was associated with an approximate 15% decrement in AUC(0-4)/mg dose/kg (P = .034). A similar nonsignificant trend was observed for G2677T polymorphisms. CONCLUSIONS: MDR1 SNPs are correlated with CsA exposure in the early post-transplant period. Polymorphisms, in conjunction with other criteria, may become a useful tool to optimize initial drug dosing in renal transplantation.

Geographical distribution of congenital heart defects in Saudi Arabia.

BACKGROUND: Congenital heart defects (CHD), which are caused by abnormalities early in fetal life, encompass over 50 diagnoses. Since the detailed etiology is unknown, the geographical distribution of defects might suggest likely risk factors. METHODS: The geographical distribution of 5 865 Saudi Arabian nationals with CHD was studied by cross-matching their residential provinces and towns with a geographical information system provided by the General Directorate for Military Survey. Population data were obtained from the 1413H census. RESULTS: CHD cases were mostly distributed across the provinces in proportion to their total population but due to their size and inhomogeneity, province-based thematic maps were found to be misleading. City-based maps were preferable and showed similar geographic distributions for cases registered in successive years. Thematic maps of the distribution of the CHD burden highlighted the southwestern provinces, nearthe border with Yemen, and the northeast section of the Eastern Province. CONCLUSIONS: Patterns of disease in Saudi Arabia are best studied at the level of individual towns and villages. The CHD registry has already attained good national coverage and can therefore support nationwide epidemiological studies. Southwestern Saudi Arabia and the northern part of the Eastern Province appear to exhibit a higher burden of CHD.