Identification of essential biofilm proteins in middle ear fluids of otitis media with effusion patients.

OBJECTIVES: Otitis media with effusion (OME) is a common disease of childhood that is largely asymptomatic. However, middle ear fluid can persist for months and negatively impact a child's quality of life. Many cases of OME remain chronic and require surgical intervention. Because biofilms are known to contribute to the persistence of many diseases, this study examined effusions collected from children with chronic OME for the presence of essential biofilm structural components, members of the DNABII family of bacterial DNA-binding proteins. METHODS: Middle ear effusions were recovered from 38 children with chronic OME at the time of tympanostomy tube insertion. A portion of each specimen was submitted for microbiology culture. The remaining material was assessed by immunoblot to quantitate individual DNABII proteins, integration host factor (IHF), and histone-like protein (HU). RESULTS: Sixty-five percent of effusions (24 of 37) were culture-positive for bacterial species or yeast, whereas 35% (13 of 37) were culture-negative. IHF was detected in 95% (36 of 38) at concentrations from 2 to 481 ng/µL effusion. HU was detected in 95% (36 of 38) and quantitated from 13 to 5,264 ng/µL effusion (P ≤ 0.05 compared to IHF). CONCLUSION: Because DNABII proteins are essential structural components of bacterial biofilms, these data lend further support to our understanding that biofilms are present in the vast majority of chronic middle ear effusions, despite negative culture results. The presence and ubiquity of DNABII proteins in OME specimens indicated that these proteins can serve as an important clinical target for our novel DNABII-directed strategy to treat biofilm diseases such as chronic OME. LEVEL OF EVIDENCE: NA Laryngoscope, 130:806-811, 2020.

Evaluation of a novel cryoballoon swipe ablation system in bench, porcine, and human esophagus models.

Current ablation devices for dysplastic Barrett's esophagus are effective but have significant limitations. This pilot study aims to evaluate the safety, feasibility, and dose response of a novel cryoballoon swipe ablation system (CbSAS) in three experimental in vitro and in vivo models. CbSAS is a through-the-scope compliant balloon that is simultaneously inflated and cooled by liquid nitrous oxide delivered from a disposable handheld unit. When the cryogen is applied through a special diffuser it covers a 90° section of the circumference of the esophagus for 3 cm length. Doses range from 0.9 to 0.5 mm/second. (1) Bench model: The fixture consisted of an 'esophagus-like' tube lined with agar at 37°C to create an inner diameter of 20 or 30 mm, within which thermocouples were embedded. (2) In vivo porcine esophagus: CbSAS ablations were performed in animals that were euthanized and histological assessments of depth and percentage of esophageal mucosa successfully ablated were done. (3) In vivo, pre-esophagectomy human esophagus. After CbSAS ablations, histological assessments were performed (at 0, 4, and 28 days) to assess the depth and percentage of ablated mucosa. As outcomes, we assessed the safety and tolerability (pain and serious, device-related adverse events); efficacy (depth and uniformity) of ablation; and device performance (ease of deployment and device malfunction). In the bench model, during CbSAS, thermocouples measured minimal temperatures of -40 to -48 °C at all doses. In the porcine model, maximal effect on the mucosa was reached with a dose of 0.8 mm/second that extended to superficial submucosa, while 0.5 mm/second extended through the submucosa. All animals tolerated the treatments and, regardless of ablation dose, continued oral intake and gained weight. In the human model, six patients (5 male, 1 female, mean age 68) tolerated the procedure without adverse events. CbSAS was simple to operate, and balloon contact with tissue was easily and uniformly maintained. The maximal effect on the mucosa is achieved with a 0.8 mm/second dose. We concluded that the CbSAS device enables uniform 3 cm long, quarter-circumferential mucosal ablation in a one-step process by using a novel, through-the-scope balloon. The CbSAS delivers predictable ablation with mucosal and limited submucosal necrosis in bench, animal, and human esophagus. Because of its ease of use, this new device merits further clinical study in the treatment of patients with dysplastic Barrett's esophagus.

Safety analysis of first 1000 patients treated with magnetic sphincter augmentation for gastroesophageal reflux disease.

Antireflux surgery with a magnetic sphincter augmentation device (MSAD) restores the competency of the lower esophageal sphincter with a device rather than a tissue fundoplication. As a regulated device, safety information from the published clinical literature can be supplemented by tracking under the Safe Medical Devices Act. The aim of this study was to examine the safety profile of the MSAD in the first 1000 implanted patients. We compiled safety data from all available sources as of July 1, 2013. The analysis included intra/perioperative complications, hospital readmissions, procedure-related interventions, reoperations, and device malfunctions leading to injury or inability to complete the procedure. Over 1000 patients worldwide have been implanted with the MSAD at 82 institutions with median implant duration of 274 days. Event rates were 0.1% intra/perioperative complications, 1.3% hospital readmissions, 5.6% endoscopic dilations, and 3.4% reoperations. All reoperations were performed non-emergently for device removal, with no complications or conversion to laparotomy. The primary reason for device removal was dysphagia. No device migrations or malfunctions were reported. Erosion of the device occurred in one patient (0.1%). The safety analysis of the first 1000 patients treated with MSAD for gastroesophageal reflux disease confirms the safety of this device and the implantation technique. The overall event rates were low based on data from 82 institutions. The MSAD is a safe therapeutic option for patients with chronic, uncomplicated gastroesophageal reflux disease.

Esophagectomy for failed endoscopic therapy in patients with high-grade dysplasia or intramucosal carcinoma.

Endoscopic therapy (ablation +/- endoscopic resection) for high-grade dysplasia and/or intramucosal carcinoma (IMC) of the esophagus has demonstrated promising results. However, there is a concern that a curable, local disease may progress to systemic disease with repeated endotherapy. We performed a retrospective review of patients who underwent esophagectomy after endotherapy at three tertiary care esophageal centers from 2006 to 2012. Our objective was to document the clinical and pathologic outcomes of patients who undergo esophagectomy after failed endotherapy. Fifteen patients underwent esophagectomy after a mean of 13 months and 4.1 sessions of endotherapy for progression of disease (53%), failure to clear disease (33%), or recurrence (13%). Initially, all had Barrett's, 73% had ≥3-cm segments, 93% had a nodule or ulcer, and 91% had multifocal disease upon presentation. High-grade dysplasia was present at index endoscopy in 80% and IMC in 33%, and some patients had both. Final pathology at esophagectomy was T0 (13%), T1a (60%), T1b (20%), and T2 (7%). Positive lymph nodes were found in 20%: one patient was T2N1 and two were T1bN1. Patients with T1b, T2, or N1 disease had more IMC on index endoscopy (75% vs. 18%) and more endotherapy sessions (median 6.5 vs. 3). There have been no recurrences a mean of 20 months after esophagectomy. Clinical outcomes were comparable to other series, but submucosal invasion (27%) and node-positive disease (20%) were encountered in some patients who initially presented with a locally curable disease and eventually required esophagectomy after failed endotherapy. An initial pathology of IMC or failure to clear disease after three treatments should raise concern for loco-regional progression and prompt earlier consideration of esophagectomy.

Decreasing prevalence of the full metabolic syndrome but a persistently high prevalence of dyslipidemia among adult Arabs.

A decade has passed since metabolic syndrome (MetS) was documented to be highly prevalent in the kingdom of Saudi Arabia. No follow-up epidemiologic study was done. This study aims to fill this gap. In this cross-sectional, observational study, a total of 2850 randomly selected Saudi adults aged 18-55 years were recruited. Subjects' information was generated from a database of more than 10,000 Saudi citizens from the existing Biomarkers Screening in Riyadh Program (RIYADH Cohort), Saudi Arabia. Anthropometrics included body mass index (BMI), blood pressure, as well as waist and hip circumferences. Fasting blood glucose and lipid profile were determined using routine laboratory procedures. The definition of ATP-III (NHANES III) was used for the diagnosis of the full MetS. The overall prevalence of complete MetS was 35.3% [Confidence-Interval (CI) 33.5-37.01]. Age-adjusted prevalence according to the European standard population is 37.0%. Low HDL-cholesterol was the most prevalent of all MetS risk factors, affecting 88.6% (CI 87.5-89.7) and hypertriglyceridemia the second most prevalent, affecting 34% (CI 32.3-35.7) of the subjects. The prevalence of the full MetS decreased from previous estimates but remains high, while dyslipidemia remains extremely high, affecting almost 90% of middle-aged Arabs. Screening for dyslipidemia among Saudi adults is warranted, especially among those most at risk. Scientific inquiry into the molecular causes of these manifestations should be pursued as a first step in the discovery of etiologic therapies.

Sleep duration and quality associated with obesity among Arab children.

The link between sleep duration and obesity has been well established in adults, but several epidemiological studies revealed inconsistent findings in adolescents and younger children. This study aimed to investigate the relationship between sleep length and obesity in Saudi students. A total of 5,877 Saudi students, boys (55.2%) and girls (44.8%), aged between 10 and 19 years were randomly selected from elementary, intermediate, and secondary schools in different regions of Riyadh. A questionnaire on sleep behaviors was given. Anthropometry included BMI and waist and hip circumferences. Sleeping

HIV is hyperendemic among men who have sex with men in San Francisco: 10-year trends in HIV incidence, HIV prevalence, sexually transmitted infections and sexual risk behaviour.

OBJECTIVES: To evaluate trends in the HIV epidemic among men who have sex with men (MSM) in San Francisco and the implications for HIV prevention. METHODS: An ecological approach assessed temporal trends in sexual risk behaviour, sexually transmitted infections (STI), HIV incidence and prevalence from multiple data sources between 1998 and 2007. RESULTS: By 2007, there were over 13 000 HIV-infected MSM living in San Francisco. No consistent upward or downward temporal trends were found in HIV incidence, newly reported HIV cases, AIDS deaths, proportion of AIDS cases using antiretroviral therapy, rectal gonorrhoea or primary and secondary syphilis cases among MSM during the study period. Trends in indicators of sexual risk behaviour among MSM were mixed. Overall, unprotected anal intercourse (UAI) increased in community-based surveys. Among HIV-positive MSM, no significant trends were noted for UAI. Among HIV-negative MSM, UAI with unknown serostatus partners decreased but increased with potentially discordant serostatus partners. Among MSM seeking HIV testing, increases were noted in insertive UAI at anonymous testing sites and at the STI clinic, in receptive UAI at anonymous test sites and in receptive UAI with a known HIV-positive partner at the STI clinic. CONCLUSIONS: Temporal trends in multiple biological and behavioural indicators over the past decade describe a hyperendemic state of HIV infection among MSM in San Francisco, whereby prevalence has stabilised at a very high level. In the absence of new, effective prevention strategies this state will persist.

Increases in sexually transmitted infections and sexual risk behaviour without a concurrent increase in HIV incidence among men who have sex with men in San Francisco: a suggestion of HIV serosorting?

BACKGROUND: Sexually transmitted infections (STI) and unprotected anal intercourse (UAI) have been increasing among men who have sex with men (MSM) in San Francisco. However, HIV incidence has stabilised. OBJECTIVES: To describe recent trends in sexual risk behaviour, STI, and HIV incidence among MSM in San Francisco and to assess whether increases in HIV serosorting (that is, selective unprotected sex with partners of the same HIV status) may contribute to preventing further expansion of the epidemic. METHODS: The study applies an ecological approach and follows the principles of second generation HIV surveillance. Temporal trends in biological and behavioural measures among MSM were assessed using multiple pre-existing DATA SOURCES: STI case reporting, prevention outreach programmatic data, and voluntary HIV counselling and testing data. RESULTS: Reported STI cases among MSM rose from 1998 through 2004, although the rate of increase slowed between 2002 and 2004. Rectal gonorrhoea cases increased from 157 to 389 while early syphilis increased from nine to 492. UAI increased overall from 1998 to 2004 (p<0.001) in community based surveys; however, UAI with partners of unknown HIV serostatus decreased overall (p<0.001) among HIV negative MSM, and among HIV positive MSM it declined from 30.7% in 2001 to a low of 21.0% in 2004 (p<0.001). Any UAI, receptive UAI, and insertive UAI with a known HIV positive partner decreased overall from 1998 to 2004 (p<0.001) among MSM seeking anonymous HIV testing and at the STI clinic testing programme. HIV incidence using the serological testing algorithm for recent HIV seroconversion (STARHS) peaked in 1999 at 4.1% at the anonymous testing sites and 4.8% at the STI clinic voluntary testing programme, with rates levelling off through 2004. CONCLUSIONS: HIV incidence among MSM appears to have stabilised at a plateau following several years of resurgence. Increases in the selection of sexual partners of concordant HIV serostatus may be contributing to the stabilisation of the epidemic. However, current incidence rates of STI and HIV remain high. Moreover, a strategy of risk reduction by HIV serosorting can be severely limited by imperfect knowledge of one's own and one's partners' serostatus.

Integration of data for gene annotation using the BioMediator system.

Gene annotation requires integration of data from multiple sources in order to functionally classify genes. We are using BioMediator, a general purpose data-integration solution, to develop a gene annotation system to automate the process of collecting data from disparate genomic databases. Integration of annotation data from multiple sources into a single format will facilitate use of analytic tools for the proper functional classification of genes.

Differences in the temporal trends of HIV seroincidence and seroprevalence among sexually transmitted disease clinic patients, 1989-1998: application of the serologic testing algorithm for recent HIV seroconversion.

The authors compared temporal trends in the prevalence and incidence of human immunodeficiency virus (HIV) infection based upon 34,866 specimens from patients who attended the San Francisco, California, municipal sexually transmitted disease clinic between 1989 and 1998. HIV infection data were collected during annual blinded HIV serologic surveys. Incidence was determined by applying a serologic testing algorithm for recent HIV seroconversion that uses both a sensitive and a less sensitive enzyme immunoassay to stored HIV positive sera. The HIV seroprevalence declined from 15.2% in 1989 to 7.2% in 1998 (odds ratio per year = 0.92, 95% confidence interval (CI): 0.91, 0.94). Among homosexual men, the HIV prevalence declined from 50.9% in 1989 to 19.9% in 1998 (odds ratio per year = 0.86, 95% CI: 0.85, 0.88). The pooled seroincidence was 1.6% and did not change significantly over time (odds ratio per year = 1.0, 95% CI: 0.98, 1.1). The pooled seroincidence among homosexual men was 6.6% per year and remained steady between 1989 and 1998 (odds ratio per year = 0.99, 95% CI: 0.92, 1.1). During a dramatic, 10-year decline in seroprevalence of HIV infection, the incidence of HIV infection remained remarkably stable.

A high-resolution radiation hybrid map of the human genome draft sequence.

We have constructed a physical map of the human genome by using a panel of 90 whole-genome radiation hybrids (the TNG panel) in conjunction with 40,322 sequence-tagged sites (STSs) derived from random genomic sequences as well as expressed sequences. Of 36,678 STSs on the TNG radiation hybrid map, only 3604 (9.8%) were absent from the unassembled draft sequence of the human genome. Of 20,030 STSs ordered on the TNG map as well as the assembled human genome draft sequence and the Celera assembled human genome sequence, 36% of the STSs had a discrepant order between the working draft sequence and the Celera sequence. The TNG map order was identical to one of the two sequence orders in 60% of these discrepant cases.

Low estimates of HIV seroconversions among clients of a drug treatment clinic in San Francisco, 1995 to 1998.

We estimated HIV incidence among injection drug users attending a drug treatment clinic in San Francisco from 1995 to 1998 using two methods. An anonymous sequential testing method identified no seroconversions among clients seen more than once during the period (one-sided upper 95% confidence limit 1.02 per 100 person-years). A sensitive/less sensitive immunoassay testing strategy detected no early infections (one-sided upper 95% confidence limit 1.90% per year). Methods were concordant and feasible in the setting. Although detection of no new HIV infections in this population of injection drug users (IDUs) is encouraging, epidemiologic studies among IDUs not in treatment are needed to monitor the HIV epidemic effectively.

Treatment of osteonecrosis of the femoral head by free vascularized fibular grafting: an analysis of surgical outcome and patient health status.

OBJECTIVE: To evaluate the limb-specific outcome and general health status of patients with osteonecrosis of the femoral head treated with vascularized fibular grafting. DESIGN: A retrospective review. SETTING: A single tertiary care centre. PATIENTS: Fifty-five consecutive patients with osteonecrosis of the femoral head who underwent fibular grafting (8 bilaterally). INTERVENTION: Vascularized fibular grafting. OUTCOME MEASURES: Limb-specific scores (Harris Hip Score, St. Michael's Hospital Hip Score), general health status (Nottingham Health Profile, SF-36 health status survey) and radiographic outcome measures (Steinberg stage). RESULTS: Patients were young (mean age 34 years, range from 18 to 52 years) and 80% had advanced osteonecrosis (Steinberg stages IV and V). Fifty-nine hips were followed up for an average of 50 months (range from 24 to 117 months) after vascularized fibular grafting. Sixteen hips (27%) were converted to total hip arthroplasty (THA). To date, 73% of hips treated with vascularized fibular grafting have required no further surgery. Preoperative and postoperative Harris Hip Scores were 57.3 and 83.6 respectively (p < 0.001). As measured by patient-oriented health status questionnaires (SF-36, Nottingham Health Profile) and compared with population controls, patients had normal mental health scores and only slight decreases in physical component scores. CONCLUSIONS: Free vascularized fibular grafting for osteonecrosis of the femoral head provides satisfactory pain relief, functional improvement and general health status and halts the progression of symptomatic disease.

Donor site morbidity following vascularized fibular grafting.

We examined donor site morbidity in thirty-nine patients with avascular necrosis of the femoral head treated by curettage and transplantation of a free ipsilateral fibular graft. Utilising our donor site morbidity questionnaire, scar, functional loss, wound healing, complications, and pain were analysed. Subjective complaints and objective findings were evaluated and compared. Subjective complaints were common and included a sense of instability in 42% and a sense of weakness in 37%. However, objective findings were limited. No clinical instability could be elicited and only great toe flexion (29%) and extension (43%) were found to be mildly weak. Only one patient required reoperation for a donor site problem (2%). Eighty-nine percent were pain free at time of follow-up, and 93% felt the scar was good. Range of motion of the knee and ankle of the donor site leg was not different from the nonoperated leg. Donor site morbidity for avascular necrosis of the femoral head is low.

From feedback to reciprocity. Developing a student-centered approach to course evaluation.

Reforms to medical education have refocused curricula on the need to produce primary care physicians through a problem-based, student-centered, community-oriented, and integrated approach to instruction. Course evaluations, originally designed for traditional lecture-based, teacher-centered curricula, provide inadequate input from students to support curriculum planning and change and to determine appropriate mixes of educational methods. At the University of Toronto Faculty of Medicine, a unique community-centered course, called "Health, Illness and the Community," developed a student-centered course evaluation to provide adequate student input to support curriculum planning and change. A 35-item evaluation was developed to obtain data to identify student concerns, student learning styles, and preferred community agency utilization. The results suggest that student-centered course evaluation can play a role in managing and identifying key relationships in integrated and systematic courses as well as establishing a method for continual improvement.

Reducing surgical length of stay: quantifying the impact.

Length-of-stay (LOS) reduction is a strategy encouraged at all levels of health care to manage within a resource limited environment. However, few organizations have attempted to quantitatively understand the impact of reducing LOS. This study examines the relationship between reducing LOS and cost through a retrospective, medical records analysis of three surgical procedures (appendectomy, cholecystectomy and caesarean section) at an Ontario community hospital Department of Surgery. Hypotheses are presented and a methodology is described. The results are discussed with a focus on the factors that hospitals, administrators and physicians might consider in a LOS reduction program.

Integrating technology assessment into the capital budgeting process.

Technology assessment can help hospitals rank the importance of capital requests by providing crucial information both about existing equipment and about new equipment that has been requested. Integrating technology assessment into the capital budgeting process is the best way for hospitals to determine what equipment should be purchased each year.

Building a decision-support system.

To make decisions in today's dynamic health care environment, hospital managers rely on accurate and timely information--much of it compiled from hospital discharge data. For hospitals, the problem is not the lack of data but the inability to convert it to information useful to hospital management. This article describes how to build a cost-effective decision-support system that can transform HMRI (Hospital Medical Records Institute) data into a powerful management tool.