Multicomponent perinatal breastfeeding support in women with BMI >25: The Latch On multi-centre randomised trial.

OBJECTIVE: To investigate the effectiveness of a multicomponent breastfeeding support intervention on breastfeeding prevalence at 3 months among women with a body mass index (BMI) >25 kg/m2. DESIGN: Multicentre multicomponent randomised controlled trial. SETTING: Four maternity centres in Ireland. POPULATION: A total of 225 primiparous women and their nominated support partners. Participants were aged 18 years and over, with BMI ≥25 kg/m2, carrying a singleton pregnancy and without contraindication for breastfeeding. METHODS: The intervention included an antenatal group breastfeeding education session for participants and their support partners, followed by a planned postnatal breastfeeding assessment and telephone support for up to 6 weeks by a lactation consultant. MAIN OUTCOME MEASURES: Any breastfeeding at 3 months postpartum. RESULTS: Any breastfeeding prevalence was 68.7% (n = 68) in the intervention group and 62.1% (n = 59) in the control group at 3 months postpartum (odds ratio 1.33, 95% confidence interval 0.72-2.46, p = 0.36). Any and exclusive breastfeeding rates did not significantly differ at any other time point. More women in the control group accessed support from private lactation consultants (intervention 23.5% [n = 12], control 45.3% [n = 24], p = 0.02). CONCLUSIONS: The control group had higher than expected breastfeeding rates, and the study found no evidence of effect on the primary outcome. Providing comprehensive education and support for women intending to breastfeed remains of paramount importance.

The Combined Use of Automated Milking System and Sensor Data to Improve Detection of Mild Lameness in Dairy Cattle.

This study aimed to develop a tool to detect mildly lame cows by combining already existing data from sensors, AMSs, and routinely recorded animal and farm data. For this purpose, ten dairy farms were visited every 30-42 days from January 2020 to May 2021. Locomotion scores (LCS, from one for nonlame to five for severely lame) and body condition scores (BCS) were assessed at each visit, resulting in a total of 594 recorded animals. A questionnaire about farm management and husbandry was completed for the inclusion of potential risk factors. A lameness incidence risk (LCS ≥ 2) was calculated and varied widely between farms with a range from 27.07 to 65.52%. Moreover, the impact of lameness on the derived sensor parameters was inspected and showed no significant impact of lameness on total rumination time. Behavioral patterns for eating, low activity, and medium activity differed significantly in lame cows compared to nonlame cows. Finally, random forest models for lameness detection were fit by including different combinations of influencing variables. The results of these models were compared according to accuracy, sensitivity, and specificity. The best performing model achieved an accuracy of 0.75 with a sensitivity of 0.72 and specificity of 0.78. These approaches with routinely available data and sensor data can deliver promising results for early lameness detection in dairy cattle. While experimental automated lameness detection systems have achieved improved predictive results, the benefit of this presented approach is that it uses results from existing, routinely recorded, and therefore widely available data.

A Phase 1 Trial of Durvalumab in Combination with Bacillus Calmette-Guerin (BCG) or External Beam Radiation Therapy in Patients with BCG-unresponsive Non-muscle-Invasive Bladder Cancer: The Hoosier Cancer Research Network GU16-243 ADAPT-BLADDER Study.

BACKGROUND: Novel treatments and trial designs remain a high priority for bacillus Calmette-Guerin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) patients. OBJECTIVE: To evaluate the safety and preliminary efficacy of anti-PD-L1 directed therapy with durvalumab (D), durvalumab plus BCG (D + BCG), and durvalumab plus external beam radiation therapy (D + EBRT). DESIGN, SETTING, AND PARTICIPANTS: A multicenter phase 1 trial was conducted at community and academic sites. INTERVENTION: Patients received 1120 mg of D intravenously every 3 wk for eight cycles. D + BCG patients also received full-dose intravesical BCG weekly for 6 wk with BCG maintenance recommended. D + EBRT patients received concurrent EBRT (6 Gy × 3 in cycle 1 only). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Post-treatment cystoscopy and urine cytology were performed at 3 and 6 -mo, with bladder biopsies required at the 6-mo evaluation. The recommended phase 2 dose (RP2D) for each regimen was the primary endpoint. Secondary endpoints included toxicity profiles and complete response (CR) rates. RESULTS AND LIMITATIONS: Twenty-eight patients were treated in the D (n = 3), D + BCG (n = 13), and D + EBRT (n = 12) cohorts. Full-dose D, full-dose BCG, and 6 Gy fractions × 3 were determined as the RP2Ds. One patient (4%) experienced a grade 3 dose limiting toxicity event of autoimmune hepatitis. The 3-mo CR occurred in 64% of all patients and in 33%, 85%, and 50% within the D, D + BCG, and D + EBRT cohorts, respectively. Twelve-month CRs were achieved in 46% of all patients and in 73% of D + BCG and 33% of D + EBRT patients. CONCLUSIONS: D combined with intravesical BCG or EBRT proved feasible and safe in BCG-unresponsive NMIBC patients. Encouraging preliminary efficacy justifies further study of combination therapy approaches. PATIENT SUMMARY: Durvalumab combination therapy can be safely administered to non-muscle-invasive bladder cancer patients with the goal of increasing durable response rates.

Migrant health and language barriers: Uncovering macro level influences on the implementation of trained interpreters in healthcare settings.

There is a knowledge translation gap between policies promoting equitable access to healthcare and person-centred care, and the use of untrained interpreters in cross-cultural consultations leading to disparities in health outcomes. An 11 member inter-sectoral working group met at four workshops to discuss and agree on levers and barriers to the provision of trained interpreters in healthcare settings in Ireland. The process was informed by Participatory Learning and Action (PLA) research to support inter-stakeholder dialogue and learning. Normalisation Process Theory (NPT) was used as a conceptual framework to analyse levers and barriers. The NPT analysis explored sense-making, engagement and enactment and found challenges with sense-making and engagement in senior level service planners, managers and governmental offices. This had negative impacts on other key actors, including healthcare providers, medical students and interpreters. This also meant that the enactment of interpreted consultations in practice settings was replete with barriers, most notably a lack of resources, training and supportive organisational structures. The emergent action plan focused on improving sense-making and engagement through inter-sectoral awareness raising, designed to stimulate a series of complementary levers for implementation. Combining PLA and NPT provided new insights into macro level influences on implementation work at the level of a national healthcare system. The approaches used in this study are applicable in other fields.

Determining a Need for Point-of-Care Ultrasound in Helicopter Emergency Medical Services Transport.

OBJECTIVE: Point-of care-ultrasound (PoCUS) is useful in evaluating unstable emergency department patients. The portability of this technology increases its potential use in prehospital settings, including helicopter emergency medical services (HEMS) programs. Identifying useful applications may support implementing a PoCUS program that develops sonography skills for prehospital providers. The aim of this study was to determine the HEMS patient population that would benefit from prehospital PoCUS for hypotension and how commonly the extended focused assessment with sonography in trauma (E-FAST) for trauma patients or the rapid ultrasound in shock (RUSH) for medical patients could be used by HEMS. METHODS: A retrospective chart review was performed over a 1-year period of adult patients transported by a midwestern HEMS system. Charts were reviewed for episodes of hypotension. RESULTS: The chart review included 216 charts, of which 3 were excluded. Of the 213 cases, 100 were trauma patients, and 113 were medical patients. Of the trauma patients, 51% experienced hypotension, as did 73 of 113 medical patients. CONCLUSION: Fifty percent of HEMS patients may benefit from PoCUS to evaluate for hypotension in flight.

Emergency and critical care applications for contrast-enhanced ultrasound.

INTRODUCTION: Contrast-enhanced ultrasound (CEUS) using intravascular microbubbles has potential to revolutionize point-of-care ultrasonography by expanding the use of ultrasonography into clinical scenarios previously reserved for computed tomography (CT), magnetic resonance imaging, or angiography. METHODS: We performed a literature search and report clinical experience to provide an introduction to CEUS and describe its current applications for point-of-care indications. RESULTS: The uses of CEUS include several applications highly relevant for emergency medicine, such as solid-organ injuries, actively bleeding hematomas, or abdominal aortic aneurysms. Compared with CT as the preeminent advanced imaging modality in the emergency department, CEUS is low cost, radiation sparing, repeatable, and readily available. It does not require sedation, preprocedural laboratory assessment, or transportation to the radiology suite. CONCLUSIONS: CEUS is a promising imaging technique for point-of-care applications in pediatric and adult patients and can be applied for patients with allergy to CT contrast medium or with impaired renal function. More high-quality CEUS research focusing on accuracy, patient safety, health care costs, and throughput times is needed to validate its use in emergency and critical care settings.

Point-of-care ultrasound education: the increasing role of simulation and multimedia resources.

This article reviews the current technology, literature, teaching models, and methods associated with simulation-based point-of-care ultrasound training. Patient simulation appears particularly well suited for learning point-of-care ultrasound, which is a required core competency for emergency medicine and other specialties. Work hour limitations have reduced the opportunities for clinical practice, and simulation enables practicing a skill multiple times before it may be used on patients. Ultrasound simulators can be categorized into 2 groups: low and high fidelity. Low-fidelity simulators are usually static simulators, meaning that they have nonchanging anatomic examples for sonographic practice. Advantages are that the model may be reused over time, and some simulators can be homemade. High-fidelity simulators are usually high-tech and frequently consist of many computer-generated cases of virtual sonographic anatomy that can be scanned with a mock probe. This type of equipment is produced commercially and is more expensive. High-fidelity simulators provide students with an active and safe learning environment and make a reproducible standardized assessment of many different ultrasound cases possible. The advantages and disadvantages of using low- versus high-fidelity simulators are reviewed. An additional concept used in simulation-based ultrasound training is blended learning. Blended learning may include face-to-face or online learning often in combination with a learning management system. Increasingly, with simulation and Web-based learning technologies, tools are now available to medical educators for the standardization of both ultrasound skills training and competency assessment.

Effect of hepatic and renal impairment on the pharmacokinetics of dalcetrapib: altered distribution of the active thiol?

BACKGROUND AND OBJECTIVE: Dalcetrapib, a cholesteryl ester transfer protein (CETP) modulator, is a thioester pro-drug that is rapidly hydrolysed to generate a pharmacologically active thiol. The thiol covalently binds to plasma proteins as mixed disulfides, extensively distributes into plasma lipoprotein fractions, and is principally cleared by metabolism, including extensive first-pass metabolism. Here we report two studies assessing the effects of hepatic and renal impairment on the pharmacokinetics of the thiol and its primary metabolites. METHODS: Adults with hepatic or renal impairment and healthy controls were recruited in two separate non-randomized, open-label studies. Eligible subjects were aged 18-70 years (hepatic impairment study) or 18-75 years (renal impairment study) with a body mass index 18-40 kg/m(2). Healthy controls were matched by age, bodyweight and sex. Each participant received a single 600 mg oral dose of dalcetrapib. Plasma and urine sampling was performed up to 3-4 days post-dalcetrapib administration for analysis of the pharmacokinetics of the thiol and its primary S-methyl and S-glucuronide metabolites. In the renal impairment study, CETP activity and mass, and lipid profiles were also assessed. RESULTS: Twenty-eight subjects were enrolled in the hepatic impairment study (mild or moderate hepatic impairment, n = 8 in each group; controls, n = 12). Thirty-five subjects participated in the renal impairment study (mild, moderate or severe renal impairment, n = 8 in each group; controls, n = 11). In patients with moderate hepatic impairment, the area under the plasma concentration-time curve from time zero to infinity (AUC(∞)) for thiol exposure was increased 34 % (geometric mean ratio [GMR] 1.34, 90 % CI 1.02-1.76), compared with matched controls. Regression analysis revealed a weak inverse relationship between thiol exposure and creatinine clearance (p = 0.0137, r(2) = 17.1 %). In patients with moderate or severe renal impairment, thiol exposures were 62 % (AUC(∞) GMR 1.62, 90 % CI 0.81-3.27) and 81 % (AUC(∞) GMR 1.81, 90 % CI 1.21-2.71) higher, respectively, than matched controls. Exposures of the S-glucuronide and S-methyl metabolites were also higher in hepatic and renal impairment groups. In the renal impairment study, CETP activity was decreased following administration of dalcetrapib, with no clear differences between groups. CONCLUSION: Hepatic and renal impairment both altered dalcetrapib pharmacokinetics and increased thiol exposure, with the extent of the effect dependent on the severity of impairment. The effect of renal impairment may be linked to altered distribution of the thiol, which illustrates the importance of assessing distribution to understand the causes and consequences of altered pharmacokinetics of thiol drugs in patient populations.

Development of a pilot family medicine hand-carried ultrasound course.

BACKGROUND AND OBJECTIVES: A hand-carried ultrasound training session was organized as an initial step in developing a long-term ultrasound education program for family medicine residents and faculty. Comparative effectiveness studies examining the potential benefits, risks, and any possible cost savings associated with this technology will be predicated on having a sufficient number of primary care physicians trained and able to use hand-carried ultrasounds as part of routine care. The proposed training described here is a first step toward this broader conversation and empirical study of hand-carried ultrasound use in family medicine. METHODS: An 8-hour training consisting of didactic lectures, case review, and hands-on experience imaging standardized patients with ultrasound machines and an ultrasound simulator. The objective of the course was to introduce focused ultrasound acquisition and interpretation of the gall bladder, kidney, heart, and abdominal aorta to family medicine physicians. Participating physicians were evaluated for changes in self-perceived comfort and proficiency with the hand-carried ultrasound before and after the training. RESULTS: Statistically significant changes for most comfort and proficiency items were demonstrated. Importantly, the only item that did not show significant change dealt with basing clinical decisions on information obtained from the device. CONCLUSION: The subjective improvement suggests this approach is one potentially useful hand-carried ultrasound training framework. Future work should attempt to further develop curricula and address issues such as longitudinal training assessments and certification and the development of competency in the necessary skill sets.

Medical interpreting and the law in the European Union.

In 2011, the Danish government announced that from June that year it would no longer cover the costs of medical interpreters for patients who had been living in Denmark for more than seven years. The Dutch Ministry of Health followed with an even more draconian approach; from 1 January 2012, the cost of translation and interpreting would no longer be covered by the state. These two announcements led to widespread concern about whether or not there is a legal foundation for interpreter provision in healthcare. This article considers United Nations treaties, conventions from the Council of Europe and European Union law. European Union member states have been slow to sign up to international agreements to protect the rights of migrant workers. The European Union itself has only recently moved into the area of discrimination and it is unclear if the Race Directive covers language. As a result, access to interpreters in healthcare, where it exists, is dependent on national anti-discrimination legislation or on positive action taken at national or local level rather than on European or international law.

Effects of food intake on the pharmacokinetic properties of dalcetrapib: findings from three phase I, single-dose crossover studies in healthy volunteers.

BACKGROUND: Preclinical studies have reported that the relative bioavailability of dalcetrapib, a modulator of cholesteryl ester transfer protein (CETP) inhibitor activity, was ∼60% higher when administered in the fed state compared with the fasting state. OBJECTIVE: This article reports on 3 studies conducted to assess the effects of food intake, timing of administration with respect to meals, and meal size and content on the relative bioavailability of dalcetrapib in healthy male subjects. METHODS: Three Phase I studies were performed in healthy subjects: (1) a 2-period crossover study of a single dose of dalcetrapib 900 mg administered in the fed and fasting states (fed versus fasting study [1999]); (2) a 3-period crossover study of a single dose of dalcetrapib 600 mg administered after a light morning meal, a standard evening meal, and a light evening meal (meal timing/size study [2005]); and (3) a 4-period crossover study of a single dose of dalcetrapib 600 mg administered 30 minutes after a high-fat meal or a standard evening meal, and 30 minutes before or 3 hours after the latter (high-fat meal study [2007]). Blood samples for pharmacokinetic analyses (AUC(0-36) or AUC(0-∞), C(max)) were collected up to 36, 144, and 96 hours after study drug administration in the fed versus fasting, meal timing/size, and high-fat meal studies, respectively. CETP activity was measured using a radioisotopic method in the fed versus fasting study and a fluorometric method in the meal timing/size and high-fat meal studies. Tolerability was assessed using monitoring of adverse events, laboratory parameters, vital signs, and ECG. RESULTS: Six men were enrolled in the fed versus fasting study (mean age, 37 years; mean body mass index [BMI], 23.6 kg/m(2)). Dalcetrapib exposure was increased by 64% (AUC(0-36)) and 126% (C(max)) after administration in the fed state. Eighteen men were enrolled in the analysis of the effects of meal timing and size on the properties of dalcetrapib (mean age, 30.5 years; mean BMI, 25.1 kg/m(2)). When dalcetrapib was administered after a light morning or a light evening meal, comparable values were found for mean dalcetrapib AUC(0-∞) (7400 and 7860 ng·h/mL, respectively) and C(max) (589 and 552 ng/mL), whereas administration after a standard evening meal was associated with increased AUC(0-∞) (14.3%-14.7%) and C(max) (25.5%-35.3%). Forty-nine men were included in the analysis in the high-fat meal study (mean age, 32.3 years; mean BMI, 23.9 kg/m(2)). Compared with administration after a standard evening meal, administration after a high-fat evening meal was associated with increased AUC(0-∞) (34.9%) and C(max) (43.7%). Between-treatment differences in exposure within each study also were reflected in apparent differences in CETP activity. All treatments were generally well tolerated. CONCLUSIONS: Dalcetrapib exposure was increased in the fed state and, to a lesser extent, was dependent on the size and fat content of the meal. Exposure was independent of dosing time. Dalcetrapib was generally well tolerated.

Safety, tolerability and pharmacokinetics of dalcetrapib following single and multiple ascending doses in healthy subjects: a randomized, double-blind, placebo-controlled, phase I study.

BACKGROUND: Dalcetrapib is a modulator of cholesteryl ester transfer protein (CETP) activity developed to raise levels of high-density lipoprotein cholesterol (HDL-C) with the goal of further reduction of cardiovascular events additive to standard of care alone. In clinical studies, dalcetrapib has been shown to effectively increase levels of HDL-C with no significant safety concerns. OBJECTIVE: The primary objective was to investigate the safety of single ascending and multiple ascending doses of dalcetrapib at doses markedly greater than that intended therapeutically (600 mg/day). Secondary objectives were to investigate the pharmacokinetics/pharmacodynamics and dose proportionality of dalcetrapib. STUDY DESIGN: Randomized, double-blind, placebo-controlled, combined single and multiple ascending dose phase I study. Healthy males (age 18-65 years, body mass index 18-32 kg/m2) were randomized to four of five dalcetrapib doses (2100, 2700, 3300, 3900 or 4500 mg) or placebo, with ≥10 days washout between doses (n = 15, single ascending doses) or to dalcetrapib (1800, 2100, 3000 or 3900 mg once daily) or placebo for 7 days (four cohorts, each n = 10, randomization 8 : 2, multiple ascending doses). MAIN OUTCOME MEASURE: Tolerability and safety were assessed by monitoring adverse events (AEs), laboratory parameters, vital signs and 12-lead ECG recordings. Primary pharmacokinetic assessments were area under the plasma concentration-time curve (AUC) from time zero to infinity (AUC(∞)) and maximum observed plasma concentration (C(max)) [single doses] and AUC from time zero to 24 hours (AUC(24)) and C(max) (multiple doses). Pharmacodynamic assessments included CETP activity and lipids (multiple dosing only). RESULTS: Exposure increased with dose but was less than proportional to increasing dose after single dosing, although deviation from dose proportionality could not be demonstrated for C(max). Dose proportionality was consistent following multiple doses. Steady state was modelled to have been reached by approximately 4 days, with little to no accumulation. CETP activity reduction was dose dependent (maximum -55% after 3900 mg; placebo -2.6%) at 6 hours post-dose on day 1, while HDL-C increased by 12-19% (placebo -13%) on day 8 following treatment with 1800-3900 mg/day for 7 days. All AEs were mild or moderate in intensity and there were no serious AEs, deaths or withdrawals due to AEs. No clinically relevant effects on laboratory parameters, cardiac parameters or vital signs were noted. CONCLUSION: Single-dose dalcetrapib up to 4500 mg and multiple doses up to 3900 mg were generally safe and well tolerated.

Lack of clinically relevant drug-drug interactions when dalcetrapib is co-administered with ezetimibe.

AIMS: Dalcetrapib, which targets cholesteryl ester transfer protein activity, is in development for prevention of cardiovascular events. Because dalcetrapib will likely be prescribed with other lipid-modifying therapies such as ezetimibe, a study was performed to investigate potential pharmacokinetic interactions between dalcetrapib and ezetimibe. Lipids changes and tolerability were secondary endpoints. METHODS: Co-administration of dalcetrapib 900 mg (higher than the phase III dose) with ezetimibe was investigated in a three period, three treatment crossover study in healthy males: 7 days of dalcetrapib, 7 days of dalcetrapib plus ezetimibe, 7 days of ezetimibe alone. A full pharmacokinetic profile was performed on day 7 of each treatment. RESULTS: Co-administration of dalcetrapib with ezetimibe was associated with minimal changes in dalcetrapib exposure compared with dalcetrapib alone. Least squares mean ratio (LSMR) (90% confidence interval) was 93.6 (87.1, 100.7) for AUC(0,24 h) and 99.0 (85.2, 115.0) for C(max) . Ezetimibe exposure was reduced with co-administration of ezetimibe with dalcetrapib compared with ezetimibe alone: LSMR 80.3 (74.6, 86.4) for AUC(0,24 h) and 88.9 (80.9, 99.9) for C(max) for total ezetimibe. High-density lipoprotein cholesterol increases associated with co-administration of dalcetrapib with ezetimibe (+29.8%) were comparable with those with dalcetrapib alone (+25.6%), while the reduction in low-density lipoprotein cholesterol with co-administration (-35.9%) was greater than with ezetimibe alone (-20.9%). Dalcetrapib was generally well tolerated when administered alone and when co-administered with ezetimibe. CONCLUSION: Co-administration of dalcetrapib with ezetimibe was not associated with clinically significant changes in pharmacokinetic parameters or tolerability and did not diminish the lipid effects of either drug.

No clinically relevant drug-drug interactions when dalcetrapib is co-administered with atorvastatin.

OBJECTIVES: Dalcetrapib, which targets cholesteryl ester transfer protein, is in clinical development for prevention of cardiovascular events and is likely to be used concomitantly with statins. Two studies investigated co-administration of dalcetrapib with atorvastatin and any effects of the timing of atorvastatin on the pharmacokinetics of dalcetrapib. RESEARCH DESIGN AND METHODS: Two crossover studies were performed in healthy subjects: a two-period study of dalcetrapib 900 mg concurrently with atorvastatin (concurrent dosing study) and a three-period study of dalcetrapib 600 mg (dose chosen for Phase III) with atorvastatin concurrently or serially 4 h after dalcetrapib (interval dosing study). MAIN OUTCOME MEASURES: The primary pharmacokinetic end points were AUC(0 - 24) and C(max); lipid effects and tolerability were secondary end points. RESULTS: In the concurrent study (n = 26), co-administration reduced dalcetrapib AUC(0 - 24) and C(max) and caused small changes in AUC(0 - 24) and C(max) of atorvastatin and its active metabolites. In the interval study (n = 52), serial and concurrent co-administration of atorvastatin resulted in similar reductions in dalcetrapib exposure that were comparable to those observed in the concurrent dosing study. Co-administration did not decrease the efficacy of dalcetrapib or atorvastatin and was generally well tolerated. CONCLUSIONS: These results indicate no clinically relevant interactions for co-administration of dalcetrapib with atorvastatin.

Coadministration of dalcetrapib with pravastatin, rosuvastatin, or simvastatin: no clinically relevant drug-drug interactions.

Dalcetrapib targets cholesteryl ester transfer protein and increases high-density lipoprotein cholesterol (HDL-C) levels. It is in clinical development for the prevention of cardiovascular events and will likely be used in combination with standard of care, including statins. Three crossover studies in healthy males investigated the pharmacokinetic drug-drug interaction potential of 900 mg dalcetrapib and statins: two 3-period studies (dalcetrapib plus pravastatin or rosuvastatin) and a 2-period study (dalcetrapib plus simvastatin). Effect on lipids and safety were secondary end points. The 900 mg dose investigated is higher than the 600 mg dose currently being investigated in Phase III. Coadministration of dalcetrapib with pravastatin, rosuvastatin, or simvastatin was not associated with significant increases in statin exposure except for a 26% increase in rosuvastatin C(max) (90% CI 1.088 to 1.468) but not AUC(0-24) (90% CI 0.931 to 1.085). Dalcetrapib AUC(0-24) and C(max) were not significantly altered by coadministration with pravastatin, and were significantly lower when dalcetrapib was coadministered with rosuvastatin or simvastatin compared with dalcetrapib alone. The HDL-C increase with dalcetrapib was not compromised by coadministration with statins, and reduction in low-density lipoprotein cholesterol with dalcetrapib coadministered with statins was greater than with statins alone. Dalcetrapib alone and coadministered with statins was generally well tolerated.

Deletion 22q13.3 syndrome.

The deletion 22q13.3 syndrome (deletion 22q13 syndrome or Phelan-McDermid syndrome) is a chromosome microdeletion syndrome characterized by neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, and minor dysmorphic features. The deletion occurs with equal frequency in males and females and has been reported in mosaic and non-mosaic forms. Due to lack of clinical recognition and often insufficient laboratory testing, the syndrome is under-diagnosed and its true incidence remains unknown. Common physical traits include long eye lashes, large or unusual ears, relatively large hands, dysplastic toenails, full brow, dolicocephaly, full cheeks, bulbous nose, and pointed chin. Behavior is autistic-like with decreased perception of pain and habitual chewing or mouthing. The loss of 22q13.3 can result from simple deletion, translocation, ring chromosome formation and less common structural changes affecting the long arm of chromosome 22, specifically the region containing the SHANK3 gene. The diagnosis of deletion 22q13 syndrome should be considered in all cases of hypotonia of unknown etiology and in individuals with absent speech. Although the deletion can sometimes be detected by high resolution chromosome analysis, fluorescence in situ hybridization (FISH) or array comparative genomic hybridization (CGH) is recommended for confirmation. Differential diagnosis includes syndromes associated with hypotonia, developmental delay, speech delay and/or autistic-like affect (Prader-Willi, Angelman, Williams, Smith-Magenis, Fragile X, Sotos, FG, trichorhinophalangeal and velocardiofacial syndromes, autism spectrum disorders, cerebral palsy). Genetic counseling is recommended and parental laboratory studies should be considered to identify cryptic rearrangements and detect parental mosaicism. Prenatal diagnosis should be offered for future pregnancies in those families with inherited rearrangements. Individuals with deletion 22q13 should have routine examinations by the primary care physician as well as genetic evaluations with referral to specialists if neurological, gastrointestinal, renal, or other systemic problems are suspected. Affected individuals benefit from early intervention programs, intense occupational and communication therapies, adaptive exercise and sport programs, and other therapies to strengthen their muscles and increase their communication skills. No apparent life-threatening organic abnormalities accompany the diagnosis of deletion 22q13.

Screening for intimate partner violence in medical settings.

Intimate partner violence (IPV) is associated with negative health consequences. Universal screening for IPV offers many opportunities for successful intervention, yet this practice in medical settings is controversial. This article examines the potential impact of the U.S. Preventive Services Task Force (USPSTF) recommendations for IPV screening and the emerging literature supporting measurable health benefits resulting from screening interventions in medical settings. Several screening tools and methods of administration that have been evaluated in various clinical settings, with goals to increase their sensitivity and to determine a best method of administration, are reviewed in this article. Mandatory reporting is closely linked to screening practices and may influence healthcare worker practice and patient disclosure. Mandatory reporting studies are lacking and show variable physician compliance, victim acceptance, and scant outcome data. Informed consent prior to screening, explaining the process of mandatory reporting statutes and victim options should be evaluated to increase sensitivity of screening tools.

Competency-based strategies for injury control and prevention curriculums in undergraduate medical education.

Injury, including unintentional injury and intentional injury, is the leading cause of death in people aged

Techniques for mammalian cell tissue culture.

This appendix opens with detailed discussions on the latest principles of sterile technique and preparation of culture media. Step-by-step protocols describe trypsinizing and subculturing monolayer cultures, passaging suspension cultures, freezing and thawing cells, counting cells using a hemacytometer, and preparing cells for transport.

Techniques for mammalian cell tissue culture.

This unit opens with detailed discussions on the latest principles of sterile technique and preparation of culture media. Step-by-step protocols describe trypsinizing and subculturing monolayer cultures, passaging suspension cultures, freezing and thawing cells, counting cells using a hemacytometer, and preparing cells for transport.