Population-based trend analysis of voiding cystourethrogram ordering practices in a single-payer healthcare system before and after the release of evaluation guidelines.

INTRODUCTION: While voiding cystourethrogram (VCUG) is a widely-accepted test, it is invasive and associated with radiation exposure. Most cases of primary vesicoureteral reflux (VUR) are low-grade and unlikely to be associated with acquired renal scarring. To select patients at greatest risk, in 2011 the American Academy of Pediatrics (AAP) published guidelines for evaluation of children ages 2 - 24 months with urinary tract infections (UTIs). Similarly, in 2010 the Society for Fetal Urology (SFU) published guidelines for patients with hydronephrosis. Herein a prospectively-collected database was queried through the Institute of Clinical Evaluative Sciences (ICES), exploring trends in VCUG ordering within the Ontario Health Insurance Program (OHIP), which guarantees universal access to care. MATERIAL AND METHODS: A dedicated ICES analyst extracted data on all patients younger than 18 years in Ontario, Canada, with billing codes for VCUG and ICD-9 codes for VUR, from 2004-2014. The baseline characteristics included patient age, gender, geographic region, specialty of ordering provider and previous diagnoses of UTI and/or antenatal hydronephrosis to determine the indication for ordering the test. Of these, patients were subsequently incurred OHIP procedure codes for endoscopic injection or ureteral reimplantation. Patients who had a VCUG in the setting of urethral trauma, posterior urethral valves, and neurogenic bladder were excluded. RESULTS AND DISCUSSION: Trend analysis demonstrated that the total number of VCUGs ordered in the province has decreased over a decade (Figure 1), with a concurrent decrease in VUR diagnosis. On multivariate regression analysis, the decrease in VCUG ordering could not be explained by changes in population demographics or other baseline patient variables. Most VCUGs obtained per year were ordered by pediatricians or family physicians (mean 2,022+523.8), compared with urologists and nephrologists (mean 616+358.3). Interestingly, while the rate of VCUG requests decreased, the annual number of surgeries performed for VUR (endoscopic or open) did not show a significant reduction over time. CONCLUSIONS: We present a large population-based analysis in a universal access to care system, reporting a decreasing trend in the number of cystograms and differences by primary care versus specialist providers. While it is reassuring to see practice patterns favorably impacted by guidelines, it is also encouraging to note that the number of surgeries has remained stable. This suggests that patients at risk continue to be detected and offered surgical correction. These data confirm previous institution-based assessments and affirm changes in VCUG ordering independent of variables not relevant to the healthcare system, such as the insurance status.

Stent-related complications after hypospadias repair: a prospective trial comparing Silastic tubing and Koyle urethral stents.

INTRODUCTION: There is a paucity of data comparing urethral stents after hypospadias repair. The aim of this study is to compare Silastic tubing vs Koyle stents (Cook Medical), addressing outcomes related to stent-related complications, added visits to healthcare providers in the early postoperative period, and postoperative complications at clinic follow-up. MATERIALS AND METHODS: Following an alternate week allocation, 150 patients were prospectively assigned to have Silastic tubes (n = 76) and Koyle stents (n = 74) after hypospadias repair. Exclusion criteria included fistula repairs, drainage via alternative catheter, or stentless repairs. Silastic tubes were secured with 5-0 Prolene and removed during a planned clinic visit. Koyle stents were secured with 7-0 PDS and left to fall out spontaneously. Questionnaires capturing postoperative outcomes were completed. RESULTS AND DISCUSSION: Median age was 13 and 11 months in the Silastic and Koyle stent groups, respectively (P = 0.48). There was no statistically significant difference in hypospadias location. Blockage/kinking of stents occurred in 8% (n = 6) of the Silastic and 9% (n = 7) Koyle stent groups, P = 0.78. Although follow-up was short, there was no difference in fistula rate among the Silastic (21%, n = 14) versus Koyle stent group (17%, n = 11), P = 0.66. There was a twofold higher rate of emergency department (ED) visits in the Silastic (32%, n = 24) versus Koyle stent group (16%, n = 12), P = 0.03. Half of ED visits in the Silastic group were related to stents falling out before planned removal. The authors propose that Silastic stents falling out before the removal date may have led to increased parental anxiety and thus a visit to the ED. With improved parental education, the authors propose that many of these visits may have been preventable. CONCLUSIONS: There were no significant differences in stent-related complications or fistula rate between the Silastic and Koyle stent groups. Although there were a twofold higher number of visits to the ED in the Silastic stent group, the authors propose that this was due to parental education rather than the stent itself.

Cancer-related hypercalcemia in oral cancer.

Cancer-related hypercalcemia (CRH) is a critical paraneoplastic disorder in advanced cancer patients. In clinical practice, patients with CRH have a poor prognosis. The medical records of 3198 oral cancer patients with CRH diagnosed at Taichung Veterans General Hospital from 1 January 2003 to 31 December 2015 were reviewed. The criteria for patient enrolment were a diagnosis of hypercalcemia or the use of antihypercalcemia medication. Patients who met any of the following criteria were excluded: use of total parenteral nutrition, incomplete serum calcium data, and unknown date of death. The total incidence of CRH was 6.95‰ per year. A total of 91 patients were enrolled; their median survival time was 28 days. The patients were divided into two groups by survival time, with a cut-off point of 30 days. Reduced serum albumin, leucocytosis, and clodronate use had a statistically significant effect on survival in the univariate analysis (all P<0.05). Forty-five patients (49.5%) had recurrence of CRH, of whom nine died within 30days. These nine patients had a shorter interval to the first episode of CRH recurrence (median 13 days) than those who survived ≥30days (median 28 days) (P<0.001). It was observed that a short interval to the first episode of CRH recurrence is a poor prognostic factor.

The long-term predictive value of the neutrophil-to-lymphocyte ratio in Type 2 diabetic patients presenting with acute myocardial infarction.

BACKGROUND: Patients with diabetes mellitus have worse long-term outcomes after acute myocardial infarction (AMI) than non-diabetics. This may be related to differential contribution of neutrophil and lymphocyte to inflammation during AMI in diabetics vs. non-diabetics. We aim to determine the predictive value of neutrophil-to-lymphocyte ratio (NLR) for major adverse events post-AMI in Type 2 diabetics vs. non-diabetics. METHODS AND RESULTS: A total of 2559 consecutive patients admitted for AMI (61 ± 14 years, 73% male and 43% diabetic) were analyzed. A complete blood count was obtained and the NLR computed for each patient on admission. Across the cohort, the 1-year reinfarction rate was 8.4% (n = 214) and 1-year mortality was 14.5% (n = 370). Univariate determinants of the composite endpoint included age, hypertension, hyperlipidemia, smoking, revascularization and NLR (P < 0.001 for all). The cohort was divided into NLR quartiles. Admission NLR was significantly higher in the diabetic group, 5.2 ± 5.8 vs. 4.6 ± 5.4 (P = 0.007). A step-wise increase in the incidence of the composite endpoint was noted across NLR quartiles for diabetic subjects; hazard ratio (HR) was 2.41 for fourth vs. first quartile (95% confidence interval = 1.63-3.53, P < 0.001). Multivariate analysis of the diabetic group showed that NLR remains as an independent predictor of the composite endpoint (adjusted HR = 1.53, 95% confidence interval = 1.00-2.33, P = 0.048). However, in non-diabetics, HR for NLR was not significant (P = 0.35). CONCLUSION: Increased NLR post-AMI is an independent predictor of major adverse cardiac events in diabetics. Monitoring this easily obtainable new index allows prognostication and risk stratification.

Protein-losing enteropathy post-valvular surgery with severe tricuspid regurgitation in Subutex-related endocarditis.

We report a 25-year-old Malay man with Subutex-related endocarditis, complicated by protein-losing enteropathy from severe tricuspid regurgitation and congestive heart failure. The intestinal protein loss was reversed with surgical valvular intervention. This case highlights the importance of recognising the rare association between protein-losing enteropathy and congestive heart failure in the setting of endocarditis.

Observation of large-scale density cavities and parametric-decay instabilities in the high-altitude discrete auroral ionosphere under pulsed electromagnetic radiation.

A large density cavity that measured 2000 km across and 500 km in height was observed by DEMETER and Formosat/COSMIC satellites in temporal and spatial relation to a new mode of propagation of electromagnetic (em) pulses between discrete magnetic field-aligned auroral plasmas to high altitudes. Recorded positive plasma potential from satellite probes is consistent with the expulsion of electrons in the creation of density cavities. High-frequency decay spectra support the concept of parametric instabilities fed by free energy sources.

Promoter polymorphisms modulating HSPA5 expression may increase susceptibility to Taiwanese Alzheimer's disease.

Endoplasmic reticulum (ER) chaperone heat shock 70 kDa protein 5 (HSPA5/GRP78) is known to be involved in the metabolism of amyloid precursor protein and neuronal death in Alzheimer's disease (AD) could arise from dysfunction of the ER. Through a case-control study and an expression assay, we investigated the association of HSPA5 -415 G/A (rs391957), -370 C/T (rs17840761) and -180 del/G (rs3216733) polymorphisms with Taiwanese AD. The overall genotype and allele frequency distribution at the completely linked -415 G/A and -180 del/G sites showed significant difference between AD cases and controls (P = 0.020 and 0.009, respectively). A decrease in risk of developing AD was demonstrated for -415 AA/-180 GG genotype [OR = 0.38, 95% confidence interval (CI) = 0.18-0.75, P = 0.007] and -415 A/-180 G allele (OR = 0.69, 95% CI = 0.51-0.91, P = 0.009). The HSPA5 transcriptional activity of the -415 A/-180 G allele was significantly lower than that of the -415 G/-180 del alleles, whereas induction of HSPA5 expression after ER stress was markedly increased in the cells with the -415 A/-180 G allele. Therefore, our preliminary results may suggest a protective role of the HSPA5 -415 A/-180 G allele in Taiwanese AD susceptibility.

Cost-effective screening for urinary tract infections in urogynaecological patients.

This study aims to test the cost-effectiveness of reagent-strip urine nitrite compared with microbiological laboratory testing for screening of urinary tract infections (UTI). The study is a retrospective review of 708 female patients who underwent cystometry during a 1-year period. Urine dipstick nitrite was used as a screening test for UTI while urine cultures were taken as an outcome. Symptoms of UTI were noted. Of 708 patients screened, 70 (9.9%) had a significant UTI. Only 32 (4.5%)of 708 patients were nitrite positive. Urine dipstick nitrite has sensitivity of 40%, specificity of 99%, positive predictive value (PPV) of 88 % and negative predictive value (NPV) of 94%. If the screening test included symptoms for UTI together with urine nitrite, the results are: sensitivity 89%, specificity 31%, PPV 12% and NPV 96%. A combination of screening with urine nitrite and UTI symptoms can increase sensitivity to 89%. A total of 29% of specimens (screen negative=nitrite negative/asymptomatic) can then be excluded from UFEME/culture testing, thus resulting in cost savings.

"Full house" proliferative glomerulonephritis: an unreported presentation of subacute infective endocarditis.

A severely ill 65-year-old man presented with symptoms of shortness of breath, edema and vasculitidic purpura over his lower extremities. He had severe mitral regurgitation which had not been surgically treated. Hematologic examination demonstrated leukocytosis with profound anemia. Other blood tests revealed impaired renal function, hypoalbuminemia, hypocomplementemia and mixed-type cryoglobulinemia. Urinalysis showed proteinuria, hematuria and pyuria, typical of a nephritic sediment. Renal biopsy indicated diffuse proliferative glomerulonephritis and a "full house" deposition in immunofluorescence study (positive for C3, C4, C1q, IgG, IgA and IgM), resembling the pathologic findings in class IV lupus nephritis. Although subacute bacterial endocarditis was initially suspected owing to a history of a predisposing valvular heart disease, probable vegetation shown by cardiac sonography and a clinical picture suggestive of a chronic infection, it was thought unlikely due to the entire afebrile course and initial sterile blood cultures. However, the blood cultures repeated 2 weeks after admission grew 3 sets of viridans streptococci. Following a course of penicillin and gentamicin treatment, his renal function, anemia and abnormal urine sediments improved gradually. Diffuse proliferative glomerulonephritis is well known to occur in infective endocarditis. However, the "full house" immunostaining in immunofluorescence study has never been reported. This case adds a new entity to the differential diagnosis of "full house" immune complex-related glomerulonephritis and exemplifies the need to maintain a high index of suspicion for underlying infectious disorders when facing glomerulonephritic or vasculitic syndrome.

Use of three-dimensional ultrasound scan to assess the clinical importance of midurethral placement of the tension-free vaginal tape (TVT) for treatment of incontinence.

The aim of the study is to illustrate that the midurethral positioning of the tension-free vaginal tape (TVT) may not be necessary to achieve continence. Our secondary aim is to highlight that a fair number of successfully performed TVT procedures do not result in midurethral position of the tape. A review of 31 women who underwent TVT operations and consecutively returned for their follow-up visits from July 2003 to November 2003 was conducted. Their TVT procedures were performed between March 2000 and August 2003. Transperineal three-dimensional ultrasound was used to identify and obtain objective measurements of the position of the TVT tape relative to the urethra. Any patients with significant coexisting vault or uterovaginal prolapse were surgically corrected at the same time. Their stress urinary incontinence was objectively diagnosed by performing urodynamic studies (dual-channel subtraction cystometry, erect stress test) in the outpatient urogynaecology clinic. Postoperatively, patients were reviewed at 1 month and then at 6 months followed by annual reviews subsequently. All women were reassessed at the 6-month follow-up visit with a filling and voiding cystometry to detect recurrent genuine stress incontinence and detrusor instability. Any woman complaining of stress urinary incontinence after that was reassessed with urodynamic studies as mentioned above. The majority of women (67.7%, 21 women) had the TVT tape located in the middle one-third of the urethra; 9.7% (3 women) and 22.6% (7 women) of women had the TVT tape situated in the proximal and distal one-third of the urethra, respectively. Despite this, all 31 women remained continent at their postoperative follow-up visits. The midurethral position of the TVT tape may not be essential in restoring continence. The TVT tape once inserted may not always rest in the midurethral position as described.

Large pelvic accessory spleen mimicking an adnexal malignancy in a teenage girl.

A large pelvic accessory spleen in a teenage female is rare and may be misdiagnosed as an adnexal tumor. A 17-year-old girl, gravida 0, had suffered from intermittent and dull pain in the lower abdomen for 1 month. Laboratory evaluation showed a low platelet count (136,000/microL). Abdominal sonography showed a large solid mass situated at the right pelvis, containing abundant vascular supply with low resistant blood flow. At laparotomy, an accessory spleen fed by a tortuous vascular pedicle from the omentum was found and then excised. Histopathologic examination revealed congestive accessory splenomegaly. Follow-up platelet count returned to normal levels (374,000/microL). The importance of including accessory spleen in the differential diagnosis of a solid adnexal tumor with thrombocytopenia is emphasized.

Holistic outcome measurement for terminally ill cancer patients in medical centers in Taiwan.

The purpose of this cross-sectional study was to examine holistic patient outcomes for terminally ill cancer patients, as well as to examine whether different care patterns affect patient outcomes differently. Holistic patient outcomes were measured by the patients' quality of life, satisfaction with care, and cost of care. A purposive sampling of 224 subjects including 123 patients and 101 nurses was drawn from four medical centers in Taiwan. Among these settings, various care patterns were adopted and categorized into 4 groups: hospice inpatients, hospice team consultation, home hospice care services, and a conventional acute care group. Results showed that hospice inpatients had a higher quality of life, a higher level of satisfaction with the care and a lower average inpatient cost, whereas conventional care tended to have the highest length of hospital stay. Home hospice care patients had better psychological well-being than those with other care patterns. In addition, nurses' work satisfaction with the inpatients care unit tended to be significantly higher than with the other groups. The study findings not only provide an instrument for evaluating the quality of care, but also contribute to identifying patterns of care that will influence the dying process, which can only be beneficial for patients. Given the wide variety of healthcare services available now, understanding and selecting the most effective care patterns to enhance patient outcomes is of utmost importance in Taiwan.

Mid-trimester beta-hCG levels incorporated in a multifactorial model for the prediction of severe pre-eclampsia.

Pre-eclampsia remains a major cause of perinatal morbidity and mortality worldwide. Proposed predicting tests for early detection of pregnant women destined to develop pre-eclampsia remain unsatisfactory. The aim of this study was to investigate the clinical utility of combining mid-trimester maternal serum beta-human chorionic gonadotrophin (MShCG) levels with selected clinical determining factors as a multifactorial predictive test for pre-eclampsia. Thirty-nine cases with mild pre-eclampsia and 56 with severe pre-eclampsia were recruited as the study groups. Normotensive women (957) were enrolled as controls. Potential determining risk factors for severe pre-eclampsia were selected using a multiple logistic regression to build various combined prediction models. A receiver-operator characteristic curve was employed to assess the performance of each prediction test for pre-eclampsia. The prediction efficacy of each test was examined by the area under the curve (AUC). Our data show that mid-trimester MShCG levels significantly correlated with severity of pre-eclampsia (Spearman rank correlation coefficient=0.195, p<0.001). Women with mild pre-eclampsia had a 2.61-times greater chance, while women with severe pre-eclampsia had a 6.13-times greater chance of having MShCG exceeding 2.0 multiples of the median than did women with a normal pregnancy. A combined prediction model composed of MShCG levels, body mass index (BMI), parity, and age as a predictive test for severe pre-eclampsia was superior to MShCG levels alone (AUC 0.765 versus 0.648). The integrated multifactorial model could identify women at risk early on for developing severe pre-eclampsia, with a sensitivity of 70% and a specificity of 71%. Thus, we demonstrate a potentially effective and convenient method by which women at risk for developing severe pre-eclampsia can be identified early, based on a multifactorial predictive model composed of midtrimester MShCG levels, BMI, parity, and age.

Pregnancy associated with gastric carcinoma.

Gastric cancer during pregnancy is very rare. We present the case of a 32-year-old woman, gravida 1 para 0, who suffered from advanced gastric cancer during pregnancy. Although the clinical symptoms of the tumor were evident early in the third trimester, the tumor was not diagnosed until 7 days postpartum, when it was too far advanced for curative resection. Only palliative procedures were carried out. The woman died of the cancer less than 3 months postpartum. Early diagnosis of this disease entity is often difficult and a poor prognosis invariably ensures, unless obstetricians maintain a high level of awareness. In pregnant patients with eccentric symptoms of the gastrointestinal tract that persist beyond the second trimester, further endoscopic evaluation should be considered. Occult blood in stool concomitant with elevated serum carcinoembryonic antigen concentration should be considered as an important indicator for thorough endoscopic investigation.

Evidence for alpha-helical conformation of an essential N-terminal region in the human Bcl2 protein.

A region occupying approximately 24 amino acids near the N terminus of human Bcl2 is essential for this cytoplasmic membrane protein's ability to inhibit apoptosis. Systematic mutagenesis of this N-terminal region indicates that only five hydrophobic and aromatic residues within it are specifically required for function. Computerized secondary structure prediction, together with circular dichroism spectroscopy of synthetic peptides, indicates that the region encompassing these five residues has the propensity to take on an alpha-helical conformation in the presence of SDS micelles, which presumably mimic the hydrophobic surfaces of cellular membranes or polypeptides. The five critical residues are predicted to be clustered on one face of this putative helix, where they might serve to mediate protein-protein contacts involved in the multimerization of Bcl2 or in the interaction of Bcl2 with other, as yet unidentified components of the apoptotic pathway. Apparent structural homologues of this helical motif are also present in at least some other anti-apoptotic proteins from the Bcl2 family but not in those family members that tend to potentiate, rather than inhibit, apoptosis.