Creating a model to predict time intervals from induction of labor to induction of anesthesia and delivery to coordinate workload.

BACKGROUND: Induction of labor continues to become more common. We analyzed induction of labor and timing of obstetric and anesthesia work to create a model to predict the induction-anesthesia interval and the induction-delivery interval in order to co-ordinate workload to occur when staff are most available. METHODS: Patients who underwent induction of labor at a single medical center were identified and multivariable linear regression was used to model anesthesia and delivery times. Data were collected on date of birth, race/ethnicity, body mass index, gestational age, gravidity, parity, indication for labor induction, number of prior deliveries, time of induction, induction agent, cervical dilation, effacement, and fetal station on admission, date and time of anesthesia administration, date and time of delivery, and delivery type. RESULTS: A total of 1746 women met inclusion criteria. Associations which significantly influenced time from induction of labor to anesthesia and delivery included maternal age (anesthesia P <0.001, delivery P =0.002), body mass index (both P <0.001), prior vaginal delivery (both P <0.001), gestational age (anesthesia P <0.001, delivery P <0.018), simplified Bishop score (both P <0.001), and first induction agent (both P <0.001). Induction of labor of nulliparous women at 02:00 h and parous women at 04:00 or 05:00 h had the highest estimated probability of the mother having her first anesthesia encounter and delivering during optimally staffed hours when our institution's specialty personnel are most available. CONCLUSIONS: Time to obstetric and anesthesia tasks can be estimated to optimize induction of labor start times, and shift anesthesia and delivery workload to hours when staff are most available.

Transoral laser microsurgery versus radiotherapy for T2 glottic squamous cell carcinoma: a systematic review of local control outcomes.

BACKGROUND: Systematic reviews comparing treatment of early glottic cancer with transoral surgery or radiotherapy demonstrate similar oncological outcomes. Most studies of 'early-stage' laryngeal cancer include Tis, T1a, T1b and T2 cases. The data are dominated by patients with T1 and Tis tumours, although extrapolating these results and applying them for T2 cases may be inappropriate. No previous systematic reviews have focused on T2 cancers as a separate group. OBJECTIVE OF REVIEW: This review compares local control outcomes for T2 glottic squamous cell carcinoma, treated with transoral microsurgery or external beam radiotherapy. TYPE OF REVIEW: This is a systematic review of case series and comparison studies, focusing on oncological outcomes. SEARCH STRATEGY: Independent searches of MEDLINE, EMBASE and the Cochrane Database were conducted by two authors, using the search terms: laryngeal/glottic/vocal cord combined with carcinoma/cancer/tumour and laser/microsurgery or radiotherapy. Studies of adult patients treated for primary T2N0 glottic squamous cell carcinoma (SCC) with laser surgery or curative radiotherapy were included. EVALUATION METHOD: Full text of studies satisfying the inclusion criteria were reviewed with extraction of local control and survival data and laryngeal preservation rates. The primary endpoint is local control at 5 years. RESULTS: Initial searches identified 3252 studies. Following full-text review of 183 papers, 59 studies met the inclusion criteria, all level IV evidence. A total of 48 studies specified 5-year local control for 1156 patients treated with transoral laser surgery and 3191 patients treated with radiotherapy. Weighted averages of local control at 5 years demonstrated similar results: 75.81% for radiotherapy versus 77.26% for transoral laser surgery. CONCLUSIONS: The results of this review indicate no difference in 5-year local control between radiotherapy and transoral surgery for T2 glottic SCC. The data demonstrated higher rates of local failure for T2b compared with T2a cases, although outcomes were similar between laser excision and radiotherapy for each substage. Further research focusing upon functional outcomes for T2 glottic tumours is imperative to guide decision-making, ideally with subgroup analysis of T2a and T2b cases.

Unilateral cochlear implantation in children with a potentially useable contralateral ear.

Increasingly, children are considered for a unilateral CI, even if the contralateral ear falls outside current audiological guidelines, especially if they are not considered to be reaching their educational potential. The primary aim was to investigate the benefit of unilateral CI in children currently outside UK [National Institute for Health and Care Excellence Technology Appraisal Guidance. 2009. Cochlear implants for children and adults with severe to profound deafness. NICE technology appraisal guidance [TAG166]. Available January 29, 2016 from http://www.nice.org.uk/ta166 ] audiological guidelines in the contralateral ear. The secondary aim was to measure compliance. A retrospective case review with standard demographic data was performed. Forty-seven children were identified as having received a unilateral CI with the contralateral ear falling outside of current UK audiological criteria. These children were allocated to two groups; with hearing between 50 and 70 dB, and 70 and 90 dB at 2 and 4 kHz in the contralateral ear, respectively. Categories of auditory performance (CAP) were assessed. Pre- and post-operative CAP scores demonstrated a statistically significant improvement in auditory perception. We would suggest that assessing candidacy in individual ears and subsequent unilateral CI, has given these children a benefit they may not otherwise have acquired if they only had bilateral hearing aid.

Factors associated with survival to hospital discharge following endoscopic treatment for synovial sepsis in 214 horses.

REASONS FOR PERFORMING STUDY: To determine risk factors involved in survival to hospital discharge of cases of synovial sepsis. OBJECTIVES: Investigate pre-, intra- and post operative factors involved in short-term survival of horses undergoing endoscopic treatment for synovial sepsis. STUDY DESIGN: Retrospective case series. METHODS: Clinical data were obtained for horses (>6 months old) undergoing endoscopic surgery as part of management for synovial sepsis over a 7-year period in a single hospital population. Descriptive data were generated for pre-, intra- and post operative variables. Multivariable logistic regression analysis was used to develop 3 models related to presurgical, surgical and post surgical stages of management with outcome defined as survival to hospital discharge. RESULTS: Two hundred and fourteen horses were included. In Model 1 (preoperative variables), increased preoperative synovial fluid total protein (TP) was associated with nonsurvival (OR 0.88, 95% CI 0.83-0.94, P<0.001) whereas the presence of a wound on admission was associated with survival (OR 4.75, 95% CI 1.21-18.65, P = 0.02). Model 2 (intraoperative variables) revealed that factors associated with decreased survival were anaesthetic induction outside of normal working hours (OR 0.36, 95% CI 0.15-0.88 P = 0.02) and presence of moderate/severe synovial inflammation at surgery (OR 0.28, 95% CI 0.12-0.67, P = 0.004). Model 3 (post operative variables) showed that increased post operative synovial fluid TP (OR 0.94, 95% CI 0.90-0.98, P = 0.013) and undertaking more than one endoscopic surgery for treatment (OR 0.19, 95% CI 0.05-0.70, P = 0.005) were associated with nonsurvival. Cut-off values for predicting survival were 55-60 g/l for preoperative and 50-55 g/l for post operative TP measurements. CONCLUSIONS: This study has identified factors associated with altered likelihood of survival to hospital discharge following endoscopic surgery for synovial sepsis. Prognosis for survival to hospital discharge can be based on evidence from this study at the key stages of management of horses with synovial sepsis.

A myostatin and activin decoy receptor enhances bone formation in mice.

Myostatin is a member of the bone morphogenetic protein/transforming growth factor-ß (BMP/TGFß) super-family of secreted differentiation factors. Myostatin is a negative regulator of muscle mass as shown by increased muscle mass in myostatin deficient mice. Interestingly, these mice also exhibit increased bone mass suggesting that myostatin may also play a role in regulating bone mass. To investigate the role of myostatin in bone, young adult mice were administered with either a myostatin neutralizing antibody (Mstn-mAb), a soluble myostatin decoy receptor (ActRIIB-Fc) or vehicle. While both myostatin inhibitors increased muscle mass, only ActRIIB-Fc increased bone mass. Bone volume fraction (BV/TV), as determined by microCT, was increased by 132% and 27% in the distal femur and lumbar vertebrae, respectively. Histological evaluation demonstrated that increased BV/TV in both locations was attributed to increased trabecular thickness, trabecular number and bone formation rate. Increased BV/TV resulted in enhanced vertebral maximum compressive force compared to untreated animals. The fact that ActRIIB-Fc, but not Mstn-mAb, increased bone volume suggested that this soluble decoy receptor may be binding a ligand other than myostatin, that plays a role in regulating bone mass. This was confirmed by the significant increase in BV/TV in myostatin deficient mice treated with ActRIIB-Fc. Of the other known ActRIIB-Fc ligands, BMP3 has been identified as a negative regulator of bone mass. However, BMP3 deficient mice treated with ActRIIB-Fc showed similar increases in BV/TV as wild type (WT) littermates treated with ActRIIB-Fc. This result suggests that BMP3 neutralization is not the mechanism responsible for increased bone mass. The results of this study demonstrate that ActRIIB-Fc increases both muscle and bone mass in mice. Therefore, a therapeutic that has this dual activity represents a potential approach for the treatment of frailty.

Brothers Leading Healthy Lives: Outcomes from the pilot testing of a culturally and contextually congruent HIV prevention intervention for black male college students.

We used a treatment group-only design to pilot test a newly developed intervention to increase condom use among higher risk heterosexually active African American/black male college students. A community-based participatory research partnership developed the intervention called Brothers Leading Healthy Lives. Following an initial screening of 245 men, 81 eligible men were contacted for participation. Of the 64 men who agreed to participate, 57 completed the intervention and 54 of those completed the 3-month follow-up assessment, for a 93% completion rate. Results show significant changes between the baseline and 3-month follow-up assessments in behavioral outcomes, including reductions in unprotected sex, increase in protection during last intercourse, and fewer condom use errors. Most potential mediators (knowledge, attitudes, intentions, and condom use self-efficacy) also changed significantly in the expected direction. These demonstrated changes provide good evidence that men exposed to this intervention will see changes that reduce their risk for HIV.

Effect of age on the pharmacokinetics of a single daily dose of gentamicin sulfate in healthy foals.

REASONS FOR PERFORMING STUDY: Therapeutic drug monitoring in a small number of foals of various ages indicates that the standard adult dose of 6.6 mg/kg bwt q. 24 h for gentamicin is too low and a dose of 12 mg/kg bwt has been proposed. The pharmacokinetics of this dosage in foals and the ages at which this higher dose should be used have not previously been investigated. OBJECTIVE: To determine the effect of age on the pharmacokinetics of a single 12 mg/kg bwt i.v. dose of gentamicin in foals. METHODS: Six healthy foals were given a single i.v. dose of gentamicin at 1-3 days, 2, 4, 8 and 12 weeks of age. Plasma concentrations were measured using LC-MS/MS. RESULTS: Elimination half-life (mean ± s.d.) was significantly longer in 1-3-day-old foals (8.2 ± 2.0 h) than in foals 4 weeks of age (3.7 ± 1.5 h) or older. Volume of distribution was significantly higher in 1-3-day-old foals (0.75 ± 0.20 l/kg bwt) than in 8- (0.27 ± 0.10 l/kg bwt) or 12-week-old foals (0.29 ± 0.11 l/kg bwt). Concentrations of gentamicin 1 h after administration were significantly lower in 1-3-day-old foals (20.52 ± 2.07 µg/ml) than in all other age groups (>42.16 ± 17.57 µg/ml). Concentrations of gentamicin 24 h after administration were significantly higher in the 1-3-day-old foals (1.97 ± 0.90 µg/ml) than in all the other age groups (<0.85 ± 0.46 µg/ml). CONCLUSIONS: The pharmacokinetics of gentamicin change considerably in the first 2 weeks of life. POTENTIAL RELEVANCE: Intravenous administration of gentamicin at a dose of 12 mg/kg bwt q. 36 h would be required in foals less than 2 weeks of age. In foals 2 weeks of age or older, a lower dose of 6.6 mg/kg bwt given q. 24 h was predicted to be adequate.

Condom use problems during anal sex among men who have sex with men (MSM): findings from the Safe in the City study.

Our research aims were to: (1) assess the prevalence of two condom use problems: breakage or slippage and partial use (delayed application or early removal) among men who have sex with men (MSM) seeking services in urban US STD clinics; and (2) examine the association between these condom use problems and participant, partner and partnership characteristics. Analysis was restricted to HIV-negative MSM who reported having anal sex at least once in the preceding 3 months and who completed both the baseline and 3 month follow-up assessments. Two models were fitted using the generalized estimating equations (GEE) approach. A total of 263 MSM (median age=32 years) reported 990 partnerships. Partnerships with no condom use 422 (42.6%) were excluded. Thus, 207 MSM and 568 partnerships were included. Among condom users, 100% use was reported within 454 partnerships (79.9%) and <100% within 114 (20.1%), and 21(3.7%) reported both condom use problems, 25 (4.4%) reported only breakage, 67 (11.8%) reported only partial use, and 455 (80.1%) reported no errors. The breakage or slippage and partial use rates per condom used were 3.4% and 11.2%, respectively. A significantly higher rate of breakage or slippage occurred among non-main partnerships. Characteristics associated with increased odds for condom breakage or slippage were: lower education level (OR=2.78; CI: 1.1-7.5), non-main partner status (OR=4.1; CI: 1.5-11.7), and drunk or high during sex (OR=2.0; CI: 1.1-3.8), and for partial use: lower education level (OR=2.6; CI: 1.0-6.6), perceived partner sexually transmitted infections (STI) risk (OR=2.4; CI: 1.3-4.2), and inconsistent condom use (OR=3.7; CI: 2.0-6.6). A high percentage of MSM partnerships reported no condom use and among condom users, a sizable proportion did not use them consistently or correctly. MSM may benefit from interventions designed to increase proficiency for condom use with a particular focus on the behaviors of inconsistent and partial condom use.

Momentary reductions of attention permit greater processing of irrelevant stimuli.

Momentary reductions of attention can have extremely adverse outcomes, but it remains unclear whether increased distraction from irrelevant stimuli contributes to such outcomes. To investigate this hypothesis, we examined trial-by-trial relationships between brain activity and response time in twenty healthy adults while they performed a cross-modal selective attention task. In each trial, participants identified a relevant visual letter while ignoring an irrelevant auditory letter, which was mapped either to the same response as the visual letter (congruent trials) or to a different response (incongruent trials). As predicted, reductions of attention (i.e., increases of response time) were associated not only with decreased activity in sensory regions that processed the relevant visual stimuli, suggesting a failure to enhance the processing of those stimuli, but also with increased activity in sensory regions that processed the irrelevant auditory stimuli, suggesting a failure to suppress the processing of those stimuli. Reductions of attention were also linked to larger increases of activity in incongruent than in congruent trials in anterior cingulate regions that detect response conflict, suggesting that failing to suppress the sensory processing of the irrelevant auditory stimuli during attentional reductions allowed those stimuli to more readily activate conflicting responses in incongruent trials. These findings indicate that heightened levels of distraction during momentary reductions of attention likely stem, at least in part, from increased processing of irrelevant stimuli.

The potential of a placebo/nocebo effect in pharmacogenetics.

Pharmacogenetic testing holds great promise to improve health outcomes and reduce adverse drug responses through enhanced selection of therapeutic agents. Since drug responses can be manipulated by verbal suggestions, it is of particular interest to understand the potential impact of pharmacogenetic test results on drug response. Placebo and nocebo-like effects may be possible due to the suggestive nature of pharmacogenetic information that a drug will or will not likely lead to improved health outcomes. For example, pharmacogenetic testing could provide further reassurance to patients that a given drug will be effective and/or cause minimal side effects. However, pharmacogenetic information could adversely affect drug response through negative expectations that a drug will be less than optimally effective or cause an adverse response, known as a nocebo-like effect. Therefore, a patient's perceived value of testing, their understanding of the test results, and the manner in which they are communicated may influence therapeutic outcome. As such, physicians should consider the potential effect of pharmacogenetic test results on therapeutic outcome when communicating results to patients. Studies are needed to investigate the impact of pharmacogenetic information of therapeutic outcome.

Condom use in the year following a sexually transmitted disease clinic visit.

Consistent condom use can prevent sexually transmitted infections (STIs), but few studies have measured how the prevalence of consistent use changes over time. We measured the prevalence and correlates of consistent condom use over the course of a year. We did a secondary analysis of data from an HIV prevention trial in three sexually transmitted disease clinics. We assessed condom use during four three-month intervals for subjects and across their partnerships using unconditional logistic regression. Condom use was also assessed for subjects during all three-month intervals combined. The 2125 subjects reported on 5364 three-month intervals including 7249 partnership intervals. Condoms were always used by 24.1% of subjects and 33.2% of partnerships during a three-month interval. Over the year, 82% used condoms at least once but only 5.1% always used condoms. Always use of condom was more likely for subjects who had sex only once (66.5%) compared with >30 times (6.4%); one-time partnerships (64.1%) compared with main partnerships (22.2%); and in new partnerships (44.0%) compared with partnerships that were not new (24.5%). Although consistent condom use may prevent STIs, condoms were rarely used consistently during the year of follow-up.

The neural mechanisms for minimizing cross-modal distraction.

The neural circuitry that increases attention to goal-relevant stimuli when we are in danger of becoming distracted is a matter of active debate. To address several long-standing controversies, we asked participants to identify a letter presented either visually or auditorily while we varied the amount of cross-modal distraction from an irrelevant letter in the opposite modality. Functional magnetic resonance imaging revealed three novel results. First, activity in sensory cortices that processed the relevant letter increased as the irrelevant letter became more distracting, consistent with a selective increase of attention to the relevant letter. In line with this view, an across-subjects correlation indicated that the larger the increase of activity in sensory cortices that processed the relevant letter, the less behavioral interference there was from the irrelevant letter. Second, regions of the dorsolateral prefrontal cortex (DLPFC) involved in orienting attention to the relevant letter also participated in increasing attention to the relevant letter when conflicting stimuli were present. Third, we observed a novel pattern of regional specialization within the cognitive division of the anterior cingulate cortex (ACC) for focusing attention on the relevant letter (dorsal ACC) versus detecting conflict from the irrelevant letter (rostral ACC). These findings indicate novel roles for sensory cortices, the DLPFC, and the ACC in increasing attention to goal-relevant stimulus representations when distracting stimuli conflict with behavioral objectives. Furthermore, they potentially resolve a long-standing controversy regarding the key contribution of the ACC to cognitive control.

Biphasic dose-related effects of morphine on dopamine release.

The effects of morphine on extracellular dopamine levels in brain have never been studied over a wide range of doses within a single study. This has made it difficult to make definitive interpretations of drug interactions with morphine. An inhibition of morphine-induced increases in dopamine could be interpreted as either antagonism or potentiation depending the shape of the morphine dose-response curve. Accordingly, the aim of the present study was to determine the effects of a wide range of morphine doses (0, 5, 10, 20 and 30 mg/kg, i.p.) on extracellular dopamine, DOPAC and HVA levels in the nucleus accumbens and striatum of awake and freely moving female Sprague-Dawley rats. The results show that, in both brain regions, the dose-response curve for morphine-induced increases in dopamine is non-monotonic while the dose-response curve for morphine-induced increases in DOPAC and HVA is monotonic in the nucleus accumbens. The results of this study are discussed in terms of their implications for interpreting drug interactions with morphine and with relationship to morphine's mode of action at mu and kappa opioid receptors.