Typologies of Family Dependency Treatment Court Participants: Parental Characteristics and Differential Child Placement Outcomes.

Background: Family Dependency Treatment Court (FDTC) is a problem-solving court for parents who have child welfare involvement and designed to address parental substance misuse by providing treatment and wrap-around services, with the goal of reunifying parents with their children. Objectives: This study aimed to identify different classes of FDTC parents and compare how child placement outcomes differ by class. Parental characteristics and permanent placement outcomes for 354 parents participating in a Central Florida FDTC were assessed using administrative data. An exploratory latent class analysis was conducted to classify parents. Results: Results revealed three distinct classes of FDTC participants: 1) co-occurring issues, 2) racial/ethnic minority participants, and 3) prescription opioid, meth, and heroin users. Regression analyses showed that parents with co-occurring issues were over two times more likely to achieve permanency (OR = 2.05, p < .05), and were two times less likely to terminate their parental rights (TPR) compared to the other two classes. Conclusions: Implications for tailoring FDTC procedures to parents' individual needs, combating racial/ethnic disparities in access to services and placement outcomes, and improved child welfare and placement outcomes are discussed.

The Association between Gut Microbiota and Osteoarthritis: Does the Disease Begin in the Gut?

Some say that all diseases begin in the gut. Interestingly, this concept is actually quite old, since it is attributed to the Ancient Greek physician Hippocrates, who proposed the hypothesis nearly 2500 years ago. The continuous breakthroughs in modern medicine have transformed our classic understanding of the gastrointestinal tract (GIT) and human health. Although the gut microbiota (GMB) has proven to be a core component of human health under standard metabolic conditions, there is now also a strong link connecting the composition and function of the GMB to the development of numerous diseases, especially the ones of musculoskeletal nature. The symbiotic microbes that reside in the gastrointestinal tract are very sensitive to biochemical stimuli and may respond in many different ways depending on the nature of these biological signals. Certain variables such as nutrition and physical modulation can either enhance or disrupt the equilibrium between the various species of gut microbes. In fact, fat-rich diets can cause dysbiosis, which decreases the number of protective bacteria and compromises the integrity of the epithelial barrier in the GIT. Overgrowth of pathogenic microbes then release higher quantities of toxic metabolites into the circulatory system, especially the pro-inflammatory cytokines detected in osteoarthritis (OA), thereby promoting inflammation and the initiation of many disease processes throughout the body. Although many studies link OA with GMB perturbations, further research is still needed.

Update on Chemoreception: Influence on Cardiorespiratory Regulation and Pathophysiology.

We examine recent findings that have revealed interdependence of function within the chemoreceptor pathway regulating breathing and sympathetic vasomotor activity and the hypersensitization of these reflexes in chronic disease states. Recommendations are made as to how these states of hyperreflexia in chemoreceptors and muscle afferents might be modified in treating sleep apnea, drug-resistant hypertension, chronic heart failure-induced sympathoexcitation, and the exertional dyspnea of chronic obstructive pulmonary disease.

The Relationship Between Mixed Race/Ethnicity, Developmental Assets, and Mental Health Among Youth.

This study assessed whether high school youth with mixed race/ethnicity are at greater risk for poor mental health conditions compared to their single race/ethnic counterparts and whether this mental health risk can be mitigated by youth developmental assets regardless of one's race/ethnicity. Methods involved secondary data analysis of the 2009-2013 Youth Risk Behavioral Survey-Anchorage, Alaska subsample. Difference in rates of mental health conditions and mean number of developmental assets (protective factors) were assessed among three racial/ethnic groups. Logistic regression models tested whether race/ethnicity has an independent association with mental health conditions and whether there is an interaction effect between race/ethnicity and protective factors. Results show that, compared to white students, mixed race/ethnic students have significantly higher rates of poor mental health condition and significantly fewer protective factors. A significant interaction effect between race/ethnicity and protective factors was also found, showing decreasing likelihood of poor mental health condition with increasing number of protective factors among all racial/ethnic groups. However, this effect was more pronounced among white students compared to both mixed and single race/ethnicity minority students. Study findings indicate that youth of mixed race/ethnicity are more likely to be at risk for poor mental health outcomes, yet less likely to mitigate this risk even with similar number of external developmental assets as their single race/ethnic counterparts. More research is needed to further understand the differential effect of certain developmental assets among different racial/ethnic groups.

Pharmacokinetic and Pharmacodynamic Analysis of Ceftazidime/Avibactam in Critically Ill Patients.

BACKGROUND: The pharmacokinetics, especially the volume of distribution (Vd), of ß-lactam antibiotics can be altered in critically ill patients. This can lead to decreased serum concentrations and a reduction in clinical cures. Ceftazidime/avibactam (CZA) is a new antimicrobial agent utilized in critically ill patients although its pharmacokinetics has not been well defined in these patients. PATIENTS AND METHODS: In this study, the serum concentrations of CZA from adult patients treated in an intensive care unit (ICU) with standard dosing regimens were measured and both pharmacokinetic and pharmacodynamic parameters were computed. The pharmacodynamic analyses included Monte Carlo simulations to determine the probability of target attainment (PTA: free ceftazidime concentrations exceed the minimum inhibitory concentration [MIC] for 50% of the dosing interval; free avibactam concentrations exceed 1 mg/L over the dosing interval) and serum time-kill curves against multi-drug-resistant Enterobacteriaceae susceptible to CZA. Serum concentrations were measured in 10 critically ill patients at two, four, six, and eight hours after multiple doses (infused over two hours) of CZA. RESULTS: A significant linear relation between creatinine clearance and total body clearance was identified for both ceftazidime (R = 0.91) and avibactam (R = 0.88). The mean clearance, volume of distribution, and half-life for ceftazidime were 6.1 ± 3.8 L/h, 35 ± 10.5 L, and 4.8 ± 2.15 h, respectively. For avibactam, these values were 11.1 ± 6.8 L/h, 50.8 ± 14.3 L, and 4.1 ± 2.1 h, respectively. Ceftazidime/avibactam achieved optimal PTA for bacteria with MICs of 16 mg/L or less. Furthermore, time-kill experiments revealed that serum concentrations of CZA, at each collection time, exhibited bactericidal (≥ 3 log10 CFU/mL reduction) activity against each of the study isolates. CONCLUSION: In conclusion, our study results suggest that the current dosing regimens of CZA can provide effective antimicrobial activity in ICU patients against CZA-susceptible (MIC ≤8 mg/L) isolates.

On the Relationship between Safety and Decision Significance.

Risk analysts are often concerned with identifying key safety drivers, that is, the systems, structures, and components (SSCs) that matter the most to safety. SSCs importance is assessed both in the design phase (i.e., before a system is built) and in the implementation phase (i.e., when the system has been built) using the same importance measures. However, in a design phase, it would be necessary to appreciate whether the failure/success of a given SSC can cause the overall decision to change from accept to reject (decision significance). This work addresses the search for the conditions under which SSCs that are safety significant are also decision significant. To address this issue, the work proposes the notion of a θ-importance measure. We study in detail the relationships among risk importance measures to determine which properties guarantee that the ranking of SSCs does not change before and after the decision is made. An application to a probabilistic safety assessment model developed at NASA illustrates the risk management implications of our work.

Peripheral chemoreceptors determine the respiratory sensitivity of central chemoreceptors to CO2 : role of carotid body CO2.

We asked if the type of carotid body (CB) chemoreceptor stimulus influenced the ventilatory gain of the central chemoreceptors to CO2 . The effect of CB normoxic hypocapnia, normocapnia and hypercapnia (carotid body PCO2 ≈ 22, 41 and 68 mmHg, respectively) on the ventilatory CO2 sensitivity of central chemoreceptors was studied in seven awake dogs with vascularly-isolated and extracorporeally-perfused CBs. Chemosensitivity with one CB was similar to that in intact dogs. In four CB-denervated dogs, absence of hyper-/hypoventilatory responses to CB perfusion with PCO2 of 19-75 mmHg confirmed separation of the perfused CB circulation from the brain. The group mean central CO2 response slopes were increased 303% for minute ventilation (V̇I)(P ≤ 0.01) and 251% for mean inspiratory flow rate (VT /TI ) (P ≤ 0.05) when the CB was hypercapnic vs. hypocapnic; central CO2 response slopes for tidal volume (VT ), breathing frequency (fb ) and rate of rise of the diaphragm EMG increased in 6 of 7 animals but the group mean changes did not reach statistical significance. Group mean central CO2 response slopes were also increased 237% for V̇I(P ≤ 0.01) and 249% for VT /TI (P ≤ 0.05) when the CB was normocapnic vs. hypocapnic, but no significant differences in any of the central ventilatory response indices were found between CB normocapnia and hypercapnia. These hyperadditive effects of CB hyper-/hypocapnia agree with previous findings using CB hyper-/hypoxia.We propose that hyperaddition is the dominant form of chemoreceptor interaction in quiet wakefulness when the chemosensory control system is intact, response gains physiological, and carotid body chemoreceptors are driven by a wide range of O2 and/or CO2 .

A pharmacokinetic/pharmacodynamic analysis of ceftaroline prophylaxis in patients with external ventricular drains.

BACKGROUND: Ceftaroline is a broad-spectrum cephalosporin antibiotic with activity against drug-resistant bacteria, including strains of methicillin-resistant Staphylococcus aureus (MRSA), and may be useful to prevent and treat ventriculostomy-related infections (VRIs). The purpose of this study was to analyze the pharmacokinetics and pharmacodynamics of prophylactic ceftaroline in neurosurgical patients with an external ventricular drain (EVD). METHODS: Adult patients in the neurosurgical intensive care unit with an EVD were given prolonged prophylaxis with ceftaroline. Serum and cerebral spinal fluid (CSF) were obtained simultaneously at 2, 6, and 12 h after initiation of the fourth dose of ceftaroline and concentrations were measured by a liquid chromatography tandem mass spectrometry assay. Time-kill curves against isolates of coagulase-negative S. aureus, methicillin-sensitive S. aureus, MRSA, and Streptococcus pneumoniae were determined in serum and CSF at each collection time point. RESULTS: A total of five patients with a mean age of 63 y and mean weight of 83 kg were enrolled. The mean CSF:serum penetration ratios of ceftaroline were 0.005 (0.5%), 0.021 (2.1%), and 0.043 (4.3%) at 2, 6, and 12 h, respectively. The mean ceftaroline exposure ratio area under the curve (AUC)csf/AUCserum) was 0.011 (1.1%). Bactericidal activity at each collection time point was observed against each strain of staphylococci from serum samples and a penicillin-sensitive strain of S. pneumoniae from CSF samples. CONCLUSION: This investigation suggests that ceftaroline could have clinical utility for the prevention of VRIs in patients with EVDs.

Pathophysiology of human ventilatory control.

We review the substantial recent progress made in understanding the underlying mechanisms controlling breathing and the applicability of these findings to selected human diseases. Emphasis is placed on the sites of central respiratory rhythm and pattern generation as well as newly described functions of the carotid chemoreceptors, the integrative nature of the central chemoreceptors, and the interaction between peripheral and central chemoreception. Recent findings that support critical contributions from cortical central command and muscle afferent feedback to exercise hyperpnoea are also reviewed. These basic principles, and the evidence supporting chemoreceptor and ventilatory control system plasticity during and following constant and intermittent hypoxaemia and stagnant hypoxia, are applied to: 1) the pathogenesis, consequences and treatment of obstructive sleep apnoea; and 2) exercise hyperpnoea and its control and limitations with ageing, chronic obstructive pulmonary disease and congestive heart failure.

Role of chemoreception in cardiorespiratory acclimatization to, and deacclimatization from, hypoxia.

During sojourn to high altitudes, progressive time-dependent increases occur in ventilation and in sympathetic nerve activity over several days, and these increases persist upon acute restoration of normoxia. We discuss evidence concerning potential mediators of these changes, including the following: 1) correction of alkalinity in cerebrospinal fluid; 2) increased sensitivity of carotid chemoreceptors; and 3) augmented translation of carotid chemoreceptor input (at the level of the central nervous system) into increased respiratory motor output via sensitization of hypoxic sensitive neurons in the central nervous system and/or an interdependence of central chemoreceptor responsiveness on peripheral chemoreceptor sensory input. The pros and cons of chemoreceptor sensitization and cardiorespiratory acclimatization to hypoxia and intermittent hypoxemia are also discussed in terms of their influences on arterial oxygenation, the work of breathing, sympathoexcitation, systemic blood pressure, and exercise performance. We propose that these adaptive processes may have negative implications for the cardiovascular health of patients with sleep apnea and perhaps even for athletes undergoing regimens of "sleep high-train low"!

The influence of bolus to infusion delays on plasma Tissue Plasminogen Activator levels.

BACKGROUND: Estimates of neuronal loss in acute ischemic stroke show that the typical patient may lose 1·9 million neurons each minute that treatment is delayed. Consequently, significant emphasis has been placed on early evaluation and thrombolysis with tissue plasminogen activator (TPA), the only approved thrombolytic therapy. TPA should be administered as a bolus followed by an immediate infusion because of its short half life. However, in the real life clinical situation, delays in starting the infusion after the bolus can occur. Similarly, once infusion has started, interruptions in the infusion of TPA can also occur. These scenarios may result in lower serum concentrations which could decrease the effectiveness of thrombolysis. We sought to simulate, the influence of bolus infusion delays and also the influence of different intervals of interruptions in the infusion of TPA on serum TPA concentrations. METHODS: We simulated the effect of multiple intervals of delay after the bolus on serum TPA concentrations using known pharmacokinetics parameters of TPA. The effect of different intervals of interruptions in the infusion of TPA was also determined. The effect of rebolusing with TPA on serum concentrations in the event of significant bolus to infusion delays or significant infusion interruption was also simulated. RESULTS: Our data show that delays in starting the infusion may have significant effects on serum TPA concentrations. After the initial bolus, there is a rapid decrease in serum TPA concentrations unless the infusion is started immediately. Greater than 5 min delays in starting the infusion results in a slow gradual increase in serum TPA levels and levels stay well below the target concentrations for significant periods of time. Similarly, interruptions in the infusion of TPA lasting longer than 5 min can also significantly influence TPA levels. Rebolusing with TPA in these scenarios rapidly restores TPA levels to target concentrations. CONCLUSION: Because of its short half life, TPA should be administered as a bolus followed by an immediate infusion. Bolus to infusion delays or interruptions in the infusion of TPA after the bolus may significantly impact serum TPA levels and may reduce the efficacy of thrombolysis. Protocols or administration regimens should be employed to prevent delays or interruptions in the infusion. When delays do occur, rebolusing of TPA may be needed to rapidly restore TPA to target levels.

Health, hope, and human development: building capacity in public housing communities on the U.S.-Mexico border.

In this paper we highlight results from our recent survey of public housing residents living in the U.S.-Mexico border region. Our data inform our interdisciplinary (public health, education, environmental engineering, sociology) efforts to improve health and educational equity in our community, and provide ripe opportunities for policy advocacy.

Instituting systems-based practice and practice-based learning and improvement: a curriculum of inquiry.

BACKGROUND: The Accreditation Council for Graduate Medical Education (ACGME) requires that training programs integrate system-based practice (SBP) and practice-based learning and improvement (PBLI) into internal medicine residency curricula. CONTEXT AND SETTING: We instituted a seminar series and year-long-mentored curriculum designed to engage internal medicine residents in these competencies. METHODS: Residents participate in a seminar series that includes assigned reading and structured discussion with faculty who assist in the development of quality improvement or research projects. Residents pursue projects over the remainder of the year. Monthly works in progress meetings, protected time for inquiry, and continued faculty mentorship guide the residents in their project development. Trainees present their work at hospital-wide grand rounds at the end of the academic year. We performed a survey of residents to assess their self-reported knowledge, attitudes and skills in SBP and PBLI. In addition, blinded faculty scored projects for appropriateness, impact, and feasibility. OUTCOMES: We measured resident self-reported knowledge, attitudes, and skills at the end of the academic year. We found evidence that participants improved their understanding of the context in which they were practicing, and that their ability to engage in quality improvement projects increased. Blinded faculty reviewers favorably ranked the projects' feasibility, impact, and appropriateness. The 'Curriculum of Inquiry' generated 11 quality improvement and research projects during the study period. Barriers to the ongoing work include a limited supply of mentors and delays due to Institutional Review Board approval. Hospital leadership recognizes the importance of the curriculum, and our accreditation manager now cites our ongoing work. CONCLUSIONS: A structured residency-based curriculum facilitates resident demonstration of SBP and practice-based learning and improvement. Residents gain knowledge and skills though this enterprise and hospitals gain access to trainees who help to solve ongoing problems and meet accreditation requirements.

Tissue penetration and antimicrobial activity of standard- and high-dose trimethoprim/sulfamethoxazole and linezolid in patients with diabetic foot infection.

OBJECTIVES: The purpose of this study was to conduct a pharmacokinetic and pharmacodynamic evaluation of high (320/1600 mg) and standard (160/800 mg) doses of trimethoprim/sulfamethoxazole and linezolid in outpatients with mild diabetic foot infections (DFIs). METHODS: Both viable skin/soft tissue from the infection site and serum were obtained at various times after antibiotic administration from 18 patients (6 per study group) being treated with linezolid, standard doses of trimethoprim/sulfamethoxazole or high doses of trimethoprim/sulfamethoxazole during a follow-up clinic visit. These samples were assayed for drug concentrations by liquid chromatography in tandem with mass spectrometry. Patient sera were also utilized in time-kill assays against two strains of Staphylococcus aureus and three strains of ß-haemolytic streptococci. RESULTS: The mean tissue/serum ratio for linezolid was 0.46 (range, 0.18-0.71). The mean tissue/serum ratio for trimethoprim was 1.2 (range, 0.3-4.5) for both standard and high doses, and 0.23 (range, 0.1-0.46) and 0.36 (range, 0.14-1.28) for standard and high doses of sulfamethoxazole, respectively. Linezolid exhibited inhibitory activity in time-kill assays against strains of S. aureus (0.45 ± 0.5 log10 cfu/mL) and ß-haemolytic streptococci (2.2 ± 0.6 log10 cfu/mL), while trimethoprim/sulfamethoxazole exhibited bactericidal (>3 log kill) activity against all of these isolates. These findings were consistent for each sampling time and for high as well as standard doses of trimethoprim/sulfamethoxazole. CONCLUSIONS: This pharmacokinetic/pharmacodynamic study found that trimethoprim/sulfamethoxazole exhibits good skin/soft tissue penetration in patients with DFIs as well as bactericidal activity in serum against strains of S. aureus and ß-haemolytic streptococci.

A friendships and dating program for adults with intellectual and developmental disabilities: a formative evaluation.

Meaningful relationships with others are often elusive for people with intellectual and developmental disabilities, but no less desired for their full inclusion and participation in society. It is well documented that people with disabilities are victims of interpersonal violence at higher rates than peers without disabilities. This article presents a formative evaluation of the Friendships and Dating Program (FDP). The FDP was designed to teach the social skills needed to develop healthy, meaningful relationships and to prevent violence in dating and partnered relationships. Thirty-one adults were recruited by 5 community agencies in Alaska to participate. The results showed the size of the participants' social networks increased and the number of incidents of interpersonal violence was reduced for participants who completed the FDP, and outcomes were maintained 10 weeks later.

Role of central/peripheral chemoreceptors and their interdependence in the pathophysiology of sleep apnea.

Unstable periodic breathing with intermittent ventilatory overshoots and undershoots commonly occurs in chronic heart failure, in hypoxia, with chronic opioid use and in certain types of obstructive sleep apnea. Sleep promotes breathing instability because it unmasks a highly sensitive dependence of the respiratory control system on chemoreceptor input, because transient cortical arousals promote ventilatory overshoots and also because upper airway dilator muscle tonicity is reduced and airway collapsibility enhanced. We will present data in support of the premise that carotid chemoreceptors are essential in the pathogenesis of apnea and periodicity; however it is the hyperadditive influence of peripheral chemoreceptor sensory input on central chemosensitivity that accounts for apnea and periodic breathing. This chemoreceptor interdependence also provides a significant portion of the normal drive to breathe in normoxia (i.e. eupnea) and in acute hypoxia. Finally, we discuss the effects of preventing transient hypocapnia (via selective increases in FICO(2)) on centrally mediated types of periodic breathing and even some varieties of cyclical obstructive sleep apnea.

Pharmacokinetics and monte carlo simulations of doripenem in patients with febrile neutropenia.

BACKGROUND: Doripenem is a group 2 carbapenem with enhanced in vitro activity against gram-negative bacteria including Pseudomonas aeruginosa. There is a paucity of pharmacokinetic/pharmacodynamic data on doripenem in patients with febrile neutropenia. OBJECTIVE: To conduct a pharmacokinetic evaluation of 2 doses of doripenem in patients with febrile neutropenia and provide probability estimates of attaining effective drug exposure against common gram-negative pathogens. METHODS: We obtained multiple blood samples from 12 adults with febrile neutropenia who were receiving either 500 mg or 1000 mg of intravenous doripenem over 4 hours every 8 hours. Following at least 2 doses, serum concentrations were measured in each subject at 1, 4, 6, and 8 hours after initiation of a dose by a validated high-performance liquid chromatography assay. The derived pharmacokinetic parameters from these serum levels were used to perform a 5000-patient Monte Carlo simulation against bacteria with minimal inhibitory concentrations (MICs) of 0.008-64 mg/L to determine probability estimates of the time in which unbound drug concentrations remain above the MIC (fT(>MIC)). RESULTS: The mean pharmacokinetic parameters in these patients were a volume of distribution of 43.9 L, an elimination rate constant of 0.37 h(-1), a total clearance of 14.4 L/h, and an area under the concentration-time curve of 57.6 mg•h/L. An optimal probability of target attainment (40% fT(>MIC)) of 90% was obtained against bacteria with MICs ≤2 mg/L and ≤4 mg/L with 500-mg and 1000-mg doses, respectively. Adverse events associated with doripenem were not observed. CONCLUSIONS: The findings from this analysis of doripenem suggest that higher doses, as well as prolonged infusions, may be necessary to optimally treat selected gram-negative bacteria (eg, P. aeruginosa) in patients with febrile neutropenia.