Clinical protocol selection for alveolar ridge augmentation at sites exhibiting slight, moderate, and severe horizontal ridge deficiencies.

FOCUSED CLINICAL QUESTION: What factors identify the optimal bone augmentation techniques for managing slight, moderate, and severe horizontal alveolar ridge deficiency (ARD) at dental implant sites? SUMMARY: Horizontal ARD is a concern at a high proportion of sites receiving dental implants, and clinicians have developed a variety of surgical procedures to address such defects. In a particular case, selection of the optimal treatment may depend predominantly on defect severity, location (anterior versus posterior), and configuration (contained versus noncontained). This report provides a framework for selecting an augmentation method when presented with a slight, moderate, or severe horizontal ARD at a site requiring dental implant placement. CONCLUSION: Multiple treatment options are available for planned implant sites exhibiting horizontal ARD; severe posterior and slight anterior defects intuitively call for different approaches. Although rigid guidelines for selecting the optimal augmentation method do not exist, some techniques are poorly suited for esthetically demanding sites. A framework considering defect severity, location, and configuration may help guide clinical decisions on this topic.

Dynamics of sputum conversion during effective tuberculosis treatment: A systematic review and meta-analysis.

BACKGROUND: Two weeks' isolation is widely recommended for people commencing treatment for pulmonary tuberculosis (TB). The evidence that this corresponds to clearance of potentially infectious tuberculous mycobacteria in sputum is not well established. This World Health Organization-commissioned review investigated sputum sterilisation dynamics during TB treatment. METHODS AND FINDINGS: For the main analysis, 2 systematic literature searches of OvidSP MEDLINE, Embase, and Global Health, and EBSCO CINAHL Plus were conducted to identify studies with data on TB infectiousness (all studies to search date, 1 December 2017) and all randomised controlled trials (RCTs) for drug-susceptible TB (from 1 January 1990 to search date, 20 February 2018). Included articles reported on patients receiving effective treatment for culture-confirmed drug-susceptible pulmonary TB. The outcome of interest was sputum bacteriological conversion: the proportion of patients having converted by a defined time point or a summary measure of time to conversion, assessed by smear or culture. Any study design with 10 or more particpants was considered. Record sifting and data extraction were performed in duplicate. Random effects meta-analyses were performed. A narrative summary additionally describes the results of a systematic search for data evaluating infectiousness from humans to experimental animals (PubMed, all studies to 27 March 2018). Other evidence on duration of infectiousness-including studies reporting on cough dynamics, human tuberculin skin test conversion, or early bactericidal activity of TB treatments-was outside the scope of this review. The literature search was repeated on 22 November 2020, at the request of the editors, to identify studies published after the previous censor date. Four small studies reporting 3 different outcome measures were identified, which included no data that would alter the findings of the review; they are not included in the meta-analyses. Of 5,290 identified records, 44 were included. Twenty-seven (61%) were RCTs and 17 (39%) were cohort studies. Thirteen studies (30%) reported data from Africa, 12 (27%) from Asia, 6 (14%) from South America, 5 (11%) from North America, and 4 (9%) from Europe. Four studies reported data from multiple continents. Summary estimates suggested smear conversion in 9% of patients at 2 weeks (95% CI 3%-24%, 1 single study [N = 1]), and 82% of patients at 2 months of treatment (95% CI 78%-86%, N = 10). Among baseline smear-positive patients, solid culture conversion occurred by 2 weeks in 5% (95% CI 0%-14%, N = 2), increasing to 88% at 2 months (95% CI 84%-92%, N = 20). At equivalent time points, liquid culture conversion was achieved in 3% (95% CI 1%-16%, N = 1) and 59% (95% CI 47%-70%, N = 8). Significant heterogeneity was observed. Further interrogation of the data to explain this heterogeneity was limited by the lack of disaggregation of results, including by factors such as HIV status, baseline smear status, and the presence or absence of lung cavitation. CONCLUSIONS: This systematic review found that most patients remained culture positive at 2 weeks of TB treatment, challenging the view that individuals are not infectious after this interval. Culture positivity is, however, only 1 component of infectiousness, with reduced cough frequency and aerosol generation after TB treatment initiation likely to also be important. Studies that integrate our findings with data on cough dynamics could provide a more complete perspective on potential transmission of Mycobacterium tuberculosis by individuals on treatment. TRIAL REGISTRATION: Systematic review registration: PROSPERO 85226.

Impact of emergency department opioid use on future health resource utilization among patients with migraine.

OBJECTIVE: The purpose of this study was to evaluate the subsequent health resource utilization (HRU) between patients with migraine who received opioid medications at their emergency department (ED) visits ("opioid recipients") versus patients with migraine who did not receive opioid medications at their ED visits ("non-recipients"). BACKGROUND: Previous studies have found that opioid use is common among patients with migraine at emergency settings. Medication overuse, especially the use of opioids, is associated with migraine progression, which can ultimately lead to substantial health resource use and costs. There is limited evidence on opioid use specifically in emergency settings and its impact on future HRU among people with migraine. METHOD: This retrospective cohort study used electronic health record data from the Baylor Scott & White Health between December 2013 and April 2017. Adult patients who had at least 6 months of continuous enrollment before (baseline or pre-index) and after (follow-up) the first date they had an ED visit with a diagnosis of migraine (defined as index date) were enrolled in the study. Opioid use and HRU during follow-up period between opioid recipients and non-recipients were summarized and compared. RESULTS: A total of 788 patients met the eligibility criteria and were included in this study. During the 6-month follow-up period, compared to patients with migraine who were non-recipients at their index ED visits, opioid recipients had significantly more all-cause (3.6 [SD = 6.3] vs. 1.9 [SD = 4.8], p < 0.0001) and migraine-related (1.6 [SD = 4.2] vs. 0.6 [SD = 2.1], p < 0.0001) opioid prescriptions (RXs), and more all-cause (2.6 [SD = 4.3] vs. 1.6 [SD = 2.6], p = 0.002) and migraine-related (0.6 [SD = 1.4] vs. 0.3 [SD = 0.8], p = 0.001) ED visits. In addition, opioid recipients had higher risk of future migraine-related ED visits controlling for covariates (HR = 1.49, 95% CI = 1.09-2.03, p = 0.013). Factors that were significantly (p < 0.05) related to future migraine-related ED visits include previous opioid use (HR = 2.12, 95% CI = 1.24-3.65, p = 0.007), previous ED visits (HR = 2.38, 95% CI = 1.23-4.58, p = 0.010), hypertension (HR = 1.46, 95% CI = 1.07-2.00, p = 0.017), age between 45 and 64 years (HR = 0.68, 95% CI = 0.48-0.97, p = 0.033), female sex (HR = 1.82, 95% CI = 1.12-2.86, p = 0.015), and tobacco use disorder (HR = 1.45, 95% CI = 1.07-1.97, p = 0.017). Sub-analyses were restricted to the group of patients who were opioid naïve at baseline (n = 274, defined as having ≤1 opioid RXs during the 6-month pre-index period). Patients who were baseline opioid naïve but received opioids during their index ED visits were more likely to have future migraine-related ED visits compared to patients who were baseline opioid naïve and did not receive any opioids during their index ED visits, controlling for covariates (HR = 2.90, 95% CI = 1.54-5.46, p = 0.001). CONCLUSION: Opioid use among patients with migraine presenting to the ED is associated with increased future HRU, which highlights the need for optimizing migraine management in emergency settings.

Gender and ethnic differences in rates of immune reconstitution, AIDS diagnosis, and survival.

In this work, we use 2011-2013 Texas HIV surveillance data (N=2,175) and apply hierarchical linear and Cox regression modeling to characterize the association of gender and race/ethnicity with rate of immune recovery and determine whether immune recovery contributes to gender and racial/ethnic disparities in AIDS diagnosis and survival. The associations between gender and rate of immune recovery and between race/ethnicity and rate of immune recovery were not statistically significant (p > 0.05). In the multivariate survival analyses, there was no statistically significant association between gender and AIDS diagnosis (Adjusted Hazard Ratio (AHR) = 1.06, p = 0.61, 95%=0.85-1.32) and between race/ethnicity and AIDS diagnosis (Blacks vs Whites: AHR = 1.10, p = 0.24, 95% CI = 0.94-1.30; Hispanics vs Whites: AHR = 1.06, p = 0.46, 95% CI = 0.91-1.24). Similarly, there were no statistically significant associations with death (males vs females: AHR = 0.88, p = 0.73, 95% CI = 0.43-1.81; Blacks vs Whites: AHR = 0.68 p = 0.25, 95% CI = 0.36-1.30; Hispanics vs Whites: AHR = 0.96, p = 0.88, 95% CI = 0.55-1.67). However, the direction of the point estimates were in the reverse direction when compared to the rate of immune recovery or the AIDS diagnosis models. Our findings suggest that differences in rate of immune recovery may better explain disparities in AIDS diagnosis than disparities in survival. Future studies with longer follow-up may potentially generate statistically significant results.

Efavirenz versus Protease Inhibitors in Patients with HIV: A Systematic Review and Meta-Analysis

Efavirenz- and protease inhibitor (PI)-based regimens remain viable options across the globe. We conducted a meta-analysis to compare the effectiveness of efavirenz-based regimens relative to PI-based regimens. EMBASE, PubMed, Cochrane, and clinicaltrials.gov were searched for randomized controlled trials conducted between 1987 and 2018 comparing efavirenz- with PI-based regimens. This was followed by title, abstract, and full-text screens. The quality of selected studies was assessed using the Cochrane risk of bias tool. Meta-analysis of the odds of virological suppression was conducted using the robust variance estimation approach. Fifteen studies met the inclusion criteria and totaled 6712 patients (efavirenz arm = 3339; PI arm = 3373), of which 1610 (24.0%) were females. Follow-up ranged from 24 to 144 weeks. Mean/median age ranged from 33 to 44 years. Mean/median baseline CD4 count ranged from 32 to 557 cells/mL while mean/median baseline viral load ranged from log10 4.5 to log10 5.5 copies/mL. Meta-analysis showed that patients receiving efavirenz-based regimens had 37% higher odds of virological suppression compared to PI-based regimens (odds ratio = 1.37, 95% confidence interval = 1.06-1.77, p = 0.02). The Egger test suggested the presence of publication bias (B = 0.927, t = 2.214, p = 0.033). The main threat to the quality of evidence was attrition bias. Regarding virological suppression, efavirenzbased regimens were more effective than PI-based regimens and, therefore, might be ideal for the management of treatment naïve patients with HIV in settings where NNRTIs and PIs are used.

Identifying subgroups within at-risk populations that drive late HIV diagnosis in a Southern U.S. state.

We aimed to identify subgroups within age, racial/ethnic, and transmission categories that drive increased risk for late HIV diagnosis (LHD).A 1996-2013 retrospective study of HIV-diagnosed individuals (N = 77,844) was conducted. The proportion of individuals with LHD (AIDS diagnosis within 365 days of HIV diagnosis) was determined, stratified by age, race/ethnicity, and transmission category. Logistic regression with interaction terms was used to identify groups/subgroups at risk for LHD during 1996-2001, 2002-2007, and 2008-2013.Respectively, 78%, 27%, 38%, and 31% were male, White, Black, and Hispanic. Overall, 39% had LHD with a 6.7% reduction for each year increase (OR = 0.93, 95% CI = 0.93-0.94, p < 0.01). Older age was significantly associated with increased odds of LHD (OR range = 1.90-4.55). Compared to their White counterparts, all Hispanic transmission categories (OR range = 1.31-2.58) and only Black female heterosexuals and men who have sex with men (MSM) (OR range = 1.14-1.33) had significantly higher odds of LHD during 1996-2001 and/or 2002-2007. Significance was limited to Hispanic MSM (all age categories), MSM/IDUs (30-59 years), and heterosexuals (18-29 years) and Black MSM (30-39 years) during 2008-2013.Older individuals and Hispanics (driven by MSM) are at increased risk for LHD. HIV testing interventions directed at seniors and Hispanic MSM can further reduce rates of LHD.

Patterns and predictors of opioid use among migraine patients at emergency departments: A retrospective database analysis.

OBJECTIVES: To compare medication use and health resource utilization between migraineurs with evidence of opioid use at emergency department visit versus no opioid use at emergency department visit, and to examine predictors of opioid use among migraineurs at emergency department visits. METHODS: This was a retrospective study using REACHnet electronic health records (December 2013 to April 2017) from Baylor Scott & White Health Plan. The index date was defined as the first migraine-related emergency department visit after ≥6 months of enrollment. Adult patients with a migraine diagnosis and ≥6 months of continuous enrollment before and after their index dates were included. Descriptive statistics and bivariate analyses were used to compare medication use and health resource utilization between opioid users and non-opioid users. Multivariable logistic regression was used to examine predictors of opioid use at emergency department visits. RESULTS: A total of 788 migraineurs met eligibility criteria. Over one-third (n = 283, 35.9%) received ≥1 opioid medication during their index date emergency department visit. Morphine (n = 103, 13.1%) and hydromorphone (n = 85, 10.8%) were the most frequently used opioids. Opioid users had more hospitalizations and emergency department visits during their pre-index period (both p < 0.05). Significant (p < 0.05) predictors of opioid use at emergency department visits included past migraine-related opioid use (2-4 prescriptions, Odds Ratio = 1.66; 5-9 prescriptions, Odds Ratio = 2.12; ≥10 prescriptions, Odds Ratio = 4.43), past non-migraine-related opioid use (≥10 prescriptions, Odds Ratio = 1.93), past emergency department visits (1-3 visits, Odds Ratio = 1.84), age (45-64 years, Odds Ratio = 1.45), and sleep disorder (Odds Ratio = 1.43), controlling for covariates. CONCLUSION: Opioids were commonly given to migraineurs at emergency departments. Previous opioid use, health resource utilization, age, and specific comorbidities might be used to identify migraineurs with a high risk of opioid use.

Fracture necrosis: A risk indicator for tooth loss.

BACKGROUND AND OVERVIEW: The term "fracture necrosis" has been used to describe the condition found in a minimally restored tooth without a history of trauma when the suspected etiology for the loss of pulpal vitality is a crown-originating fracture. Teeth with fracture necrosis have a poor prognosis, and, when accompanied by characteristic radiographic findings, extraction may be considered the primary treatment option. CASE DESCRIPTIONS: Two adult men with crown-originating fractures and suspected fracture necrosis had localized periodontal bone and attachment loss associated with severe pain on mastication from mandibular second molars. In case 1, the patient desired to retain the tooth despite an unfavorable prognosis. Nonsurgical root canal therapy and a crown prolonged tooth survival for only 30 months. The patient in case 2 requested extraction after a thorough review of his dental condition and tooth prognosis. CONCLUSIONS: A tooth with fracture necrosis may continue to harbor virulent microorganisms after root canal therapy. When these microorganisms have access to the periodontal attachment, progressive loss of supporting tissues can be expected. PRACTICAL IMPLICATIONS: When weighing treatment options for teeth with fracture necrosis associated with characteristic radiographic findings, preference toward extraction and tooth replacement, rather than treatment aimed at tooth retention, may represent a sound clinical approach.

Association between quality-of-care indicators for HIV infection and healthcare resource utilization and costs.

OBJECTIVES: Multiple care quality indicators for HIV infection exist but few studies examine their impact on health outcomes. This study assessed which HIV care quality indicators were associated with healthcare resource utilization and costs. DESIGN: Retrospective analysis of Texas Medicaid claims data (01 January 2012 to 31 September 2016). METHODS: Included patients had at least two HIV-related medical claims during the identification period (01 July 2012 to 31 August 2014) (index = date of first HIV claim), were 18-62 years at index, and were continuously enrolled in the 6-month pre-index and 1-year post-index periods. Dependent variables included emergency department (ED) visits, inpatient hospitalizations, prescription count, and all-cause healthcare costs. Independent variables included CD4 cell count monitoring, syphilis, chlamydia, gonorrhea, hepatitis B, hepatitis C, and tuberculosis screenings, influenza and pneumococcal vaccinations, retention in care, and HAART initiation. Covariates included age, chronic hepatitis C virus infection, AIDS diagnosis, sex, and baseline healthcare cost. The study objective was addressed using generalized linear modeling. RESULTS: CD4 cell count monitoring and HAART initiation were significantly associated with reduced emergency department visits (P < 0.0001 for each). Influenza vaccination was significantly associated with reduced inpatient hospitalization (P < 0.0001). CD4 cell count monitoring (P < 0.0001), TB screening (P = 0.0006), influenza vaccination (P < 0.0001), and HAART initiation (P < 0.0001) were significantly associated with increase prescription claims. CD4 cell count monitoring, TB screening, and HAART initiation (P < 0.0001 for each) were significantly associated with all-cause healthcare costs. CONCLUSION: HAART may reduce use of emergency care services as early as 1 year following initiation.

The Tissue-Supported Sling Suture: Technique and Clinical Applications.

INTRODUCTION: Continuous and interrupted sling sutures (ISSs) are used around teeth in contemporary periodontics. However, conventional ISSs depend upon favorable tooth morphology for stability through the early healing period. The purpose of this report is to present a variation of the classic ISS that does not rely on favorable tooth morphology. CASE SERIES: Tissue-supported sling sutures (TSSs) were used for six patients undergoing root coverage, gingival augmentation, or pontic site development (guided bone regeneration) procedures. CONCLUSIONS: Although techniques such as vertical mattress suturing may support greater coronal flap advancement, the TSS technique does maintain coronal flap position while minimizing trauma to papillae. TSS stability is independent of tooth morphology and may offer clinicians flexibility in achieving reliable closure over hard and soft tissue implants. Like mattress sutures, TSSs reduce tension at the crestal incision line in tissue grafting procedures.

Rhabdomyolysis Associations with Antibiotics: A Pharmacovigilance Study of the FDA Adverse Event Reporting System (FAERS).

Introduction: Daptomycin, macrolides, trimethoprim-sulfamethoxazole, linezolid, fluoroquinolones, and cefdinir are known to be associated with rhabdomyolysis. Other antibiotics may also lead to rhabdomyolysis, but no study has systemically compared rhabdomyolysis associations for many available antibiotics. Objectives: The objective of this study was to evaluate the association between rhabdomyolysis and many available antibiotics using the FDA Adverse Event Report System (FAERS). Methods: FAERS reports from January 1, 2004 to December 31, 2017 were included in the study. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify rhabdomyolysis cases. Reporting Odds Ratios (RORs) and corresponding 95% confidence intervals (95%CI) for the association between antibiotics and rhabdomyolysis were calculated. An association was considered statistically significant when the lower limit of the 95%CI was greater than 1.0. Results: A total of 2,334,959 reports (including 7,685 rhabdomyolysis reports) were considered, after inclusion criteria were applied. Daptomycin had the greatest proportion of rhabdomyolysis reports, representing 5.5% of all daptomycin reports. Statistically significant rhabdomyolysis RORs (95% CI) for antibiotics were (in descending order): daptomycin 17.94 (14.08-22.85), cefditoren 8.61 (3.54-20.94), cefaclor 7.16 (2.28-22.49), erythromycin 5.93 (3.17-11.10), norfloxacin 4.50 (1.44-14.07), clarithromycin 3.95 (2.77-5.64), meropenem 3.19 (1.51-6.72), azithromycin 2.94 (1.96-4.39), cefdinir 2.84 (1.06-7.62), piperacillin-tazobactam 2.61 (1.48-4.61), trimethoprim-sulfamethoxazole 2.53 (1.52-4.21), linezolid 2.49 (1.47-4.21), ciprofloxacin 2.10 (1.51-2.92). Conclusions: This study confirms prior evidence for rhabdomyolysis associations with daptomycin, macrolides, trimethoprim-sulfamethoxazole, linezolid, fluoroquinolones, and cefdinir. This study also identifies previously unknown rhabdomyolysis associations with meropenem, cefditoren, cefaclor, and piperacillin-tazobactam.

Comparison of Prostaglandin Analog Treatment Patterns in Glaucoma and Ocular Hypertension.

BACKGROUND: Prostaglandin analogs (PGAs) are considered an initial therapy to manage increased intraocular pressure (IOP) for patients with glaucoma. When the initial PGA treatment fails to lower IOP adequately, the patient may add or change medications or have surgery/laser treatment. OBJECTIVE: To compare medication adherence, duration of therapy, and treatment patterns among 3 PGAs-latanoprost, travoprost, and bimatoprost-as initial therapies for patients with glaucoma or ocular hypertension. METHODS: This was a retrospective cohort study using administrative claims data. The cohort consisted of patients newly diagnosed with glaucoma or ocular hypertension with at least 1 prescription claim for latanoprost, travoprost, or bimatoprost and enrolled in a Medicare Advantage plan between 2007 and 2012. The 24-month medication possession ratio (MPR) was used to measure medication adherence. Discontinuation of first-line PGA therapy was defined as nonpersistence (90-day gap allowance) of the index PGA or a change in therapy during the 24-month follow-up period. Types of second-line therapy (i.e., switch, addition, and surgery) were identified. The 1:1:1 propensity score matching was used. RESULTS: Patients who met the inclusion criteria were propensity score matched, resulting in 1,296 patients per PGA group. Latanoprost users showed higher adherence (50.1%) than travoprost (48.8%) and bimatoprost (43.0%) users. The latanoprost and travoprost groups had significantly higher MPRs than bimatoprost (P < 0.0001). The latanoprost group showed significantly longer duration of first-line therapy (372 days) than the bimatoprost group (343 days; P = 0.003) but not the travoprost group (361 days). After controlling for demographic and clinical characteristics, a Cox proportional hazards model showed that the travoprost and bimatoprost groups had a higher risk of discontinuation of first-line therapy than the latanoprost group (P < 0.0001). The percentage of patients continuing on the index PGA without treatment pattern change (i.e., switches, additions, and surgery) was higher for latanoprost users (52.9%) compared with travoprost (39.0%) or bimatoprost users (42.1%; P < 0.001). CONCLUSIONS: Patients who used latanoprost as their initial therapy were more likely to adhere and persist to the index PGA compared with bimatoprost users. The latanoprost group demonstrated a lower risk of discontinuing first-line therapy than the travoprost and bimatoprost groups. The results may assist ophthalmologists in determining the optimal management of this patient population with respect to treatment patterns. DISCLOSURES: No outside funding supported this study. All authors except Heo and Nair are employed by The University of Texas at Austin College of Pharmacy. Heo was with the Health Outcomes Division, The University of Texas at Austin College of Pharmacy during a portion of this study and is employed by Genesis Research. Nair is employed by Humana. The authors have no financial relationships relevant to this article to disclose. This study was presented as a poster at the 2016 International Society for Pharmacoeconomics and Outcomes Research Annual Meeting, May 2016, Washington, DC.

Frequency of adequate mesiodistal space and faciolingual alveolar width for implant placement at anterior tooth positions.

BACKGROUND: Prior studies have defined minimum mesiodistal space (MS) and faciolingual alveolar width (FAW) requirements for dental implant sites, and failure to observe these constraints may adversely impact peri-implant health and esthetics. However, to the authors' knowledge, no previous reports have established frequencies at which anterior tooth positions present favorable MS and FAW for implant accommodation. METHODS: A single examiner analyzed 205 cone-beam computed tomographic images, recording MS and FAW available for implant placement at anterior tooth positions. The examiner compared measurements with standardized implant diameters to assess anticipated implant-to-tooth distances and peri-implant bone thicknesses. RESULTS: In the esthetic zone, lateral incisor sites most frequently failed to present favorable MS. At maxillary lateral incisor positions, 22% (left) and 27% (right) of sites offered less than 2 millimeters between the proposed implant platform and the adjacent teeth. In mandibular incisor positions, implant-to-tooth distance was less than 2 mm at 79% through 97% of sites and less than 1.5 mm at 35% through 76% of sites. Over one-half of maxillary incisor sites and 78% through 95% of mandibular incisor sites exhibited FAW of less than 4 mm beyond implant diameter. CONCLUSIONS: In the population evaluated, mandibular incisor positions frequently presented unfavorable MS to accommodate conventional narrow-diameter implants. In addition, considerable proportions of mandibular incisor and maxillary lateral incisor sites may be at risk of developing unfavorable peri-implant bone thickness when conventional narrow-diameter implants are used. PRACTICAL IMPLICATIONS: Practitioners should consider small-diameter implants and nonimplant tooth replacement methods for many patients missing single mandibular incisors or maxillary lateral incisors.

Bait-attending amphipods of the Tonga Trench and depth-stratified population structure in the scavenging amphipod Hirondellea dubia Dahl, 1959.

BACKGROUND: The hadal zone encompasses the deepest parts of the world's ocean trenches from depths of ∼6,000-11,000 m. The communities observed at these depths are dominated by scavenging amphipods that rapidly intercept and consume carrion as it falls to the deepest parts of the trenches. New samples collected in the Tonga Trench provide an opportunity to compare the amphipod assemblages and the population structure of a dominant species, Hirondellea dubia Dahl, 1959, between trenches and with earlier data presented for the Tonga Trench, and other trenches in the South Pacific. METHODS: Over 3,600 individual scavenging amphipods across 10 species were collected in seven baited traps at two sites; in the Horizon Deep site, the deepest part of the Tonga Trench (10,800 m) and a site directly up-slope at the trench edge (6,250 m). The composition of the bait-attending amphipods is described and a morphometric analysis of H. dubia examines the bathymetric distribution of the different life stages encountered. RESULTS: The amphipod assemblage was more diverse than previously reported, seven species were recorded for the first time from the Tonga Trench. The species diversity was highest at the shallower depth, with H. dubia the only species captured at the deepest site. At the same time, the abundance of amphipods collected at 10,800 m was around sevenfold higher than at the shallower site. H. dubia showed clear ontogenetic vertical structuring, with juveniles dominant at the shallow site and adults dominant at the deep site. The amphipods of the deeper site were always larger at comparable life stage. DISCUSSION: The numbers of species encountered in the Tonga Trench is less than reported from the New Hebrides and Kermadec trenches, and six species encountered are shared across trenches. These findings support the previous suggestion that the fauna of the New Hebrides, Tonga and Kermadec Trenches may represent a single biogeographic province. The ontogenetic shift in H. dubia between the two Tonga Trench sites supports the hypothesis of interspecific competition at the shallower bathymetric range of the species, and the presence of competitive physiological advantages that allow the adults at the trench axis to exploit the more labile organic material that reaches the bottom of the trench.

Patterns of antiepileptic drug use in patients with potential refractory epilepsy in Texas Medicaid.

OBJECTIVES: Antiepileptic drug (AED) monotherapy is usually effective in 60% of the patients with epilepsy while the remaining patients have refractory epilepsy. This study compared treatment patterns (adherence, persistence, addition, and switching) associated with refractory and nonrefractory epilepsy. METHODS: Texas Medicaid claims from 09/01/07-12/31/13 were analyzed, and patients eligible for the study 1) were between 18 and 62 years of age, 2) had a prescription claim for an AED during the identification period (03/01/08-12/31/11) with no prior baseline AED use (6-month), and 3) had evidence of epilepsy diagnosis within 6 months of AED use. Based on AED use in the identification period, patients were categorized into "refractory" (≥3AEDs) and "nonrefractory" (<3AEDs) cohorts. The index date was the date of the first AED claim. Patients in both cohorts were matched 1:1 using propensity scoring and compared for adherence (proportion of days covered (PDC) ≥80% vs. <80%), persistence, addition (yes/no), and switching (yes/no) using multivariate conditional regression models. Conditional logistic regression and Cox proportional hazard models were used to address the study objectives. RESULTS: Of the 10,599 eligible patients, 2798 (26.5%) patients in the refractory cohort were matched to patients in the nonrefractory cohort. Patients in the refractory cohort had significantly higher (p < 0.005) mean (±Standard deviation (SD)) adherence (88.6% (±19.1%) vs. 77.0% ±â€¯(25.8%)) and persistence (328.0 (±87.3) days vs. 294.9 ±â€¯(113.4) days) as compared with patients in the nonrefractory cohort. Compared with patients with nonrefractory epilepsy, patients with refractory epilepsy were 3.6 times (odds ratio (OR) = 3.553; 95% confidence interval (CI) = 3.060-4.125; p < 0.0001) more likely to adhere to AEDs and had a 34.7% (hazard ratio (HR) = 0.653; 95% CI = 0.608-0.702; p < 0.0001) lower hazard rate of discontinuation of AEDs. Also, patients with refractory epilepsy were 3.7 times (OR = 3.723; 95% CI = 2.902-4.776; p < 0.0001) more likely to add an alternative AED and 3.6 times (OR = 3.591; 95% CI = 3.010-4.284; p < 0.0001) more likely to switch to an alternative AED. CONCLUSION: Patients with refractory epilepsy were significantly more likely to adhere and persist to AED regimen and were significantly more likely to add and switch to an alternative AED than patients with nonrefractory epilepsy.

Trends in Racial/Ethnic Disparities Among Patients Living with HIV in Texas, 1996 to 2013.

National studies show that Blacks with HIV have higher mortality rates compared to Whites. This study aimed to identify trends in Black racial disparities among Texas residents living with HIV. Using HIV surveillance data from the Texas Department of State Health Services, a cohort of HIV-diagnosed patients (N = 70,996) were identified and grouped according to year of diagnosis, 1996-1997 (T1), 1998-2006 (T2), 2007-2010 (T3), and 2011-2013 (T4). Survival analysis was used to examine racial differences in death rate (analysis 1) and clinical progression to AIDS (analysis 2) for each subcohort, using Blacks as the reference group. In analysis 1, Whites (hazard ratio, HR = 0.80, 95% confidence interval, CI = 0.74-0.87, p < 0.001; HR = 0.82, 95% CI = 0.78-0.87, p < 0.001; respectively) and Hispanics (HR = 0.72, 95% CI = 0.66-0.79, p < 0.001; HR = 0.77, 95% CI = 0.74-0.81, p < 0.001, respectively) had lower death rates in T1 and T2. This remained significant after adjusting for covariates. In T3, death rate was higher for Hispanics after adjustment (HR = 1.13, 95% CI = 1.00-1.28, p < 0.05). In T4, death rate was higher for Whites (HR = 1.66, 95% CI = 1.30-2.13, p < 0.001) and Hispanics (HR = 1.66, 95% CI = 1.34-2.06, p < 0.001). These relationships became non-significant after adjusting for covariates. In analysis 2, the rate of clinical progression to AIDS was higher for Hispanics in all subcohorts. The significance remained after adjusting for covariates. The rate of clinical progression to AIDS was lower for Whites after adjustments in T2 and T3. Additional studies are needed to understand factors that may explain this unexpected finding of improved survival for Blacks over time. Such studies may inform decision-making in HIV care to reduce Black HIV disparities.

Development of a synthetic Vi polysaccharide vaccine for typhoid fever.

Typhoid fever remains a serious public health problem with a high impact on toddlers and young children. Vaccines against the Vi capsular polysaccharide are efficacious against typhoid fever demonstrating that antibodies against Vi confer protection. The currently licensed Vi typhoid vaccines have however limited efficacy and are manufactured by a complex process from wild-type bacteria. Due to these inherent issues with the current vaccines, an alternative vaccine based on an O-acetylated high molecular weight (HMW) polygalacturonic acid (GelSite-OAc™) was generated. The HMW polygalacturonic acid shares the same backbone as the Vi polysaccharide of Salmonella Typhi. The GelSite-OAc™ has a high molecular weight (>1 × 106 Da) and a high degree of O-acetylation (DOAc) (>5 µmole/mg), both exceeding the potency specifications of the current Vi vaccine. Studies in Balb/c mice demonstrated that GelSite-OAc™ was highly immunogenic, inducing a strong antigen-specific antibody response in a DOAc- and dose-dependent manner which was comparable to or higher than those induced by the licensed Vi vaccine. Importantly, the GelSite-OAc™ was shown to be fully protective in mice against lethal challenge with Salmonella Typhi. Furthermore, the GelSite-OAc™ demonstrated a boosting effect or memory response, exhibiting a >2-fold increase in antibody levels upon the second immunization with either GelSite-OAc™ or the Vi vaccine. This novel boosting effect is unique among polysaccharide antigens and potentially makes GelSite-OAc™ effective in people under 2 years old. Together these results suggest that the GelSite-OAc™ could be a highly effective vaccine against Salmonella Typhi.

Lick of death: Capnocytophaga canimorsus is an important cause of sepsis in the elderly.

A 70-year-old Caucasian woman was treated for Capnocytophaga canimorsus septicaemia. The source of bacteraemia was very likely to be her household pet, an Italian greyhound. The patient presented with a presumed complex partial seizure but deteriorated rapidly with sepsis and multiorgan dysfunction. Neither scratch nor bite was established, although close petting including licks was reported. Blood cultures grew Gram-negative rods, identified by molecular techniques as C. canimorsus-a bacterium frequently isolated in the oral cavities of dogs and cats. A full recovery was made following 2 weeks of intensive care support and broad-spectrum antibiotics. No underlying immune dysfunction was found.

Use of Statins and the Risk of Incident Diabetes: A Retrospective Cohort Study.

INTRODUCTION: Even though several landmark statin trials have demonstrated the beneficial effects of statin therapy in both primary and secondary prevention of cardiovascular disease, several studies have suggested that statins are associated with a moderate increase in risk of new-onset diabetes. These observations prompted the US FDA to revise statin labels to include a warning of an increased risk of incident diabetes mellitus as a result of increases in glycosylated hemoglobin (HbA1c) and fasting plasma glucose. However, few studies have used US-based data to investigate this statin-associated increased risk of diabetes. OBJECTIVE: The primary objective of our study was to examine whether the use of statins increases the risk of incident diabetes mellitus using data from the Thomson Reuters MarketScan (®) Commercial Claims and Encounters Database. METHOD: This study was a retrospective cohort analysis utilizing data for the period 2003-2004. The study population included new statin users aged 20-63 years at index who did not have a history of diabetes. RESULTS: The proportion (3.4 %) of statin users (N = 53,212) who had incident diabetes was higher than the proportion (1.2 %) of non-statin users (N = 53,212) who had incident diabetes. Compared with no statin use and controlling for demographic and clinical covariates, statin use was significantly associated with increased risk of incident diabetes (hazard ratio 2.01; 99 % confidence interval 1.74-2.33; p < 0.0001). In addition, risk of diabetes was highest among users of lovastatin, atorvastatin, simvastatin, and fluvastatin. Diabetes risk was lowest among pravastatin and rosuvastatin users. DISCUSSION: Because the potential for diabetogenicity differs among different statin types, healthcare professionals should individualize statin therapy by identifying patients who would benefit more from less diabetogenic statin types.

Medication Adherence and Persistence in Patients with Severe Major Depressive Disorder with Psychotic Features: Antidepressant and Second-Generation Antipsychotic Therapy Versus Antidepressant Monotherapy.

BACKGROUND: Major depressive disorder with psychotic features, or psychotic depression, is a severe mental health disorder often associated with a worse depression-related symptom profile when compared with major depressive disorder without psychotic features. While combination pharmacotherapy with an antidepressant and an antipsychotic is recommended as first-line therapy, antidepressant monotherapy has been found to be useful and efficacious in psychotic depression. OBJECTIVE: To assess the rates of antidepressant adherence and antidepressant persistence in Texas Medicaid patients with psychotic depression who used antidepressant plus second-generation antipsychotic (AD/SGA) therapy or antidepressant (AD) monotherapy. METHODS: Using Texas Medicaid prescription and medical claims data from September 2007 to December 2012, adult patients aged 18-63 years were included if they had no confounding psychiatric disorders, no antidepressant claims during a 6-month pre-index period, and at least 1 diagnosis for severe major depressive disorder with psychotic features (ICD-9-CM codes 296.24 and 296.34). The first claim date for an antidepressant served as the index date. All patients were required to have at least 2 antidepressant claims, and those in the AD/SGA cohort were required to have 2 or more claims for an SGA. Study covariates included age, gender, race/ethnicity, residence, Charlson Comorbidity Index (CCI) score, and tobacco use/dependence. Statistical analyses included descriptive statistics, univariate analyses, logistic regression, and Cox proportional hazards regression. RESULTS: A total of 926 patients met study criteria (AD cohort = 510; AD/SGA cohort = 416). The overall sample had a mean [±SD] age of 40.5 [±13.2] years and was primarily female (66.8%) and non-Caucasian (74.8%). When compared with the AD cohort, patients in the AD/SGA cohort had a 52.3% higher likelihood of being adherent to antidepressant therapy based on proportion of days covered (PDC; OR = 1.523; 95% CI = 1.129-2.053; P = 0.006). Similarly, antidepressant adherence was 42.0% higher for the AD/SGA cohort based on medication possession ratio (MPR; OR = 1.420; 95% CI = 1.062-1.898; P = 0.018). Younger patients, African Americans, and tobacco users/dependents had significantly worse likelihoods of antidepressant medication adherence based on PDC and MPR. The risk of antidepressant nonpersistence was 23.2% lower for patients in the AD/SGA cohort (HR = 0.768; 95% CI = 0.659-0.896; P = 0.001), compared with those in the AD cohort. Antidepressant nonpersistence was significantly higher in younger patients, African Americans, Hispanics, and tobacco users/dependents. CONCLUSIONS: Better antidepressant adherence and persistence outcomes were associated with combination pharmacotherapy with an AD and an SGA antipsychotic. This study provides real-world estimates that support the current first-line treatment recommendations for psychotic depression; however, it should be noted that the majority of study patients used AD therapy only. Future research in psychotic depression is needed. DISCLOSURES: Kim-Romo received funding to conduct this study from the PhRMA Foundation Pre-Doctoral Fellowship in Health Outcomes. Rascati, Richards, Ford, Wilson, and Beretvas declare no conflict of interest in relation to this manuscript. Kim-Romo and Rascati collaborated on the study design, data analysis, study interpretation, and writing of this manuscript. Richards, Ford, Wilson, and Beretvas provided critical evaluation of the study design, analysis, and interpretation, as well as edited this manuscript.