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Aim Ultrasound estimation and evaluation of amniotic fluid volume (AFV) is an important component of pregnancy surveillance and fetal well-being. The purpose of this study was to compare and contrast four statistical methods used to construct gestational age-specific reference intervals for the assessment of AFV. Methods A total of 1095 normal AFV derived from four studies that measured AFV using dye-dilution or direct measurement at the time of hysterotomy were used to construct reference intervals using polynomial regression, quantile regression, Royston and Wright mean and SD, and Cole's lambda mu sigma (LMS) methods. The 2.5th, 5th, 50th, 95th, and 97.5th centiles were derived for each statistical method. Results AFV increased curvilinearly from 15 gestational weeks and onward. Based on the 50th centile, the maximum value occurred at 30 weeks’ gestation for the polynomial regression and mean and SD methods while the maximum was achieved at week 31 for the quantile regression and LMS methods. When data were sparse, the quantile regression method produced dramatically different estimates at the higher centile. Conclusion The four statistical methods produced similar results at gestational ages in which AFV was high. The quantile regression approach, however, produces results that are more reflective of the data when the data are sparse. Given the flexibility and robustness of the quantile regression method, we recommend its use in constructing reference intervals when the interest lies in the tails of the reference distribution.

Objective To examine characteristics associated with the publication and timeliness of publication of randomized controlled trials (RCTs) of treatment of rheumatoid arthritis (RA). Methods RA RCTs (phases II–IV) registered at ClinicalTrials.gov and completed by December 31, 2009 were identified. A standardized strategy was used to determine publication status and outcome assessment. The association of RCT characteristics recorded at ClinicalTrials.gov and study outcome with publication and time to publication were assessed. Results A search conducted at least 30 months after trial completion revealed that among 143 eligible RCTs, 95 (64.4%) were published. The 48 unpublished RCTs had enrolled >10,000 patients. Efficacy outcomes could be ascertained for 127 of the RCTs. RCT publication was associated with positive outcome, with an adjusted odds ratio [OR] of 4.3 (95% confidence interval [95% CI] 1.8–10.2) (P = 0.001), and marginally with RCT registration before completion (adjusted OR 0.4 [95% CI 0.1–1.0], P = 0.06). The estimated median time to publication was 38 months. Positive outcome was associated with earlier publication (adjusted hazard ratio 1.9 [95% CI 1.2–2.9], P = 0.006). RCTs completed in 2006–2007 or 2008–2009 were likely to be published sooner than RCTs completed in or before 2005. Sensitivity analyses to assess the impact of 16 RCTs with unknown outcome did not alter these findings, except in the highly implausible scenario of all such trials being positive. Conclusion Positive study outcome was associated with publication and timeliness of publication despite registration in a publicly available registry. A substantial minority of RA RCTs remained unpublished. Efforts to improve transparency in reporting of clinical trials need to continue.

We investigated the in vivo relevance of the impact of sarA and saeRS on protease production using derivatives of the USA300 strain LAC. The results confirmed that mutation of saeRS or sarA reduces virulence in a bacteremia model to a comparable degree. However, while eliminating protease production restored virulence in the sarA mutant, it had little impact in the saeRS mutant. Additionally, constitutive activation of saeRS (saeRS(C)) enhanced the virulence of LAC and largely restored virulence in the isogenic sarA mutant. Based on these results, together with our analysis of the representative virulence factors alpha toxin, protein A (Spa), and extracellular nucleases, we propose a model in which the attenuation of saeRS mutants is defined primarily by decreased production of such factors, while constitutive activation of saeRS increases virulence, and reverses the attenuation of sarA mutants, because it results in both increased production and decreased protease-mediated degradation of these same factors. This regulatory balance was also apparent in a murine model of catheter-associated infection, with the results suggesting that the impact of saeRS on nuclease production plays an important role during the early stages of these infections that is partially offset by increased protease production in sarA mutants.

The University HealthSystem Consortium (UHC) database collects discharge information on patients treated at academic health centers throughout the United States. We sought to use this database to identify outcome predictors for patients undergoing total laryngectomy. A secondary end point was to assess the validity of the UHC's predictive risk mortality model in this cohort of patients.Retrospective review.Academic medical centers (tertiary referral centers) and their affiliate hospitals in the United States.Using the UHC discharge database, we retrieved and analyzed data for 4648 patients undergoing total laryngectomy who were discharged between October 2007 and January 2011 from all of the member institutions. Demographics, comorbidities, institutional data, and outcomes were retrieved.The length of stay and overall costs were significantly higher among female patients (P.0001), while age was a predictor of intensive care unit stay (P = .014). The overall complication rate was higher among Asians (P = .019) and in patients with anemia and diabetes compared with other comorbidities. The average institutional case load was 1.92 cases/mo; we found an inverse correlation (R = -0.47) between the institutional case load and length of stay (P.0001). The UHC admit mortality risk estimator was found to be an accurate predictor not only of mortality (P.0002) but also of intensive care unit admission and complication rate (P.0001).This study provides an overview of laryngectomy outcomes in a contemporary cohort of patients treated at academic health centers. UHC admit mortality risk is an excellent outcome predictor and a valuable tool for risk stratification in these patients.

To compare the cost of same-day vs 23-hour observation outpatient thyroidectomy at US academic medical centers.Cross-sectional analysis of a national database.The University HealthSystem Consortium (UHC) data collected from discharge summaries.Discharge data were collected from the first quarter of 2009 through the second quarter of 2013. The UHC database, compiled from more than 200 affiliated hospitals, was searched based on diagnosis codes for outpatient thyroid procedures. Cost data, calculated based on reported charges, were collected in addition to demographics. Comparisons were made between same-day vs 23-hour observation based on cost. Additional stratification was performed based on the extent of thyroidectomy.During the study period, 49,936 outpatient thyroidectomies were performed. Overnight observation (63%) was more common than same-day discharge (37%). The overall mean cost of outpatient thyroidectomy was $5617, with a mean cost of same-day surgery of $4642 compared with $6101 for overnight observation (P.0001). When stratifying by extent of thyroidectomy, the cost of same-day surgery was consistently lower than that for overnight observation.Outpatient thyroidectomy is commonly performed in the United States. It is most commonly performed on a 23-hour overnight observation basis. Overnight stay and complications were chief among other factors associated with higher cost, independent of the type of thyroid procedure performed. In appropriately selected patients, same-day thyroidectomy is a safe and cost-effective alternative to overnight observation or inpatient thyroid procedures.

Mutation of staphylococcal accessory regulator (sarA) results in increased production of extracellular proteases in Staphylococcus aureus, which has been correlated with decreased biofilm formation and decreased accumulation of extracellular toxins. We used murine models of implant-associated biofilm infection and S. aureus bacteremia (SAB) to compare virulence of USA300 strain LAC, its isogenic sarA mutant, and derivatives of each of these strains with mutations in all 10 of the genes encoding recognized extracellular proteases. The sarA mutant was attenuated in both models, and this was reversed by eliminating production of extracellular proteases. To examine the mechanistic basis, we identified proteins impacted by sarA in a protease-dependent manner. We identified 253 proteins where accumulation was reduced in the sarA mutant compared to the parent strain, and was restored in the sarA/protease mutant. Additionally, in SAB, the LAC protease mutant exhibited a hypervirulent phenotype by comparison to the isogenic parent strain, demonstrating that sarA also positively regulates production of virulence factors, some of which are subject to protease-mediated degradation. We propose a model in which attenuation of sarA mutants is defined by their inability to produce critical factors and simultaneously repress production of extracellular proteases that would otherwise limit accumulation of virulence factors.

To better understand relationships of parathyroid hormone (PTH) production, adenoma gamma counts, and adenoma mass in patients undergoing minimally radioguided invasive parathyroidectomy for primary hyperparathyroidism from single-gland disease.A prospective review of 104 patients operated on by a single surgeon.University tertiary hospital.Adults who have primary hyperparathyroidism due to a single gland.There were 23 men and 81 women with an average age of 63 years. The mean (SD) adenoma mass was 0.78 (0.69) g (median, 0.57 g). The mean (SD) percent of background for the adenoma was 120.2 (90.5). Preoperative PTH and percent of background gamma count of the adenoma showed a likely correlation with a Spearman ρ value of 0.2039 and a P value of .037. There were significant correlations between both percent of background of the adenoma and adenoma mass (Spearman ρ = 0.4991 and P.0001). Preoperative PTH and adenoma mass also showed a significant positive correlation (Spearman ρ = 0.308 and P = .002).There exist correlations between gland mass, radioactivity, and PTH level. Adenoma radiation counts do not appear to be a proxy for changes in PTH levels measured during surgery as has been reported. Intraoperative PTH has been shown by others not to be necessary when doing radioguided parathyroid surgery if the Norman rule is observed. However, a radioguided technique and intraoperative PTH can provide complementary information in making an assessment of completion of parathyroid procedures.

Background The purpose of this study was to determine the patient reasoning behind treatment choice after palliative surgical consultation. Methods Patients undergoing palliative surgical consultation were prospectively enrolled in this observational cohort study (11/2009–5/2011) and administered an open-ended questionnaire asking for their reasoning in choosing their treatment strategy. Results Of 98 patients enrolled, 54 were treated non-operatively and 44 with surgery. Patient responses indicating their reason for treatment selection were categorized into (1) quality of life or symptom relief, (2) unclear or response not related to treatment strategy, (3) increase length of life, (4) treat the cancer, (5) concerns over surgical complications, (6) doctor's recommendation, (7) religious reasons for treatment choice, and (8) for family. The most frequently cited reason for treatment selection was symptom relief or quality of life improvement in 46 patients. Thirty-eight patients cited their doctor's recommendation while 20 patients selected their treatment to increase length of life or treat their cancer. Only 2 patients cited concerns over surgical complications as their reason for choosing their treatment strategy. Conclusions The most common reasons for treatment selection in palliative surgical consultation include symptom relief or improvement in quality of life and the doctor's recommendation with few patients listing concerns over surgical morbidity. J. Surg. Oncol. 2013;107:372–375. © 2012 Wiley Periodicals, Inc.

A dramatic increase in pharmaceutical industry funding and support of biomedical research has occurred in the past few decades (1, 2). This has led to strong concerns regarding inappropriate influence of industry funding on the biomedical research (3). Preponderance of evidence shows that industry funded research is associated with increased likelihood of pro-industry results and conclusions (4–11). Randomized controlled trials (RCTs) are considered the “gold standard” means to assess healthcare interventions. They are designed to eliminate bias by randomly distributing known and unknown confounding factors. RCTs need to be methodological sound to eliminate sources of bias that may appear at various stages. Bias make the results differ systematically from the truth through the combination of various study design, data analysis, and presentation factors (12). Substantial evidence shows that methodological quality of RCTs affects estimates of intervention efficacy (13–15). Limited data on the association of industry funding with RCT methodological quality shows conflicting results with some studies showing no difference (5, 16), while others showing either a trend towards higher quality (17, 18) or significantly higher quality compared to non-industry funded RCTs (8, 19–21). Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that chiefly manifests as inflammatory destructive arthritis, and affects 0.5–1% of the adults (22). Drug therapy options for RA treatment have remarkably improved over the past fifteen years. In particular, the discovery and availability of biologics as therapeutic agents for RA treatment was facilitated by the funding of clinical trials from pharmaceutical companies. A study to assess secular changes in the methodological quality of published RCTs in rheumatology found no differences between industry and non-profit funded RCTs (23). However, this study included both drug and non-pharmaceutical therapy RCTs, and only 102 (42.5%) of the 240 study RCTs were for RA treatment. There are no data on the influence of industry funding on outcome of RA drug therapy RCTs. The objective of this study was to determine the association of industry funding with the characteristics, outcome and the reported methodological quality of drug therapy RCTs for RA.

Objective Study the survival of patients with cervical lymphatic squamous cell carcinoma recurrence. Study Design Review of tumor registry database. Setting Academic health science center. Subjects and Methods Forty-seven isolated neck recurrence patients identified from 224 recurrences from a total of 1291 patients treated between 1998 and 2007. The main outcome measurements were neck lymph nodal recurrence, treatment-specific survival, and overall survival. Results A total of 47 patients had neck recurrence; 10 of the neck recurrence patients (21.3%) had regional disease (N+) at initial presentation. Median survival for patients with neck recurrence was 14.7 months (95% confidence interval [CI] 8.6-18.1 mo), and five-year survival for this group was five percent (95% CI 0%-30%). Neck dissection salvage therapy for neck recurrence resulted in the best survival. Conclusion Neck dissection as a salvage therapy for neck recurrence resulted in the best survival, and there was no survival benefit in terms of whether a patient had a neck dissection or not as his or her initial therapy.

Background: One major risk factor for cutaneous melanoma is chronic sun-exposure and oxidative stress. Among various oxidative DNA damages, 8-oxoquanine is the most abundant and is potentially mutagenic if not sufficiently repaired. The human 8-oxoquanine DNA glycosylase 1 (hOGG1) gene specifically repairs 8-oxoguanine, and this gene shows frequent loss of heterozygosity (LOH) in human tumors. In this study, we investigate whether hOGG1 LOH occurs in melanoma in situ (MIS) and adjacent atypical melanocytic hyperplasia (AMH). Methods: Twelve skin biopsies with MIS and adjacent AMH were included. DNA samples derived from manual microdissection of tissues were subjected to polymerase chain reaction amplification using three fluorescent-labeled microsatellite makers, followed by fragment analysis. Results: Five of 12 cases were informative for both telomeric (3S1297) and centromeric (3S1289 or 3S1300) markers, bordering the hOGG1 locus. Among them, four (80%) MIS and three (60%) AMH showed hOGG1 LOH at both markers. Conclusions: These results shows that LOH at hOGG1 gene is associated with MIS and AMH and suggest that the hOGG1 gene may play a role in melanocytic tumor progression.

Background The purpose of this study was to demonstrate a role for observation of patients with differentiated thyroid cancer (DTC) with persistent, nonlocalizable disease. Methods Our study was conducted on outpatients seen at our institution from 1999 to 2009 having total thyroidectomy, radioactive iodine (RAI) ablation, measurable serum thyroglobulin (Tg), and no evidence of disease on whole body or positron emission tomography (PET) scans. Results Nineteen patients in our study group aged 20 to 73 with an average follow-up of 5.5 years (range, 2–12 years); all were treated with postoperative RAI (99–210 mCi, average 119). Mean Tg ranged from 0.41 to 4.34. Tg levels remained stable or gradually decreased in all patients. Conclusion After total thyroidectomy and RAI therapy, patients may present with mildly elevated Tg values without localizable disease. These patients may have additional RAI treatments based on the Tg elevation. However, our clinical experience has shown that many of these patients will have Tg levels that either achieve stability or decrease over time without further treatment. © 2013 Wiley Periodicals, Inc. Head Neck 36: 155–157, 2014

Background Pesticide exposure has been suggested as one causal factor for the rise in asthma prevalence. The goal of this investigation was to determine the effect of pesticide exposure on respiratory symptoms and lung function in workers with occupational exposure to pesticides. Methods A prospective, case-controlled study was conducted among pesticide aviators (AV) and community controls (Con). In Phase I, subjects completed an asthma survey and baseline spirometry. In Phase II, subjects reported symptoms, lung function monitoring, and pesticide exposure during two, 14-day periods. Results Phase I—Self-reported asthma and symptoms were similar among AV (n = 135) and Con (n = 118) with 4–6% prevalence reported but with higher rates among smokers. Baseline lung function was similar; although, a higher proportion of AV had forced expiratory volume in one second (FEV1)

Objectives:Compare the cost of outpatient and inpatient thyroidectomy at US academic medical centers.Methods:Discharge data were collected from the first quarter of 2009 through the fourth quarter of 2012 from the University Health System Consortium (UHC) on over 50,000 patients. The UHC database, compiled from over 100 academic health centers and their 200 affiliated hospitals, was searched based on diagnosis codes for outpatient and inpatient thyroid procedures. The Agency for Healthcare and Research Quality (AHRQ) chronic conditions were collected in addition to demographic, length of stay (LOS), and cost data. Comparisons were made between inpatient and outpatient thyroidectomy stratified by number of chronic conditions.Results:The cost of outpatient thyroidectomy was consistently less than that for inpatient thyroidectomy. More outpatient thyroidectomies were performed on patients with 0 or 1 chronic condition, while more inpatient thyroidectomies were performed on patients with 2 or greater chronic ...

Objective: Better understand the relationships of parathyroid hormone production (PTH), adenoma gamma counts, and adenoma weight in patients undergoing minimally invasive parathyroidectomy for prim...

Objective: Determine whether the type (paramedian forehead [PMFF] vs nasolabial [NLF]) or the defect thickness (full vs partial) play a role in take rates of interpolation flaps in nasal reconstruction.Method: A retrospective chart review was performed on patients who underwent nasal reconstruction with 2-stage paramedian forehead or nasolabial flaps between 2002 and present. Defect characteristics recorded were thickness, size, location; flap type used for repair, utilization of cartilage grafts; and comorbidities, including diabetes, peripheral vascular or coronary artery disease, and smoking habits.Results: A total of 107 total patients; 82 (76%) reconstructed using 2-stage paramedian forehead flap; 25 (24%) using a 2-stage nasolabial flap (NLF). A total of 47 PMFF and 12 NLF were used for full thickness defects. Overall failure rate was 5%, both partial and complete. Five PMFF failed (7%), 3 full thickness. One NLF failed (4%), also full thickness. Any use of cartilage in reconstruction did not affect...

Objective: Provide prognostic data for the physicians and patients when a decision is made for primary or salvage ablative surgery of the upper aerodigestive tract with the aide of microvascular reconstruction.Method: Retrospective chart review of patients with primary or recurrent upper aerodigestive tract squamous cell carcinoma treated with free flap reconstruction between 1993 and 2009. Prior treatment, recurrence time and site, sex, age, complications, cause of death, stage, and survival rates were analyzed.Results: A total of 219 patients were identified. Mean age was 59.6 years. A total of 136 patients underwent primary resection with immediate reconstruction, 83 patients underwent salvage treatment. A total of 196 patients had advanced clinical stage oral (n = 129) and oropharyngeal squamous cell carcinomas (n = 51). Median overall survival for all patients was 21.7 months (CI 16.2, 33.1) with median recurrence free survival of 12.6 months (CI 8.8, 16.6). Median overall survival was 31.3 months (C...