The effect of opioids on the cognitive function of older adults: results from the Personality and Total Health through life study.

BACKGROUND: chronic pain, a common complaint among older adults, affects physical and mental well-being. While opioid use for pain management has increased over the years, pain management in older adults remains challenging, due to potential severe adverse effects of opioids in this population. OBJECTIVE: we examined the association between opioid use, and changes in cognitive function of older adults. DESIGN: prospective study. SETTING: community dwelling older adults. SUBJECTS: study population consisted of 2,222 individuals aged 65-69 years at baseline from the Personality and Total Health Through Life Study in Australia. METHODS: medication data were obtained from the Pharmaceutical Benefits Scheme. Cognitive measures were obtained from neuropsychological battery assessment. Opioid exposure was quantified as Total Morphine Equivalent Dose (MED). The association between change in cognitive function between Wave 2 and Wave 3, and cumulative opioid use was assessed through generalized linear models. RESULTS: cumulative opioid exposure exceeding total MED of 2,940 was significantly associated with poorer performance in the Mini Mental State Examination (MMSE). Compared with those not on opioids, individuals exposed to opioids resulting in cumulative total MED of greater than 2,940 had significantly lower scores in the MMSE (Model 1: ß = -0.34, Model 2: ß = -0.35 and Model 3: ß = -0.39, P < 0.01). Performance in other cognitive assessments was not associated with opioid use. CONCLUSION: prolonged opioid use in older adults can affect cognitive function, further encouraging the need for alternative pain management strategies in this population. Pain management options should not adversely affect healthy ageing trajectories and cognitive health.

Young adult US-born Latina women's thoughts, feelings and beliefs about unintended pregnancy.

Current measures of unintended pregnancy underestimate the co-occurring, complex set of social, cultural, economic and structural factors that influence how women interpret unintended pregnancy. The purpose of this study was to prospectively explore young adult US-born Latinas' thoughts, feelings and beliefs about pregnancy, specifically unintended pregnancies and the sociocultural factors identified as contributors to those beliefs. In-depth interviews (n = 20) were conducted with US-born, English-speaking Latinas aged 18-25 years in south Florida. Seventeen participants did not intend to get pregnant, while the remaining participants (n = 3) reported that their intentions kept changing. Participants' beliefs regarding their unintended pregnancy were influenced by social and economic hardship and cultural factors such as fatalism and familismo. Ideas and the meaning of pregnancy differed based on the woman's pregnancy resolution decision. Many women felt the term 'unintended pregnancy' placed blame on women and was stigmatising. When discussing pregnancy planning, most participants felt that women should not plan their pregnancies and doing so was going against fate. Findings suggest that salient influences such as culture and the social determinants related to unintended pregnancy should be incorporated into measurements examining unintended pregnancy.

Linking the work environment to missed nursing care in labour and delivery.

AIM: To measure the association between the nurse work environment (NWE) and missed nursing care on labour and delivery (L&D) units. BACKGROUND: L&D units provide a sizable fraction of acute hospital services to a unique population that is a national and global priority. L&D nurses are the frontline providers during labour. Maternal morbidity and mortality may be influenced by the NWE and missed care. METHODS: This cross-sectional study utilized secondary data from 1,313 L&D staff nurses in 247 hospitals from a four-state nurse survey collected in 2005-2008. RESULTS: Half of nurses missed care (range: zero to 100% across hospitals). Nurses on average missed 1.25 of 10 activities. The most commonly missed activities were comforting/talking with patients and teaching/counselling. In better as compared to poor NWEs, the odds and frequency of missed care were significantly lower. CONCLUSIONS: L&D nurses routinely miss necessary nursing activities. Labouring women's psychosocial, comfort and educational needs are compromised most often, likely impacting quality and outcomes. Nurse communication with colleagues and managers about missed care is warranted. IMPLICATIONS FOR NURSING MANAGEMENT: The L&D NWE is modifiable and appears to influence missed care. Managers should discuss missed care with staff and measure their NWE to identify actionable weaknesses.

Post-traumatic stress disorder and hypertensive disorders of pregnancy among military women.

BACKGROUND: Women are more likely to develop post-traumatic stress disorder (PTSD) than men. Limited research exists evaluating the risk of hypertensive disorders of pregnancy (HDP) among military women with PTSD. METHODS: We conducted a retrospective cohort study using US Department of Defense (DoD) data comprised of all active-duty women giving birth to their first, liveborn singleton infant using DoD-sponsored health insurance from 1 January 2004 to 31 December 2008 (n = 34 176). Birth hospitalisation records, maternal mental health visits, and Post-Deployment Health Assessment (PDHA) and Reassessment (PDHRA) screenings were included. The HDP outcome (yes vs no) was defined using ICD-9-CM codes in the maternal birth hospitalisation record. Women fit into one of four PTSD exposure categories (confirmed, probable, possible, none). Confirmed cases had a PTSD ICD-9-CM diagnosis code. Probable/possible cases were classified using PDHA screening items. We used multiple log-linear regression to assess PTSD (confirmed, any vs none) and the risk of HDP overall, and then explored effect modification by military service and demographic variables. We assessed the risk of HDP among deployed mothers with PTSD (confirmed, probable/possible vs none) who completed a PDHA, and explored effect modification by race/ethnicity. We also assessed risk of HDP with differing PTSD lead times. RESULTS: Overall, PTSD was not associated with HDP except among mothers whose PTSD was diagnosed ≥1 year prior to conception (RR 1.42, 95% CI 1.06, 1.90). CONCLUSIONS: Post-traumatic stress disorder preceding conception by at least a year appeared to confer an increased risk of HDP, but further research is needed using more thorough PTSD assessment.

Assigning methyl resonances for protein solution-state NMR studies.

Solution-state NMR is an important tool for studying protein structure and function. The ability to probe methyl groups has substantially expanded the scope of proteins accessible by NMR spectroscopy, including facilitating study of proteins and complexes greater than 100 kDa in size. While the toolset for studying protein structure and dynamics by NMR continues to grow, a major rate-limiting step in these studies is the initial resonance assignments, especially for larger (>50 kDa) proteins. In this practical review, we present strategies to efficiently isotopically label proteins, delineate NMR pulse sequences that can be used to determine methyl resonance assignments in the presence and absence of backbone assignments, and outline computational methods for NMR data analysis. We use our experiences from assigning methyl resonances for the aromatic biosynthetic enzymes tryptophan synthase and chorismate mutase to provide advice for all stages of experimental set-up and data analysis.

Institution of a Comprehensive Postpartum Hemorrhage Bundle at a Large Academic Center does not Immediately Reduce Maternal Morbidity.

OBJECTIVE: Obstetric hemorrhage is a leading cause of morbidity and mortality. We sought to assess whether institution of a postpartum hemorrhage (PPH) bundle could improve maternal morbidity in our population. STUDY DESIGN: Preintervention data (PRE) was collected on all deliveries at Hospital of the University of Pennsylvania between October 15, 2013 and December 15, 2013. A two-pronged, multidisciplinary educational and procedural intervention related to PPH was instituted from March 2015 to June 2015. Postintervention data (POST) was collected on all deliveries from October 20, 2015 to December 20, 2015. RESULTS: Note that 592 of 626 (95%) PRE and 583 of 613 (95%) POST deliveries were included. The rates of PPH by estimated blood loss (EBL) ≥ 1,000 mL and by 3 g hemoglobin drop were not significantly different from PRE to POST (9.0% versus 12.2%, p = 0.07 and 10.5% versus 13.5%, p = 0.10, respectively). There was no significant change in transfusion rate (3.4% versus 5.1%, p = 0.13). Use of uterotonics was reduced from 9.8 to 6.3% from PRE to POST (p = 0.03). CONCLUSION: While institution of a PPH bundle is designed to improve the morbidity of PPH, our data demonstrate that it cannot be expected to do so within 6 months of implementation. Further studies will need to assess the long-term effects of such a resource-intensive protocol, including perceptions of improved safety by all providers, nurses, and staff.

Implementation of Quantification of Blood Loss Does Not Improve Prediction of Hemoglobin Drop in Deliveries with Average Blood Loss.

OBJECTIVE: The National Partnership for Maternal Safety released a postpartum hemorrhage bundle in 2015 recommending quantification of blood loss (QBL) for all deliveries. We sought to determine whether QBL more accurately predicts hemoglobin (Hb) drop than visually estimated blood loss (EBL). STUDY DESIGN: This is a prospective observational study. Preintervention data (PRE) were collected on all deliveries between October 15, 2013 and December 15, 2013. Deliveries were included if EBL, admission Hb, and 12-hour postpartum Hb (12hrCBC) were available. QBL was implemented in July 2015. Postintervention data (POST) were collected between October 20, 2015 and December 20, 2015. A total of 500 mL EBL was predicted to result in 1 g/dL Hb drop at 12hrCBC. Student's t-test was used to compare the means. RESULTS: A total of 592 of 626 (95%) PRE and 583 of 613 (95%) POST deliveries were included. Overall, 278 (48%) POST deliveries had QBL recorded. In both PRE and POST, actual Hb drop differed from predicted by 0.6 g/dL in both groups of deliveries. When evaluating deliveries with EBL > 1,000 mL, QBL in POST was slightly better at predicting Hb drop versus EBL in PRE, although not statistically significant (0.2 vs. 0.5 g/dL, p = 0.17). CONCLUSION: In all deliveries, QBL does not predict Hb drop more accurately than EBL. The decision to perform QBL needs to balance accuracy with a resource intense measurement process.

Implementation of Fee-Free Maternal Health-Care Policy in Ghana: Perspectives of Users of Antenatal and Delivery Care Services From Public Health-Care Facilities in Accra.

In 2008, the government of Ghana implemented a national user fee maternal care exemption policy through the National Health Insurance Scheme to improve financial access to maternal health services and reduce maternal as well as perinatal deaths. Although evidence shows that there has been some success with this initiative, there are still issues relating to cost of care to beneficiaries of the initiative. A qualitative study, comprising 12 focus group discussions and 6 interviews, was conducted with 90 women in six selected urban neighborhoods in Accra, Ghana, to examine users' perspectives regarding the implementation of this policy initiative. Findings showed that direct cost of delivery care services was entirely free, but costs related to antenatal care services and indirect costs related to delivery care still limit the use of hospital-based midwifery and obstetric care. There was also misunderstanding about the initiative due to misinformation created by the government through the media.We recommend that issues related to both direct and indirect costs of antenatal and delivery care provided in public health-care facilities must be addressed to eliminate some of the lingering barriers relating to cost hindering the smooth operation and sustainability of the maternal care fee exemption policy.

Sleep duration, obesity, and asthma, in Florida adolescents: analysis of data from the Florida Youth Risk Behavior Survey (2009-2013).

PURPOSE: To examine the association between sleep duration and asthma among Florida high school students and whether body mass index (BMI) modifies this association. METHODS: This cross-sectional analysis included 16,728 participants in the Florida Youth Risk Behavior Survey (2009-2013). Using logistic regression, we examined the association between sleep duration and asthma, and, after controlling for potential confounders, analyzed the interaction between sleep duration and BMI. RESULTS: Sleeping for less than 7 h or more than 8 h on school night was associated with increased odds of current asthma. Compared with 7-8 h of sleep per night, sleeping for <7 h had an OR of 1.22 (95% CI 1.07, 1.40), while sleeping for ≥9 h had and OR of 1.31 (1.06, 1.63). When stratified by body mass index (BMI), these associations were significant only in overweight adolescents, with those sleeping for <7 or ≥9 h having approximately twice the odds of having current asthma (OR = 1.75 (1.45, 2.11) and OR = 2.00 (1.32, 3.02) respectively), compared with normal weight adolescents who slept for 7-8 h per night. CONCLUSION: The association between sleep duration and asthma in adolescents is modified by BMI. Short and long sleep durations are associated with asthma in overweight adolescents while no significant association is seen in those with normal BMI.

Post-traumatic stress disorder following emergency peripartum hysterectomy.

PURPOSE: Our objective was to explore if women who experience emergency peripartum hysterectomy (EPH), a type of severe maternal morbidity, are more likely to screen positive for post-traumatic stress disorder (PTSD) compared to women who did not experience EPH. METHODS: Using a retrospective cohort design, women were sampled through online communities. Participants completed online screens for PTSD. Additionally, women provided sociodemographic, obstetric, psychiatric, and psychosocial information. We conducted bivariate and logistic regression analyses, then Monte Carlo simulation and propensity score matching to calculate the risk of screening positive for PTSD after EPH. RESULTS: 74 exposed women (experienced EPH) and 335 non-exposed women (did not experience EPH) completed the survey. EPH survivors were nearly two times more likely to screen positive for PTSD (aOR: 1.90; 95 % CI: 1.57, 2.30), and nearly 2.5 times more likely to screen positive for PTSD at 6 months postpartum compared to women who were not EPH survivors (aOR: 2.46; 95 % CI: 1.92, 3.16). CONCLUSION: The association of EPH and PTSD was statistically significant, indicating a need for further research, and the potential need for support services for these women following childbirth.

Cesarean section and the risk of emergency peripartum hysterectomy in high-income countries: a systematic review.

INTRODUCTION: Our objective was to determine the incidence and mortality rates associated with emergency peripartum hysterectomy, factors that lead to uncontrolled hemorrhage and emergency peripartum hysterectomy, and to determine the relationship between cesarean section and risk of emergency peripartum hysterectomy. MATERIALS AND METHODS: Studies published between January 1, 2000 and December 31, 2012 were identified using PubMed, OVID and Web of Science databases. Studies were included if they reported incidence rates for emergency peripartum hysterectomy, factors that lead to hemorrhage and emergency peripartum hysterectomy, or the association of emergency peripartum hysterectomy with cesarean section in high-income countries. RESULTS: Four hundred and fifty-one studies were identified, and 52 were included. The incidence of emergency peripartum hysterectomy ranged from 0.20 to 5.09 per 1000 deliveries with a median incidence rate of 0.61 per 1000 deliveries. These rates have increased over time. Rates varied by region/country, specifically with the United States reporting higher rates than North American, Asian, Oceania, and European countries. The most common factor leading to emergency peripartum hysterectomy was placental abnormalities. Both cesarean section and prior cesarean section were strong risk factors for emergency peripartum hysterectomy with higher risks conferred for each additional cesarean section. The mean percentage of maternal deaths for EPH survivors was 3.0 %. CONCLUSION: Given the association of cesarean section with emergency peripartum hysterectomy, the increased risk of emergency peripartum hysterectomy should be factored into the decision of whether to proceed with cesarean delivery, particularly for women who desire more children.

Amino acid networks in a (ß/α)8 barrel enzyme change during catalytic turnover.

Proteins can be viewed as small-world networks of amino acid residues connected through noncovalent interactions. Nuclear magnetic resonance chemical shift covariance analyses were used to identify long-range amino acid networks in the α subunit of tryptophan synthase both for the resting state (in the absence of substrate and product) and for the working state (during catalytic turnover). The amino acid networks observed stretch from the surface of the protein into the active site and are different between the resting and working states. Modification of surface residues on the network alters the structural dynamics of active-site residues over 25 Å away and leads to changes in catalytic rates. These findings demonstrate that amino acid networks, similar to those studied here, are likely important for coordinating structural changes necessary for enzyme function and regulation.

Women's experiences, emotional responses, and perceptions of care after emergency peripartum hysterectomy: a qualitative survey of women from 6 months to 3 years postpartum.

BACKGROUND: Little is known of the experience and perceptions of care for survivors of emergency peripartum hysterectomy (EPH), an obstetric event that is increasing in incidence. We sought to explore women's experiences of EPH to make recommendations for care. METHODS: This qualitative study utilized purposive sampling through an online support group of women who experienced EPH. Eligible participants were at least 18 years old, had their hysterectomy at least 6 months but no more than 3 years before the interview, had a surviving infant associated with the delivery, and did not report suicidal ideation. In-depth, semi-structured telephone interviews were conducted and analyzed using Constant Comparative Analysis. Kappa statistics assessed interrater reliability for two independent coders. RESULTS: Fifteen women participated with a mean age of 32.5 years. Most had a cesarean section, with uterine atony as the most common indication for EPH. Kappa statistics indicated near-perfect interrater agreement between two coders, ranging from .82 to .89. Seven major themes were identified: fear; pain; death and dying; numbness or delay in emotional reaction; bonding with baby; communication; and the need for information. Psychological upset occurred postpartum and was often delayed. A major finding is the need for additional follow-up visits to address the emotional after-effects and to fill in gaps in women's understanding and memory of what had occurred. CONCLUSION: Understanding women's experiences with EPH can help practitioners address not only women's initial complications but provide needed long-term support.

Sunlight exposure and cutaneous human papillomavirus seroreactivity in basal cell and squamous cell carcinomas of the skin.

BACKGROUND: Ultraviolet radiation exposure may interact synergistically with cutaneous human papillomavirus (HPV) infection in the development of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin. METHODS: To investigate differences in the risk of sunlight-associated BCC and SCC by cutaneous genus-specific HPV serostatus, a case-control study was conducted among 204 BCC and 156 SCC cases who were recruited from a university dermatology clinic and 297 controls who had no history of cancer and screened negative for current skin cancer. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations between measures of sunlight exposure and BCC/SCC, stratified by genus-specific HPV serostatus, with adjustment for age and sex. RESULTS: Sunburn due to cutaneous sensitivity to sunlight exposure (P = .006) and poor tanning ability (P = .003) were associated with a higher seroprevalence for genus beta HPV types. Poor or no tanning ability was more strongly associated with SCC among individuals who were seropositive for antibodies to cutaneous HPV types in genera alpha (OR, 15.60; 95% CI, 5.40-45.1; P = .01 for interaction) and beta (OR, 6.86; 95% CI, 3.68-12.80; P = .001 for interaction), compared with individuals who were seronegative for these HPV types. CONCLUSIONS: Seropositivity for HPV types in genera alpha or beta increased the risk of SCC associated with poor tanning ability.

Patterns and timing of sunlight exposure and risk of basal cell and squamous cell carcinomas of the skin--a case-control study.

BACKGROUND: Non-melanoma skin cancer (NMSC), comprised of basal (BCC) and squamous (SCC) cell carcinomas, is the most common cancer in Caucasians. Ultraviolet radiation (UVR) exposure is the most important environmental risk factor for NMSC. However, the precise relationship between UVR and the risk of NMSC is complex, and the relationship may differ by skin cancer type. METHODS: A case-control study was conducted among Florida residents to investigate measures of patterns (intermittent vs. continuous) and timing (childhood vs. adulthood) of sunlight exposure in BCC and SCC. Participants included 218 BCC and 169 SCC cases recruited from a university dermatology clinic and 316 controls with no history of skin or other cancers. RESULTS: A history of blistering sunburn (a measure of intermittent sunlight exposure) was associated with both BCC (OR = 1.96, 95% CI = 1.27-3.03) and SCC (OR = 2.02, 95% CI = 1.22-3.33). Additionally, having a job in the sun for ≥ 3 months for 10 years or longer (a measure of continuous sunlight exposure) was also associated with both BCC and SCC in our study population. With the exception of younger age at first blistering sunburn, measures of younger age at sunlight exposure tended to be associated with SCC, but not BCC risk. CONCLUSIONS: Results from the current study suggest that sunlight exposure is associated with both BCC and SCC risk regardless of the pattern in which the exposure was received (i.e. intermittent vs. continuous). The data also suggest that sunlight exposure at a younger age may be more important for SCC but not BCC, however additional studies are needed to further characterize sunlight exposure-response relationships in different types of NMSC.

Newborns With Neonatal Abstinence Syndrome Are Concentrated in Poorer-Quality Hospitals.

OBJECTIVES: To determine the extent to which newborns with neonatal abstinence syndrome (NAS) are concentrated in some hospitals as compared with newborns without NAS and whether care quality and safety differed among these hospitals. We hypothesized that newborns with NAS would be cared for in poorer-quality hospitals. METHODS: Secondary analysis of 3 2016 data sets: (1) the panel study of effects of changes in nursing on patient outcomes-US survey of hospital registered nurses regarding work conditions and safety, (2) inpatient discharge abstracts, and (3) the American Hospital Association annual survey. Newborns in 266 hospitals from the 4 states where the panel study of effects of changes in nursing on patient outcomes was conducted were included. We used Lorenz curves to determine if newborns with NAS were concentrated in different hospitals than newborns without NAS and whether care quality and safety differed among those hospitals. Quality and safety were assessed by staff nurses by using standard survey questions. RESULTS: Of the 659 403 newborns in this study, 3130 were diagnosed with noniatrogenic NAS. We found that newborns with NAS were cared for in different hospitals compared with newborns without NAS (Gini coefficient 0.62, 95% confidence interval, 0.56-0.68) and that the hospitals in which they received care were rated as having poorer quality and safety (Gini coefficient 0.12, 95% confidence interval, 0.01-0.23). CONCLUSIONS: Newborns with NAS are cared for in poorer-quality hospitals than other newborns. Our findings are of concern because poorer-quality care is linked to patient outcomes. As stakeholders seek to address the opioid epidemic and improve outcomes of newborns with NAS, our findings suggest the importance of examining hospital factors.

Distinct conformational dynamics and allosteric networks in alpha tryptophan synthase during active catalysis.

Experimental observations of enzymes under active turnover conditions have brought new insight into the role of protein motions and allosteric networks in catalysis. Many of these studies characterize enzymes under dynamic chemical equilibrium conditions, in which the enzyme is actively catalyzing both the forward and reverse reactions during data acquisition. We have previously analyzed conformational dynamics and allosteric networks of the alpha subunit of tryptophan synthase under such conditions using NMR. We have proposed that this working state represents a four to one ratio of the enzyme bound with the indole-3-glycerol phosphate substrate (E:IGP) to the enzyme bound with the products indole and glyceraldehyde-3-phosphate (E:indole:G3P). Here, we analyze the inactive D60N variant to deconvolute the contributions of the substrate- and products-bound states to the working state. While the D60N substitution itself induces small structural and dynamic changes, the D60N E:IGP and E:indole:G3P states cannot entirely account for the conformational dynamics and allosteric networks present in the working state. The act of chemical bond breakage and/or formation, or possibly the generation of an intermediate, may alter the structure and dynamics present in the working state. As the enzyme transitions from the substrate-bound to the products-bound state, millisecond conformational exchange processes are quenched and new allosteric connections are made between the alpha active site and the surface which interfaces with the beta subunit. The structural ordering of the enzyme and these new allosteric connections may be important in coordinating the channeling of the indole product into the beta subunit.

Within-Hospital Concordance of Opioid Exposure Diagnosis Coding in Mothers and Newborns.

BACKGROUND AND OBJECTIVES: We measured within-hospital concordance of mothers with opioid use disorder (OUD) and newborns with neonatal abstinence syndrome (NAS) or opioid exposure (OE). Secondarily, we described the demographics of mothers and newborns with and without opioid-related diagnoses. METHODS: We used hospital discharge abstracts from California, Florida, New Jersey, and Pennsylvania in 2016. Descriptive statistics were used to compare newborns and mothers with and without opioid-related diagnoses. Within-hospital frequencies of mothers with OUD and newborns with NAS and OE were compared. Pearson's correlation coefficients were calculated. RESULTS: In 474 hospitals, we found 896 702 mothers (0.6% with OUD) and 910 867 newborns (0.47% with NAS, 0.85% with OE, and 0.07% with both). Although the frequency of mothers and newborns with opioid-related diagnoses in a hospital was strongly correlated (r = 0.81), more infants were identified than mothers in most hospitals (68.3%). Mothers with OUD were more likely to be white (79% vs 40.9%), on Medicaid (75.4% vs 44.0%), and receive care in rural hospitals (20.6% vs 17.6%), compared with mothers without OUD. Newborns with NAS had demographics similar to women with OUD. Newborns with OE were disproportionately Black (22% vs 7%) or Hispanic (22% vs 9%). CONCLUSIONS: More newborns are diagnosed with opioid-related disorders than mothers are. Although infants diagnosed with NAS had demographics similar to mothers with OUD, infants with OE were more likely to be Black or Hispanic. The lack of diagnostic coding of maternal OUD and the racial differences in diagnoses warrant attention.

Trends in anticholinergic and opioid dispensing in older adults from 2004 to 2015: Results from the Personality and Total Health (PATH) Through Life Study.

OBJECTIVE: Due to potential adverse effects, guidelines recommend that anticholinergics and opioids be avoided in older adults unless necessary. This study examines the dispensing trends of these medications among older Australians. METHODS: Data of 2222 PATH study (60+ cohort) participants were analysed. Medication dispensing data were obtained from the Pharmaceutical Benefits Scheme from April 2004 to March 2015. Temporal trends of prescriptions dispensed were assessed using joinpoint regression analysis. RESULTS: Of all dispensed prescriptions, 5.5% were for anticholinergics and opioids, and 46.2% of anticholinergics dispensed were anti-depressants. Anticholinergic dispensing trend increased in 2004-2015 (annual per cent change, APC = 3.4%), particularly for moderately anticholinergic medications (APC = 6.8%). Dispensing trend for opioids increased in 2004-2011 (APC = 11.3%) and declined in 2011-2015 (APC = -4.4%). CONCLUSION: While guidelines urge caution in prescribing these medications to older adults, dispensing increased over time in this study population.

Substitution of a Surface-Exposed Residue Involved in an Allosteric Network Enhances Tryptophan Synthase Function in Cells.

Networks of noncovalent amino acid interactions propagate allosteric signals throughout proteins. Tryptophan synthase (TS) is an allosterically controlled bienzyme in which the indole product of the alpha subunit (αTS) is transferred through a 25 Å hydrophobic tunnel to the active site of the beta subunit (ßTS). Previous nuclear magnetic resonance and molecular dynamics simulations identified allosteric networks in αTS important for its function. We show here that substitution of a distant, surface-exposed network residue in αTS enhances tryptophan production, not by activating αTS function, but through dynamically controlling the opening of the indole channel and stimulating ßTS activity. While stimulation is modest, the substitution also enhances cell growth in a tryptophan-auxotrophic strain of Escherichia coli compared to complementation with wild-type αTS, emphasizing the biological importance of the network. Surface-exposed networks provide new opportunities in allosteric drug design and protein engineering, and hint at potential information conduits through which the functions of a metabolon or even larger proteome might be coordinated and regulated.