The transvaginal mesh class action: a tertiary teaching hospital experience of all mid-urethral sling procedures performed between 1999 and 2017.

INTRODUCTION AND HYPOTHESIS: Class action against Ethicon (J&J), manufacturer of transvaginal mesh devices, including mid-urethral slings (MUS), was brought to the Federal Court of Australia in 2016 by Shine Lawyers. As a result, subpoenas to all hospitals and networks were received, which overrode patient privacy concerns. This medical record search allowed a complete audit and communication with patients to offer clinical review. This enabled a review of complications, readmission and re-operation for women who underwent a MUS for stress urinary incontinence. METHODS: A cohort study of women who underwent MUS treatment for stress urinary incontinence (SUI) at a single tertiary teaching hospital between 1999 and 2017 was carried out. The main outcome measures were the rate of readmission and re-operation following MUS procedures. These include voiding dysfunction managed by sling loosening or sling division, mesh pain or exposure managed by mesh removal and reoperation for recurrent stress urinary incontinence. RESULTS: Between 1999 and 2017, a total of 1,462 women were identified as having a MUS; of these, 1,195 (81.7%) had full patient records available. Voiding dysfunction requiring surgical intervention with sling loosening or division was 3%, excision for mesh exposure was 2%, and partial or complete excision for pain was 1% at a median of 10 years from index surgery. The reoperation rate for recurrent stress urinary incontinence was 3%. CONCLUSION(S): This audit of all MUS procedures performed at a tertiary centre confirms an overall low rate of readmission for complications and recurrent SUI surgery; this justifies its continued availability with appropriate informed consent.

CO2 surgical laser for treatment of stress urinary incontinence in women: a randomized controlled trial.

BACKGROUND: Stress urinary incontinence is a common condition that can be treated conservatively and/or surgically. Given the risks of surgery, developing effective nonsurgical treatment options would be beneficial. Some studies have suggested that laser therapy may improve or cure stress urinary incontinence. However, there is a lack of sham-controlled randomized controlled trials to judge treatment efficacy. OBJECTIVE: This study aimed to compare the effects of CO2 vaginal laser vs sham therapy for treating stress urinary incontinence. STUDY DESIGN: This was a multicenter, participant-blinded, sham-controlled, parallel group (1:1) superiority randomized controlled trial performed in outpatient clinics in 2 hospitals. We included women aged 18 to 80 years with objective and subjective stress urinary incontinence. Participants had undertaken or declined supervised pelvic floor muscle training. Intervention was performed using a CO2 fractionated vaginal laser. Participants underwent 3 treatments, 4 weeks apart, with increasing energy and density settings. Sham treatment was performed using an identical technique with a deactivated pedal. The primary outcome was the subjective stress urinary incontinence rate (proportion with leak with cough, sneeze, or laughter) at 3 months after completion of treatment. Secondary outcomes included objective stress urinary incontinence, change in the disease-specific patient-reported outcomes, health-related quality of life, and adverse effects. Categorical outcomes were compared using the chi square test and continuous outcomes using analysis of covariance, adjusting for the baseline score. RESULTS: There were 52 participants who received laser and 49 who received sham treatment. One participant in each group withdrew from the study before the endpoint, and 2 participants in the laser group did not participate in the follow-up visits. Participant mean age was 53 (34-79) years. Mean body mass index was 26.1 (18.1-49.6); 90% were vaginally parous. At 3 months, there was no difference between the sham and active treatment arm in subjective stress urinary incontinence (46 [96%] vs 48 [98%]; relative risk, 0.98 [95% confidence interval, 0.91-1.05]; P=.55) or in objective stress urinary incontinence (37 [80%] vs 33 [80%]; relative risk, 0.99 [95% confidence interval, 0.81-1.23]; P=.995). Patient-reported outcomes and health-related quality of life were also comparable between the groups. Vaginal bleeding occurred in 3 participants after laser and 1 participant after sham treatment. Pain during treatment did not differ between laser and sham treatment. CONCLUSION: We were unable to show an improvement in stress urinary incontinence after CO2 vaginal laser therapy compared with sham treatment.

Vaginal pressure sensor measurement during maximal voluntary pelvic floor contraction correlates with vaginal birth and pelvic organ prolapse-A pilot study.

AIMS: To measure the force applied along the anterior and posterior vaginal walls in a cohort of 46 patients measured by a fiber-optic pressure sensor and determine if this correlates with vaginal parity and pelvic organ prolapse (POP). METHODS: An intravaginal fiber-optic sensor measured pressure at nine locations along the anterior and posterior vaginal walls during a maximal voluntary pelvic floor muscle contraction (MVC). An automated probe dilation cycle measured the tissue resistance incorporating the vagina and surrounding anatomy. MVC and resting tissue resistance (RTR) were assessed between subjects grouped by the number of vaginal births and prolapse stage. RESULTS: A previous vaginal birth was associated with a significant threefold decrease in the overall anterior pressure measurement during MVC. Decreased anterior pressure measurements were observed at Sensors 1 and 3 (distal vagina) and, posteriorly at Sensors 4-6 (midvagina). Women with Stage 2 posterior prolapse exhibited a decreased MVC pressure in the midvagina than those with Stage 0/1. In this pilot study, there was no difference in the vaginal wall RTR according to previous vaginal birth or stage of prolapse. CONCLUSION: This pilot study found that a decrease in vaginal pressure measured during MVC is associated with vaginal birth and with posterior POP. Greater sample size is required to assess the role of resting tissue pressure measurement.

Outcomes following sacrocolpopexy using ultralight and lightweight mesh.

INTRODUCTION AND HYPOTHESIS: This study reports the long-term anatomic and subjective outcomes following sacrocolpopexy based on mesh weight and provides device-specific data. METHODS: This cohort study compared ultra-lightweight (≤ 20 g/m2) with lightweight mesh (≥ 25 g/m2). The primary outcome was composite failure defined as at least one of ≥ stage 2 apical prolapse, anterior or posterior vaginal wall beyond hymen, complaint of bulge or retreatment. Effect measure estimates were calculated as the incidence rate ratio of composite failure comparing the use of ultra-light with lightweight mesh. Crude and adjusted incidence rate ratios (IRRs) were obtained using uni- and multivariable Poisson regression models. RESULTS: Of 358 women who met inclusion criteria, 220 (61%) agreed to attend for review; 95 (43%) had ultra-lightweight mesh and 125 (57%) had lightweight mesh including UpsylonTM. Median follow-up for ultra-light and lightweight mesh was 36 (IQR 22-42) and 63 (IQR 48-87) months, respectively (p < 0.001). Accounting for differences in follow-up time, there was no significant difference in composite failure between ultra-light and lightweight mesh groups (IRR 1.47, 95% CI 0.83-2.52, p = 0.15). This persisted after adjustment for age, body mass index, parity, smoking and presence of advanced prolapse prior to surgery (IRR 1.52, 95% CI 0.94-2.47, p = 0.087). Mesh exposure for both groups was mostly asymptomatic, and the rate was 7% for the ultra-light group and 8% in the lightweight group. Overall, repeat surgery for recurrent apical prolapse and mesh exposure occurred in 4% and 2%, respectively. CONCLUSIONS: Ultra-lightweight mesh appears to have similar incidence rate of failure compared to lightweight mesh. UpsylonTM mesh has a similar low rate of recurrent apical prolapse and mesh exposure.

Hysterectomy with uterosacral suspension or Uphold™ hysteropexy in women with apical prolapse: a parallel cohort study.

INTRODUCTION AND HYPOTHESIS: The aim was to compare objective and subjective cure rates between Uphold™ hysteropexy (HP) and vaginal hysterectomy (VH) with uterosacral suspension. METHODS: A sample size of 49 in each arm would be required to detect a clinical difference of 20% between the groups. Owing to delayed recruitment, this originally planned randomised controlled trial was changed to a patient preference study after randomising initial 6 participants. Women with symptomatic stage ≥2 uterine descent wishing a surgical solution were included. Routine follow-up was scheduled at 6 weeks, 6 months, 12 months, and annually thereafter. Primary outcome was absence of stage ≥2 apical prolapse. Secondary outcomes included a composite cure of no leading edge beyond the hymen, absence of bulge symptoms and no retreatment; patient-reported outcomes were based on quality-of-life questionnaires (PFDI-20, PFIQ-7, PISQ-12, PGI-I, EQ5D and a health score). RESULTS: We recruited 50 patients undergoing VH between 2011 and 2013 and 51 patients undergoing HP between 2011 and 2016. Participants were followed up for a median of 25 months (23-96). Five women from the VH (10%) and 7 from the HP (14%) group were lost to follow-up. Combined anatomical and symptomatic outcomes were available for 41 (82%) VH and 39 (76%) in the HP group. There was no difference in objective apical outcomes; the incidence of stage 2 prolapse was 0% in the VH group and 2% in HP group (p = 0.50). We found no difference in the composite cure rate (78% VH vs 85% HP, 0.45) between the groups. There was no significant difference in surgical complications (p = 0.33), assessed using Clavien-Dindo classification. There was a 2% surgery rate for mesh exposure in the HP group. CONCLUSIONS: Uphold™ uterine suspension and VH appear to have similar objective and subjective cure at 25 months, with no significant difference in surgical complications.

Evaluation of the ease of use and acceptability of an innovative device - the 'Episiometer', in ensuring an accurate mediolateral episiotomy: a pilot study.

The present study was undertaken at the Port Moresby General Hospital, Papua New Guinea, to evaluate the ease of use and acceptability of a perineal measuring device (Episiometer) for giving a correct length and angle of a mediolateral episiotomy. An Episiometer was placed on the perineum to guide the angle and length immediately before giving an episiotomy. A feedback survey was collected and the angle and length of the episiotomy were measured at the time of delivery and at 6 weeks postpartum. The length and angle of episiotomy were found to be accurate in 86% of the cases. Forty-two of the fifty (86%) clinicians felt that the Episiometer was easy or very easy to use. They also found this device to be beneficial (92%). The Episiometer seems to be an easy-to-use and feasible device that is well accepted by clinicians and patients and may aid in standardising the length and angle of an episiotomy. Impact statement What is already known on this subject? Episiotomy is the commonest obstetric procedure performed worldwide. However, the angle and length of an episiotomy vary greatly amongst operators. It is also recognised that birth trauma and an inaccurate episiotomy result in debilitating anal sphincter injury. Therefore, a pilot study was conducted to evaluate the ease of use and acceptability of a new, inexpensive, low- tech device "Episiometer" to guide clinicians and midwives to perform an appropriate episiotomy. What do the results of this study add? This pilot study to evaluate the usability of the new innovation amongst clinician and patients revealed high acceptance of the device amongst clinicians and positive attitude of the patients towards the device. The clinicians also felt the device to be an effective teaching tool. Usage if the device results in a more accurate length and angle of an episiotomy. What are the implications of these findings for clinical practice and/or further research? Further research and multicentre randomised control trials are needed to establish the effectiveness of the device in reducing the complications of episiotomy and risk of OASIS. The present study has shown the Episiometer as an acceptable and easy to use device amongst clinicians and can benefit the young clinicians as a teaching tool in directing a correct angle and length of episiotomy.

Nanotechnology-based mucoadhesive and mucus-penetrating drug-delivery systems for transbuccal drug delivery.

Buccal drug-delivery systems present a promising approach for the drug delivery to the buccal mucosa, addressing oral cavity-specific problems, enabling systemic delivery and minimizing adverse effects on biological systems. Numerous strategies have been proposed to load drug-containing nanoparticles (NPs) to the buccal mucosa for local and systemic applications. There has been considerable interest in the development of mucoadhesive buccal formulations, particularly hydrogel composites utilizing mucoadhesive films incorporating NPs. Drug permeability and controlled drug release through buccal drug delivery continues to pose a challenge despite the availability of various remedies. This review highlights the need for, mechanisms and latest advances in NP-based transbuccal drug delivery with a focus on various pathological disorders and examples and limitations of the different methods.

Drug Rash With Eosinophilia and Systemic Symptoms (DRESS) Syndrome Due to Vancomycin.

Drug rash with eosinophilia and systemic symptoms (DRESS) syndrome is a severe adverse drug reaction characterized by skin rash, fever, lymph node enlargement, and single or multiple organ involvement. Prompt diagnosis and withdrawal of the offending drug reduce mortality. We report a case of DRESS syndrome along with a review of the literature. We identified the case as DRESS syndrome based on the skin rash, fever, eosinophilia, and liver and kidney involvement. According to the European Registry of Severe Cutaneous Adverse Reactions to Drugs and Collection of Biological Samples (RegiSCAR), our patient had a score of 6. Drug rash with eosinophilia and systemic symptoms syndrome is a severe form of drug reaction with the potential for significant morbidity and mortality. Human leukocyte antigens (HLA) screening may be performed to prevent disease in susceptible patients. Steroids in a tapering dose are helpful in the resolution of symptoms.

Cardiovascular Morbidity in Ankylosing Spondylitis: A Focus on Inflammatory Cardiac Disease.

Ankylosing spondylitis (AS) is associated with an increase in cardiovascular (CV) morbidity when compared to the general population. The increased risk of CV involvement in AS is likely multifactorial including inflammation accelerating atherosclerosis and the cardiac inflammation itself in the form of aortitis and conduction anomalies. Establishing indisputable evidence linking AS and CV disease is challenging due to AS being relatively rare and it affects 1:1,000 and all studies analyzing the association between AS and CV disease involve a small sample size making long-term outcome measurements limited. The article reviews the literature studying the association between AS and CV disease as well as the impact of therapies for AS on the CV system (CVS).

Efficacy and safety of E-OA-07 in moderate to severe symptoms of osteoarthritis: a double-blind randomized placebo-controlled study.

The efficacy and safety of a polyherbal preparation E-OA-07 was compared against placebo in patients with moderate to severe symptoms of osteoarthritis (OA) of the knee, in a double-blind, randomized, parallel groups study. Male or female subjects with American Rheumatism Association functional class II/III and Kellgren Lawrence grade 2 or 3 OA of the knee, who had moderate to severe OA symptoms as recorded by a score of at least 60 on the modified version of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index, and an overall pain score of at least 70 mm on a 100 mm Visual analogue (VAS) scale were studied. Subjects received 2 capsules of E-OA-07 or placebo twice daily for 12 weeks and paracetamol up to 2 gm per day as rescue medication. Efficacy outcome measures were WOMAC and VAS scores, functional tests for joint mobility and gait, consumption of rescue medication, investigator's global assessment and subjects' opinion. Safety was assessed through incidence of adverse events and subject's assessment of tolerability. After 12 weeks of treatment, there was a significant reduction of WOMAC scores in the E-OA-07 group as compared with placebo (P < 0.01). Mean (±SEM) reductions in WOMAC scores of pain, stiffness, and physical function for E-OA-07 versus placebo were 8.86 (1.77) versus 2.50 (0.76), 3.00 (0.65) versus 0.75 (0.45), and 30.00 (5.22) versus 10.87 (2.18). Significant between-group differences were also observed for VAS scores of pain and stiffness. The symptom alleviating effect of E-OA-07 persisted over a follow-up period of 4 and 6 weeks as VAS pain and stiffness scores continued to remain statistically lower (P < 0.01) in the E-OA-07 group than placebo. Subject's opinion was significantly greater in favor of E-OA-07 than placebo, whereas both groups received favorable responses from investigator. Consumption of rescue medication and tolerability ratings were similar between the 2 groups. One E-OA-07 subject was hospitalized due to accidental fall and withdrawn from the study. No other serious adverse event occurred. The effect of E-OA-07 in relieving moderate to severe symptoms of OA of the knee is well tolerated, superior, and more persistent than placebo.

Efficacy and safety of two polyherbal combinations: E-MA-H and E-MA-HP in male sexual dysfunction.

Efficacy and safety of 2 herbal products--E-MA-H at 2 dose levels, low (HLD) and high (HHD), and E-MA-HP (HP) capsules--versus placebo (PL) was evaluated in subjects with male sexual dysfunction. Males aged 21-60 with erectile dysfunction, premature ejaculation, or other form of sexual dysfunction were studied in this triple-blind, randomized, placebo-controlled, parallel-groups trial. Subjects received any one of the following 4 interventions: E-MA-H 2 capsules at night (HLD) for 60 days; E-MA-H 2 capsules twice daily for 30 days, followed by 2 capsules at night for 30 days (HHD); E-MA-HP (HP) 2 capsules twice daily for 60 days; or placebo (PL) 2 capsules twice daily for 60 days. All dosage regimens were standardized to 2 capsules twice daily by using 2 matching placebo capsules as the morning dose for HLD and on days 31-60 for HHD. Efficacy outcome measures were the international index of erectile function; index for premature ejaculation; erectile dysfunction inventory of treatment satisfaction; subjects' and investigators' global assessment. Safety was assessed through adverse events; hematology; blood chemistry. Of 148 subjects enrolled, 1 was excluded from analysis; data on the intention-to-treat population of 147 (PL = 36, HLD = 38, HHD = 37, HP = 36) were analyzed. There was a significant (P < 0.01) increase in the total international index of erectile function score (mean ± SEM) in subjects receiving HLD (16.28 ± 1.39), HHD (15.40 ± 1.22), and HP (18.55 ± 1.36) compared with PL (6.83 ± 1.52). The same pattern was seen with increase in index for premature ejaculation scores: HLD (9.68 ± 1.17), HHD (10.27 ± 1.05), HP (11.36 ± 1.20) versus PL (3.77 ± 1.04). There was no significant difference in effect among the active treatment groups. The incidence of adverse events was similar in all the groups. Laboratory evaluations did not show any clinically significant abnormality in any of the groups. Treatment with HLD, HHD, and HP is well tolerated, and more effective than placebo (P < 0.01), in subjects with erectile dysfunction, premature ejaculation, and other forms of sexual dysfunction.

Can the ethnic differences in IVF cycle outcome be influenced by the impact of BMI?

The objective of this study was to investigate the role of Body Mass Index (BMI) in influencing ethnic variation in IVF outcomes. This retrospective cohort study included women (having BMI between 19 to 30 kg/m2) undergoing their first IVF cycle with fresh blastocyst transfer at a single IVF unit between 2010 and 2015. In summary, South Asian women had a lower live birth rate (LBR) (27% vs 44.7%, aOR 0.41, 95% CI 0.29 to 0.59) than Caucasian women. Subgroup analysis revealed a significantly lower LBR for South Asian women when their BMI was 25-25.9 kg/m2 (21.4% vs 47.4%, aOR 0.19, 95% CI 0.04 to 0.84), 26-26.9 kg/m2 (30.0% vs 55.0%, aOR 0.26, 95% CI 0.08 to 0.86) and 27-27.9 kg/m2 (14.3% vs 39.4%, aOR 0.14, 95% CI 0.03 to 0.70) with no significant differences in the other BMI subgroups. These results suggest that a lower BMI cut-off may be indicated for South Asian women having IVF when compared to Caucasian women. These findings are novel but are limited because they are from a single centre. However, the results should prompt further research into the subject by multi-centre studies with larger number of IVF cycles analysed.

A review of paediatric and adolescent gynaecology services in a tertiary outpatient clinic.

Adolescence is a distinctive stage in human development during which many simple and complex medical conditions can present for the first time. Paediatric and adolescent gynaecological conditions need careful multidisciplinary clinical management with a sensitive approach understanding the patients' psychological and physiological circumstances. The objective of this study is to review the tertiary paediatric and adolescent gynaecology service in Leeds, United Kingdom and to present an overview of the various conditions that present to such a clinic. A total of 985 patients were seen over a 16-year period and the increasing number of patients seen over this time establishes the need for such a service to exist. Complex developmental anomalies of the genital tract and disorders of sexual differentiation formed a major portion of the referrals. Presence of a significant number of referrals for simple gynaecological conditions including menstrual irregularities, gynaecological pain, vulvovaginitis, polycystic ovary syndrome and concerns about labial appearance indicates the reluctance of general gynaecologists and general practitioners to manage such conditions in young patients. This emphasizes the need for continued education of primary health care professionals and establishment of clear guidelines and care pathways for the management of this special patient group.