An internal pilot study of a novel rectal mucocellular sampling device to allow next-generation sequencing for colorectal disease.

BACKGROUND: The ORI-EGI-02 study was designed to test the hypothesis that rectal mucus collected using a novel rectal sampling device (OriCol™), contains sufficient human deoxyribonucleic acid (DNA) of the required quality for Next Generation Sequencing (NGS), for colorectal disease genetic signature discovery. METHODS: Using National Institute for Health and Care Research methodology, an internal pilot study was performed in January 2020-May 2021, at four sites in the United Kingdom, to assess the process of recruitment, consent, specimen acquisition and viability for analysis. Following an OriCol™ test, the sample was stabilized with a buffer solution to preserve the material, which was posted to the laboratory. Samples were processed using QIAamp® DNA Blood Midi kit to extract DNA and Quant-iT™ PicoGreen® dsDNA Reagent to quantify the retrieved DNA. DNA integrity was measured by Agilent TapeStation system. 25 ng of human amplifiable DNA was prepared for Next Generation Sequencing (NGS), which was performed on an Illumina NextSeq550 sequencer using the 300-cycle high output kit v2.5. RESULTS: This study assessed the first 300 patients enrolled to the ORI-EGI-02 Study (n = 800). 290/300 (96.67%) were eligible to undergo OriCol™ sampling procedure and 285/290 (98.27%) had a successful OriCol™ sample taken. After transportation, extraction and quantification of DNA, 96.20% (279/290) of the samples had NGS successfully performed for bioinformatic analysis. CONCLUSIONS: Our internal pilot study demonstrated that the OriCol™ sampling device can capture rectal mucus from unprepared bowel in subjects who could undergo a digital rectal examination. The technique could be applied irrespective of age, frailty, or co-morbidity. Completion of the study to 800 patients and analysis of NGS data for colorectal cancer mutations will now proceed.

Stepped-wedge randomized controlled trial of laparoscopic ventral mesh rectopexy in adults with chronic constipation.

BACKGROUND: The effectiveness of laparoscopic ventral mesh rectopexy (LVMR) in patients with defecatory disorders secondary to internal rectal prolapse is poorly evidenced. A UK-based multicenter randomized controlled trial was designed to determine the clinical efficacy of LVMR compared to controls at medium-term follow-up. METHODS: The randomized controlled trial was conducted from March 1, 2015 TO January 31, 2019. A stepped-wedge RCT design permitted observer-masked data comparisons between patients awaiting LVMR (controls) with those who had undergone surgery. Adult participants with radiologically confirmed IRP refractory to conservative treatment were randomized to three arms with different delays before surgery. Efficacy outcome data were collected at equally stepped time points (12, 24, 36, 48, 60, and 72 weeks). Clinical efficacy of LVMR compared to controls was defined as ≥ 1.0-point reduction in Patient Assessment of Constipation-Quality of Life and/or Symptoms (PAC-QOL and/or PAC-SYM) scores at 24 weeks. Secondary outcome measures included 14-day diary data, the Generalized Anxiety Disorder scale (GAD-7), the Patient Health Questionnaire-9 (PHQ-9), St Marks incontinence score, the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire (PISQ-12), the chronic constipation Behavioral Response to Illness Questionnaire (CC-BRQ), and the Brief Illness Perception Questionnaire (BIPQ). RESULTS: Of a calculated sample size of 114, only 28 patients (100% female) were randomized from 6 institutions (due mainly to national pause on mesh-related surgery). Nine were assigned to the T0 arm, 10 to T12, and 9 to T24. There were no substantial differences in baseline characteristics between the three arms. Compared to baseline, significant reduction (improvement) in PAC-QOL and PAC-SYM scores were observed at 24 weeks post-surgery (- 1.09 [95% CI - 1.76, - 0.41], p = 0.0019, and - 0.92 [- 1.52, - 0.32], p = 0.0029, respectively) in the 19 patients available for analysis (9 were excluded for dropout [n = 2] or missing primary outcome [n = 7]). There was a clinically significant long-term reduction in PAC-QOL scores (- 1.38 [- 2.94, 0.19], p = 0.0840 at 72 weeks). Statistically significant improvements in PAC-SYM scores persisted to 72 weeks (- 1.51 [- 2.87, - 0.16], p = 0.0289). Compared to baseline, no differences were found in secondary outcomes, except for significant improvements at 24 and 48 weeks on CC-BRQ avoidance behavior (- 14.3 [95% CI - 23.3, - 5.4], and - 0.92 [- 1.52, - 0.32], respectively), CC-BRQ safety behavior (- 13.7 [95% CI - 20.5, - 7.0], and - 13.0 [- 19.8, - 6.1], respectively), and BIPQ negative perceptions (- 16.3 [95% CI - 23.5, - 9.0], and - 10.5 [- 17.9, - 3.2], respectively). CONCLUSIONS: With the caveat of under-powering due to poor recruitment, the study presents the first randomized trial evidence of short-term benefit of LVMR for internal rectal prolapse. TRIAL REGISTRATION: ISRCTN Registry (ISRCTN11747152).

Osteopathic manipulative treatment (OMT) use among osteopathic physicians in the United States.

CONTEXT: Updated data on the use of Osteopathic Manipulative Treatments (OMT) by osteopathic physicians in the United States is overdue. This data would provide an up-to-date point of reference for evaluating the current use of OMT as a distinguishing feature of the osteopathic profession. OBJECTIVE: To determine the prevalence of OMT use, barriers to its use, and factors that correlate with increased use. METHODS: The American Osteopathic Association (AOA) distributed its triannual survey on professional practices and preferences of osteopathic physicians, including questions on OMT, to a random sample of 10,000 osteopathic physicians in August 2018 through Survey Monkey (San Mateo, CA). Follow-up efforts included a paper survey mailed to nonrespondents one month after initial distribution and three subsequent email reminders. The survey was available from August 15, 2018 to November 5, 2018. The OMT questions focused on frequency of OMT use, perceived barriers, and basic demographic information of osteopathic physician respondents. Statistical analysis (including a one sample test of proportion, chi-square, and Spearman's rho) was performed to identify significant factors influencing OMT use. RESULTS: Of 10,000 surveyed osteopathic physicians, 1,683 (16.83%) responded. Of those respondents, 1,308 (77.74%) reported using OMT on less than 5% of their patients, while 958 (56.95%) did not use OMT on any of their patients. Impactful barriers to OMT use included lack of time, lack of reimbursement, lack of institutional/practice support, and lack of confidence/proficiency. Factors positively correlated with OMT use included female gender, being full owner of a practice, and practicing in an office-based setting. CONCLUSION: Our data suggest that OMT use among osteopathic physicians in the US continues to decline. Barriers to its use appear to be related to the difficulty that most physicians have with successfully integrating OMT into the country's insurance-based system of healthcare delivery. Follow-up investigations on this subject in subsequent years will be imperative in the ongoing effort to monitor and preserve the distinctiveness of the osteopathic profession.

Surgery for constipation: systematic review and practice recommendations: Results II: Hitching procedures for the rectum (rectal suspension).

AIM: To assess the outcomes of rectal suspension procedures (forms of rectopexy) in adults with chronic constipation. METHOD: Standardised methods and reporting of benefits and harms were used for all CapaCiTY reviews that closely adhered to PRISMA 2016 guidance. Main conclusions were presented as summary evidence statements with a summative Oxford Centre for Evidence-Based Medicine (2009) level. RESULTS: Eighteen articles were identified, providing data on outcomes in 1238 patients. All studies reported only on laparoscopic approaches. Length of procedures ranged between 1.5 to 3.5 h, and length of stay between 4 to 5 days. Data on harms were inconsistently reported and heterogeneous, making estimates of harm tentative and imprecise. Morbidity rates ranged between 5-15%, with mesh complications accounting for 0.5% of patients overall. No mortality was reported after any procedures in a total of 1044 patients. Although inconsistently reported, good or satisfactory outcome occurred in 83% (74-91%) of patients; 86% (20-97%) of patients reported improvements in constipation after laparoscopic ventral mesh rectopexy (LVMR). About 2-7% of patients developed anatomical recurrence. Patient selection was inconsistently documented. As most common indication, high grade rectal intussusception was corrected in 80-100% of cases after robotic or LVMR. Healing of prolapse-associated solitary rectal ulcer syndrome occurred in around 80% of patients after LVMR. CONCLUSION: Evidence supporting rectal suspension procedures is currently derived from poor quality studies. Methodologically robust trials are needed to inform future clinical decision making.

[Infant-juvenile malnutrition in Fo-Boure (Benin): Anthropometric data and management of malnourished children]. / Malnutrition infantojuvénile à Fo-Bouré (Bénin): données anthropométriques et prise en charge des enfants malnutris.

UNLABELLED: Acute malnutrition or emaciation in childhood is defined by a low ratio weight/height. In Benin, 8% of the children are concerned. In the north of Benin, the situation is alarming. The aim of this survey is to specify: (1) the characteristics of infantile malnutrition in rural area in the north of Benin and (2) the management of the malnourished children. SUBJECTS AND METHODS: A descriptive survey was conducted in a paediatric dispensary. Anthropometric data of children from 0 to 60 months were collected. The children with severe malnutrition were admitted to a nutritional rehabilitation centre. The methods were those recommended by the World Health Organization and were adapted to the local resources. RESULTS: The anthropometric data of 239 children were analyzed. The prevalence of emaciation was 33%. Thirty-eight children were admitted to the centre. Twenty-nine of the children recovered. DISCUSSION: This survey confirms the precarious situation in the north of Benin, which may be explained by socio-economic and climatic factors. It can be prevented partly by better food availability, but also by an education on mothers. The strategies must be updated according to their effectiveness in terms of public health and their local acceptability. CONCLUSION: The prevalence of malnutrition in Fo-Bouré is beyond the value used by WHO to define the zones where the nutritional situation requires nutritional rehabilitation centres.

1994 William J. Stickel Silver Award. Closing base wedge versus Austin bunionectomies for metatarsus primus adductus.

Hallux abducto valgus with concomitant metatarsus primus adductus was treated by either an isolated Austin bunionectomy or by a combination of a modified McBride bunionectomy, along with a closing base wedge osteotomy, on a total of 73 patients (88 feet) from 1983 to 1993. Both subjective and objective similarities and differences were compared between these two groups of patients. Long-term elevation or depression of the first ray was analyzed by using a technique termed sagittal plane displacement. The prevalent preoperative symptoms were significantly reduced postoperatively in both groups of patients. Initial postoperative elevation of the first ray occurred in approximately one third of the cases in both groups. Long-term elevation of the first ray was greater with the base wedge osteotomy and did not change appreciably with the Austin procedure. The sagittal plane displacement method is a helpful tool in analyzing changes in the position of the first ray perioperatively.

[Efficacy and tolerability of morniflumate in acute otitis in infants: results of a randomized study versus placebos]. / Efficacité et tolérance du morniflumate dans les otites aiguës du nourrisson: résultats d'une étude randomisée contre placebo.

In a randomized double-blind placebo-controlled, parallel group study, 79 infants with acute otitis media received treatment with suppositories containing either Nifluril (400 mg daily, morniflumate) or placebo for five days. Both groups of patients also received amoxicilline (50 mg/kg daily) for eight days. The combination of Nifluril with antibiotic therapy gave significantly greater relief from abnormalities of the tympanic membrane (after two days treatment), inflammation of the throat and nasal congestion than did antibiotic therapy alone. Overall clinical assessment confirmed a significantly greater recover rate in the Nifluril group compared with the placebo group. Very few side effects were recorded, limited to diarrhoea, without any drug interruption. Nifluril may be recommended as an effective safe adjuvant to the antibiotic treatment of acute otitis media in infants.

Apparatus for dry stress corrosion kinetic studies.

An apparatus for carrying out kinetic studies on the dry stress corrosion of threadlike metal specimens in well-determined conditions of uniaxial stress is described. The results obtained by electrical conductivity measurements can easily be related to those obtained by thermogravimetry.

Ultrastructural study of hepatic effects of a contraceptive steroid in baboon.

PIP: Observations were made of the chronic administration of norethindron e orally to 2 male baboons (Papio anubis), 1 mg/day daily for 1 month and then 5 mg/day for 5 months. A third animal was given the biscuits used for administration but without the drug. Liver biopsies were made 1 week prior to treatment, each month during treatment, and for 2 months following termination of treatment. Under electron microscopic magnification of 3000-12000 diameters, ultrastructural observations revealed dilatation and vesiculation of the endoplasmic reticulum as well as of the Golgi complexes. Cells with depleted glycogen granules w ere frequent and usually seen next to cells with glycogen. Accumulation of increased numbers and sizes of electron-dense microbodies was observed as treatment continued. Cells with large vacuolated inclusion bodies were always associated with anomalous bile canaliculi. Endothelial sinusoids included both macrophages and numerous electron-dense microbodies, especially in the later stages of treatment. A collagen substance appeared to have infiltrated the sinusoids of some of the parenchymal cells. When therapy was terminated the ultrastructure of the biopsy material showed progressive regeneration toward normal morphology. At the end of 2 months this structure was similar to control materials. Hepatic changes observed in this study are similar to those reported by others as occurring in women using oral contraceptives. The hepatocellurlar changes were temporary and reversible.^ieng