Continuous monitoring of bovine spongiform encephalopathy rapid test performance by weak positive tissue controls and quality control charts

Bovine spongiform encephalopathy (BSE) rapid tests and routine BSE-testing laboratories underlie strict regulations for approval. Due to the lack of BSE-positive control samples, however, full assay validation at the level of individual test runs and continuous monitoring of test performance on-site is difficult. Most rapid tests use synthetic prion protein peptides, but it is not known to which extend they reflect the assay performance on field samples, and whether they are sufficient to indicate on-site assay quality problems. To address this question we compared the test scores of the provided kit peptide controls to those of standardized weak BSE-positive tissue samples in individual test runs as well as continuously over time by quality control charts in two widely used BSE rapid tests. Our results reveal only a weak correlation between the weak positive tissue control and the peptide control scores. We identified kit-lot related shifts in the assay performances that were not reflected by the peptide control scores. Vice versa, not all shifts indicated by the peptide control scores indeed reflected a shift in the assay performance. In conclusion these data highlight that the use of the kit peptide controls for continuous quality control purposes may result in unjustified rejection or acceptance of test runs. However, standardized weak positive tissue controls in combination with Shewhart-CUSUM control charts appear to be reliable in continuously monitoring assay performance on-site to identify undesired deviations.

Risk charts to guide targeted HIV-1 viral load monitoring of ART: development and validation in patients from resource-limited settings.

BACKGROUND HIV-1 RNA viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not available in many resource-limited settings. We developed and validated CD4-based risk charts to guide targeted VL testing. METHODS We modeled the probability of virologic failure up to 5 years of ART based on current and baseline CD4 counts, developed decision rules for targeted VL testing of 10%, 20% or 40% of patients in seven cohorts of patients starting ART in South Africa, and plotted cut-offs for VL testing on colour-coded risk charts. We assessed the accuracy of risk chart-guided VL testing to detect virologic failure in validation cohorts from South Africa, Zambia and the Asia-Pacific. FINDINGS 31,450 adult patients were included in the derivation and 25,294 patients in the validation cohorts. Positive predictive values increased with the percentage of patients tested: from 79% (10% tested) to 98% (40% tested) in the South African, from 64% to 93% in the Zambian and from 73% to 96% in the Asia-Pacific cohorts. Corresponding increases in sensitivity were from 35% to 68% in South Africa, from 55% to 82% in Zambia and from 37% to 71% in Asia-Pacific. The area under the receiver-operating curve increased from 0.75 to 0.91 in South Africa, from 0.76 to 0.91 in Zambia and from 0.77 to 0.92 in Asia Pacific. INTERPRETATION CD4-based risk charts with optimal cut-offs for targeted VL testing may be useful to monitor ART in settings where VL capacity is limited.

Implementation and Operational Research: Risk Charts to Guide Targeted HIV-1 Viral Load Monitoring of ART: Development and Validation in Patients From Resource-Limited Settings.

BACKGROUND HIV-1 RNA viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not available in many resource-limited settings. We developed and validated CD4-based risk charts to guide targeted VL testing. METHODS We modeled the probability of virologic failure up to 5 years of ART based on current and baseline CD4 counts, developed decision rules for targeted VL testing of 10%, 20%, or 40% of patients in 7 cohorts of patients starting ART in South Africa, and plotted cutoffs for VL testing on colour-coded risk charts. We assessed the accuracy of risk chart-guided VL testing to detect virologic failure in validation cohorts from South Africa, Zambia, and the Asia-Pacific. RESULTS In total, 31,450 adult patients were included in the derivation and 25,294 patients in the validation cohorts. Positive predictive values increased with the percentage of patients tested: from 79% (10% tested) to 98% (40% tested) in the South African cohort, from 64% to 93% in the Zambian cohort, and from 73% to 96% in the Asia-Pacific cohort. Corresponding increases in sensitivity were from 35% to 68% in South Africa, from 55% to 82% in Zambia, and from 37% to 71% in Asia-Pacific. The area under the receiver operating curve increased from 0.75 to 0.91 in South Africa, from 0.76 to 0.91 in Zambia, and from 0.77 to 0.92 in Asia-Pacific. CONCLUSIONS CD4-based risk charts with optimal cutoffs for targeted VL testing maybe useful to monitor ART in settings where VL capacity is limited.

Limitations of balloon sinuplasty in frontal sinus surgery

Balloon sinuplasty is a tool that is used to treat selected patients with paranasal sinus pathologies. No studies have investigated the aetiology of failed access to the frontal sinus. The aim of our study was to specify the intraoperative technical failure rate and to analyse the aetiology of the failed access to predict potential technical difficulties before surgery. We retrospectively analysed the charts of patients who underwent balloon sinuplasty from November 2007 to July 2010 at three different ENT-Centres. CT-analysis of the patients with failed access was performed. Of the 104 frontal sinuses, dilation of 12 (12%) sinuses failed. The anatomy of all failed cases revealed variations in the frontal recess (frontoethmoidal-cell, frontal-bulla-cell or agger-nasi-cell) or osteoneogenesis. In one patient, a lymphoma was overlooked during a balloon only procedure. The lymphoma was diagnosed 6 months later with a biopsy during functional endoscopic sinus surgery. In complex anatomical situations of the frontal recess, balloon sinuplasty may be challenging or impossible. In these situations, it is essential to have knowledge of classical functional endoscopic sinus surgery of the frontal recess area. The drawbacks of not including a histopathologic exam should be considered in balloon only procedures.

Variation in partner notification outcomes for chlamydia in UK genitourinary medicine clinics: multilevel study

Objectives To compare different ways of measuring partner notification (PN) outcomes with published audit standards, examine variability between clinics and examine factors contributing to variation in PN outcomes in genitourinary medicine (GUM) clinics in the UK. Methods Reanalysis of the 2007 BASHH national chlamydia audit. The primary outcome was the number of partners per index case tested for chlamydia, as verified by a healthcare worker or, if missing, reported by the patient. Control charts were used to examine variation between clinics considering missing values as zero or excluding missing values. Hierarchical logistic regression was used to investigate factors contributing to variation in outcomes. Results Data from 4616 individuals in 169 genitourinary medicine clinics were analysed. There was no information about the primary outcome in 41% of records. The mean number of partners tested for chlamydia ranged from 0 to 1.5 per index case per clinic. The median across all clinics was 0.47 when missing values were assumed to be zero and 0.92 per index case when missing values were excluded. Men who have sex with men were less likely than heterosexual men and patients with symptoms (4-week look-back period) were less likely than asymptomatic patients (6-month look-back) to report having one or more partners tested for chlamydia. There was no association between the primary outcome and the type of the health professional giving the PN advice. Conclusions The completeness of PN outcomes recorded in clinical notes needs to improve. Further research is needed to identify auditable measures that are associated with successful PN that prevents repeated chlamydia in index cases.

Temporomandibular disorders/myoarthropathy of the masticatory system. Costs of dental treatment and reimbursement by Swiss federal insurance agencies according to the Health Care Benefits Ordinance (KLV)

The goal of the study was to calculate the direct costs of therapy for patients with MAP. This retrospective study included 242 MAP patients treated at the Department of Prosthodontics of the University of Bern between 2003 and 2006. The following parameters were collected from the clinical charts: chief complaint, diagnosis, treatment modalities, total costs, costs of the dental technician, number of appointments, average cost per appointment, length of treatment, and services reimbursed by health insurance agencies. The average age of the patients was 40.4 ± 17.3 years (76.4% women, 23.6% men). The chief complaint was pain in 91.3% of the cases, TMJ noises (61.2%) or limitation of mandibular mobility (53.3%). Tendomyopathy (22.3%), disc displacement (22.4%), or a combination of the two (37.6%) were more often diagnosed than arthropathy alone (7.4%). Furthermore, 10.3% of the MAP patients had another primary diagnosis (tumor, trauma, etc.). Patients were treated with counseling and exercises (36.0%), physiotherapy (23.6%), or occlusal splints (32.6%). The cost of treatment reached 644 Swiss francs for four appointments spread over an average of 21 weeks. In the great majority of cases, patients can be treated with inexpensive modalities. 99.9% of the MAP cases submitted to the insurance agencies were reimbursed by them, in accordance with Article 17d1-3 of the Swiss Health Care Benefits Ordinance (KLV) and Article 25 of the Federal Health Insurance Act (KVG). The costs of treatment performed by dentists remain modest. The more time-consuming services, such as providing information, counseling and instructions, are poorly remunerated. This aspect should be re-evaluated in a future revision of the tariff schedule.

Urogenital manifestations in Wegener granulomatosis: a study of 11 cases and review of the literature

We describe the main characteristics and treatment of urogenital manifestations in patients with Wegener granulomatosis (WG). We conducted a retrospective review of the charts of 11 patients with WG. All patients were men, and their median age at WG diagnosis was 53 years (range, 21-70 yr). Urogenital involvement was present at onset of WG in 9 cases (81%), it was the first clinical evidence of WG in 2 cases (18%), and was a symptom of WG relapse in 6 cases (54%). Symptomatic urogenital involvement included prostatitis (n = 4) (with suspicion of an abscess in 1 case), orchitis (n = 4), epididymitis (n = 1), a renal pseudotumor (n = 2), ureteral stenosis (n = 1), and penile ulceration (n = 1). Urogenital symptoms rapidly resolved after therapy with glucocorticoids and immunosuppressive agents. Several patients underwent a surgical procedure, either at the time of diagnosis (n = 3) (consisting of an open nephrectomy and radical prostatectomy for suspicion of carcinoma, suprapubic cystostomy for acute urinary retention), or during follow-up (n = 3) (consisting of ureteral double J stents for ureteral stenosis, and prostate transurethral resection because of dysuria). After a mean follow-up of 56 months, urogenital relapse occurred in 4 patients (36%). Urogenital involvement can be the first clinical evidence of WG. Some presentations, such as a renal or prostate mass that mimics cancer or an abscess, should be assessed to avoid unnecessary radical surgery. Urogenital symptoms can be promptly resolved with glucocorticoids and immunosuppressive agents. However, surgical procedures, such as prostatic transurethral resection, may be mandatory in patients with persistent symptoms.

Tumor thrombus of inferior vena cava in patients with renal cell carcinoma - clinical and oncological outcome of 50 patients after surgery

Background To evaluate oncological and clinical outcome in patients with renal cell carcinoma (RCC) and tumor thrombus involving inferior vena cava (IVC) treated with nephrectomy and thrombectomy. Methods We identified 50 patients with a median age of 65 years, who underwent radical surgical treatment for RCC and tumor thrombus of the IVC between 1997 and 2010. The charts were reviewed for pathological and surgical parameters, as well as complications and oncological outcome. Results The median follow-up was 26 months. In 21 patients (42%) distant metastases were already present at the time of surgery. All patients underwent radical nephrectomy, thrombectomy and lymph node dissection through a flank (15 patients/30%), thoracoabdominal (14 patients/28%) or midline abdominal approach (21 patients/42%), depending upon surgeon preference and upon the characteristics of tumor and associated thrombus. Extracorporal circulation with cardiopulmonary bypass (CPB) was performed in 10 patients (20%) with supradiaphragmal thrombus of IVC. Cancer-specific survival for the whole cohort at 5 years was 33.1%. Survival for the patients without distant metastasis at 5 years was 50.7%, whereas survival rate in the metastatic group at 5 years was 7.4%. Median survival of patients with metastatic disease was 16.4 months. On multivariate analysis lymph node invasion, distant metastasis and grading were independent prognostic factors. There was no statistically significant influence of level of the tumor thrombus on survival rate. Indeed, patients with supradiaphragmal tumor thrombus (n = 10) even had a better outcome (overall survival at 5 years of 58.33%) than the entire cohort. Conclusions An aggressive surgical approach is the most effective therapeutic option in patients with RCC and any level of tumor thrombus and offers a reasonable longterm survival. Due to good clinical and oncological outcome we prefer the use of CPB with extracorporal circulation in patients with supradiaphragmal tumor thrombus. Cytoreductive surgery appears to be beneficial for patients with metastatic disease, especially when consecutive therapy is performed. Although sample size of our study cohort is limited consistent with some other studies lymph node invasion, distant metastasis and grading seem to have prognostic value.

Handlebar injuries in children

Introduction: Handlebar injuries in children may lead to severe organ lesions despite minimal initial signs and without visible skin bruise. We present our experiences applying a diagnostic and therapeutic algorithm for blunt abdominal trauma, and present the history of two selected cases. Materials and methods: We retrospectively assessed the charts of children below 16 years of age, only who were observed for 24 h or more in our institution due to a handlebar injury between 2004 and 2011. All children were treated according to an institutional algorithm. Results: 40 patients with a median age of 9.5 years were included. Diagnosed lesions were: ruptures of the liver (n = 6), spleen (n = 5), kidney (n = 1), and pancreas (n = 2), small bowel perforation (n = 3), and hernias of the abdominal (n = 2) or thoracic wall (n = 1). Surgical interventions were performed in 8 patients. The outcome was favorable in all the cases. Overall median hospitalization duration was 4.5 days (range 1–19 days). The overall duration between the accident and arrival at our emergency unit was 2.75 h (median, range 1–19 h). 20 children presented directly at our emergency unit after a median of 1.7 h (range 1–19.5 h). 20 children were referred by a family physician or a primary hospital after a median of 4.0 h (range 1–46 h). Conclusion: Handlebar injuries in children resulted in serious trunk lesions in half of the present patient series. The spectrum of injuries in handlebar accidents varies widely, especially injuries to the abdomen can unmask often only in the course. We advocate close observation of patients with thoracic and abdominal handlebar injuries which may be regarded as blunt stab wounds. An institutional algorithm for blunt abdominal trauma management is supportive for emergency care in patients with handlebar injuries.

Different fever definitions and the rate of fever and neutropenia diagnosed in children with cancer: a retrospective two-center cohort study

Background. The definition of fever, and thus fever and neutropenia (FN), varies between different pediatric oncology centers. Higher temperature limit should reduce FN rates, but may increase rates of FN with complications by delaying therapy. This study determined if different fever definitions are associated with different FN rates. Procedure. Two pediatric oncology centers had used three fever definitions in 2004–2011: ear temperature >=38.5°C persisting >=2 hours (low definition); axillary temperature >=38.5°C >=2 hours or >=39.0°C once (middle); and ear temperature >=39.0°C once (high). Clinical information was retrospectively extracted from charts. FN rates were compared using mixed Poisson regression. Results. In 521 pediatric patients with cancer, 783 FN were recorded during 6,009 months cumulative chemotherapy exposure time (501 years; rate, 0.13/month [95% CI, 0.12–0.14]), 124 of them with bacteremia (16%; 0.021/month [0.017–0.025]). In univariate analysis, the high versus low fever definition was associated with a lower FN rate (0.10/month [0.08–0.11] vs. 0.15/month [0.13–0.16]; rate ratio, 0.66 [0.45–0.97]; P ¼ 0.036), the middle definition was intermediate (0.13/month [0.11–0.15]). This difference was not confirmed in multivariate analysis (rate ratio, 0.94 [0.67–1.33]; P ¼ 0.74). The high versus low definition was not associated with an increased rate of FN with bacteremia (multivariate rate ratio, 1.39 [0.53–3.62]; P ¼ 0.50). Conclusion. A higher fever definition was not associated with a lower FN rate, nor with an increased rate of FN with bacteremia. These may be false negative findings due to methodological limitations. These questions, with their potential impact on health-related quality of life, and on costs, need to be assessed in prospective studies.

The syndromology of anorectal malformations revisited: from patterns of associated malformations to the recognition of syndromes

ackground: Although the frequency of associated malformation is high, the incidence of inheritable syndromes is widely underestimated in children with anorectal malformation (ARM). Data sources: OMIM database, patient records and charts of the Department of Pediatric Surgery, Johannes Gutenberg-University, Mainz, Germany. Methods: We analyzed all associations, sequences and syndromes listed in the OMIM database that can be accompanied by ARM. A large cohort of children born with ARM was then retrospectively investigated as to the type of ARM, presence of additional malformations and possible categorization as a syndrome, sequence or association. For this process a syndrome finder was developed and employed. This simplistic tool allows for a rapid first check of possible syndromes before a more complex analysis is started using the OMIM database and consulting specialists. Results: Among 317 children with ARM, associated malformations were present in 77.7% of 127 children with high ARM, in 68.7% of 32 with intermediate ARM, and in 25.3% of 158 with a low type ARM. Three or more organ systems were involved in 29.1% children with high type ARM and 25% with intermediate ARM and 8.2% with a low type ARM. An association of the vertebral anal tracheo-esophageal renal (VATER) and vertebral anal cardiac tracheo-esophageal renal limb (VACTERL) type was found in a total of 35 patients. Before analysis, 11 syndromes and 35 associations which were not clear previously in this patient cohort were described. In other 17 patients, 14 syndromes and 3 associations were identified. Conclusions: The high number of only retrospectively identified syndromes suggests that a routine search is necessary in every patient with ARM and additional malformations.

Treatment and prognosis of AIDS-related lymphoma in the era of highly active antiretroviral therapy: findings from the Swiss HIV Cohort Study

OBJECTIVE: To assess the characteristics of combination antiretroviral therapy (cART) administered concomitantly with chemotherapy and to establish prognostic determinants of patients with AIDS-related non-Hodgkin's lymphoma. METHODS: The study included 91 patients with AIDS-related non-Hodgkin's lymphoma from the Swiss HIV Cohort Study enrolled between January 1997 and October 2003, excluding lymphomas of the brain. We extracted AIDS-related non-Hodgkin's lymphoma- and HIV-specific variables at the time of lymphoma diagnosis as well as treatment changes over time from charts and from the Swiss HIV Cohort Study database. Cox regression analyses were performed to study predictors of overall and progression-free survival. RESULTS: During a median follow up of 1.6 years, 57 patients died or progressed. Thirty-five patients stopped chemotherapy prematurely (before the sixth cycle) usually due to disease progression; these patients had a shorter median survival than those who completed six or more cycles (14 versus 28 months). Interruptions of cART decreased from 35% before chemotherapy to 5% during chemotherapy. Factors associated with overall survival were CD4+ T-cell count (<100 cells/microl) (hazard ratio [HR] 2.95 [95% confidence interval (CI) 1.53-5.67], hepatitis C seropositivity (HR 2.39 [95% CI 1.01-5.67]), the international prognostic index score (HR 1.98-3.62 across categories) and Burkitt histological subtypes (HR 2.56 [95% CI 1.13-5.78]). CONCLUSIONS: Interruptions of cART were usually not induced by chemotherapy. The effect of cART interruptions on AIDS-related non-Hodgkin's lymphoma prognosis remains unclear, however, hepatitis C seropositivity emerged-as a predictor of death beyond the well-known international prognostic index score and CD4+ T-cell count.

Diagnostic workup of patients with acute transverse myelitis: spectrum of clinical presentation, neuroimaging and laboratory findings

STUDY DESIGN: Retrospective 9-year survey. OBJECTIVES: Clinical presentation of acute myelitis syndromes is variable, and neuroimaging and laboratory findings are not specific enough to establish the diagnosis with certainty. We evaluated the spectrum clinical features and paraclinical findings encountered during diagnostic workup and aiding the diagnosis. SETTING: Department of Neurology, Inselspital Bern, Switzerland. MATERIAL: Charts and magnetic resonance imaging (MRI) of 63 patients discharged with the diagnosis of acute transverse myelitis. RESULTS: The diagnosis was supported by abnormal MRI and cerebrospinal fluid (CSF) findings in 52 patients (82.5%) and suspected in the remaining either because of a spinal cord MRI lesion suggestive of myelitis (n=5), or abnormal CSF findings (n=4), or electrophysiological evidence of a spinal cord dysfunction (n=2). Clinical impairment was mild (ASIA D) in the majority. All patients had sensory disturbances, whereas motor deficit and autonomic dysfunction were less frequent. Neurological levels were mainly located in cervical or thoracic dermatomes. Spinal cord lesions were visualized by MRI in 90.4% of the patients and distributed either in the cervical or thoracic cord, or both. Multiple lesions were present in more than half of the patients, and lateral, centromedullary and posterior locations were most common. A high percentage of multiple sclerosis (MS)-typical brain lesions and CSF findings suggested a substantial number of MS-related myelitis in our cohort. CONCLUSION: The diagnostic workup of acute myelitis discloses a broad spectrum of CSF or MRI findings, and may be associated with diagnostic uncertainty due to lack of specific CSF or MRI features, or pathological findings.

Implant Failure Predictors in the Posterior Maxilla: A Retrospective Study of 273 Consecutive Implants

Background: The goal of this study was to retrospectively analyze a cohort of 136 patients who underwent dental implant placement in the posterior maxilla at the University of Connecticut Health Center to assess and identify predictors for implant failure in the posterior maxilla. Methods: Data were retrieved from patient charts to identify subjects older than 21 years of age who received dental implant(s) in the posterior maxilla. Patients without a postoperative baseline radiograph were excluded. A recall radiograph was taken 3 to 6 months after implant placement. If there was no recall radiograph, the subject was contacted for a recall visit that included a clinical evaluation and radiographs to determine the implant status. Based on a univariate screening, variables considered potential implant failure predictors included gender, diabetes, smoking, implant length, implant diameter, membrane use, sinus-elevation technique, and surgical complications. These parameters were further assessed, and a multivariable logistic regression was performed with implant failure as a dependant variable. All tests of significance were evaluated at the 0.05 error level. Results: Two hundred seventy-three implants were placed in the posterior maxilla. Fourteen implants failed (early and late failures combined), resulting in a 94.9% overall survival rate. The survival rates for the sinus-elevation group and native bone group were 92.2% and 96.7%, respectively (P = 0.090). Based on the multivariable analysis, sinus floor-elevation procedures were not associated with increased risk for implant failure (P = 0.702). In contrast, smoking and surgical complications had a statistically significant effect on implant failure; the odds ratios for implant failure were 6.4 (P = 0.025) and 8.2 (P = 0.004), respectively. Conclusion: Sinus-elevation procedures with simultaneous or staged implant placement do not increase the risk for implant failure, whereas smoking and surgical complications markedly increase the risk for implant failure.