Pharmacologic Drug Detection and Self-Reported Adherence in the HPTN069/ACTG5305 Phase II PrEP Trial.

Adherence drives efficacy in PrEP clinical trials. We compared drug concentrations and self-reported adherence in HPTN069/ACTG5305, a double-blinded, randomized trial of the safety and tolerability of candidate PrEP regimens that included maraviroc (MVC), tenofovir (TDF), and emtricitabine (FTC). Plasma drug concentrations and self-reported adherence by computer-assisted self-interview (CASI) were assessed at study weeks 24 and 48. Descriptive statistics and a generalized linear model were used to assess the association between selected demographic factors, self-report of daily medication adherence and plasma drug concentrations consistent with daily adherence. Among 718 paired observations from 370 participants, 43% (306/718) reported daily adherence by CASI, 65% (467/718) had drug concentrations consistent with daily adherence and 11% (81/718) had CASI responses that reported daily adherence despite having drug concentrations consistent with less-than-daily adherence. In adjusted analyses, participants who were assigned male at birth (aOR 1.42 [95% CI 1.02, 1.97]), older (5-year increments aOR 1.10 [95% CI 1.09, 1.11]), White (aOR 2.2 [95% CI 1.88, 2.56]), had advanced education (aOR 3.89 [95% CI 2.97, 5.09]), were employed (aOR 1.89 [95% CI 1.50, 2.40]), or partnered/married (aOR 2 [95% CI 1.72, 2.32]) were more likely to have drug concentrations consistent with daily adherence. Participants who were not employed (aOR 2.7 [95% CI 1.31, 5.55]) or who were single/not partnered (aOR 2.33 [CI 95% 1.25, 4.34]) were more likely to have drug concentrations that did not reflect daily adherence despite self-reported PrEP adherence. These findings support the need for ongoing adherence counseling in clinical trials of new PrEP regimens.

Recovering the status quo: tipping points and earthquake aftermaths in colonial India.

Scholars of disaster politics debate how far natural hazards cause or catalyse political change. This paper builds on recent scholarship on tipping points and social contracts to argue that two case studies of historical earthquakes in 1930s British-colonised India invite a focus on the dynamics of cooperation and conflict between state and non-state actors. Officials of the colonial state and its nationalist rivals cooperated after one earthquake even though they otherwise bitterly opposed each other. Cooperation broke down after the second event, just one year later. Yet, in both cases, officials and nationalist leaders shared a broad vision for Indian society, which pushed both sides actively to seek to recover the social and economic status quo ante, preventing potential tipping points from crystallising. These case studies reveal how and why highly fraught social contracts can survive major disasters. The colonial state's transient and reactive approach to disaster governance continued to impact on post-independence India.

Anaesthetic management of a patient with severe pulmonary hypertension, moderate tricuspid regurgitation and moderate right ventricular dysfunction presenting for a dilation and curettage.

A primigravida woman in her 30s with severe pulmonary hypertension, tricuspid regurgitation and depressed right ventricular function presented for therapeutic termination of pregnancy at 7 weeks gestation after referral and multidisciplinary recommendation. A slowly titrated lumbar epidural was chosen for the primary anaesthetic. Under standard American Society of Anesthesiologists (ASA) monitoring, invasive blood pressure monitoring and continuous transthoracic echocardiography, the patient's right ventricular systolic function was monitored throughout the case using qualitative and quantitative metrics and was notable for a right ventricular systolic pressure of 102.4 mm Hg. Milrinone, started prior to epidural titration, was used for inotropic support. Vasopressin was used in conjunction to sustain systemic vascular resistance while having little effect on the pulmonary vascular resistance. The patient experienced no complications or exacerbation of her pulmonary hypertension and was discharged home the following day.

Virginia Apgar (1909-1974): The Mother of Neonatal Resuscitation.

Dr. Virginia Apgar was an American anesthesiologist and researcher who heavily influenced the development of neonatal resuscitation in the immediate postpartum period with her simple five-point scoring system. Today, the APGAR scoring system is used around the world in delivery rooms to guide clinicians in the evaluation of newborns and to distinguish which might need urgent resuscitation. With a simple scoring system, timer, and clipboard, Dr. Virginia Apgar shifted focus from the parturient to the neonate, improving infant mortality as a result.

Urgent Cesarean Section in a Patient on Venovenous Extracorporeal Membrane Oxygenation.

A G7P6 40-year-old female at 20 weeks gestation, with a history of polysubstance use disorder and hepatitis C, presented to the emergency department with severe shortness of breath and hypoxia requiring intubation. After a thorough workup, she was diagnosed with aspiration pneumonitis and was treated with a course of antibiotics. After progressing well, she was soon extubated and transferred to a subacute rehabilitation facility (SAR). There, she acutely decompensated, requiring readmission, reintubation, and venovenous extracorporeal membrane oxygenation (ECMO) cannulation. After a brief period of improvement, the patient became increasingly unstable with hypotension, anemia, and downtrending fibrinogen. Bedside imaging indicated a possible placental abruption. After extensive discussion among the care teams and patient's healthcare proxy, an urgent cesarean section was performed. Although the fetus was determined to be nonviable, the patient tolerated the procedure well and was eventually decannulated from ECMO and transferred to a SAR.

Oxidation-potential tuning of tungsten-alkylidyne complexes over a 2 V range.

The electrochemistry and electronic structures of over 30 tungsten-alkylidyne compounds of the form W(CR)L(n)L'(4-n)X (R = H, Bu(t), Ph, p-C6H4CCH, p-C6H4CCSiPr(i)3; X = F, Cl, Br, I, OTf, Bu(n), CN, OSiMe3, OPh; L/L' = PMe3, 1/2 dmpe, 1/2 depe, 1/2 dppe, 1/2 tmeda, P(OMe)3, CO, CNBu(t), py), in which the alkylidyne R group and L and X ligands are systematically varied, have been investigated using cyclic voltammetry and density functional theory calculations in order to determine the extent to which the oxidation potential may be tuned and its dependence on the nature of the metal-ligand interactions. The first oxidation potentials are found to span a range of ∼2 V. Symmetry considerations and the electronic-structure calculations indicate that the highest occupied molecular orbital (and redox orbital) is of principal d(xy) orbital parentage for most of the compounds in this series. The dependence of the oxidation potential on ligand is a strong function of the symmetry relationship between the substituent and the d(xy) orbital, being much more sensitive to the nature of the equatorial L ligands (π symmetry, with respect to d(xy), ΔE1/2 ≅ 0.5 V/L) than to the axial CR and X ligands (nonbonding with respect to d(xy), ΔE(1/2) < 0.3 V/L). The oxidation potential is linearly correlated with the calculated d(xy) orbital energy (slope ≅ 1, R(2) = 0.97), which thus provides a convenient computational descriptor for the potential. The strength of the correlation and slope of unity are proposed to be manifestations of the small inner-sphere reorganization energy associated with one-electron oxidation.

Civil aircraft accident investigation.

This talk reviews some historic aircraft accidents and some more recent. It reflects on the division of accident causes, considering mechanical failures and aircrew failures, and on aircrew training. Investigation results may lead to improved aircraft design, and to appropriate crew training.

Double Lumen Endobronchial Tube Placement for Lung Separation via a Tracheostomy Stoma in a Patient Status-Post Laryngectomy.

A 63-year-old male with a history of chronic obstructive pulmonary disease and squamous cell carcinoma of the larynx status-post laryngectomy and tracheostomy presented for a robotic-assisted right upper lobectomy for neoplasm excision. On physical examination, he was noted to have moderate hypoxia with an SpO2 of 93% on room air. In order to facilitate potential apneic oxygen insufflation and continuous positive airway pressure in the operative lung, a traditional left-sided 35-French double-lumen endobronchial tube was placed through his tracheostomy, and utilized to facilitate lung separation and to improve surgical manipulation. The patient tolerated the procedure well and was extubated to a tracheostomy collar with a 100% fraction of inspired oxygen delivered with 15 liters per minute of flow.

World-Class Innovation, but at What Cost? A Brief Examination of the American Healthcare System.

The American healthcare system, often counted among the world's best, offers expedient access to a highly subspecialized network of physicians who work at the forefront of developing and utilizing novel, cutting-edge procedures, and medications. Patients typically have access to large numbers of qualified physicians in every metropolitan area and thus are afforded the luxury of individual choice in hospital, physician, and experience. Unfortunately, the costs of maintaining such a system are quite profound, and the higher investments do not pay dividends in health outcomes. Here, we elaborate on the greatest achievement and worst flaw in the American healthcare system.

Spinal Radiofrequency Ablation Combined with Cement Augmentation for Painful Spinal Vertebral Metastasis: A Single-Center Prospective Study.

BACKGROUND: The spine is the most common site of skeletal metastatic disease. Vertebral body metastases (VBM) can cause crippling pain, fractures, and spinal cord compression. Radiofrequency ablation (RFA) is a minimally invasive technique that has proven to be a safe method of targeted tissue destruction. Studies have shown that RFA combined with cement vertebral augmentation is safe and effective and has been associated with significant improvements in pain and quality of life. OBJECTIVES: The purpose of this study was continued evaluation of the safety and efficacy of this technique. STUDY DESIGN: Prospective cohort. SETTING: A single academic medical center. METHODS: Patients undergoing RFA with cement vertebral augmentation for a painful thoracic or lumbar VBM were eligible for inclusion. Additional inclusion criteria included pain concordant with a metastatic lesion on cross-sectional imaging, aged 18 years or older, and considered candidates for spinal tumor ablation by the operating physician. Patients with vertebral metastatic disease in the cervical spine or patients with spinal cord compression from posterior tumor extension were excluded. Ablation within each VBM was performed using a bipolar radiofrequency probe with an extensible electrode and available articulation, permitting vertebral body navigation percutaneously. Patients were evaluated at baseline, 3 days, one week, one month, and 3 months using the Numeric Rating Scale (NRS-11) and Functional Assessment of Cancer Therapy-General 7 (FACT-G7) to assess pain and quality-of-life, respectively. A one-sample t test was performed, and 95% confidence intervals were calculated to assess changes in average NRS-11 and FACT-G7 scores. RESULTS: A total of 30 patients met inclusion criteria and underwent RFA of one or more VBM. Patients with 13 different primary cancers types underwent treatment. Patients received RFA to either one (n = 26; 87%) or 2 vertebral body levels (n = 4; 13%). Of the 34 levels, 13 were thoracic vertebra (38%) and 21 were lumbar vertebra (62%). Average NRS-11 scores decreased from a baseline of 5.77 to 4.65 (3 days; P = 0.16), 3.33 (one week; P < 0.01), 2.64 (one month; P < 0.01), and 2.61 (3 months; P < 0.01). FACT-G7 increased from a baseline average of 13.0 to 14.7 (3 days; P = 0.13), 14.69 (one week; P = 0.15), 14.04 (one month; P = 0.35), and 15.11 (3 months; P = 0.07). No major adverse events were reported. LIMITATIONS: A heterogeneous patient population, small sample size, and potential confounders of concurrent variable adjuvant therapies were limitations. Additionally, most patients received both cement augmentation and targeted RFA, making it difficult to distinguish independent analgesic benefits of the therapies. CONCLUSIONS: This study demonstrates that minimally invasive targeted RFA with cement augmentation of spinal metastatic lesions is an effective treatment for patients with VBM. KEY WORDS: Cancer, cancer pain, spinal metastasis, radiofrequency ablation, tumor ablation, cement augmentation.

A Retrospective, Pilot Study of De Novo Antidepressant Medication Initiation in Intensive Care Unit Patients and Post-ICU Depression.

Post-ICU Syndromes (PICS) remain a devastating problem for intensive care unit (ICU) survivors. It is currently unknown if de novo initiation of an antidepressant medication during ICU stay decreases the prevalence of post-ICU depression. We performed a retrospective, pilot study evaluating patients who had not previously been on an antidepressant medication and who were started on an antidepressant while in the trauma surgical, cardiothoracic, or medical intensive care unit (ICU). The PHQ-2 depression scale was used to ascertain the presence of depression after ICU discharge and compared this to historical controls. Of 2,988 patients admitted to the ICU, 69 patients had de novo initiation of an antidepressant medication and 27 patients were alive and available for study inclusion. We found the prevalence of depression in these patients to be 26%, which is not statistically different than the prevalence of post-ICU depression in historical controls [95% CI (27.6%, 51.6%)]. De novo initiation of an antidepressant medication did not substantially decrease the prevalence of post-ICU depression in this retrospective, pilot study.

Signal and sensitivity enhancement through optical interference coating for DNA and protein microarray applications.

Optical inteference (OI) coated slides with unique optical properties were utilized in microarray analyses, demonstrating their enhanced detection sensitivity over traditional microarray substrates. The OI coating is comprised of a proprietary multilayered, dielectric, thin-film interference coating located beneath the functional coating (aminosilane or epoxysilane). It is designed to enhance the fluorescence in the Cy3 and Cy5 channel by increasing the light absorption of the dyes by about 6-fold and by redirecting emitted fluorescence into the detector during scanning, resulting in a theoretical limit of about 12-fold signal amplification. Two-color DNA microarray experiments conducted on the OI slides showed over 8-fold signal amplification, conservation of gene expression ratios, and increased signal-to-noise ratio when compared to control slides, indicating enhanced detection sensitivity. Protein microarray assays also exhibited over 8-fold signal amplification at three different target concentrations, demonstrating the versatility of the OI slides for different microarray applications. Further, the DNA and protein assays performed on the OI slides exhibited excellent detection sensitivity even at the low target amounts essential for diagnostic applications. The OI slides are compatible with commonly used protocols, printers, scanners and other microarray equipment. Therefore, the OI slides offer an attractive alternative to traditional microarray substrates, where enhanced detection sensitivity is desired.