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.

Impact of a double catastrophe, war and COVID-19, on health service utilization of a tertiary care hospital in Tigray: an interrupted time-series study.

BACKGROUND: In developing nations with fragile healthcare systems, the effect of war is likely to be much worse than it would be in more developed countries. The presence of COVID-19 will also likely exacerbate the war's impact. This study set out to determine the effect of armed conflict and the COVID-19 pandemic on health service utilization at Ayder Comprehensive Specialized Hospital, in the Tigray region of Ethiopia. METHODS: An interrupted time-series study design was used to analyze patient visits over forty-eight consecutive months (from July 2017 to June 2021) at inpatient, outpatient, and emergency departments. Data were analyzed using segmented regression analysis with a defined outcome of level and trend changes in the number of patient visits. In addition, negative binomial regression analysis was also used to estimate the impact of both COVID-19 and the war on patient flow. RESULTS: There were 59,935 admissions, 876,533 outpatient visits, and 127,872 emergency room visits. The effect of COVID-19 was seen as soon as the Tigray regional government imposed comprehensive restrictions. Immediately after COVID-19 appeared, all the service areas exhibited a significant monthly drop in visits; [-35.6% (95% CI: -48.2%, -23.1%)] for inpatient, [-60.6% (95% CI: -71.6%, -49.5%)] for outpatient, and [-44.1% (95% CI: -59.5%, -28.7%)] for emergency department visits. The impact of the war became apparent after a lag time of one month. Controlling the effects of time and COVID-19, the war led to a significant fall in inpatient visits [-44.3% (95% CI: -67.2%, -21.5%)], outpatients [-52.1% (95% CI: -82.7%, -21.5%)], and emergency-room attendances [-45.0% (95% CI: -74.8%, -15.2%)]. An upward trend in outpatient flow was observed after the war [1,219.4 (95% CI: 326.1, 2,112.8)]. CONCLUSIONS: The present study has clearly indicated that the war and COVID-19 have led to a large reduction in admissions, outpatient attendance, and emergency department visits. The evidence from this study suggests that due to this double catastrophe, thousands of patients could not gain access to healthcare, with probable negative consequences. Governments and organizations should implement measures to buttress the healthcare system to maintain pre-war status of service.

"Menstruation is a Fearful Thing": A Qualitative Exploration of Menstrual Experiences and Sources of Information About Menstruation Among Adolescent Schoolgirls.

Background: Although menstruation is a biological phenomenon, it is still subjected to secrecy, shame, and negativity. Schoolgirls lack access to appropriate sources of information about menstruation. Little is known about the content of the information provided to schoolgirls concerning menstruation in northern Ethiopia. This study explored schoolgirls' experiences and the content of information they receive concerning menstrual hygiene management in Tigray. Methods: A qualitative design was implemented. Focus group discussions and in-depth interviews were conducted using the local language among 79 schoolgirls who had experienced menarche. Data were audio-recorded, transcribed, translated, and imported into ATLAS.ti-7.5.18 computer software for analysis. Data were coded and analyzed using a thematic analysis. Results: Five themes have emerged from the analysis: 1) there is an indistinct and haphazard source of menstrual information; 2) menstruation is perceived as "a natural gift"; 3) menstruation is also considered fearful and embarrassing; 4) negative community perceptions of menstruation lead to menstrual restrictions, and 5) lack of privacy for dealing with menstrual issues as well as the scarcity of menstrual hygiene management materials is an on going problem. Schoolgirls have indistinct and haphazard sources of information concerning menstrual hygiene management, obtaining it from teachers, mothers, sisters, and friends, but the information they receive is shrouded in secrecy and often is factually incorrect. Menstruation is commonly linked to notions of sexuality, shame, and the approach of marriageability. Conclusion: The information that schoolgirls in rural Tigray receive about menstrual hygiene management is inaccurate, insufficient, and encumbered with social taboos. Thus, schoolgirls do not have an adequate understanding of the physiology of menstruation and do not receive adequate emotional support at menarche, leaving them with feelings of embarrassment and anxiety. There should be efforts to implement programs that change community perceptions about menstruation.

Neoadjuvant tyrosine kinase inhibitor therapy in locally advanced differentiated thyroid cancer: a single centre case series.

OBJECTIVE: Primary surgical resection remains the mainstay of management in locally advanced differentiated thyroid cancer. Tyrosine kinase inhibitors have recently shown promising results in patients with recurrent locally advanced differentiated thyroid cancer. This study discussed four patients with locally advanced differentiated thyroid cancer managed with tyrosine kinase inhibitors used prior to surgery in the 'neoadjuvant' setting. METHOD: Prospective data collection through a local thyroid database from February 2016 identified four patients with locally advanced differentiated thyroid cancer unsuitable for primary surgical resection commenced on neoadjuvant tyrosine kinase inhibitor therapy. RESULTS: All cases had T4a disease at presentation. Three cases tolerated tyrosine kinase inhibitor therapy for more than 14 months while the last case failed to tolerate treatment at 1 month. All patients subsequently underwent total thyroidectomy to facilitate adjuvant radioactive iodine treatment. Disease-specific survival remains at 100 per cent currently (range, 29-75 months). CONCLUSION: Neoadjuvant tyrosine kinase inhibitors in locally advanced differentiated thyroid cancer can be effective in reducing primary tumour extent to potentially facilitate a more limited surgical resection for local disease control.

Dabrafenib and Trametinib Therapy for Advanced Anaplastic Thyroid Cancer - Real-World Outcomes From UK Centres.

AIMS: Anaplastic thyroid cancer (ATC) is a rare but aggressive form of thyroid cancer with a median survival of 4 months. Recent advances in molecular profiling have shown that up to half of ATCs harbour the BRAF-V600E mutation. The aim of this study was to provide real-world data and experience on the use of combination therapy dabrafenib and trametinib in patients with BRAF-V600E-mutated advanced ATC. MATERIALS AND METHODS: We retrospectively evaluated patients with confirmed BRAF-V600E-mutated ATC, defined as patients with locally advanced or metastatic ATC with no locoregional, radical treatment options. Outcomes measured were overall survival, progression-free survival, response rate, discontinuation rate, dose reduction rate and toxicity data. RESULTS: Seventeen patients were evaluated and the mean age was 68 years. Ten patients died by the time of censoring. The median duration of follow-up was 12 months (3-43 months). The estimated median overall survival was 6.9 months (95% confidence interval 2.46 months - upper confidence interval not reached) and the median progression-free survival was 4.7 months (95% confidence interval 1.4-7.8 months). Dose interruptions and/or reductions were common, but none of the patients had to permanently discontinue treatment because of toxicities. Severe toxicities (grades 3 and 4) were uncommon. CONCLUSIONS: This study supports the indication of dabrafenib and trametinib in BRAF-V600E-mutated ATC as an effective and well-tolerated treatment in an historically difficult to treat cancer.

Infectious Complications of Abortion.

This article reviews the infectious complications of abortion (both spontaneous and induced) and the management of this condition. The key points are: (1) Making abortion illegal does not reduce its incidence or prevalence; rather, it only makes abortions unsafe, increasing the likelihood of infectious complications. (2) Timely recognition of developing sepsis in the pregnant patient is critical. This requires constant vigilance and a high index of suspicion. (3) Rapid intravenous administration of broad-spectrum antibiotics targeted to the likely intrauterine source of infection as soon as sepsis is diagnosed is critical to prevent severe sepsis, septic shock, and multisystem organ failure. (4) The mainstay of treatment is prompt evacuation of any residual products of conception from within the uterine cavity under broad-spectrum antibiotic cover targeting the likely intrauterine source of infection. (5) Prompt engagement of specialists in both critical care and obstetrics-gynecology is necessary to optimize outcomes in patients with septic abortion.

Study protocol for a parallel-group randomized controlled multi-center trial evaluating the additional effect of continuous ultrasound bladder monitoring in urotherapy for children with functional daytime urinary incontinence (SENS-U trial).

BACKGROUND: Lower urinary tract dysfunction or functional urinary incontinence is a common condition with a prevalence up to 21% between 6 and 8 year-old children. It is associated with an impaired quality of life, lower self-esteem, and social stigmatization. Urotherapy is the first treatment of choice for functional daytime urinary incontinence (DUI) in children. Alarm therapy can be a part of urotherapy as it provides the child adequate feedback on wetting accidents. Current alarm systems notify either at a set interval or give a notification when wetting has already occurred to prompt the child to go to the toilet. These alarms do not teach the child the interpretation of the bladder sensation preceding wetting accidents. A new wearable bladder sensor, the SENS-U, recently became available. This is a relative small, wireless ultrasonic sensor, which continuously monitors bladder filling. The SENS-U is able to provide an alarm at the exact moment voiding is warranted. It facilitates the child to learn the sensation of bladder filling preceding voiding in an easier way, increasing the learning curve throughout treatment. Its additional effect in urotherapy on continence and cost-effectiveness is to be determined. METHODS/DESIGN: This is a multi-center clinical superiority parallel-group randomized controlled trial including a total of 480 children. Participants between 6 and 16 years of age with functional DUI in which urotherapy is offered as the next treatment of choice are eligible. Four centers, two academic hospitals, and two general care (peripheral) centers are participating. Participants will be randomized at a 1:1:1 ratio into three groups: urotherapy (care as usual), urotherapy with the SENS-U added for 3 consecutive weeks throughout the training, or urotherapy with a SHAM device for 3 weeks. The primary outcome is number of wetting accidents per week after 3 months of training, compared between the SENS-U and the SHAM device. The magnitude of the placebo effect will be assessed by comparing the results of the SHAM group versus the control (care as usual) group. DISCUSSION: To our knowledge, this is the first trial studying not only the effect but also the cost-effectiveness of alarm interventions as commonly added in urotherapy. TRIAL REGISTRATION: ISRCTN44345202 . Registered on March 2022.

The Siege of Ayder Hospital: A Cri de Coeur From Tigray, Ethiopia.

ABSTRACT: In November 2020, the federal government of Ethiopia invaded its northern region of Tigray, in collusion with the Government of Eritrea and ethnic Amhara militias. The invading forces pillaged the schools, destroyed the transportation infrastructure, burned crops and killed livestock, and looted the health care system. Thousands of civilians were killed, often in extrajudicial executions. Thousands of Tigrayan women were raped. Tens of thousands of Tigrayans fled to Sudan as refugees. Hundreds of thousands face famine and millions more have been internally displaced. The region is under a total communications blackout. The banking system has collapsed. The federal government has harassed external aid workers and imposed a de facto blockade on all medicines and famine relief. A man-made humanitarian catastrophe unlike any in recent memory is unfolding. The world medical community must speak up. The madness must stop.

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.

Long-term functional and psychosocial outcome in adolescents and young adults treated for lower urinary tract dysfunction in childhood.

BACKGROUND: Lower urinary tract dysfunction (LUTD) in childhood might affect lower urinary tract function and psychological wellbeing later in life. This study presents long-term functional outcome, psychological outcome and quality of life (QOL) of adolescents and young adults treated for childhood LUTD compared to healthy age-matched controls. In addition, association with past treatment outcomes is evaluated. STUDY DESIGN: A single-centre cross-sectional study of former patients treated in childhood (currently 16-26 years old) was conducted. Participants completed a survey composed from validated questionnaires: the Overactive Bladder Questionnaire, the Hospital Anxiety and Depression Scale, the Pediatric Quality of Life Inventory and the Short Form 36 Health Survey. RESULTS: Fifty-two former patients (out of 133) agreed to participate and returned the survey (mean age 21 ± 4.1 years). Sixty-nine control subjects were included (mean age 21 ± 2.9 years). Urinary tract symptoms were more common in former patients than controls. Storage symptoms more frequently reported were (urge) urinary incontinence, stress urinary incontinence (SUI) and nocturia. Voiding symptoms more frequently reported were intermittency and feeling of incomplete emptying, Fig. 1. There were no differences in urinary tract symptoms or urinary incontinence subdivided by childhood treatment outcome (complete response, partial response or no response), respectively p = 0.17 and p = 0.58. Results of the overactive bladder questionnaire revealed higher urinary symptom bother scores (score 14 versus 5 p < 0.01) and lower disease-specific QOL (score 95 versus 98 p = 0.02) in former patients compared to controls. General QOL and psychosocial wellbeing were not significantly different between the two groups. A childhood treatment duration extending 2,5 years was an independent prognostic factor for subsequent urinary tract symptoms later in life (OR = 1.5, 95% CI 1.1-2.0). Psychological comorbidity was more often present in former patients (35%) versus controls (10%), p < 0.01. CONCLUSION: Adolescents and young adults treated for childhood LUTD are more prone to report urinary tract symptoms later in life, especially if treatment duration was extensive. However general QOL and psychosocial wellbeing later in life are not or only mildly affected.

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.

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.