Characterizing persistent urinary incontinence after successful fistula closure: the Uganda experience.

BACKGROUND: Obstetric fistula is a devastating childbirth injury. Despite successful closure of the fistula, 16% to 55% of women suffer from persistent urinary incontinence after surgery. OBJECTIVE: This study assessed the type and severity of persistent incontinence after successful fistula closure and its impact on the quality of life of Ugandan women post-fistula treatment. STUDY DESIGN: This cross-sectional study enrolled women with a history of obstetric fistula repair who continued to have persistent urinary incontinence (cases, N=36) and women without incontinence (controls, N=52) after successful fistula closure. Data were collected in central and eastern Uganda between 2017 and 2019. All the participants completed a semistructured questionnaire. Cases underwent a clinical evaluation and a 2-hour pad test and completed a series of incontinence questionnaires, including two novel tools designed to assess the severity of incontinence in low-literacy populations. RESULTS: Cases were more likely to have acquired a fistula during their first delivery (63% vs 37%, P=.02), were younger when they developed a fistula (20.3±5.8 vs 24.8±7.5 years old, P=.003), and were more likely to have had >2 fistula surgeries (67% vs 2%, P≤.001). Cases reported a much higher rate of planned home birth for their index pregnancy compared to controls (44% vs 11%), though only 14% of cases and 12% of controls actually delivered at home. Cases reported higher rates of pain with intercourse (36% vs 18%, P=.05), but recent sexual activity status (intercourse within the previous six months) was not significantly different between the groups (47% vs 62%, P=.18). Among cases, 67% reported stress incontinence, 47% reported urgency incontinence, and 47% reported mixed incontinence. The cough stress test was successfully done with 92% of the cases, and of these, almost all (97%) had a positive cough stress test. More than half (53%) rated their incontinence as "very severe," which was consistent with objective findings. The 24-hour voiding diary indicated both high urinary frequency (average 14) and very frequent leakage episodes (average 20). Two-hour pad-tests indicated that 86% of cases had >4 g change in pad weight within 2 hours. Women with more severe incontinence reported a more negative impact on their quality of life. The mean score of the International Consultation on Incontinence Questionnaire-Quality of Life was 62.77±12.76 (range, 28-76, median=67), with a higher score indicating a greater impact on the quality of life. There was also a high mental health burden, with both cases and controls reporting high rates of suicidal ideation at any point since developing fistula (36% vs 31%, P=.67). CONCLUSION: Women with obstetric fistulas continue to suffer from severe persistent urinary incontinence even after successful fistula closure. Both stress and urgency incontinence are highly prevalent in this population. Worsening severity of incontinence is associated with a greater negative impact on the quality of life.

The Sims position and the Sims vaginal speculum, re-examined.

INTRODUCTION AND HYPOTHESIS: American gynecologist J. Marion Sims (1813-1883) is known for developing the first consistently successful operation for the repair of vesico-vaginal fistula, for inventing the Sims vaginal speculum, and for popularizing the left lateral decubitus position for gynecological examination and treatment. METHODS AND RESULTS: This article reviews the history of the Sims vaginal speculum, charting its evolution from a bent pewter spoon to the lever speculum and finally to its now-familiar form as the two-bladed Sims speculum. CONCLUSION: The article also reviews the origins of the Sims position, correcting popular misconceptions concerning both the position and the speculum and advocating for greater familiarity with the use of both of these valuable tools by practicing clinicians.

Contemporary Issues in Obstetric Fistula.

We discuss a variety of contemporary issues relating to obstetric fistula. These include definitions of these injuries, the etiologic mechanisms by which fistulas occur, the role of specialist fistula centers in diagnosis and management, the classification of fistulas, and the assessment of surgical outcomes. We also review the growing need for complex reconstructive surgical procedures, follow-up challenges, and the transition to a fistula-free world in which other pathologies (such as pelvic organ prolapse) will be of increasing importance. Finally, we discuss the need to develop responsive systems of maternal health care that treat women with competence, compassion, respect, and fairness.

Scheduling nab-paclitaxel combined with gemcitabine as first-line treatment for metastatic pancreatic adenocarcinoma.

BACKGROUND: Nab-paclitaxel plus gemcitabine (nabP+gemcitabine) offers modest survival gains for patients with metastatic pancreatic ductal adenocarcinoma (PDAC). Sequential scheduling of nabP+gemcitabine in a PDAC mouse model improved efficacy; this hypothesis was tested in a clinical trial. METHODS: Patients with previously untreated metastatic PDAC were randomised to receive nabP+gemcitabine administered either concomitantly on the same day, or sequentially, with gemcitabine administered 24 h after nabP. The primary outcome measure was progression-free survival (PFS). Secondary outcome measures were objective response rate (ORR), overall survival (OS), safety, quality of life (QoL) and predictive biomarkers. RESULTS: In total, 71 patients received sequential (SEQ) and 75 concomitant (CON) treatment. Six-month PFS was 46% with SEQ and 32% with CON scheduling. Median PFS (5.6 versus 4.0 months, hazard ratio [HR] 0.67, 95% confidence interval [95% CI] 0.47-0.95, p = 0.022) and ORR (52% versus 31%, p = 0.023) favoured the SEQ arm; median OS was 10.2 versus 8.2 months (HR 0.93, 95% CI 0.65-1.33, p = 0.70). CTCAE Grade ≥3 neutropaenia incidence doubled with SEQ therapy but was not detrimental to QoL. Strongly positive tumour epithelial cytidine deaminase (CDA) expression favoured benefit from SEQ therapy (PFS HR 0.31, 95% CI 0.13-0.70). CONCLUSIONS: SEQ delivery of nabP+gemcitabine improved PFS and ORR, with manageable toxicity, but did not significantly improve OS. CLINICAL TRIAL REGISTRATION: ISRCTN71070888; ClinialTrials.gov (NCT03529175).

The controversial Dr. J. Marion Sims (1813-1883).

J. Marion Sims (1813-1883) is often regarded as the founder of modern surgical gynecology. Widely known and respected during his lifetime, he was honored after death with a statue erected in New York City's Bryant Park. It was later relocated to Central Park, where it remained until 2018, when it was removed after persistent public protests over its presence. The controversy arose over perceptions of Sims's most famous achievement: the development of the first reliable surgical cure for vesico-vaginal fistula, a catastrophic complication of prolonged obstructed labor, which was common in the nineteenth century. Sims developed his surgical technique by operating on a group of enslaved African-American women with fistulas between 1846 and 1849. Modern attacks on Sims are based more on a presentist revulsion over the institution of slavery than on a clear understanding of what Sims actually did within the context of his time and place. Modern critics attack his "experimental" surgeries, the patients' lack of "informed consent," and Sims's failure to use anesthesia during fistula surgery. None of these criticisms takes into consideration the appalling nature of the injuries these women had received, the suffering their condition caused them, the lack of any effective "standard-of-care" treatment for fistulas at that time, the social and legal constraints facing doctors who treated slaves, or the uncertain and problematic early history of anesthesiology. Although "retrospective indignation" may be emotionally satisfying, it does not illuminate the past nor help us understand difficult decision-making in surgery, whatever the time or place.

Henry van Roonhuyse and the first repair of a vesico-vaginal fistula (~1676).

INTRODUCTION AND HYPOTHESIS: Obstetric vesico-vaginal fistula is a traumatic complication of prolonged obstructed labor in which pressure necrosis from the impacted fetal head destroys portions of the vesico-vaginal septum, resulting in continuous and uncontrollable urinary incontinence. Ancient evidence suggests that fistula cases have probably been occurring since the development of rotational delivery mechanics in anatomically modern humans hundreds of thousands of years ago. It is likely that attempts to repair such injuries also have a long history. The early history of vesico-vaginal fistula surgery was investigated to determine the earliest credible report of successful cure of this condition. METHODS: Historical review of vesico-vaginal fistula surgery was undertaken, focusing on the work of Henry Van Roonhuyse, a seventeenth century Dutch surgeon living in Amsterdam. RESULTS: Van Roonhuyse's clinical treatise entitled Medico-Chirurgical Observations (1676) was reviewed in detail and is described in this article. His technique for vesico-vaginal fistula repair included six essential steps that are still recognizable today: (1) use of the lithotomy position; (2) exposure of the fistula with a speculum; (3) sharp paring of the fistula edge prior to attempted closure; (4) careful approximation of the denuded edges of the fistula; (5) dressing of the wound with absorbent vaginal packing; (6) immobilization of the patient in bed until the repair has healed. CONCLUSIONS: Henry Van Roonhuyse is the most credible candidate presently known for having successfully repaired a vesico-vaginal fistula in the pre-modern era.

Capacity building in female pelvic medicine and reconstructive surgery: Global Health Partnership beyond fistula care in Ethiopia.

OBJECTIVE: Obstetric fistula is a devastating childbirth injury that leaves women incontinent, stigmatized and often isolated from their families and communities. In Ethiopia, although much attention has focused on treating and preventing obstetric fistula, other more prevalent childbirth-related pelvic floor disorders, such as pelvic organ prolapse, non-fistula-related incontinence and post-fistula residual incontinence, remain largely unattended. The lack of international and local attention to addressing devastating pelvic floor disorders is concerning for women in low- and middle-income countries. The objective of this article is to highlight the need for a more comprehsive approach to pelvic floor care and to share our experience in addressing it. METHODS: Here, we share our experience launching one of the first formal training programs in Female Pelvic Medicine and Reconstructive Surgery (FPMRS) in Ethiopia. RESULTS: This fellowship program provides quality care while strengthening the health system in its local context. This program has positioned Ethiopia to be a regional leader by providing comprehensive training of surgeons and allied health professionals, building appropriate health system and research infrastructure, and developing a formal FPMRS training curriculum. CONCLUSION: We hope that sharing this experience will serve as a template for others championing comprehensive pelvic floor care for women in low- and middle-income countries.

Characteristics of persistent urinary incontinence after successful fistula closure in Ethiopian women.

INTRODUCTION AND HYPOTHESIS: Obstetric fistulas have devastating consequences for women. Although surgical repair is largely successful in closing the defect, many women with successful fistula closure report persistent urinary incontinence. Our study is aimed at characterizing incontinence after successful fistula repair and its impact on quality of life. METHODS: This cross-sectional study enrolled women with a history of successful obstetric fistula closure with (n = 51; cases) or without (n = 50; controls) persistent urinary incontinence. Data were collected in Mekelle, Ethiopia, between 2016 and 2018. All cases underwent clinical evaluation and completed questionnaires characterizing the type, severity, and impact of incontinence. RESULTS: Cases were significantly more likely to have acquired their fistula at an earlier age and with their first vaginal delivery compared with controls. Almost all cases reported both stress (98%) and urgency (94%) incontinence, and half reported constant urinary leakage (49%) despite successful fistula closure. Of cases who completed urodynamic evaluation (n = 22), all had genuine stress incontinence and none had detrusor overactivity. All cases reported moderate to severe (80.4%) or very severe (19.6%) incontinence (measured by ICIQ-SF) and this had a moderate to severe negative impact on their quality of life (as measured by ICIQ-QoL). Although history of suicidal ideation was not significantly different between the groups, among those with suicidal ideation, cases were more likely to report having made a plan and/or attempted to commit suicide. CONCLUSIONS: When urinary incontinence persists after successful fistula closure, it tends to be severe and of mixed etiology and has a significant negative impact on quality of life and mental health.

Reintegration needs of young women following genitourinary fistula surgery in Uganda.

INTRODUCTION AND HYPOTHESIS: Genitourinary fistulas (usually arising following prolonged obstructed labor) are particularly devastating for women in low-income counties. Surgical repair is often difficult and delayed. While much attention has been devoted to technical surgical issues, the challenges of returning to normal personal, family, and community life after surgical treatment have received less scrutiny from researchers. We surveyed young Ugandan women recovering from genitourinary fistula surgery to assess their social reintegration needs following surgery. METHODS: A cross-sectional survey of 61 young women aged 14-24 years was carried out 6 months postoperatively. Interviews were carried out in local languages using a standardized, interviewer-administered, semistructured questionnaire. Data were entered using EpiData and analyzed using SPSS. RESULTS: Ongoing reintegration needs fell into interrelated medical, economic, and psychosocial domains. Although >90% of fistulas were closed successfully, more than half of women had medical comorbidities requiring ongoing treatment. Physical limitations, such as foot drop and pelvic muscle dysfunction impacted their ability to work and resume their marital relationships. Anxieties about living arrangements, income, physical strength, future fertility, spouse/partner fidelity and support, and possible economic exploitation were common. Sexual dysfunction after surgery-including dyspareunia, loss of libido, fear of intercourse, and anxieties about the outcome of future pregnancies-negatively impacted women's relationships and self-esteem. CONCLUSIONS: Young women recovering from genitourinary fistula surgery require individualized assessment of their social reintegration needs. Postoperative social reintegration services must be strengthened to do this effectively.

Health worker text messaging for blended learning, peer support, and mentoring in pediatric and adolescent HIV/AIDS care: a case study in Zimbabwe.

BACKGROUND: In sub-Saharan Africa, shortages of trained healthcare workers and limited resources necessitate innovative and cost-effective approaches for training, supervising, and mentoring. This qualitative case study describes participants' and trainers' perspectives and experiences with a text messaging component of a blended training course in HIV counseling and testing in Zimbabwe, using minimal resources in terms of staff time and equipment requirements. This component included a whole-group discussion forum as well as two-person partner discussions designed to promote reflection and analysis, teamwork, and active learning. CASE PRESENTATION: The Ministry of Health and Child Care (MoHCC) of Zimbabwe collaborated with the International Training and Education Center for Health (I-TECH) on adaptation of a 5-day in-service training in HIV Testing Services for Children and Adolescents. The new 7-week blended format included in-person sessions, tablet-based self-study, and discussions using the text messaging application, WhatsApp. Between August 2016 and January 2017, 11 cohorts (293 participants in total) were trained with this new curriculum, incorporating text messaging to support peer-to-peer and work-based education. Data collected included training participants' feedback, key informant interviews with the training team, and thematic analysis of WhatsApp messages from full-cohort discussions and a sampling of one-to-one partner discussions. A total of 293 healthcare workers from 233 health facilities across all provinces in Zimbabwe completed the blended learning course. Participants strongly endorsed using WhatsApp groups as part of the training. In the whole-group discussions, the combined cohorts generated over 6300 text messages. Several categories of communication emerged in analysis of group discussions: (1) participants' case experiences and questions; (2) feedback and recommendations for work issues raised; (3) inquiries, comments, and responses about course assignments and specific course content; (4) encouragement; and (5) technical challenges encountered using the blended learning methodology. Case discussions were complex, including patient history, symptoms, medications, and psychosocial issues-child abuse, adherence, and disclosure. CONCLUSIONS: Using text messaging in a communication platform that is an ongoing part of healthcare workers' daily lives can be an effective adjunct to in-service training, minimizing isolation and providing interactivity, supporting students' ability to fully integrate content into new skill attainment.

Gurya cutting and female genital fistulas in Niger: ten cases.

INTRODUCTION AND HYPOTHESIS: The objective was to determine the contribution of female genital cutting to genital fistula formation in Niger from the case records of a specialist fistula hospital. METHODS: A retrospective review was undertaken of the records of 360 patients seen at the Danja Fistula Center, Danja, Niger, between March 2014 and September 2016. Pertinent clinical and socio-demographic data were abstracted from the cases identified. RESULTS: A total of 10 fistulas resulting from gurya cutting was obtained: 9 cases of urethral loss and 1 rectovaginal fistula. In none of the cases was genital cutting performed for obstructed labor or as part of ritual coming-of-age ceremonies, but all cutting procedures were considered "therapeutic" within the local cultural context as treatment for dyspareunia, lack of interest in or unwillingness to engage in sexual intercourse, or female behavior that was deemed to be culturally inappropriate by the male spouse, parents, or in-laws. Clinical cure (fistula closed and the patient continent) was obtained in all 10 cases, although 3 women required more than one operation. CONCLUSIONS: Gurya cutting is an uncommon, but preventable, cause of genital fistulas in Niger. The socio-cultural context which gives rise to gurya cutting is explored in some detail.

Obstetric fistula in Niger: 6-month postoperative follow-up of 384 patients from the Danja Fistula Center.

INTRODUCTION AND HYPOTHESIS: The impoverished West African country of Niger has high rates of obstetric fistula. We report a 6-month postoperative follow-up of 384 patients from the Danja Fistula Center and assess factors associated with operative success or failure. METHODS: The medical records of 384 women who had completed a 6-month follow-up after fistula surgery were reviewed. Cases were categorized as "easy," "of intermediate complexity," or "difficult" based on a preoperative points system. Data were analyzed using simple chi-squared statistics and logistic regression. RESULTS: The patients were predominantly of Hausa ethnicity (73%), married young (average 15.9 years), had teenage first pregnancies (average first delivery 16.9 years), and experienced prolonged labor (average 2.3 days) with poor outcomes (89% stillbirth rate). The average parity was four. Patients commonly developed their fistula during their first delivery (43.5%), but over half sustained a fistula during a subsequent delivery (56.5%). Prior fistula surgery elsewhere (average 1.75 operations) was common. The overall surgical success ("closed and dry") was 54%. When the 134 primary operations were analyzed separately, the overall success rate was 80%. Increasing success was seen with decreasing surgical difficulty: 92% success for "easy" cases, 68% for "intermediate" cases, and 57% success for "difficult" cases. Success decreased with increasing numbers of previous attempts at surgical repair. CONCLUSIONS: These data provide further evidence that clinical outcomes are better when primary fistula repair is performed by expert surgeons in specialist centers with the support of trained fistula nurses.

Tending the 'monthly flower:' a qualitative study of menstrual beliefs in Tigray, Ethiopia.

BACKGROUND: Menstruation is a universal aspect of human female reproductive life. Management of menstrual flow presents hygiene challenges to girls and women in low-income countries, especially when they first start their periods. As part of a project to improve menstrual hygiene management in the Tigray Region of Ethiopia, we explored the local understanding of menstruation through focus-group discussions and individual interviews. METHODS: A detailed ethnographic survey of menstrual beliefs was carried out through 40 focus group discussions, 64 in-depth key informant interviews, and 16 individual case histories in the Tigray Region of northern Ethiopia. A total of 240 individuals participated in six types of focus groups (pre-menarchal girls, menstruating adolescents, married women of reproductive age, post-menopausal women, adolescent males, and married men). In-depth interviews were also carried out with 80 individuals, including Orthodox Christian priests, imams from the Muslim community, principals of primary and secondary schools, teachers and nurses, as well as menstruating schoolgirls and women. Audio data were transcribed and translated, then broken down into discrete codes using Atlas Ti software (version 7.5.4, Atlas.ti Scientific Software Development Mnbh, Berlin) and further grouped into related families and sub-families based on their content. The results were then synthesized to produce a cohesive narrative concerning menstruation in Tigray. RESULTS: Recurrent themes identified by participants included descriptions of the biology of menstruation (which were sometimes fanciful); the general unpreparedness of girls for menarche; cultural restrictions imposed by menstruation on females (particularly the stigma of ritual uncleanliness in both Christian and Muslim religious traditions); the prevalence and challenges of unmet menstrual hygiene needs at schools (including lack of access to sanitary pads and the absence of acceptable toilet/washing facilities); and the stigma and shame associated with menstrual hygiene accidents in public. CONCLUSIONS: Changes in the educational system in northern Ethiopia are required to improve student understanding of the biology of menstruation, to foster gender equity, to overcome the barriers to school attendance presented by poor menstrual hygiene management, and to create a society that is more understanding and more accepting of menstruation.

Hypospadias, all there is to know.

Hypospadias is one of the most common congenital anomalies in men. The condition is typically characterized by proximal displacement of the urethral opening, penile curvature, and a ventrally deficient hooded foreskin. In about 70%, the urethral meatus is located distally on the penile shaft; this is considered a mild form that is not associated with other urogenital deformities. The remaining 30% are proximal and often more complex. In these cases, endocrinological evaluation is advised to exclude disorders of sexual differentiation, especially in case of concomitant unilateral or bilateral undescended testis. Although the etiology of hypospadias is largely unknown, many hypotheses exist about genetic predisposition and hormonal influences. The goal of hypospadias repair is to achieve cosmetic and functional normality, and currently, surgery is recommended between 6 and 18 months of age. Hypospadias can be corrected at any age with comparable complication risk, functional, and cosmetic outcome; however, the optimal age of repair remains conclusive. Although long-term overall outcome concerning cosmetic appearance and sexual function is fairly good, after correction, men may more often be inhibited in seeking sexual contact. Moreover, lower urinary tract symptoms occur twice as often in patients undergoing hypospadias repair and can still occur many years after the initial repair. CONCLUSION: This study explores the most recent insights into the management of hypospadias. What is Known: • Guidelines advise referral for treatment between 6 and 18 months of age. • Cosmetic outcome is considered satisfactory in over 70% of all patients. What is New: • Long-term complications include urinary tract symptoms and sexual and cosmetic issues. • New developments allow a more individualized approach, hopefully leading to less complications and more patient satisfaction.

A case-control study of the risk factors for obstetric fistula in Tigray, Ethiopia.

INTRODUCTION AND HYPOTHESIS: We tested the null hypothesis that there were no differences between patients with obstetric fistula and parous controls without fistula. METHODS: A unmatched case-control study was carried out comparing 75 women with a history of obstetric fistula with 150 parous controls with no history of fistula. Height and weight were measured for each participant, along with basic socio-demographic and obstetric information. Descriptive statistics were calculated and differences between the groups were analyzed using Student's t test, Mann-Whitney U test where appropriate, and Chi-squared or Fisher's exact test, along with backward stepwise logistic regression analyses to detect predictors of obstetric fistula. Associations with a p value <0.05 were considered significant. RESULTS: Patients with fistulas married earlier and delivered their first pregnancies earlier than controls. They had significantly less education, a higher prevalence of divorce/separation, and lived in more impoverished circumstances than controls. Fistula patients had worse reproductive histories, with greater numbers of stillbirths/abortions and higher rates of assisted vaginal delivery and cesarean section. The final logistic regression model found four significant risk factors for developing an obstetric fistula: age at marriage (OR 1.23), history of assisted vaginal delivery (OR 3.44), lack of adequate antenatal care (OR 4.43), and a labor lasting longer than 1 day (OR 14.84). CONCLUSIONS: Our data indicate that obstetric fistula results from the lack of access to effective obstetrical services when labor is prolonged. Rural poverty and lack of adequate transportation infrastructure are probably important co-factors in inhibiting access to needed care.

Validation of a culturally compliant voiding platform for urodynamics in African vesicovaginal fistula patients.

INTRODUCTION AND HYPOTHESIS: Most patients in regions where obstetric vesicovaginal fistulas (VVF) are endemic void using a squatting posture. Additionally, many patients continue to have lower urinary tract symptoms (LUTS) following fistula closure. We designed and validated a prototype platform that allows urodynamic studies to be performed in a squatting position and conducted a pilot study to assess uroflowmetry in this patient population. METHODS: Sixteen patients with persistent LUTS following fistula surgery were recruited. Posture measurements were taken in each patient's natural voiding posture on the ground and were then repeated using the platform. Nine patients with persistent urinary incontinence also underwent uroflowmetry. The data were compared with normal values in different nomograms. Paired t tests were used to determine significant differences in posture. One-way ANOVA was used to determine statistical significance between flow rate values. RESULTS: Only the heel-to-heel distance (H-H) measure of posture was significantly increased on the platform compared with on the ground. The mean corrected Qmax was 0.89 ± 0.46. Flow rate values were significantly lower than mean normal flow rates obtained from the nomograms. In general, the patients' uroflowmetry patterns were similar to those indicative of impaired detrusor function. CONCLUSION: A platform for conducting urodynamic studies in a squatting posture was successfully validated in the VVF patient population. The finding of increased H-H on the platform is expected, since the patient must accommodate a large funnel for urine collection. The pilot data suggest that patients with persistent urinary incontinence following VVF closure may also have significant voiding dysfunction.

Phase I/II trial of formoterol fumarate combined with megestrol acetate in cachectic patients with advanced malignancy.

PURPOSE: The aim of this study was to test the safety, tolerability and efficacy of a novel combination of an anabolic ß2-agonist and an appetite stimulant in patients with cancer cachexia. METHODS: Thirteen patients (M/F 5:8) with advanced malignancy and involuntary weight loss received oral formoterol (80 µg/day) and megestrol acetate (480 mg/day) for up to 8 weeks. Quadriceps size (MRI), quadriceps and hand-grip strength, lower limb extensor power, physical activity and quality of life were measured at baseline and at 8 weeks. Response criteria were specified pre-trial, with a major response defined as an increase in muscle size ≥ 4 % or function ≥ 10 %. RESULTS: Six patients withdrew before 8 weeks, reflecting the frail, comorbid population. In contrast, six out of seven (86 %) patients completing the course achieved a major response for muscle size and/or function. In the six responders, mean quadriceps volume increased significantly (left 0.99 vs. 1.05 L, p=0.012; right 1.02 vs. 1.06 L, p=0.004). There was a trend towards an increase in quadriceps and handgrip strength (p>0.05). The lack of appetite symptom score declined markedly (76.2 vs. 23.8; p=0.005), indicating improvement. Adverse reactions were few, the commonest being tremor (eight reports), peripheral oedema (three), tachycardia (two) and dyspepsia (two). CONCLUSIONS: In this frail cohort with advanced cancer cachexia, an 8-week course of megestrol and formoterol in combination was safe and well tolerated. Muscle mass and/or function were improved to a clinically significant extent in most patients completing the course. This combination regimen warrants further investigation in larger, randomized trials.

High-grade Vesicoureteral Reflux in Patients With Anorectal Malformation From the ARM-Net Registry: Is Our Screening Sufficient?

BACKGROUND: Vesico-ureteral reflux (VUR) is a common associated urological anomaly in anorectal malformation (ARM)-patients. High-grade VUR requires antibiotic prophylaxis to prevent urinary tract infections (UTI's), renal scarring and -failure. The exact prevalence of high-grade VUR in ARM patients is unknown. Hence, the aim of this study was determining the incidence of high-grade VUR in ARM-patients, and its associated risk factors. METHODS: A multicenter retrospective cohort study was performed using the ARM-Net registry, including data from 34 centers. Patient characteristics, screening for and presence of renal anomalies and VUR, sacral and spinal anomalies, and sacral ratio were registered. Phenotypes of ARM were grouped according to their complexity in complex and less complex. Multivariable analyses were performed to detect independent risk factors for high-grade (grade III-V) VUR. RESULTS: This study included 2502 patients (50 % female). Renal screening was performed in 2250 patients (90 %), of whom 648 (29 %) had a renal anomaly documented. VUR-screening was performed in 789 patients (32 %), establishing high-grade VUR in 150 (19 %). In patients with a normal renal screening, high-grade VUR was still present in 10 % of patients. Independent risk factors for presence of high-grade VUR were a complex ARM (OR 2.6, 95 %CI 1.6-4.3), and any renal anomaly (OR 3.3, 95 %CI 2.1-5.3). CONCLUSIONS: Although renal screening is performed in the vast majority of patients, only 32 % underwent VUR-screening. Complex ARM and any renal anomaly were independent risk factors for high-grade VUR. Remarkably, 10 % had high-grade VUR despite normal renal screening. Therefore, VUR-screening seems indicated in all ARM patients regardless of renal screening results, to prevent sequelae such as UTI's, renal scarring and ultimately renal failure. TYPE OF STUDY: Observational Cohort-Study. LEVEL OF EVIDENCE: III.

Prevalence of depression in adults with cancer: a systematic review.

BACKGROUND: Depression has substantial effects on cancer patients' quality of life. Estimates of its prevalence vary widely. We aimed to systematically review published studies to obtain the best estimate of the prevalence of depression in clinically meaningful subgroups of cancer patients. DESIGN: Systematic review that addressed the limitations of previous reviews by (i) including only studies that used diagnostic interviews; (ii) including only studies that met basic quality criteria (random or consecutive sampling, ≥70% response rate, clear definition of depression caseness, sample size ≥100); (iii) grouping studies into clinically meaningful subgroups; (iv) describing the effect on prevalence estimates of different methods of diagnosing depression. RESULTS: Of 66 relevant studies, only 15 (23%) met quality criteria. The estimated prevalence of depression in the defined subgroups was as follows: 5% to 16% in outpatients, 4% to 14% in inpatients, 4% to 11% in mixed outpatient and inpatient samples and 7% to 49% in palliative care. Studies which used expert interviewers (psychiatrists or clinical psychologists) reported lower prevalence estimates. CONCLUSIONS: Of the large number of relevant studies, few met our inclusion criteria, and prevalence estimates are consequently imprecise. We propose that future studies should be designed to meet basic quality criteria and employ expert interviewers.