Evaluation of opioid prescribing after rescheduling of hydrocodone-containing products.

PURPOSE: Institutional prescribing trends of hydrocodone-containing products (HCPs) before and after the Drug Enforcement Administration's rescheduling of HCPs were evaluated. METHODS: A retrospective evaluation was performed on 6 oral opioid analgesics on the hospital formulary that were prescribed to patients treated at Texas Children's Hospital and Pavilion for Women for the 6 months before and after the rescheduling of HCPs on October 6, 2014. Patients were eligible for inclusion if they were prescribed any of the following oral agents: HCPs (e.g., hydrocodone with acetaminophen), codeine-containing products (e.g., codeine, codeine with acetaminophen), morphine, hydromorphone, oxycodone-containing products (e.g., oxycodone, oxycodone with acetaminophen), and tramadol. RESULTS: During the 12-month study period, a total of 38,928 inpatient orders and outpatient prescriptions were processed for the studied agents in both locations; the majority were orders for inpatients. An overall reduction in the total number of opioid prescriptions was observed after the rescheduling of HCPs. Substantial increases in the proportional use of codeine were observed in all 4 settings after HCP rescheduling. Data for each of the agents revealed a shift in prescribing patterns centered along the HCP rescheduling date of October 6, 2014, and revealed a decrease in HCP use across all areas with an accompanying increase in codeine-containing products, oxycodone-containing products, and tramadol. CONCLUSION: The rescheduling of HCPs resulted in a reduction in HCP prescriptions but was accompanied by increases in the use of codeine-containing products and tramadol in all settings.

Taking culture seriously: Can we improve the developmental health and well-being of Australian Aboriginal children in out-of-home care?

BACKGROUND: Children in out-of-home care have well-documented health and developmental needs. Research suggests that Aboriginal children in care have unmet health and intervention needs. In metropolitan Sydney, Kari Aboriginal Resources Inc. (KARI), an Aboriginal organization, provides support to indigenous children in care, including clinical assessment and intervention. We wanted to determine the health and developmental needs of a subset of children in out-of-home care with KARI, who had been in stable care for at least a year. We wanted to identify child, carer, and intervention characteristics that contributed to children doing well. We also wanted to identify enablers and barriers to providing culturally competent intervention. METHODS: We used mixed methods. From the KARI clinic database over the past 3 years, we identified children who had been in stable care with KARI for >12 months. We compared clinical measures and outcomes for these children with results from previous audits. We carried out a group discussion and key informant interviews with therapists and caseworkers to identify risk and resilience factors for each child, as well as enablers and barriers to culturally competent intervention. RESULTS: The health and developmental profile of the 26 children identified as being in stable care was similar to that of previous audits. Most (88%) were getting speech pathology intervention; one third were getting occupational therapy and psychological intervention; most children and their carers attended cultural programmes. The majority of children (25/26) improved in their developmental health. Caseworkers and therapists identified risk and resilience factors related to child, carer, and home characteristics. They also identified elements of good practice; systemic issues prevented some interventions from being carried out. CONCLUSIONS: There are challenges delivering a trauma-informed, culturally respectful service to Aboriginal children in out-of-home care in an urban setting, but it can be done if attention is paid to culture and the enablers and barriers are identified.

An Outbreak of Burkholderia cepacia Complex Infections Associated with Contaminated Liquid Docusate.

OBJECTIVE To investigate an outbreak of Burkholderia cepacia complex and describe the measures that revealed the source. SETTING A 629-bed, tertiary-care, pediatric hospital in Houston, Texas. PATIENTS Pediatric patients without cystic fibrosis (CF) hospitalized in the pediatric and cardiovascular intensive care units. METHODS We investigated an outbreak of B. cepacia complex from February through July 2016. Isolates were evaluated for molecular relatedness with repetitive extragenic palindromic polymerase chain reaction (rep-PCR); specific species identification and genotyping were performed at an independent laboratory. The investigation included a detailed review of all cases, direct observation of clinical practices, and respiratory surveillance cultures. Environmental and product cultures were performed at an accredited reference environmental microbiology laboratory. RESULTS Overall, 18 respiratory tract cultures, 5 blood cultures, 4 urine cultures, and 3 stool cultures were positive in 24 patients. Among the 24 patients, 17 had symptomatic infections and 7 were colonized. The median age of the patients was 22.5 months (range, 2-148 months). Rep-PCR typing showed that 21 of 24 cases represented the same strain, which was identified as a novel species within the B. cepacia complex. Product cultures of liquid docusate were positive with an identical strain of B. cepacia complex. Local and state health departments, as well as the CDC and FDA, were notified, prompting a multistate investigation. CONCLUSIONS Our investigation revealed an outbreak of a unique strain of B. cepacia complex isolated in clinical specimens from non-CF pediatric patients and from liquid docusate. This resulted in a national alert and voluntary recall by the manufacturer. Infect Control Hosp Epidemiol 2017;38:567-573.

Avoidance of Hospital-Acquired Infections in Pediatric Cardiac Surgical Patients.

OBJECTIVES: The objectives of this review are to discuss the prevalence and risk factors associated with the development of hospital-acquired infections in pediatric patients undergoing cardiac surgery and the published antimicrobial prophylaxis regimens and rational approaches to the diagnosis, prevention, and treatment of nosocomial infections in these patients. DATA SOURCE: MEDLINE and PubMed. CONCLUSION: Hospital-acquired infections remain a significant source of potentially preventable morbidity and mortality in pediatric cardiac surgical patients. Through improved understanding of these conditions and implementation of avoidance strategies, centers caring for these patients may improve outcomes in this vulnerable population.

Tetanus and diphtheria toxoids and acellular pertussis vaccine uptake during pregnancy in a metropolitan tertiary care center.

OBJECTIVES: Tetanus, diphtheria and acellular pertussis (Tdap) vaccine is recommended during each pregnancy, but national uptake is poor. We assessed Tdap uptake in a tertiary referral hospital served by university-affiliated and private obstetrical offices. METHODS: Review of women delivering at Texas Children's Hospital Pavilion for Women, Houston, Texas, during April 2013-June 2014. RESULTS: 6577 deliveries occurred during the study period. Mean maternal age was 29.8 years (range 13-49); race/ethnicity was 43.6% White, 27% Hispanic, 21% Black, 7.1% Asian, and 1.3% other. 252 were multiple gestations; 229 sets of twins, 21 triplets and 2 quadruplets. 3678 (56%) women received Tdap during pregnancy, 249 (3.8%) postpartum and 100 (1.5%) received Tdap pre-conception only. Tdap uptake during pregnancy increased from 36% in April 2013 to a sustained uptake of greater than 61% since November 2013, with increases noted coincidental with presentations highlighting Tdap maternal immunization recommendations at faculty and staff meetings, and the release of the ACOG "toolkit". When antenatal Tdap vaccine was administered, mean gestation at receipt of Tdap was 31.4 weeks and 95% of vaccinated women received Tdap at the recommended gestation interval of 27-36 weeks, 71.6% during the 28-32 week window believed optimal for placental transport and 98.5% at least 7 days before delivery. Of 19 women with two pregnancies during the study period, four (21%) had Tdap during both. Black women were less likely to receive antenatal Tdap than women of other race/ethnicity (41% versus 60%; P<0.001). CONCLUSIONS: Sustained antenatal Tdap uptake rates exceeding 61% were achieved after strategies to increase awareness of recommendations were introduced and 95% of women were immunized at a gestation optimal for efficient maternal antibody placental transport. Further increases in uptake will require system changes such as best practice alerts in electronic medical records.

Evaluation of off-label recombinant activated factor VII for multiple indications in children.

Despite a paucity of safety and efficacy data, the use of recombinant activated factor VII in children for off-label indications has now surpassed its use in hemophilia. A retrospective chart review was conducted of 46 subjects (age, 6.7 +/- 6 years; weight, 26 +/- 20 kg) who received recombinant activated factor VII for nonhemophiliac indications between January 1, 2004, and September 1, 2005. Indications for use included prevention (n = 6) or treatment (n = 40) of bleeding due to general surgery, hepatic failure, gastrointestinal bleeding, severe traumatic brain injury, bone marrow transplant, cardiac, acetaminophen overdose, and multiorgan system failure. Decreases in prothrombin time, partial thromboplastin time, and international normalized ratio were observed. No inappropriate thrombotic events were noted. Administration of recombinant activated factor VII was associated with a reduction in coagulation markers without obvious adverse thrombotic events at cost of $4189 per dose. These findings should be confirmed in a prospective trial.

The effect of shoulder movements on thoracic spine 3D motion.

OBJECTIVE: To investigate whether there is any repeatable coupling pattern of upper thoracic movements, during right arm elevation in sagittal and scapular plane. METHODS: Upper thoracic movement patterns (T2-T7) were examined during right arm elevation, in the sagittal and scapular plane using an electromagnetic device. The participants were 25 asymptomatic woman aged between 45 and 64 years. RESULTS: The majority of the participants performed an ipsilateral coupling pattern between lateral flexion and rotation which was repeatable and comparable for both arm elevation planes. Ipsilateral coupling of right lateral flexion and rotation in association with extension occurred in 23 subjects during arm elevation in sagittal plane, and in 19 subjects during arm elevation in scapular plane. CONCLUSIONS: Analysis revealed that the participants demonstrated a repeatable upper thoracic movement pattern within and between subjects, during arm elevation in sagittal and scapular planes. RELEVANCE: The biomechanical relationship between the arm and the thoracic spine is important to clinical practice because of the contribution of spinal to shoulder movements and vice versa, in the recognition, prevention and restoration of musculoskeletal function.

Proteolytic activation of cholera toxin and Escherichia coli labile toxin by entry into host epithelial cells. Signal transduction by a protease-resistant toxin variant.

Cholera and Escherichia coli heat-labile toxins (CT and LT) require proteolysis of a peptide loop connecting two major domains of their enzymatic A subunits for maximal activity (termed "nicking"). To test whether host intestinal epithelial cells may supply the necessary protease, recombinant rCT and rLT and a protease-resistant mutant CTR192H were prepared. Toxin action was assessed as a Cl- secretory response (Isc) elicited from monolayers of polarized human epithelial T84 cells. When applied to apical cell surfaces, wild type toxins elicited a brisk increase in Isc (80 microA/cm2). Isc was reduced 2-fold, however, when toxins were applied to basolateral membranes. Pretreatment of wild type toxins with trypsin in vitro restored the "basolateral" secretory responses to "apical" levels. Toxin entry into T84 cells via apical but not basolateral membranes led to nicking of the A subunit by a serine-type protease. T84 cells, however, did not nick CTR192H, and the secretory response elicited by CTR192H remained attenuated even when applied to apical membranes. Thus, T84 cells express a serine-type protease(s) fully sufficient for activating the A subunits of CT and LT. The protease, however, is only accessible for activation when the toxin enters the cell via the apical membrane.

A pH-dependent conformational change in the B-subunit pentamer of Escherichia coli heat-labile enterotoxin: structural basis and possible functional role for a conserved feature of the AB5 toxin family.

The non-covalently associated B-subunit moieties of AB5 toxins, such as cholera toxin and related diarrheagenic enterotoxins, exhibit exceptional pH stability and remain pentameric at pH values as low as 2.0. Here, we investigate the structural basis of a pH-dependent conformational change which occurs within the B5 structure of Escherichia coli heat-labile enterotoxin (EtxB) at around pH 5.0. The use of far-UV CD and fluorescence spectroscopy showed that EtxB pentamers undergo a fully reversible pH-dependent conformational change with a pKa of 4.9 +/- 0.1 (R2 = 0.999) or 5.13 +/- 0.01 (R2 = 0.999), respectively. This renders the pentamer susceptible to SDS-mediated disassembly and decreases its thermal stability by 18 degrees C. A comparison of the pH-dependence of the structural change in EtxB5, with that of a mutant containing a Ser substitution at His 57, revealed that the pKa of the conformational change was shifted from ca. 5.1 to 4.4. This finding suggests that protonation of the imidazole side chain of His 57 might facilitate disruption of a spatially adjacent salt bridge, located between Glu 51 and Lys 91 in each B-subunit, thus triggering the conformational change in the pentameric structure. The pH-dependent conformational change was found to be inhibited when B-subunits bound to monosialoganglioside, GMI; and to have no effect on the stability of interaction between A- and B-subunits within the AB5 complex. This suggests that the conformational change is unlikely to have a direct involvement in toxicity. Conservation of the pH-dependent conformational change in the AB5 toxin family, combined with the potential exposure of the hydrophobic core of beta-barrel in the monomeric units, leads to the proposal that the conformational change may be the common feature that ensures the secretion of these proteins from the Vibrionaceae.

Three-dimensional analysis of active cervical motion: the effect of age and gender.

OBJECTIVE: To describe the effects of age and gender on three-dimensional (3D) active cervical spine motion. DESIGN: This was a descriptive study. BACKGROUND: This study expanded on previous investigations of age and gender effects on single plane motion of the cervical spine. METHODS: Sixty female and 60 male asymptomatic, normal volunteers, aged between 20 and 59 years, were examined in a standardized seated position. The 3 SPACE Isotrak system was used to measure simultaneous 3D motion of the cervical spine. RESULTS: The mean range of all the primary movements decreased significantly with age. For flexion/extension the greatest decrease occurred between the 20- and 30-year-olds, whereas for both lateral flexion and rotation, significant differences were demonstrated in subjects aged two decades apart. The coupling of motion associated with rotation was significantly related to age. CONCLUSION: Age had a significant effect on all of the primary movements. Age had less effect on the range of the coupled movements, in that the only movements to be affected were lateral flexion and extension occurring during cervical rotation. Gender had no marked effect on the primary or the coupled movements. RELEVANCE: This study provides normative data for the effects of age and gender on three-dimensional analysis of active cervical spine motion, which can be used for comparison with specific patient populations. The high level of intra-subject test-retest reliability renders the3 SPACE system of value for clinical measurement of movement pre- and post-treatment intervention for cervical spine disorders.

Kinetics of acid-mediated disassembly of the B subunit pentamer of Escherichia coli heat-labile enterotoxin. Molecular basis of pH stability.

The B-subunit pentamer of Escherichia coli heat-labile enterotoxin (EtxB) is highly stable, maintaining its quaternary structure in a range of conditions that would normally be expected to cause protein denaturation. In this paper the structural stability of EtxB has been studied as a function of pH by electrophoretic, immunochemical, and spectroscopic techniques. Disassembly of the cyclic pentameric structure of human EtxB occurs only below pH 2. As determined by changes in intrinsic fluorescence this process follows first-order kinetics, with the rate constant for disassembly being proportional to the square of the H+ ion concentration, and with an activation energy of 155 kJ mol-1. A C-terminal deletion mutant, hEtxB214, similarly shows first-order kinetics for disassembly but with a higher pH threshold, resulting in disassembly being seen at pH 3.4 and below. These findings are consistent with the rate-limiting step for disassembly of human EtxB being the simultaneous disruption of two interfaces by protonation of two C-terminal carboxylates. By comparison, disassembly of the B-subunit of cholera toxin (CtxB), a protein which shows 80% sequence identity with EtxB, exhibits a much lower stability to acid conditions; with disassembly of CtxB occurring below pH 3.9, with an activation energy of 81 kJ mol-1. Reasons for the observed differences in acid stability are discussed, and the implications of these findings to the development of oral vaccines using EtxB and CtxB are considered.

Targeting of cholera toxin and Escherichia coli heat labile toxin in polarized epithelia: role of COOH-terminal KDEL.

Vibrio cholerae and Escherichia coli heat labile toxins (CT and LT) elicit a secretory response from intestinal epithelia by binding apical receptors (ganglioside GM1) and subsequently activating basolateral effectors (adenylate cyclase). We have recently proposed that signal transduction in polarized cells may require transcytosis of toxin-containing membranes (Lencer, W. I., G. Strohmeier, S. Moe, S. L. Carlson, C. T. Constable, and J. L. Madara. 1995. Proc. Natl. Acad. Sci. USA. 92:10094-10098). Targeting of CT into this pathway depends initially on binding of toxin B subunits to GM1 at the cell surface. The anatomical compartments in which subsequent steps of CT processing occur are less clearly defined. However, the enzymatically active A subunit of CT contains the ER retention signal KDEL (RDEL in LT). Thus if the KDEL motif were required for normal CT trafficking, movement of CT from the Golgi to ER would be implied. To test this idea, recombinant wild-type (wt) and mutant CT and LT were prepared. The COOH-terminal KDEL sequence in CT was replaced by seven unrelated amino acids: LEDERAS. In LT, a single point mutation replacing leucine with valine in RDEL was made. Wt and mutant toxins displayed similar enzymatic activities and binding affinities to GM1 immobilized on plastic. Biologic activity of recombinant toxins was assessed as a Cl- secretory response elicited from the polarized human epithelial cell line T84 using standard electrophysiologic techniques. Mutations in K(R)DEL of both CT and LT delayed the time course of toxin-induced Cl- secretion. At T1/2, dose dependencies for K(R)DEL-mutant toxins were increased > or = 10-fold. KDEL-mutants displayed differentially greater temperature sensitivity. In direct concordance with a slower rate of signal transduction. KDEL-mutants were trafficked to the basolateral membrane more slowly than wt CT (assessed by selective cell surface biotinylation as transcytosis of B subunit). Mutation in K(R)DEL had no effect on the rate of toxin endocytosis. These data provide evidence that CT and LT interact directly with endogenous KDEL-receptors and imply that both toxins may require retrograde movement through Golgi cisternae and ER for efficient and maximal biologic activity.