Engagement in Prescription Opioid Tapering Research: the EMPOWER Study and a Coproduction Model of Success.

Patients with chronic pain experience stigma within the healthcare system. This stigma is compounded for those taking long-term prescription opioids. Often, public messaging and organizational policies have telegraphed that opioid treatment is a problem to be solved by focusing only on medication reduction efforts. Lack of data has contributed to misperceptions and poor opioid policies. In part, data collection remains poor because patients feel fractured from systems of care and are often not interested in engaging with opioid reduction mandates and research. Similarly, clinicians may fail to engage with opioid stewardship and research due to complexities that exceed their training or capacities. The EMPOWER study applies a coproduction model that engages researchers, patients, clinicians, managers, and other health system users. Key stakeholders shaped the design of the study to best ensure acceptability and engagement of the "end users"-patients who enroll in the study and the clinicians who implement the opioid tapers. Targeting the needs of any stakeholder group in isolation is suboptimal. Accordingly, we detail the EMPOWER patient-centered opioid tapering clinical research framework and specific strategies to address stakeholder concerns. We also discuss how this framework may be applied to enhance engagement in healthcare research broadly.

Comparative Effectiveness of Cognitive Behavioral Therapy for Chronic Pain and Chronic Pain Self-Management within the Context of Voluntary Patient-Centered Prescription Opioid Tapering: The EMPOWER Study Protocol.

OBJECTIVE: Evidence to date, while sparse, suggests that patients taking long-term opioids require special considerations and protections to prevent potential iatrogenic harms from opioid de-prescribing, such as increased pain or suffering. Following this study protocol, the EMPOWER study seeks to address multiple unmet needs of patients with chronic pain who desire to reduce long-term opioid therapy, and provide the clinical evidence on effective methodology. METHODS: EMPOWER applies patient-centered methods for voluntary prescription opioid reduction conducted within a comprehensive, multi-state, 3-arm randomized controlled comparative effectiveness study of three study arms (1) group cognitive behavioral therapy for chronic pain; (2) group chronic pain self-management; and (3) usual care (taper only). Specialized electronic data capture systems collect patient reported symptoms and satisfaction data weekly and monthly during the taper, with real-time clinical alerts and electronic feedback loops informing, documenting, and steering needed care actions. CONCLUSION: The EMPOWER study seeks to provide granular evidence on patient response to voluntary opioid tapering, and will provide evidence to inform clinical systems changes, clinical care, patient satisfaction, and patient outcomes for opioid reduction.

A Randomized Controlled Trial Comparing Trainee-Directed Virtual Reality Simulation Training and Box Trainer on the Acquisition of Laparoscopic Suturing Skills.

OBJECTIVE: To compare the proficiency of novices in acquiring laparoscopic suturing skills following training in a virtual reality simulator or box trainer compared to no training. METHODS: This was a RCT in a university-affiliated teaching hospital recruiting participants who had no laparoscopic suturing experience to have suturing skill training in the virtual reality simulator, box trainer, or no training as control. Trainees were allowed to terminate training when they perceived competence in the procedure. Suturing skills were tested in the box trainer and scored using a modified Global Operative Assessment of Laparoscopic Skills questionnaire by their own self-evaluation and two experienced gynaecological laparoscopists. RESULTS: Of the 36 participants recruited, 27 (75%) had no laparoscopic experience. Participants with no laparoscopic experience took longer to complete training than those with experience (median 90 minutes [interquartile range (IQR) 80-115] vs. 55 min [IQR 40-65], respectively; P = 0.044). There were no differences in successful completion of the task (7/12 [58.3%], 10/12 [83.3%], 7/12 [58.3%]; P = 0.325), median suturing time in seconds (628 [IQR 460-835], 611 [IQR 434-691], 609 [IQR 540-837]; P = 0.702), mean subjective (mean ± SD 9.8 ± 1.8, 10.4 ± 2.8, 9.3 ± 2.4; P = 0.710), and objective (7.2 ± 1.8, 8.2 ± 2.1, 7.6 ± 1.7; P = 0.426) modified Global Operative Assessment of Laparoscopic Skills score in the simulator, pelvic trainer, and control groups, respectively. The intraclass correlation coefficient of the two reviewers was 0.422 (95% CI 0.159-0.717). CONCLUSION: Trainees were unable to accurately assess themselves as to skill level in laparoscopic suturing. A longer training time is required for novices to master laparoscopic suturing using a simulator or box trainer.

Clinical Significance of Pyometra.

OBJECTIVE: To review the clinical profiles and management outcomes of patients with pyometra. STUDY DESIGN: A retrospective review of all women admitted with a confirmed diagnosis of pyometra over an 8-year period (January 2003 to December 2010). The medical records, including operation notes, histological and microbiological results, were reviewed. RESULTS: A total of 57 patients accounting for 76 admissions were identified. The mean patient age was 82.0 ± 11.3 years. The most common presenting symptom was postmenopausal bleeding (59.2%), followed by vaginal discharge (40.8%), fever (6.6%), and abdominal pain (5.3%). Drainage of pyometra was either by uterine Foley catheter insertion (48 patients [84.2%]) or repeated endometrial aspiration (2 patients [3.5%]). Antibiotics were prescribed to 49 patients (86.0%). Diagnostic hysteroscopy with mechanical cervical dilation was performed in 6 patients (10.5%). Gynecological malignancy was identified in only 1 patient, while colorectal cancer was identified in 2 patients. No patient had spontaneous uterine perforation or sepsis. Sixteen patients had recurrent pyometra within a mean follow-up period of 5.1 ± 5.8 months (range, 0.5-23 months). CONCLUSION: Pyometra usually presents with postmenopausal bleeding and can be treated with drainage and antibiotics treatment. In contrast to previous reports, our study indicates that spontaneous uterine perforation and gynecological malignancies are not commonly associated with pyometra.

Second trimester medical abortion in a woman with prior classical caesarean section and a uterine leiomyoma--a case report.

BACKGROUND: Medical abortion in women with the scar of a classical caesarean section (CS) and a large uterine leiomyoma is rarely attempted; it carries the risk of uterine rupture and haemorrhage. CASE: A 34-year-old multiparous woman with prior classical CS and a 14 × 10 × 9 cm leiomyoma arising from the uterine isthmus had an induced abortion at 14 weeks' gestation. Mechanical cervical priming with Dilapan(®)-S followed by vaginal misoprostol administration resulted in the uncomplicated expulsion of the uterine contents. CONCLUSIONS: An early second trimester medical abortion with misoprostol was successfully performed in a woman with prior classical CS and a large uterine leiomyoma.

Re-envisioning community genetics: community empowerment in preventive genomics.

As genomic technologies rapidly develop, polygenic scores (PGS) are entering into a growing conversation on how to improve precision in public health and prevent chronic disease. While the integration of PGS into public health and clinical services raises potential benefits, it also introduces potential harms. In particular, there is a high level of uncertainty about how to incorporate PGS into clinical settings in a manner that is equitable, just, and aligned with the long-term goals of many healthcare systems to support person-centered and value-based care. This paper argues that any conversation about whether and how to design and implement PGS clinical services requires dynamic engagement with local communities, patients, and families. These parties often face the consequences, both positive and negative, of such uncertainties and should therefore drive clinical translation. As a collaborative effort between hospital stakeholders, community partners, and researchers, this paper describes a community-empowered co-design process for addressing uncertainty and making programmatic decisions about the implementation of PGS into clinical services. We provide a framework for others interested in designing clinical programs that are responsive to, and inclusive and respectful of, local communities.

Randomized study of vaginoscopy and H Pipelle vs traditional hysteroscopy and standard Pipelle.

STUDY OBJECTIVE: To compare the use of vaginoscopic vs traditional hysteroscopy in evaluation of the endometrial cavity. DESIGN: Prospective, randomized, single blinded, clinical trial (Canadian Task Force classification I). SETTING: University-affiliated hospital in Hong Kong. PATIENTS: Ninety women scheduled to undergo diagnostic hysteroscopy without anesthesia. INTERVENTIONS: Women were randomized to undergo either vaginoscopic hysteroscopy using the H Pipelle for endometrial sampling (n = 45) or traditional hysteroscopy using the standard Pipelle (n = 45). Both procedures were performed without anesthesia and using a rigid 4.5-mm hysteroscope. Main outcome measures analyzed were pain scores using a 10-point visual analog scale during hysteroscopy, endometrial biopsy, and overall pain score of the procedure, success and duration of each procedure, and adequacy of the endometrial sample obtained. MEASUREMENTS AND MAIN RESULTS: The success rates for vaginoscopic and traditional hysteroscopy were 93.33% and 100%, respectively (p = .24). There was no significant difference in the mean pain score and procedure duration between the 2 hysteroscopic approaches. Endometrial sampling using the H Pipelle was significantly quicker by about 45 seconds compared with use of the standard Pipelle (mean [SD] duration, 1.46 [0.72] min vs 2.20 [1.19] min, respectively; p = .001), with similar biopsy adequacy. Most women (95.5% in both approaches) found the procedure acceptable. There were no intraoperative or postoperative complications. CONCLUSIONS: Vaginoscopic and traditional hysteroscopic approaches are similar in safety, feasibility, and associated pain. Although the time needed to obtain an endometrial sample using the H Pipelle was quicker than with the standard Pipelle, there is no difference in overall procedure duration.

A prospective randomized trial to compare immediate and 24-hour delayed catheter removal following total abdominal hysterectomy.

OBJECTIVE: To assess whether early or immediate removal of a 12F in-dwelling Foley catheter after total abdominal hysterectomy affects the level of subjective pain assessment postoperatively. DESIGN: Randomized controlled trial. SETTING: University Hospital. POPULATION: Seventy women underwent total abdominal hysterectomies for various benign gynecological diseases. METHODS: Women were randomized to have the urinary catheter removed in the operating room after the surgical procedure or to have it removed on postoperative day 1. MAIN OUTCOME MEASURES: The primary outcome was patients' pain assessment and the secondary outcomes were rate of re-catheterization and symptomatic urinary tract infection. RESULTS: There was no difference in the pain assessment between the two groups. A significantly higher number of urinary retention episodes requiring re-catheterization were found in the immediate removal group compared with the delayed removal group (20 vs. 0%; p= 0.011). The incidence of symptomatic urinary tract infection did not differ between the two groups. CONCLUSIONS: There are pros and cons regarding the policy of one-day in-dwelling catheterization compared to immediate catheter removal.

Left upper quadrant approach in gynecologic laparoscopic surgery.

OBJECTIVE: To review the use of the left upper quadrant approach in benign gynecologic laparoscopic surgery over a nine-year period. DESIGN: Retrospective review. Setting. University-affiliated hospital. POPULATION: Women who underwent laparoscopic gynecologic surgery the upper quadrant approach between January 2002 and December 2010. METHODS: Medical records were reviewed. MAIN OUTCOME MEASURES: Demographic data, past surgical histories, indications for surgery and the use of the left upper quadrant approach, intraoperative findings, diagnosis and any complications. RESULTS: 143 patients were identified, accounting for 4.9% of all gynecologic laparoscopic surgery. The indications for using the left upper quadrant approach were: previous open abdominal surgery (113, 79.0%), surgery in the second trimester of pregnancy (16, 11.1%), presence of large pelvic mass (9, 6.2%), previous transverse rectus abdominis myocutaneous flap for breast reconstruction (3, 2.0%), previous periumbilical hernia repair (1, 0.6%) and previous laparoscopic umbilical wound dehiscence (1, 0.6%). In women with previous abdominal surgery, the overall incidence of adhesions between omentum and/or bowel to the anterior abdominal wall in the umbilical region was 58.4%. Twelve (8.3%) patients required conversion to laparotomy. One patient had subcutaneous surgical emphysema over the left upper quadrant entry site. CONCLUSIONS: The left upper quadrant approach is an effective, safe and easy technique for peritoneal cavity access in women undergoing laparoscopic gynecologic surgery and should be considered in women with risk factors of periumbilical adhesions and in the presence of a large pelvic mass.

Online Consent Enables a Randomized, Controlled Trial Testing a Patient-Centered Online Decision-Aid for Medicare Beneficiaries to Meet Recruitment Goal in Short Time Frame.

Online consenting allows potential participants of research projects to deliberate their participation at their own pace and may be more cost-effective than conventional approaches. Yet, online consenting is not widespread in health services research due partly to concerns about security, confidentiality, and lack of established processes. We report our use of online consenting to successfully enroll over 1185 Medicare beneficiaries in a short 9-week time frame for a research study.

Machine-Based Expert Recommendations And Insurance Choices Among Medicare Part D Enrollees.

Choosing a health insurance plan is difficult for many people, and patient-centered decision support may help consumers make these choices. We tested whether providing a patient-centered decision-support tool-with or without machine-based, personalized expert recommendations-influenced decision outcomes for Medicare Part D enrollees. We found that providing an online patient-centered decision-support tool increased older adults' satisfaction with the process of choosing a prescription drug plan and the amount of time they spent choosing a plan. Providing personalized expert recommendations as well increased rates of plan switching. Many people who could have accessed the tool chose not to, and the characteristics of people who used the tool differed from those who did not. We conclude that a patient-centered decision-support tool providing personalized expert recommendations can help people choose a plan, but different approaches may be necessary to encourage more people to periodically reevaluate their options.

Comparative Usability Study of a Newly Created Patient-Centered Tool and Medicare.gov Plan Finder to Help Medicare Beneficiaries Choose Prescription Drug Plans.

INTRODUCTION: In response to reported difficulties in selecting a Medicare Part D prescription drug plan, we designed a patient-centered online Part D plan selection tool (CHOICE1.0) to simplify the selection process and to provide personalized, expert recommendations. METHODS: This ethnographic comparative usability study observed 44 patients using the first version of the tool during Medicare 2016 Open Enrollment. Participants were observed as they chose their drug plan using Medicare.gov and 1 of 3 versions of CHOICE1.0 that varied in amount of expert guidance. Descriptive statistics were used to analyze exit survey data. The observations were video-recorded, and field notes were analyzed thematically. RESULTS: Participants were significantly more satisfied with CHOICE1.0 for choosing a plan, understanding information, and ease of use compared to Medicare.gov. Those using expert versions of CHOICE1.0 were more likely to indicate their intention to switch plans than those using Medicare.gov, though they wanted to know the source and content. CONCLUSION: The more patient-centered prescription drug choice tool improved user experience and enabled users to choose plans more consistent with expert recommendations.

Tranexamic acid-associated necrosis and intralesional thrombosis of uterine leiomyomas: a clinicopathologic study of 147 cases emphasizing the importance of drug-induced necrosis and early infarcts in leiomyomas.

INTRODUCTION: Women with menorrhagia have increased levels of plasminogen activators in the endometrium. Tranexamic acid (cyklokapron), an antifibrinolytic agent, is commonly prescribed worldwide to women with menorrhagia, including those with fibroids. Necrosis in uterine leiomyomas may be associated with pregnancy, and progestogen or oral contraceptive use but its association with tranexamic acid has not been investigated. Four hundred ninety patients with uterine leiomyomas in 2004 and 2005 were reviewed. Their ages ranged from 22 to 86 (mean 47.2). One hundred forty-seven (30%) were treated with tranexamic acid. RESULTS: Infarct-type necrosis was observed in the leiomyomas of 38 patients, 22 of whom had tranexamic acid (15%) whereas the remaining 16 had no drug exposure (4.7%) (odds ratio=3.60; 95% confidence interval: 1.83-6.07; P=0.0003). Two patients who took the drug less than 2 weeks before surgery had early infarcts with appearance resembled coagulative type necrosis. Eleven of the 22 cases of drug-induced necrotic leiomyoma (50%) also showed intralesional thrombus formation, and 4 showed organization of the thrombi. CONCLUSIONS: Infarct-type necrosis and thrombosis of leiomyoma was more commonly observed in patients treated with tranexamic acid. Although the drug is effective for menorrhagia, clinicians should be aware of the possible complications associated with leiomyoma necrosis such as pain and fever. Distinguishing between types of necrosis may not always be straightforward particularly in early infarcts when the reparative connective tissue reaction between the viable and necrotic cells is not well-developed, resulting in an appearance similar to coagulative necrosis. When the overall gross and microscopic features of a leiomyoma with coagulative necrosis favor a benign lesion, the drug history should be reviewed so that this type of early and healing infarct-type necrosis is considered as the underlying cause of the apparent coagulative necrosis. This may otherwise result in a diagnosis of smooth muscle tumor of uncertain malignant potential, leading to prolonged follow-up and unnecessary further surgical intervention.

Prevalence of Domestic Violence in Hong Kong Chinese Women Presenting with Urinary Symptoms.

OBJECTIVES: To determine the prevalence of domestic violence and its risk factors in women presenting with urinary symptoms. METHODS: The study was carried out in the urogynecology clinic and general gynecology clinic, Department of Obstetrics and Gynecology, Queen Mary Hospital, Hong Kong from 1st May 2013 till 31st October 2014. Two hundred and twenty-five women presenting to the urogynecology clinic with urinary symptoms were categorized according to their symptoms and were asked to complete the Modified Abuse Assessment Screen. Demographic data of the subjects and their partners were collected. Mann-Whitney U test were used for analysis of continuous variables, while Chi-square test and Fisher Exact test were used for analysis of categorical variables between the abused and non-abused group. Prevalence of domestic violence were calculated and compared. RESULTS: The prevalence of domestic violence among this group of patients (7.6%) was found to be lower when compared with other studies. Verbal abuse was the commonest form of violence in our locality. The median age of the abused group and the non-abused group were both 56 years old, with the age ranging from 40 to 64 and 29 to 70 years old respectively. The prevalence of domestic violence among patients with overactive bladder syndrome, stress urinary incontinence and mixed urinary incontinence were 19.5%, 4.2% and 5.5% respectively (Fisher Exact test for whole group, P<0.05). CONCLUSION: The prevalence and nature of abuse in our locality was different from the quoted figures worldwide. Patients with overactive bladder syndrome were more likely to be victims of abuse than patients with other urinary symptoms. The difference in the prevalence of domestic violence among patients with different urinary symptoms could be related to their underlying pathophysiology. When encountering patients with overactive bladder syndrome, clinicians should consider this high incidence of domestic violence and provide prompt referral whenever necessary.

Positive predictive value of endometrial polyps in Pipelle aspiration sampling: a histopathological study of 195 cases.

OBJECTIVE: To estimate the positive predictive value of Pipelle endometrial sampling in detecting the presence of an underlying endometrial polyp. The secondary objective is to examine the histologic features that can predict the presence of endometrial polyps. STUDY DESIGN: This is a retrospective case review study. 195 women who had undergone diagnostic hysteroscopy and/or polypectomy were identified in a University teaching hospital. All patients had a prior polyp diagnosis in the Pipelle endometrial sample. The histology of these samples were compared and analyzed with subsequent DH findings and final hysteroscopic biopsies. Slides were reviewed by 2 gynaecological pathologists. RESULTS: 162 women were premenopausal (mean age 46.1, SD=4.6) and 33 were postmenopausal (mean age 57.2, SD=8.1). The commonest indication for a Pipelle endometrial sampling was abnormal uterine bleeding. Presence of polyp was confirmed by DH in 56.3% (111/195) cases. Of these, 81.1% (90/111) were confirmed histologically. The positive predictive value of detection of polyps in Pipelle endometrial samples for premenopausal and postmenopausal women was 53.7% and 72.7%, respectively (p=.05). The most reliable histologic features that can predict the presence of an underlying polyp was fibrous stroma (p=.01) and focal glandular clustering (p=.03). The prevalence of endometrial hyperplasia and carcinoma in women who was confirmed to have polyp was 11.7% (13/111). CONCLUSION: The positive predictive value of Pipelle endometrial samples in detecting endometrial polyps was 56.3%. It was higher in the postmenopausal women (72.7%) compared to premenopausal women (53.7%). The prevalence of endometrial hyperplasia and carcinoma in women who was confirmed to have polyp was consistent with the rate reported in the literature. Using ultrasonography as an adjunct maybe helpful in diagnosing endometrial polyps.

Treating a recurrent uterine arteriovenous malformation with uterine artery embolization. A case report.

BACKGROUND: Uterine arteriovenous malformation is a rare condition. Uterine artery embolization offers the possibility of conservative management as opposed to the traditional hysterectomy. We report a case with recurrent uterine arteriovenous malformation confirmed by angiography and successfully treated with a second embolization procedure. CASE: A 33-year-old woman presented with heavy vaginal bleeding. The diagnosis of uterine arteriovenous malformation was suspected on Doppler ultrasonography and confirmed by angiography. The first embolization procedure was performed using polyvinyl alcohol and steel coils. Recurrence was diagnosed 1 year later with the same imaging techniques. The second embolization procedure was performed using histoacryl. The patient remained asymptomatic at 1-year of follow-up. CONCLUSION: Minimally invasive management is an option in recurrent uterine arteriovenous malformation.

Surgical management of adnexal masses in pregnancy.

BACKGROUND AND OBJECTIVES: Our objective was to review the surgical management, surgical outcomes, and obstetric outcomes of adnexal masses in pregnancy. METHODS: A retrospective review was performed of pregnant women before 20 weeks of gestation who underwent laparoscopy or laparotomy for management of an adnexal mass during the period of January 2005 to June 2012 at a university-affiliated hospital. RESULTS: Thirty-five pregnant women underwent surgical removal of adnexal masses during the 7.5-year study period: 21 (60.0%) underwent laparoscopic surgery, and 14 (40.0%) underwent laparotomy. The left upper quadrant entry technique was used in 20 women. Conversion to laparotomy was required in 2 women because of extensive pelvic adhesions. The mean gestational age at surgery was 15.2 ± 1.9 weeks. All women had undergone ovarian cystectomy. A malignant mass was found in 3 (8.6%) women. The laparoscopy group had a significantly less blood loss (67.4 ± 55.8 vs 153.6 ± 181.0 mL, P = .048) and shorter mean hospital stay (2.8 ± 1.0 vs 3.8 ± 1.1 days, P = .006) than the laparotomy group. One woman miscarried soon after surgery. There was no significant difference in obstetric outcomes between the laparoscopy and laparotomy groups. CONCLUSION: Surgical management of adnexal masses during pregnancy appears to have favorable outcomes for the mother and the fetus.

A pilot study of pre-operative misoprostol in reducing operative blood loss during hysterectomy.

OBJECTIVE: To investigate the effectiveness of a single pre-operative dose of sublingual misoprostol on reducing blood loss in abdominal hysterectomies performed for symptomatic uterine leiomyomas. STUDY DESIGN: A cohort of 64 women undergoing total abdominal hysterectomy for symptomatic uterine leiomyomas were randomly assigned to receive a single dose of sublingual 400 mcg misoprostol (n=32) or placebo containing 20mg vitamin B(6) (n=32) 30 min before the operation. The primary outcome was the operative blood loss. The secondary outcomes were requirement for blood transfusion, change in haemoglobin level after operation, and the incidence of side effects. RESULTS: Women who had misoprostol were found to have similar operative blood loss to those who had placebo (570.9 ± 361.3 ml versus 521.4 ± 297.4 ml, for misoprostol and placebo group respectively; P=0.803). This study with a sample size of 64 was sufficient to have 80% power at the 5% level of significance to detect a reduction of blood loss greater than or equal to 30%. There were no observed differences in the need for post-operative blood transfusion (25% versus 15.6%, for misoprostol and placebo group respectively; P=0.536), the change in haemoglobin level after the operation, and the side effects profiles between the two groups. CONCLUSION: A single pre-operative dose of sublingual misoprostol is not effective in reducing intra-operative blood loss and need for post-operative blood transfusion after total abdominal hysterectomies for symptomatic uterine leiomyomas.

Comparison of the different types of "laparoscopic total hysterectomy".

STUDY OBJECTIVE: To review the operative outcomes among different types of laparoscopic total hysterectomy (LH) classified according to the Munro and Parker classification system. DESIGN: Prospective observational cohort study (Canadian Task Force classification II). SETTING: 6 major public hospitals in Hong Kong. PATIENTS: 143 patients underwent LH in a 6-month period. INTERVENTIONS: Type I to type IV LH according to the Munro and Parker classification system. MEASUREMENTS AND MAIN RESULTS: We studied 56 type I, 49 type II, 25 type III, and 13 type IV LH. The median operative time was 105 minutes, which was significantly longer in the type IV LH group (160 minutes). The median blood loss was significantly higher in the type I LH group (300 mL). The incidence of urinary tract infection in type I LH was 8.9%, which was significantly higher than other LH groups. The overall operative complication rate was 20.3%, which was highest in the type III hysterectomy group (36%), although the difference did not reach statistical significance among the various types of hysterectomy groups. CONCLUSION: There has been a change from abdominal hysterectomy to LH in the past decades, and it is time for us to explore the best type of LH. Our findings suggest that type I LH is associated with significantly more blood loss and urinary tract infection; whereas type IV LH is associated with significantly longer operating time. However, we still cannot conclude which is the best type of LH until results from a randomized controlled trial will become available.