Gender Differences in Colonoscopy: Implications for Clinical Practice and Female Gastroenterologists.

BACKGROUND AND AIMS: Performing colonoscopy can be technically challenging in female patients. Female patients may prefer having a female endoscopist. This preference, coupled with the fact that there are fewer female endoscopists, may result in gender differences in colonoscopy practice. We hypothesized that the duration of female colonoscopy is longer and that female endoscopists perform a higher proportion of female colonoscopy than male colleagues. We explored the potential revenue implications of gender differences in screening colonoscopy. METHODS: We analyzed procedure time and gender differences in 16,573 screening colonoscopies performed by 27 male and 7 female endoscopists over a three-year period in one large academic practice. We modeled the potential revenue impacts of differences in procedure duration, proportion of female colonoscopy and the frequency of detected adenomas. RESULTS: We found that screening colonoscopy takes 8.8% more time to complete in female patients compared to male patients for all endoscopists (p < 0.001), and that female endoscopists perform an average of 71.2% female exams compared to male endoscopists, who perform an average of 50.8% female exams (p < 0.001). Female patients had a lower detection adenoma rate (ADR), reducing the frequency of polypectomy and reimbursement in an RVU model. The observed gender differences could account for an estimated 9.6% revenue loss per 8-h session for a female gastroenterologist performing screening colonoscopy compared to a male counterpart. CONCLUSION: Longer colonoscopy duration in females, increased proportion of female colonoscopies for female endoscopists and lower ADR in females may contribute to the gender gap in physician pay in gastroenterology.

Hepatology Consultants Often Disagree on Etiology of Abnormal Liver Biochemistries in COVID-19 but Agree on Management.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is associated with elevated liver biochemistries in approximately half of hospitalized patients, with many possible etiologies. AIM: To assess agreement on the etiology of abnormal liver biochemistries and diagnostic recommendations in COVID-19. METHODS: Twenty hepatology consultations were reviewed by three senior hepatologists who provided a differential diagnosis and diagnostic recommendations. Kappa agreement on the primary etiology was calculated. RESULTS: Kappa agreement between hepatologists on the primary etiology of elevated liver biochemistries was 0.10 (p = 0.03). Agreement was greater around drug-induced liver injury 0.51 (p < 0.0001) and SARS-CoV-2-related liver injury 0.17 (p = 0.03). Serial liver biochemistries were recommended in all consultations over other evaluations. CONCLUSION: In COVID-19, elevated liver biochemistries present a diagnostic challenge and can often be monitored conservatively.

High grade cervical intraepithelial neoplasia positive biopsy: the importance of accurate pre-operative workup.

BACKGROUND: In cervical cancer screening programs, women with abnormal cytology and confirmation by biopsy are referred for colposcopy for histological evaluation. METHODS: We characterized the presence and the genotype of HPV by Linear Array HPV genotyping assay in cytological samples collected from about 400 women undergoing conization, with reported high CIN grade after biopsy. RESULTS: The most prevalent genotype was HPV 16, with an increasing presence depending on the severity of the CIN and with the highest incidence in the 26-35 age range. In the group of younger women (<25) we found the highest percentage of CIN3 (39.3%) and the lowest of CIN1 (17.9%). An increase of CIN1 with increasing age was observed. A different distribution of HPV presence was observed depending on CIN grade (P<0.001): CIN1 HPV negative samples were 46.3%, CIN2: 5.8% and CIN3: 1.4%. Interesting, in the analyzed cohort, we observed the presence of 30% of CIN1. Moreover, within CIN1, 85% of them were associated to negative HPV detection, this observation suggested that the detection of HPV presence may be useful to identify low CIN grade that should be reconsidered for surgical treatment. CONCLUSIONS: These findings suggest implementing the protocol for the management of women with high risk precancer lesions, with a further HPV test before surgical treatment. The evaluation of HPV presence and genotype before conization might represent a useful tool in reducing or postpone the conization treatment.

Peripartum Maternal Hepatitis B Care in a US Nationwide Data Set.

BACKGROUND: Hepatitis B virus (HBV) screening during pregnancy is standard of care to prevent vertical transmission to infants, yet the mothers themselves may not receive appropriate follow-up. GOALS: Using a national database, we sought to determine rates of maternal peripartum follow-up with a HBV specialist and identify factors associated with a lack of follow-up. MATERIALS AND METHODS: We identified women who delivered in 2000 to 2012 and were diagnosed with HBV according to International Classification of Diseases-9 codes using a national database (Optum) derived from commercial insurance claims with ∼46 million members ages 0 to 64 in all 50 states. Our primary outcome was follow-up during or after pregnancy with a HBV specialist (gastroenterology/infectious diseases). RESULTS: The prevalence of HBV was 0.27% (2558/959,747 pregnancies), and median follow-up was 45 months. Only 21% of women had peripartum HBV specialist follow-up. On multivariable regression, predictors of peripartum follow-up at 1-year included younger age [odds ratio (OR), 0.97/y; 95% confidence interval (CI), 0.94, 0.99], Asian race/ethnicity (OR, 1.56 vs. white; 95% CI, 1.13, 2.17), and residing in the Northeast (OR, 1.70; 95% CI, 1.09, 2.66) and Midwest (OR, 1.73; 95% CI, 1.07, 2.81) versus West. Predictors of testing for HBV DNA and alanine aminotransferase at 1 year included Asian race (OR, 1.72; 95% CI, 1.23, 2.41), a primary care physician visit within 2 years of delivery (OR, 1.63; 95% CI, 1.19, 2.22), and peripartum HBV specialist follow-up within 1 year (OR, 15.68; 95% CI, 11.38, 21.60). CONCLUSIONS: Maternal HBV specialist follow-up rates were extremely low in this large, diverse cohort representing all United States regions. Referral to a HBV specialist was the strongest predictor of appropriate postpartum HBV laboratory testing. Follow-up rates may be even lower in uninsured populations.

Aberrant expression of genes associated with stemness and cancer in endometria and endometrioma in a subset of women with endometriosis.

STUDY QUESTION: Is there molecular evidence for a link between endometriosis and endometriosis-associated ovarian cancers (EAOC)? STUDY ANSWER: We identified aberrant gene expression signatures associated with malignant transformation in a small subgroup of women with ovarian endometriosis. WHAT IS KNOWN ALREADY: Epidemiological studies have shown an increased risk of EAOC in women with ovarian endometriosis. However, the cellular and molecular changes leading to EAOC are largely unexplored. STUDY DESIGN, SIZE, DURATION: CD73+CD90+CD105+ multipotent stem cells/progenitors (SC cohort) were isolated from endometrium (n = 18) and endometrioma (n = 11) of endometriosis patients as well as from the endometrium of healthy women (n = 14). Extensive phenotypic and functional analyses were performed in vitro on expanded multipotent stem cells/progenitors to confirm their altered characteristics. Aberrant gene signatures were also validated in paired-endometrium and -endometrioma tissue samples from another cohort (Tissue cohort, n = 19) of endometriosis patients. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Paired-endometrial and -endometriotic biopsies were obtained from women with endometriosis (ASRM stage III-IV) undergoing laparoscopic surgery. Control endometria were obtained from healthy volunteers. Isolated CD73+CD90+CD105+ SC were evaluated for the presence of known endometrial surface markers, colony forming efficiency, multi-lineage differentiation, cell cycle distribution and 3D-spheroid formation capacity. Targeted RT-PCR arrays, along with hierarchical and multivariate clustering tools, were used to determine both intergroup and intragroup gene expression variability for stem cell and cancer-associated markers, in both SC+ and tissue cohorts. MAIN RESULTS AND THE ROLE OF CHANCE: Isolated and expanded SC+ from both control and patient groups showed significantly higher surface expression of W5C5+, clonal expansion and 3D-spheroid formation capacity (P < 0.05) compared with SC-. The SC+ cells also undergo mesenchymal lineage differentiation, unlike SC-. Gene expression from paired-endometriosis samples showed significant downregulation of PTEN, ARID1A and TNFα (P < 0.05) in endometrioma compared with paired-endometrium SC+ samples. Hierarchical and multivariate clustering from both SC+ and tissue cohorts together identified 4 out of 30 endometrioma samples with aberrant expression of stem cell and cancer-associated genes, such as KIT, HIF2α and E-cadherin, altered expression ratio of ER-ß/ER-α and downregulation of tumour suppressor genes (PTEN and ARID1A). Thus, we speculate that above changes may be potentially relevant to the development of EAOC. LARGE-SCALE DATA: N/A. LIMITATIONS, REASON FOR CAUTION: As the reported frequency of EAOC is very low, we did not have access to those samples in our study. Moreover, by adopting a targeted gene array approach, we might have missed several other potentially-relevant genes associated with EAOC pathogenesis. The above panel of markers should be further validated in archived tissue samples from women with endometriosis who later in life developed EAOC. WIDER IMPLICATIONS OF THE FINDINGS: Knowledge gained from this study, with further confirmation on EAOC cases, may help in developing screening methods to identify women with increased risk of EAOC. STUDY FUNDING/COMPETING INTEREST(S): The study is funded by the Swedish Research Council (2012-2844), a joint grant from Stockholm County and Karolinska Institutet (ALF), RGD network at Karolinska Institutet, Karolinska Institutet for doctoral education (KID), Estonian Ministry of Education and Research (IUT34-16), Enterprise Estonia (EU48695), Horizon 2020 innovation program (WIDENLIFE, 692065), European Union's FP7 Marie Curie Industry-Academia Partnerships and Pathways funding (IAPP, SARM, EU324509) and MSCA-RISE-2015 project MOMENDO (691058). All authors have no competing interest.

Reactivation of a Vaccine Escape Hepatitis B Virus Mutant in a Cambodian Patient During Anti-Hepatitis C Virus Therapy.

A 76-year-old Cambodian man co-infected with hepatitis B virus (HBV) and hepatitis C virus (HCV) 6c-1 presented for care. HBV DNA was intermittently detectable despite anti-HBs levels being above the protective threshold. During treatment for HCV, HBV DNA levels increased. Sequencing revealed multiple mutations including vaccine escape mutation and mutations predicted to enhance fitness. This case represents exacerbation of an HBV vaccine escape mutant during a direct-acting antiviral therapy.

Peripartum Care for Mothers Diagnosed with Hepatitis B During Pregnancy: A Survey of Provider Practices.

Objectives Hepatitis B (HBV) remains a significant public health burden, despite effective therapy. Routine HBV screening is recommended during pregnancy to reduce the risk of vertical transmission, but the rates of follow-up care peri-partum are low. The aim of this study was to evaluate physician practices and knowledge regarding HBV in women diagnosed perinatally. Methods A survey was distributed to obstetricians and midwives within the Partners HealthCare system at Brigham and Women's Hospital and Massachusetts General Hospital. Results Of 118 survey respondents (response rate 56%), 97% reported that they always tested for hepatitis B, and 77% referred new diagnoses of HBV during pregnancy to a HBV specialist for further care. Only 10% of respondents reported that there was formal referral mechanism in place to facilitate follow-up care for mothers diagnosed with hepatitis B infection. 91% of survey respondents selected hepatitis B surface antigen as the correct screening test, and 76% selected hepatitis B immune globulin with vaccination for the newborn as the correct prophylaxis regimen. Only 40 and 51% of respondents accurately identified serologies that were consistent with acute and chronic infection, respectively. Conclusions for Practice Routine screening for HBV in this population presents an important opportunity to identify cases and to reduce the public health burden of this disease. Providers were somewhat knowledgeable about HBV, but the lack of formal referral mechanism may explain why HBV follow-up is suboptimal in this healthcare system. Supplemental provider education and formal linkage to care programs may increase rates of follow-up HBV care.

Cost-Effectiveness of Risk Score-Stratified Hepatocellular Carcinoma Screening in Patients with Cirrhosis.

OBJECTIVES: Hepatocellular carcinoma (HCC) surveillance with biannual ultrasound is currently recommended for all patients with cirrhosis. However, clinical implementation of this "one-size-fits-all" approach is challenging as evidenced by its low application rate. We aimed to evaluate the cost-effectiveness of risk-stratified HCC surveillance strategies in patients with cirrhosis. METHODS: A Markov decision-analytic modeling was performed to simulate a cohort of 50-year-old subjects with compensated cirrhosis. Risk-stratified HCC surveillance strategies was implemented, in which patients were stratified into high-, intermediate-, or low-risk groups by HCC risk biomarker-based scores and assigned to surveillance modalities tailored to HCC risk (2 non-risk-stratified and 14 risk-stratified strategies) and compared with non-stratified biannual ultrasound. RESULTS: Quality-adjusted life expectancy gains for biannual ultrasound in all patients and risk-stratified strategies compared with no surveillance were 1.3 and 0.9-2.1 years, respectively. Compared with the current standard of biannual ultrasound in all cirrhosis patients, risk-stratified strategies applying magnetic resonance imaging (MRI) and/or ultrasound only in high- and intermediate-risk patients, without screening in low-risk patients, were cost-effective. Abbreviated MRI (AMRI) for high- and intermediate-risk patients had the lowest incremental cost-effectiveness ratio (ICER) of $2,100 per quality-adjusted life year gained. AMRI in intermediate- and high-risk patients had ICERs <$3,000 across a wide range of HCC incidences. CONCLUSIONS: Risk-stratified HCC surveillance strategies targeting high- and intermediate-risk patients with cirrhosis are cost-effective and outperform the currently recommended non-stratified biannual ultrasound in all patients with cirrhosis.

Lupus-like Immune Complex-mediated Glomerulonephritis in Patients with Hepatitis C Virus Infection Treated with Oral, Interferon-free, Direct-acting Antiviral Therapy.

Novel, all-oral interferon-free direct-acting antiviral agents have revolutionized the management of hepatitis C virus (HCV) infection by producing exceptional cure rates with minimal adverse events. While provocation or exacerbation of autoimmunity has been reported in HCV-infected patients receiving interferon, this phenomenon has not been reported in patients receiving interferon-free HCV therapy. We report the occurrence of three cases of lupus-like immune complex-mediated glomerulonephritis occurring shortly after exposure to sofosbuvir-based direct-acting antiviral therapies. In all three cases, renal function quickly improved with immunosuppression. However, two of the three patients developed infectious complications of immunosuppression and died. This is the first report of a lupus-like immune complex mediated glomerulonephritis occurring in the context of HCV eradication with all-oral direct-acting antiviral therapies.

Postpartum Laboratory Follow-up in Women With Hepatitis B in Massachusetts From 2007 to 2012.

GOALS: To determine postpartum hepatitis B virus (HBV) laboratory testing rates and identify factors associated with a lack of follow-up testing in Massachusetts. BACKGROUND: Screening for HBV infection in pregnant women is standard of care. Guidelines recommend that patients with chronic HBV have ongoing care and laboratory testing, but little is known about postpartum maternal HBV care outcomes. STUDY: We conducted a retrospective cohort study using Massachusetts Virtual Epidemiologic Network, an electronic public health surveillance system maintained by the Massachusetts Department of Public Health. We identified women who tested hepatitis B surface antigen positive during their first reported (index) pregnancy in Massachusetts from 2007 to 2012 and measured HBV-related laboratory tests reported to Massachusetts Department of Public Health during and after pregnancy. RESULTS: We identified 983 hepatitis B surface antigen positive pregnant women. Half (492/983) did not have evidence of additional postpartum HBV laboratory testing following their index pregnancy. Women who had postpartum laboratory tests reported were younger [mean age (SD): 29 (5.3) vs. 31 (5.5) y, P=0.0001] and more likely to have >1 pregnancy during the study period (41% vs. 1%, P<0.0001). There were no differences in race, ethnicity, and US born status. On multivariable logistic regression, older age predicted a lower likelihood of having postpartum laboratory testing (odds ratio, 0.77; 95% confidence interval, 0.70-0.90). CONCLUSIONS: Postpartum maternal HBV follow-up laboratory testing occurred in only half of Massachusetts women and did not vary by race, ethnicity, or US born status. Our results were limited to a single state surveillance database, which likely underestimates the number of tests ordered.

Postpartum care for mothers diagnosed with hepatitis B during pregnancy.

OBJECTIVE: We sought to determine rates of maternal postpartum hepatitis B virus (HBV) follow-up with a HBV specialist and identify factors associated with poor follow-up, as prior research has focused on infant outcomes and not maternal care. STUDY DESIGN: We conducted a retrospective review of data from Partners HealthCare system, the largest health care system in Massachusetts, and identified women with chronic HBV who delivered from 2002 through 2012. RESULTS: We identified 291 women (mean age 31.5 years, 51% Asian) with incident HBV during pregnancy. In all, 47% had postpartum follow-up with a HBV specialist, but only 19% also had appropriate laboratory tests (hepatitis B e antigen [HBeAg], hepatitis B e antibody, HBV DNA, and ALT) within 1 year of their HBV diagnosis. Mothers with HBV follow-up were more likely to have a primary care physician (PCP) within the Partners HealthCare system (66% vs 38%, P < .0001), a positive HBeAg (20% vs 8%, P = .004), and elevated AST values (17% vs 8%, P = .02). On multivariable logistic regression analysis, a mother who had a PCP (odds ratio, 2.50; 95% confidence interval, 1.37-4.59) or positive HBeAg (odds ratio, 4.45; 95% confidence interval, 1.64-12.06) had a greater likelihood of having HBV follow-up. CONCLUSION: Only 19% of HBV-infected mothers met care guidelines 1 year after being diagnosed with HBV. Inadequate postpartum HBV care affects women of all races/ethnicities. Women who had a PCP as well as those who were HBeAg positive were more likely to be referred for postpartum follow-up with a HBV specialist, suggesting that providers might be referring patients when they perceive HBV to be more serious or complex.

Hypermethylation of HOXA10 gene in mid-luteal endometrium from women with ovarian endometriomas.

A decrease in HOXA10 gene expression in eutopic mid-secretory endometrium has been found in women with endometriosis-associated infertility. Promoter hypermethylation of HOXA10 is thought to be the leading mechanism for epigenetic gene regulation in patients with endometriosis. In our series we documented significantly higher HOXA10 promoter methylation levels in women with ovarian endometriomas than in healthy controls during the mid-luteal phase. Development of epigenetic-based strategies for non-surgical treatment of infertility related to ovarian endometriomas could be an attractive field of research in the coming years.

Prophylaxis of hepatitis B infection in solid organ transplant recipients.

Rates of transmission of hepatitis B virus (HBV) infection from organ donors with HBV markers to recipients along with reactivation of HBV during immunosuppression following transplantation have fallen significantly with the advent of hepatitis B immune globulin (HBIg) and effective antiviral therapy. Although the availability of potent antiviral agents and HBIg has highly impacted the survival rate of HBV-infected patients after transplantation, the high cost associated with this practice represents a major financial burden. The availability of potent antivirals with high genetic barrier to resistance and minimal side effects have made it possible to recommend an HBIg-free prophylactic regimen in selected patients with low viral burden prior to transplant. Significant developments over the last two decades in the understanding and treatment of HBV infection necessitate a re-appraisal of the guidelines for prophylaxis of HBV infection in solid organ transplant recipients.

Prognostic gene expression signature for patients with hepatitis C-related early-stage cirrhosis.

BACKGROUND & AIMS: Cirrhosis affects 1% to 2% of the world population and is the major risk factor for hepatocellular carcinoma (HCC). Hepatitis C cirrhosis-related HCC is the most rapidly increasing cause of cancer death in the United States. Noninvasive methods have been developed to identify patients with asymptomatic early-stage cirrhosis, increasing the burden of HCC surveillance, but biomarkers are needed to identify patients with cirrhosis who are most in need of surveillance. We investigated whether a liver-derived 186-gene signature previously associated with outcomes of patients with HCC is prognostic for patients with newly diagnosed cirrhosis but without HCC. METHODS: We performed gene expression profile analysis of formalin-fixed needle biopsy specimens from the livers of 216 patients with hepatitis C-related early-stage (Child-Pugh class A) cirrhosis who were prospectively followed up for a median of 10 years at an Italian center. We evaluated whether the 186-gene signature was associated with death, progression of cirrhosis, and development of HCC. RESULTS: Fifty-five (25%), 101 (47%), and 60 (28%) patients were classified as having poor-, intermediate-, and good-prognosis signatures, respectively. In multivariable Cox regression modeling, the poor-prognosis signature was significantly associated with death (P = .004), progression to advanced cirrhosis (P < .001), and development of HCC (P = .009). The 10-year rates of survival were 63%, 74%, and 85% and the annual incidence of HCC was 5.8%, 2.2%, and 1.5% for patients with poor-, intermediate-, and good-prognosis signatures, respectively. CONCLUSIONS: A 186-gene signature used to predict outcomes of patients with HCC is also associated with outcomes of patients with hepatitis C-related early-stage cirrhosis. This signature might be used to identify patients with cirrhosis in most need of surveillance and strategies to prevent the development of HCC.

Non-high-density lipoprotein cholesterol as a biomarker for nonalcoholic steatohepatitis.

BACKGROUND & AIMS: There are no clinically available biomarkers for nonalcoholic steatohepatitis (NASH); differentiating between steatosis and NASH requires histologic evaluation. Noninvasive methods are needed to replace liver biopsy and its associated risks. Production of very low density lipoprotein (VLDL) contributes to the development of NASH and might be used to distinguish steatosis from NASH. However, it is not possible to measure levels of VLDL directly in the clinic. Non-high-density lipoprotein-cholesterol (non-HDL-C) encompasses all apolipoprotein-B-containing lipoproteins, including VLDL, and can be calculated from standard lipid panels without additional cost. METHODS: We evaluated the ability of non-HDL-C to differentiate steatosis from NASH in a prospective study of 218 patients with suspected NASH (steatosis, n = 100 and NASH, n = 118). RESULTS: Patients with NASH had a trend toward increased levels of non-HDL-C, compared with those with steatosis (P = .08). However, among subjects not on lipid-lowering medications, those with NASH had significantly higher levels of non-HDL-C (144.6 mg/dL) than those with steatosis (129.3 mg/dL; P = .025). This difference remained significant when adjusted for levels of cholesterol and triglycerides, indicating that the difference results from increased levels of apolipoprotein B including VLDL. These findings were validated in a cohort of 40 patients with steatosis or NASH who were not taking lipid-lowering agents. The NASH group had significantly higher levels of non-HDL-C than the steatosis group (162.8 vs 145.9 mg/dL; P = .04). CONCLUSIONS: NASH is associated with significantly higher levels of non-HDL-C than steatosis in patients who do not take lipid-lowering agents. This low-cost biomarker could be used in noninvasive differentiation between steatosis and NASH.

Mini-laparotomy versus vaginal surgery for class II-III obese patients with early-stage endometrial cancer.

AIM: To compare minilaparotomic and vaginal surgery in selected obese patients with early-stage endometrial cancer at high surgical risk. PATIENTS AND METHODS: Data of 37 consecutive class II-III obese patients submitted to minilaparotomic surgery were retrospectively reviewed. Thirty-seven women matched for demographic characteristics, BMI and stage of disease submitted to vaginal surgery in the same period comprised the control group. RESULTS: No difference was observed concerning intra- and postoperative data among the two groups. The patients who were submitted to general anesthesia exhibited a larger use of supplemental drugs for pain control (p>0.01), a higher incidence of thromboembolic events (p>0.005) and a longer hospitalization (p>0.02). No statistical difference was observed in terms of pattern of recurrence, disease-free survival and overall survival between the two groups of patients. CONCLUSION: Obese patients with endometrial cancer unfit for vaginal surgery can be safely managed through mini-laparotomy with the same surgical and oncological outcomes.

Hepatotoxicity from ingestion of wild mushrooms of the genus Amanita section Phalloideae collected in Mexico City: two case reports.

We present two cases of acute liver injury resulting from consumption of wild mushrooms. The first case was a male who developed acute hepatitis after ingestion of diverse mushrooms including Amanita species. His clinical course was favorable with complete recovery of liver function. The second case was a male who developed acute liver failure (ALF) after ingestion of Amanita bisporigera. He required MARS therapy as a bridge to liver transplantation but transplantation was not performed because he succumbed to multiorgan failure. There are few trials demonstrating the efficacy of the different treatments for mushroom poisoning. These cases demonstrate that the consumption of wild mushrooms without proper knowledge of toxic species represents a serious and under recognized health problem.

Use of a No. 11 blade scalpel and reusable blunt trocar to establish pneumoperitoneum: description of a safe and inexpensive technique.

First access is crucial in laparoscopic surgery because of its potentially life-threatening complications. A number of procedures using a variety of instruments have been previously described; however, the safest approach remains uncertain. Herein, we describe a simple and inexpensive method for direct trocar insertion using reusable instruments that was developed over 10 years in a series of 4721 consecutive gynecologic laparoscopic procedures. Observed data revealed that the technique is feasible, rapidly performed, and safe, with a likely cost savings, using a small set of reusable instruments. This procedure should be compared with other access methods in randomized studies to confirm the observed advantages.