Search

Objectives: Demand for rapid coagulation testing for massive transfusion events led to development of an emergency hemorrhage panel (EHP; hemoglobin, platelet count, prothrombin time/international normalized ratio, and fibrinogen), with laboratory turnaround time (TAT) of less than 20 minutes. Ten years on, we asked if current laboratory practices were meeting that TAT goal and differences were evident in TAT between the 2 major institutions in our system., Methods: We identified EHPs ordered at our 2 largest hospitals, February 2, 2021, to July 17, 2022, comparing order to specimen draw time, specimen draw to specimen received time, laboratory analytic time, and total TAT results from emergency department and operating room. Site 1 houses a level I trauma center; site 2 includes tertiary care, transplant, and obstetrics services., Results: In total, 1137 EHPs were recorded in our study period. Laboratory TAT was significantly faster at site 1 (~14 vs ~27 minutes, P < .01). Average laboratory TAT was under 20 minutes at site 1 but only for 50% of specimens at site 2. Outlier specimens were collection delays at site 1 and specimen processing delays at site 2., Conclusions: The EHP can be performed as rapidly as described. However, compromises in laboratory location, available personnel, and processing differences can degrade performance., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: To describe the proportion and identify predictors of community-dwelling individuals with traumatic spinal cord injury (TSCI) who were dispensed ≥1 publicly funded opioid in the year after injury using a retrospective cohort study., Setting: Ontario, Canada., Participants, Interventions, Outcome Measures: We used administrative data to identify predictors of receiving publicly funded prescription opioids during the year after injury for individuals who were injured between April 2004 and March 2015. Our outcome was modeled using robust Poisson multivariable regression and we reported adjusted relative risks (aRR) with 95% confidence intervals., Results: In our retrospective cohort of 934 individuals with TSCI who were eligible for the provincial drug program, 510 (55%) received ≥1 prescription opioid in the year after their injury. Most individuals were male (71%) and the median age was 63 years (interquartile range: 42-72). Being male (aRR 1.15, 95% confidence interval [CI] 1.01-1.31), having chronic obstructive pulmonary disease (aRR 1.25, 95% CI 1.05-1.50), and using prescription opioids before injury (aRR 1.46, 95% CI 1.29-1.66) were significantly associated with receiving opioids in the year after TSCI. Short durations of hospital stay after injury were also identified as being a significant risk factor of outpatient opioid use (aRR = 1.28, 95% CI = 1.08-1.51) when compared to longer hospital stays., Conclusion: This study presented evidence showing that most individuals eligible for Ontario's public drug program who experienced a TSCI used opioids in the year following their injury. Due to the paucity of research on this population and their potential for elevated risks of adverse events, it is important for additional studies to be conducted on opioid use in this population to understand short-term and long-term risks and benefits.

Solitary fibrous tumors are mesenchymal fibroblastic tumors that were originally described as intrathoracic lesions but have since been found to occur in many other locations. They may rarely occur as paratesticular masses. Here we present a peculiar case of a solitary fibrous tumor arising in the paratesticular region and exhibiting leiomyoma-like morphology. Confirmation of the tumor as a solitary fibrous tumor was achieved by RNA sequencing showing NAB2::STAT6 fusion. Possible explanations for the unusual tumor morphology include entrapment of normal smooth muscle elements and tumor differentiation into smooth muscle type cells.

Complex medication regimens are highly prevalent, burdensome for residents and staff, and associated with poor health outcomes in residential aged care facilities (RACFs). The SIMPLER study was a non-blinded, matched-pair, cluster randomized controlled trial in eight Australian RACFs that investigated the one-off application of a structured 5-step implicit process to simplify medication regimens. The aim of this study was to explore the processes underpinning study implementation and uptake of the medication simplification intervention. A mixed methods process evaluation with an explanatory design was undertaken in parallel with the main outcome evaluation of the SIMPLER study and was guided by an established 8-domain framework. The qualitative component included a document analysis and semi-structured interviews with 25 stakeholders (residents, family, research nurses, pharmacists, RACF staff, and a general medical practitioner). Interviews were transcribed verbatim and reflexively thematically content analyzed. Descriptive statistics were used to summarize quantitative data extracted from key research documents. The SIMPLER recruitment rates at the eight RACFs ranged from 18.9% to 48.6% of eligible residents (38.4% overall). Participation decisions were influenced by altruism, opinions of trusted persons, willingness to change a medication regimen, and third-party hesitation regarding potential resident distress. Intervention delivery was generally consistent with the study protocol. Stakeholders perceived regimen simplification was beneficial and low risk if the simplification recommendations were individualized. Implementation of the simplification recommendations varied between the four intervention RACFs, with simplification implemented at 4-month follow-up for between 25% and 86% of residents for whom simplification was possible. Good working relationships between stakeholders and new remunerated models of medication management were perceived facilitators to wider implementation. In conclusion, the one-off implicit medication simplification intervention was feasible and generally delivered according to the protocol to a representative sample of residents. Despite variable implementation, recommendations to simplify complex regimens were valued by stakeholders, who also supported wider implementation of medication simplification in RACFs.

Study Design: Cohort study., Objective: To determine the prevalence and to identify predictors of prescription opioid use among persons with nontraumatic spinal cord dysfunction within 1 year after discharge from inpatient rehabilitation., Setting: Ontario, Canada., Methods: We conducted a retrospective cohort study using administrative data to determine predictors of receiving prescription opioids during the 1 year after discharge from inpatient rehabilitation among persons with nontraumatic spinal cord dysfunction between April 1, 2004 and March 31, 2015. We modeled the outcome using a Poisson multivariable regression and reported relative risks with 95% confidence intervals., Results: We identified 3468 individuals with nontraumatic spinal cord dysfunction (50% male) with 67% who were aged ≥66. Over half of the cohort (60%) received opioids during the observation period. Older adults (≥66 years old) were significantly more likely to experience comorbidities (p < 0.05) but less likely to be dispensed opioids following rehabilitation discharge. Being female, previous opioid use before rehabilitation, experiencing lower continuity of care, increasing comorbidity level, low functional status, and having a previous diagnosis of osteoarthritis or mental illness were significant risk factors for receiving opioids after discharge, as shown in a multivariable analysis. Increasing length of rehabilitation stay and higher income were protective against opioid receipt after discharge., Conclusion: Many individuals with nontraumatic spinal cord dysfunction in Ontario are prescribed opioids after discharge from inpatient rehabilitation. This may be problematic due to the number of severe complications that may arise from opioid use and their use in this population warrants future research.

Novel ways to track and verify items of a high value or security is an ever-present need. Taggants made from deoxyribonucleic acid (DNA) have several advantageous properties, such as high information density and robust synthesis; however, existing methods require laboratory techniques to verify, limiting applications. Here, we leverage DNA nanotechnology to create DNA taggants that can be validated in the field in seconds to minutes with a simple equipment. The system is driven by toehold-mediated strand-displacement reactions where matching oligonucleotide sequences drive the generation of a fluorescent signal through the potential energy of base pairing. By pooling different "input" oligonucleotide sequences in a taggant and spatially separating "reporter" oligonucleotide sequences on a paper ticket, unique, sequence-driven patterns emerge for different taggant formulations. Algorithmically generated oligonucleotide sequences show no crosstalk and ink-embedded taggants maintain activity for at least 99 days at 60 °C (equivalent to nearly 2 years at room temperature). The resulting fluorescent signals can be analyzed by the eye or a smartphone when paired with a UV flashlight and filtered glasses.

Study Design: Retrospective cohort study., Objectives: To examine the prevalence of polypharmacy for individuals with nontraumatic spinal cord dysfunction (NTSCD) following inpatient rehabilitation and to determine associated risk factors., Setting: Ontario, Canada., Methods: Administrative data housed at ICES, Toronto, Ontario were used. Between 2004 and 2015, we investigated prescription medications dispensed over a 1-year period for persons following an NTSCD-related inpatient rehabilitation admission. Descriptive and analytical statistics were conducted. Using a robust Poisson multivariable regression model, relative risks related to polypharmacy (ten or more drug classes) were calculated. Main independent variables were sex, age, income quintile, and continuity of care with outpatient physician visits., Results: We identified 3468 persons with NTSCD during the observation window. The mean number of drug classes taken post-inpatient rehabilitation was 11.7 (SD = 6.0), with 4.0 different prescribers (SD = 2.5) and 1.8 unique pharmacies (SD = 1.0). Significant predictors for post-discharge polypharmacy were: being female, lower income, higher comorbidities prior to admission, lower Functional Independence Measure at discharge, previous number of medication classes dispensed in year prior to admission, and lower continuity of care with outpatient physician visits. The most common drugs dispensed post-inpatient rehabilitation were antihypertensives (70.0%), laxatives (61.6%), opioids (59.5%), and antibiotics (57.8%)., Conclusion: Similar to previous research with traumatic spinal cord injury, our results indicate that polypharmacy is prevalent among persons with NTSCD. Additional research examining medication therapy management for NTSCD is suggested.

Rationale/aim: Medication administration is a complex and time-consuming task in residential aged care facilities (RACFs). Understanding the time associated with each administration step may help identify opportunities to optimize medication management in RACFs. This study aimed to investigate the time taken to administer medications to residents, including those with complex care needs such as cognitive impairment and swallowing difficulties., Method: A time-and-motion study was conducted in three South Australian RACFs. A representative sample of 57 scheduled medication administration rounds in 14 units were observed by a single investigator. The rounds were sampled to include different times of day, memory support units for residents living with dementia and standard units, and medication administration by registered and enrolled nurses. Medications were administered from pre-prepared medication strip packaging. The validated Work Observation Method By Activity Timing (WOMBAT) software was used to record observations., Results: Thirty nurses were observed. The average time spent on scheduled medication administration rounds was 5.2 h/unit of average 22 residents/day. The breakfast medication round had the longest duration (1.92 h/unit). Resident preparation, medication preparation and provision, documentation, transit, communication, and cleaning took an average of 5 minutes per resident per round. Medication preparation and provision comprised 60% of overall medication round time and took significantly longer in memory support than in standard units (66 vs 49 seconds per resident per round for preparation, 79 vs 58 for provision; P < .001 for both). Almost half (42%) of tablets/capsules were crushed in memory support units. The time taken for medication administration was not significantly different among registered and enrolled nurses., Conclusions: Nurses took an average of 5 minutes to administer medications per resident per medication round. Medication administration in memory support units took an additional minute per resident per round, with almost half of tablets and capsules needing to be crushed., (© 2020 John Wiley & Sons, Ltd.)

Objectives: To examine prescription opioid claims among individuals with traumatic spinal cord injury (SCI) and to identify factors associated with both chronic opioid and chronic high-dose opioid use., Design: Retrospective cohort study using population-level administrative data., Setting: Ontario, Canada., Participants: Individuals (N=1842) with traumatic SCI between April 1, 2004 and March 31, 2015., Interventions: Not applicable., Main Outcome Measures: Proportion of cohort with chronic opioid use (≥90d supply) and proportion with chronic high-dose opioid use (≥90d supply exceeding 90 mg morphine equivalent) between April 1, 2016 and March 31, 2017 (observation period)., Results: A total of 1842 individuals with traumatic SCI were identified (74% men), with a median age of 51 years (interquartile range [IQR], 34-64y) and median duration of injury of 6 years (IQR, 4-9y). During the observation period, 35% were dispensed at least 1 opioid and 19.8% received chronic opioids, 39% of whom received more than 90 mg daily (chronic high dose). The median daily morphine equivalent dose was 212 mg morphine equivalent (IQR, 135.5-345.3 mg) for chronic high-dose users. Significant risk factors for chronic opioid use were male sex; age between 40 and 60 years; lower income; multimorbidity; thoracic, lumbar, or sacral level of injury; and having a previous diagnosis of osteoarthritis. Risk factors for chronic high-dose opioid use were an extended time since injury, age between 40 and 50 years, and increasing comorbidity., Conclusions: A large proportion of individuals with traumatic SCI were dispensed an opioid in a recent 1-year period. A substantial proportion were dispensed more than 90 mg of morphine equivalents, which is the maximum recommended by the Canadian opioid guideline. Further research is needed to understand the risk factors associated with chronic, high-dose opioid use in this population., (Copyright © 2020 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.)

Purpose: Being able to manage a complex medication regimen is key to older people continuing to live at home. This study determined the feasibility of a multi-component intervention to simplify medication regimens for people receiving community-based home care services., Patients and Methods: Research nurses recruited people receiving community-based home care services to participate in this non-randomized pilot and feasibility study (Australian New Zealand Clinical Trials Registry ACTRN12618001130257). Participants received a one-off clinical pharmacist intervention comprising medication reconciliation, assessment of capacity to self-manage medications, and application of a structured 5-step tool to identify medication simplification opportunities. A mixed-methods feasibility assessment with an explanatory design was undertaken to assess recruitment, protocol adherence and stakeholder acceptability. Data from interviews with 12 stakeholders were thematically analyzed. Secondary outcome measures, including medication discrepancies, and changes in number of medication administration times per day, quality of life, medication adherence and health service utilization, were determined over a 4-month follow-up., Results: Twenty-five out of the target 50 participants were recruited. Initial recruitment was impacted by apparent uncertain role responsibilities in medication management, with some clients who declined to participate perceiving they would be unlikely to benefit or being reluctant to change regimens. However, with few exceptions, participants who received intervention did so with a high degree of protocol adherence and acceptability. Stakeholders valued the intervention and supported wider implementation. Discrepancies between the baseline medication history from the general medical practitioner and the pharmacist-compiled "best possible medication history" were identified for all participants' regimens (median of 6 per participant), with one-third resolved at follow-up. Simplification was possible for 14 participants (56%) and implemented for 7 (50%) at follow-up. No significant changes in other secondary outcomes were observed., Conclusion: The intervention was delivered as planned, and valued by stakeholders. Recruitment barriers should be addressed before wider implementation., Competing Interests: This study was funded through the NHMRC CDPC and the community-based home care provider organization involved in this research is one of the NHMRC CDPC funding partners. The authors report grants from the National Health and Medical Research Council Cognitive Decline Partnership Centre, during the conduct of the study. JKS is supported by an NHMRC Early Career Fellowship. JSB is supported by an NHMRC Dementia Leadership Fellowship. MC, JVE, MH and TC are employed by the organization providing the community-based home care services., (© 2020 Sluggett et al.)

Objective: Canada's cesarean delivery (CD) rate continues to increase. The Society of Obstetricians and Gynaecologists of Canada advocates the use of the modified Robson classification for comparisons. This study describes national and provincial CD rates according to this classification system., Methods: All 2016-2017 in-hospital births in Canada (outside Québec) reported to the Discharge Abstract Database were categorized using the modified Robson classification system. CD rates, group size, and contributions of each group to the overall volume of CD were reported. Rates by province and hospital peer group were also examined (Canadian Task Force Classification III)., Results: A total of 286 201 women gave birth; among these, 83 262 (29.1%) had CDs. Robson group 5 (term singleton previous CD) had a CD rate of 80.5% and was the largest contributing group to the overall number of CD (36.6%). Women whose labour was induced (Robson group 2A) had a CD rate almost double the rate of women with spontaneous labour (Robson group 1): 33.5% versus 18.4%. These latter two groups made the next largest contributions to overall CD (15.7% and 14.1%, respectively). There were substantial variations in CD rates across provinces and among hospital peer groups., Conclusion: The study found large variations in CD rates across provinces and hospitals within each Robson group, thus suggesting that examining variations to determine the groups contributing the most to CD rates (Robson groups 5, 2A, and 1) may provide valuable insight for reducing CD rates. This study provides a benchmark for measuring the impact of future initiatives to reduce CD rates in Canada., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

The licensed pharmaceutical industry and regulators use many approaches to control counterfeiting, but it remains a very difficult task to differentiate between counterfeit and real products. Moreover, there is a lack of techniques available for providing a batch specific molecular bar code for tablets that has the required traceability, specificity and sensitivity to be fit for purpose. The aim of this study was to evaluate DNA molecular tags as a potential anti-counterfeiting technology in tablets. Lactose tablets (400 mg) were used as a model to investigate incorporation DNA molecular tag into a solid dosage form: DNA authentication was carried out on an Applied DNA SigNify® qPCR instrument. Tablet batches were subjected to accelerated stability conditions (40 °C and 75% RH) for up to 6 months. All batches passed the monograph specifications of the British Pharmacopoeia (hardness, friability and mass uniformity) throughout the storage period. In all of recovery plots, the number of cycles required for DNA detection (Cq values) increased as a function of storage time, which indicated a reduction in tag levels, but it should be noted for all storage experiments the tag was clearly detected. It would appear that DNA molecular tags could feasibly be applied within the pharmaceutical development cycle when a new solid dosage form is brought to the market so as to mitigate the risk and dangers of counterfeiting., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Rationale: Inhaled corticosteroids (ICS) are established medications for the management of both asthma and chronic obstructive pulmonary disease (COPD), two common chronic airway diseases. However, there is still uncertainty with respect to their use in some cases, specifically in older adults with asthma, people with concurrent asthma and COPD, and some people with COPD (given the association of ICS with pneumonia). Objectives: To compare the effectiveness and safety of ICS in older adults with asthma, COPD, or features of both in a real-word setting. Methods: In this retrospective longitudinal population cohort study, individuals 66 years of age or older in Ontario, Canada, who met a validated case definition of physician-diagnosed COPD and/or asthma between 2003 and 2014 were followed until March 2015 through provincial health administrative data. Overlap in COPD and asthma diagnoses was permitted and stratified for in subgroup analyses. The exposure was new receipt of ICS. The primary effectiveness and safety outcomes were hospitalizations for obstructive lung disease (OLD) and hospitalizations for pneumonia, respectively. Propensity scores were used to adjust for confounders. Results: The study included 87,690 individuals with asthma (27% with concurrent COPD) and 150,593 individuals with COPD (25% with concurrent asthma). In terms of effectiveness, controlling for confounders, ICS was associated with fewer hospitalizations for OLD (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.79-0.88) in subjects with asthma alone, with concurrent COPD attenuating the benefit. A similar association was seen in subjects with COPD and concurrent asthma (HR, 0.88; 95% CI, 0.84-0.92), but not in those with COPD alone, where ICS receipt had little impact on hospitalizations. In terms of safety, ICS receipt was associated with a marginally increased risk of pneumonia hospitalizations in people with COPD and no asthma (HR, 1.03; 95% CI, 1.00-1.06), but not in the other groups. Conclusions: ICS was associated with fewer hospitalizations for OLD in older adults with asthma and concurrent asthma and COPD, but had little impact on OLD and pneumonia hospitalizations in those with COPD alone.

A small PCR-generated DNA fragment was introduced into a pharmaceutical grade ink as a molecular taggant, and the DNA tagged ink was delivered onto the surface of capsules by standard high-speed offset printing. The amount of DNA in the ink on each capsule is roughly 10-12 fold lower than that allowed as safe by the United States Food and Drug Administration (FDA) and the WHO with regards to acceptable limits of residual DNA. The printed ink on the capsule surface was sampled by swabbing, followed by direct analysis of the DNA-swab complex, without subsequent DNA purification. It was shown that DNA recovered from the ink by swabbing was suitable for PCR-CE analysis-a widely used method in forensic science and was also suitable for qPCR and isothermal DNA amplification, when coupled with portable devices similar to those used for environmental sampling and food safety testing. The data set a precedent: A small DNA fragment could be introduced as an excipient into a pharmaceutical application, and thereafter tracked through the pharmaceutical supply chain via forensic DNA authentication., Competing Interests: This study was funded by Applied DNA Sciences, Inc. http://adnas.com/. All authors are employed by Applied DNA Sciences, Inc. The work related to this publication is in product development to be commercialized in the upcoming year. The following patent is pending [Method for authenticating active pharmaceutical ingredients - US20180016627A1]. There are no further patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on financial disclosure, competing interest, sharing data and materials.

Background: Owing to lack of adequate healthcare financing, access to at least the basic health services is still a problem in Ethiopia. With the intention of raising funds and ensuring universal health coverage, a mandatory health insurance scheme has been introduced. The Community Based Health Insurance has been implemented in all regions of the country, while implementation of social health insurance was delayed mainly due to resistance from public servants. This study was, therefore, aimed to assess willingness to pay for social health insurance and its determinant factors among public servants in Mekelle city, Northern Ethiopia., Methods: A concurrent mixed approach of cross-sectional study design using double bound dichotomous choice contingent valuation method and qualitative focus group discussions was employed. A total 384 public servants were recruited from randomly selected institutions and six focus group discussions (n = 36) were carried out with purposively selected respondents. Participants' mean willingness to pay (WTP) and independent predictors of WTP were identified using an interval data logit model. Qualitative data were analyzed using thematic analysis., Results: From the 384 participants, 381 completed the interview, making a response rate of 99.2%. Among these respondents 85.3% preferred social health insurance and were willing to pay for the scheme. Their estimated mean WTP was 3.6% of their monthly salary. Lack of money to pay (42.6%) was the major stumbling block to enrolling in the scheme. Respondents' WTP was significantly positively associated with their level of income but their WTP decreased with increasing age and educational status. On the other hand, a majority of focus group discussion participants were not willing to pay the 3% premium set by the government unless some preconditions were satisfied. The amount of premium contribution, benefit package and poor quality of health service were the major factors affecting their WTP., Conclusion: The majority of the public servants were willing to be part of the social health insurance scheme, with a mean WTP of 3.6% of their monthly salary. This was greater than the premium proposed by the government (3%). This can pave the way to start the scheme but attention should focus on improving the quality of health services.

Study Design: Retrospective cohort study., Objectives: The objectives for this study were to examine the prevalence of polypharmacy for people with traumatic spinal cord injury (SCI) following injury and to determine risk factors., Setting: Ontario, Canada METHODS: We used provincial-level administrative health services data of publicly funded healthcare encounters housed at the Institute for Clinical Evaluative Sciences, Toronto, Ontario. We examined prescription medications dispensed over a 1 year period post injury for persons 66+ years with an index traumatic SCI between 2004 and 2014. Polypharmacy was defined as being on 10 or more drug classes. Descriptive and analytical statistics were conducted. Relative risks and 95% confidence limits for factors related to polypharmacy were calculated using a robust Poisson multivariate regression model., Results: We identified 418 cases of persons with traumatic SCI during the observation window. A total of 233 patients (56%) were taking at least 10 drug classes in the year following discharge from care for traumatic SCI. The mean number of drug classes taken post injury was 11 (SD = 6). Continuity of care was significantly associated with polypharmacy, with a higher continuity of care (having at least 75% of visits with the same doctor) reducing the risk of polypharmacy. The most common drugs prescribed were laxatives, opioids and cardiovascular-related drugs., Conclusion: Findings suggest that polypharmacy is extensive among older adults with traumatic SCI. Persons with better continuity of care are less likely to have polypharmacy compared to those with less continuity., Sponsorship: This project was funded by a Connaught New Investigator Award (University of Toronto), and the Craig H. Neilsen Foundation Psychosocial Research Pilot Grant (Grant #441259).

Major advances in understanding the diversity, distribution, and activity of marine N 2 -fixing microorganisms (diazotrophs) have been made in the past decades, however, large gaps in knowledge remain about the environmental controls on growth and mortality rates. In order to measure diazotroph net growth rates and microzooplankton grazing rates on diazotrophs, nutrient perturbation experiments and dilution grazing experiments were conducted using free-floating in situ incubation arrays in the vicinity of Station ALOHA in March 2016. Net growth rates for targeted diazotroph taxa as well as Prochlorococcus, Synechococcus and photosynthetic picoeukaryotes were determined under high (H) and low (L) nitrate:phosphate (NP) ratio conditions at four depths in the photic zone (25, 45, 75, and 100 m) using quantitative PCR and flow cytometry. Changes in the prokaryote community composition in response to HNP and LNP treatments were characterized using 16S rRNA variable region tag sequencing. Microzooplankton grazing rates on diazotrophs were measured using a modified dilution technique at two depths in the photic zone (15 and 125 m). Net growth rates for most of the targeted diazotrophs after 48 h were not stimulated as expected by LNP conditions, rather enhanced growth rates were often measured in HNP treatments. Interestingly, net growth rates of the uncultivated prymnesiophyte symbiont UCYN-A1 were stimulated in HNP treatments at 75 and 100 m, suggesting that N used for growth was acquired through continuing to fix N 2 in the presence of nitrate. Net growth rates for UCYN-A1, UCYN-C, Crocosphaera sp. (UCYN-B) and the diatom symbiont Richelia (associated with Rhizosolenia ) were uniformly high at 45 m (up to 1.6 ± 0.5 d -1 ), implying that all were growing optimally at the onset of the experiment at that depth. Differences in microzooplankton grazing rates on UCYN-A1 and UCYN-C in 15 m waters indicate that the grazer assemblage preyed preferentially on UCYN-A1. Deeper in the water column (125 m), both diazotrophs were grazed at substantial rates, suggesting grazing pressure may increase with depth in the photic zone. Constraining in situ diazotroph growth and mortality rates are important steps for improving parameterization for diazotrophs in global ecosystem models.

Androgen-deprivation therapy (ADT) is an effective treatment for men with advanced prostate cancer, but loss of bone mineral density (BMD) is a major risk factor for fractures. This review compared the efficacy of available treatments to provide prescribing guidance to healthcare professionals. This is the first review to compare the effectiveness of different osteoporotic treatments (bisphosphonates, denosumab, toremifene, and raloxifene) on BMD in patients with non-metastatic prostate cancer on ADT using network meta-analysis. Results suggest that all evaluated treatments are effective in improving BMD compared to placebo. Zoledronic acid (ZA) was found to have a greater improvement in BMD compared to other active treatments at all three studied sites, except for risedronate, which had better BMD improvement compared to ZA at the femoral neck site in one small study. Our study did not identify evidence that one drug is unequivocally more effective than another. All drugs appeared to be effective in reducing the rate of bone loss. Healthcare professionals should also consider patient preference, costs, and local availability as part of the decision process., (© 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.)

Health utilities are a preference-based measure of health-related quality of life that facilitates comparison of disease burden across conditions. We estimated utilities using a population-based, matched sample of adolescents and adults with and without chronic pain, controlling for comorbidity. Ontarians aged ≥12 years with and without chronic pain were identified from the Canadian Community Health Survey (CCHS) 2000-2001 and 2009-2010 and linked to their provincial health care administrative data. Individuals with chronic pain were matched to those without using age, sex, survey year, and a propensity score for having chronic pain estimated from a rurality index, income quintile, and comorbidity. The Health Utilities Index Mark 3 instrument, included in the Canadian Community Health Survey, was used. Mean utilities were calculated for each group. Utility decrement for chronic pain was also calculated for each matched pair. A total of 65,246 responses were available for analysis. After matching, there were 12,146 matched pairs with and without pain. In the matched cohort, mean age was 54 years (SD 12); 61% were female. The matched cohort with chronic pain had a mean utility of 0.59 (95% confidence interval 0.58-0.59), and the decrement associated with chronic pain was 0.32 (95% confidence interval 0.31-0.32). Utilities in people with chronic pain were lower than, and decrements larger than, those seen with most other chronic diseases including heart disease, diabetes, and chronic obstructive pulmonary disease. These data will be useful to inform priorities and future strategies for the prevention and control of chronic pain.

Little is known about the economic burden of chronic pain and how chronic pain affects health care utilization. We aimed to estimate the annual per-person incremental medical cost and health care utilization for chronic pain in the Ontario population from the perspective of the public payer. We performed a retrospective cohort study using Ontario health care databases and the electronically linked Canadian Community Health Survey (CCHS) from 2000 to 2011. We identified subjects aged ≥12 years from the CCHS with chronic pain and closely matched them to individuals without pain using propensity score matching methods. We used linked data to determine mean 1-year per-person health care costs and utilization for each group and mean incremental cost for chronic pain. All costs are reported in 2014 Canadian dollars. After matching, we had 19,138 pairs of CCHS respondents with and without chronic pain. The average age was 55 years (SD = 18) and 61% were female. The incremental cost to manage chronic pain was $1742 per person (95% confidence interval [CI], $1488-$2020), 51% more than the control group. The largest contributor to the incremental cost was hospitalization ($514; 95% CI, $364-$683). Incremental costs were the highest in those with severe pain ($3960; 95% CI, $3186-$4680) and in those with most activity limitation ($4365; 95% CI, $3631-$5147). The per-person cost to manage chronic pain is substantial and more than 50% higher than a comparable patient without chronic pain. Costs are higher in people with more severe pain and activity limitations.

Background: Stable dry-state storage of DNA is desirable to minimize required storage space and to reduce electrical and shipping costs. DNA purified from various commercially available dry-state stabilization matrices has been used successfully in downstream molecular applications (e.g., quantitative polymerase chain reaction [qPCR], microarray, and sequence-based genotyping). However, standard DNA storage conditions still include freezing of DNA eluted in aqueous buffers or nuclease-free water. Broad implementation of dry-state, long-term DNA storage requires enhancement of such dry-state DNA stabilization products to control for temperature fluctuations at specimen collection, transit, and storage. This study tested the integrity of genomic DNA subjected to long-term storage on GenTegra(™) DNA stabilization matrices (GenTegra LLC, Pleasanton, CA) at extreme conditions, as defined by a 4-year storage period at ambient temperature with an initial incubation for 7 months at 37°C, 56°C, or ambient temperature. Subsequently, purified DNA performance and integrity were measured by qPCR and next-generation sequencing (NGS)-based human leokocyte antigen (HLA) genotyping., Results: High molecular weight genomic DNA samples were recovered from the GenTegra product matrix and exhibited integrity comparable to a highly characterized commercial standard under assessment by qPCR. Samples were genotyped for classical HLA loci using next generation sequencing-based methodolgy on the Roche 454 GS Junior instrument. Amplification efficiency, sequence coverage, and sequence quality were all comparable with those produced from a cell line DNA sequenced as a control. No significant differences were observed in the mean, median, or mode quality scores between samples and controls (p≥0.4)., Conclusions: Next generation HLA genotyping was chosen to test the integrity of GenTegra-treated genomic DNA due to the requirment for long sequence reads to genotype the highly polymorphic classical HLA genes. Experimental results demonstrate the efficacy of the GenTegra product as a suitable genomic DNA preservation tool for collection and long-term biobanking of DNA at fluctuating and high temperatures.

Background: Studies of vapocoolants for pain reduction from venipuncture have demonstrated conflicting results., Objective: Our aim was to systematically review the literature regarding the analgesic effectiveness of vapocoolants in children and adults., Methods: We searched MEDLINE, EMBASE, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Cochrane Central Register of Trials using key words: vapocoolant, pain, venipuncture, and cannulation. We included randomized or quasi-randomized studies comparing vapocoolants to placebo or no treatment. Two authors reviewed titles and abstracts and extracted data. Quality was assessed by consensus using the Cochrane risk of bias tool. The primary outcome was self-reported pain using a 100-mm visual analog scale, a 0- to 10-point numerical scale, or observational scale for preverbal children. Data were pooled using a random effects model., Results: Twelve studies including 1266 patients (509 children, 757 adults) were identified. No significant pain reduction was found in children receiving vapocoolants vs. placebo or no treatment (mean difference -10 mm; 95% confidence interval [CI] -26 to 6). In adults, less pain was reported when vapocoolants were compared with no treatment: -10 mm on a 100-mm scale (95% CI -17 to -4); but not when compared to placebo (-12 mm; 95% CI -26 to 2). Pain from application of vapocoolants was greater than placebo (8 mm; 95% CI 4 to 2)., Conclusions: Vapocoolants were ineffective in children and adults when compared to placebo, and effective in adults only when compared to no treatment. The magnitude of effect was low and was offset by increased pain from application. They cannot be recommended for routine use in children or adults., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Clinician-led tactile stimulation (rubbing the skin adjacent to the injection site or applying pressure) has been demonstrated to reduce pain in children and adults undergoing vaccination., Objective: To evaluate the analgesic effectiveness of clinician-led tactile stimulation in infants undergoing vaccination., Methods: This was a partially blinded randomized controlled trial that included infants undergoing vaccination in a private clinic in Toronto. Infants were randomly allocated to tactile stimulation or no tactile stimulation immediately prior to, during, and after vaccination. The primary outcome was infant pain, assessed using a validated observational measure, the Modified Behavioral Pain Scale (MBPS; range = 0-10)., Results: Altogether, 121 infants participated (n = 62 tactile stimulation; n = 59 control); demographics did not differ (P > .05) between groups. MBPS scores did not differ between groups: mean = 7.2 (standard deviation = 2.4) versus 7.6 (1.9); P = .245., Conclusion: Tactile stimulation cannot be recommended as a strategy to reduce vaccination pain in infants because of insufficient evidence of a benefit., (© The Author(s) 2014.)

Objective: To determine the effectiveness of parent-led tactile stimulation for pain reduction when added to a combination of evidence-based pain-reducing interventions in infants undergoing immunization injections., Methods: Healthy infants aged 4 to 6 months undergoing routine immunization at a primary care practice were eligible. Infants were randomized to tactile stimulation by a parent or usual care. Parents in the tactile stimulation group rubbed the ipsilateral thigh distal to the site for 15 seconds before, during, and after injections. In addition, all infants received evidence-based pain-relieving interventions including: sucrose solution, holding by a parent, and intramuscular injection without aspiration. The primary outcome was pain, measured by a validated tool, the Modified Behavioral Pain Scale (MBPS), by an observer unaware of treatment allocation using videotapes of the procedure. MBPS scores could range from 0 (no pain) to 10 (maximum pain). Parents, unaware of the study hypothesis, also rated infant pain in real time using a 100 mm visual analogue scale., Results: One hundred twenty infants participated. Infant characteristics did not differ (P>0.05) between the tactile stimulation and control groups. Mean MBPS scores and parent visual analogue scale scores did not differ between groups (8.2 [1.1] vs. 8.0 [1.3]; P=0.57) and (60 [20] vs. 53 [22] mm; P=0.10), respectively., Discussion: Parent-led tactile stimulation did not reduce pain in infants undergoing immunization injections when combined with other pain-relieving interventions. Potential reasons for the lack of effectiveness are discussed. Investigation of the effectiveness of clinician-led tactile stimulation in this population is recommended.

Background: The deep inferior epigastric artery perforator (DIEP) free flap is the optimal autogenous reconstructive technique in many patients undergoing postmastectomy. Our aim was to evaluate the standard DIEP free flap design in relation to the dominant perforating vessels using computed tomography angiography (CTA)., Methods: We retrospectively reviewed CTAs from 75 patients who had undergone perforator flap reconstruction within the past year. Locations of the largest perforator with a minimum diameter of 2.0 mm piercing the anterior rectus fascia were recorded., Results: Of 150 hemiabdomens reviewed, 146 (97.3%) had a dominant perforator. The median location for the dominant perforator was 3.3 cm lateral and 0.9 cm below the umbilicus. One hundred twenty-one (83%) of the dominant perforators arose within 3 cm of the umbilicus. One hundred one (69%) arose at or below the level of the umbilicus. Forty-five (31%) arose above the level of the umbilicus. Thirteen (9%) arose more than 2 cm above the umbilicus., Conclusions: The standard DIEP flap design incorporates most of the dominant perforating vessels. However, a significant number of perforators arise at or above the umbilicus, which would be near the edge or out of the standard design of the DIEP. Our findings support the use of preoperative CTA in the evaluation of patients undergoing DIEP free flap reconstruction. Modification of flap design to include the dominant perforating vessels should be considered when the dominant vessel is outside the standard design of the DIEP.

Background: A previous audit performed at a tertiary ⁄ quaternary pediatric hospital in Toronto, Ontario, demonstrated suboptimal assessment and treatment of children's pain. Knowledge translation (KT) initiatives (education, reminders, audit and feedback) were implemented to address identified care gaps; however, the impact is unknown., Objectives: To determine the impact of KT initiatives on pain outcomes including process outcomes (eg, pain assessment and management practices) and clinical outcomes (eg, pain prevalence and intensity); and to benchmark additional pain practices, particularly opioid administration and painful procedures., Methods: Medical records at The Hospital for Sick Children (Toronto, Ontario) were reviewed on a single day in September 2007. Pain assessment and management practices, and pain prevalence and intensity in the preceding 24 h were recorded on a standardized data collection form. Where possible, pain outcomes were compared with previous audit results., Results: Records of 265 inpatients were audited. Sixty-three per cent of children underwent a documented pain assessment compared with 27% in an audit conducted previously (P<0.01). Eighty-three per cent of children with documented pain received at least one pain management intervention. Overall, 51% of children received pharmacological therapy, and 15% received either a psychological or physical pain-relieving intervention. Of those assessed, 44% experienced pain in the previous 24 h versus 66% in the previous audit (P<0.01). Fewer children experienced severe pain compared with the first audit (8.7% versus 26.1%; P<0.01). One-third of children received opioids; 19% of these had no recorded pain assessment. Among 131 children who underwent a painful procedure, 21% had a concurrent pain assessment. Painful procedures were accompanied by a pain-relieving intervention in 12.5% of cases., Conclusions: Following KT initiatives, significant improvements in pain processes (pain assessment documentation and pain management interventions) and clinical outcomes (pain prevalence, pain intensity) were observed. Further improvements are recommended, specifically with respect to procedural pain practices and opioid utilization patterns.

Objective: Pain from vaccine injections remains undertreated, despite the availability of numerous pain-relieving strategies. Healthcare providers report lack of time within current office workflows as a major barrier to routine pain management. The objective was to document the total time involved in outpatient vaccine appointments to test the hypothesis that offering pain-relieving strategies can be practically implemented when considering the element of time to vaccine injection., Patients and Methods: Prospective naturalistic study in 8 urban outpatient primary care clinics (4 pediatric and 4 family practice) in Toronto. For 48 to 59 consecutive childhood vaccination appointments at each site, child waiting time from clinic arrival until first vaccine injection was tracked., Results: Altogether, 405 vaccine appointments were included. The median age of the child undergoing vaccination was 12 months. The mean (SD) time from clinic arrival until first vaccine injection was 41.6 minutes (20.9), with a range of 7 to 132 minutes. Linear regression identified a significant (P<0.05) difference according to clinic [ranging from 19.4 min (6.5) to 57.5 min (20.2)] and number of family members in the appointment [ranging from 40.6 min (21.0) for an appointment in the index child only to 50 min (14.3) for an appointment in the index child and 2 other family members]., Conclusions: Contrary to healthcare provider perceptions, the timing of outpatient childhood vaccine appointments allows for the inclusion of pain management interventions. Efforts should now focus on educating healthcare providers and parents about the value of pain management and how to implement evidence-based strategies.

Study Objective: Local anesthetics are the main class of analgesics used for pain management during laceration repair and other minor surgeries; however, they are administered by injection, which is painful. Warming local anesthetics has been proposed as a cost-free intervention that reduces injection pain. A systematic review of the effectiveness of this technique has not yet been undertaken. We determine the effectiveness of warming local anesthetics to reduce pain in adults and children undergoing local anesthetic infiltration into intradermal or subcutaneous tissue., Methods: We used published articles from MEDLINE (1950 to June 2010), EMBASE (1980 to June 2010), CINAHL (1982 to June 2010), the Cochrane Library (second quarter 2010), International Pharmaceutical Abstracts (1970 to June 2010), and ProQuest Dissertations and Theses database (1938 to June 2010). We included studies with randomized or pseudorandomized designs and healthy subjects or patients receiving subcutaneous or intradermal injection of local anesthetics that were warmed (body temperature) or not (room temperature). Studies of regional anesthesia and intraarticular, spinal, or periorbital administration of local anesthetics were excluded. Data were extracted onto predesigned forms and verified by 2 reviewers. Quality was assessed with the Cochrane risk of bias tool. The primary outcome was self-reported pain as assessed by a visual analog or numeric rating scale. Data were combined with mean differences with 95% confidence intervals (CIs) by using a random-effects model., Results: Twenty-nine studies were retrieved for close examination and 19 studies met inclusion criteria. A total of 18 studies with 831 patients could be included in a meta-analysis. Seventeen studies had an unclear risk of bias and 1 had a high risk of bias. A mean difference of -11 mm (95% CI -14 to -7 mm) on a 100-mm scale was found in favor of warming local anesthetics. Subgroup analysis of 8 studies investigating the effect of warming on buffered local anesthetics yielded similar results: -7 mm (95% CI -12 to -3 mm)., Conclusion: Warming local anesthetics leads to less pain during injection and therefore should be done before administration., (Copyright © 2011 American College of Emergency Physicians. Published by Mosby, Inc. All rights reserved.)

Objective: To determine the relative effectiveness of liposomal lidocaine, sucrose, and their combination for reducing pain in term newborns., Methods: Ours was a double-blind, randomized, controlled, double-dummy trial of 330 healthy term newborns. Before venipuncture for the newborn screening test, neonates received (1) 1 g of liposomal lidocaine cream topically, (2) 2 mL of 24% sucrose solution orally, or (3) sucrose and liposomal lidocaine. The facial grimacing score (0-100) was used to assess pain. Adverse events and lidocaine levels were used to assess safety., Results: Infant characteristics did not differ among groups. Facial grimacing scores were lower in the sucrose group compared with those in the liposomal lidocaine group (mean difference: -27 [95% confidence interval (CI): -36 to -19; P < .001) and for the sucrose plus liposomal lidocaine group compared with those in the liposomal lidocaine group (mean difference: -23 [95% CI: -31 to -14]; P < .001). The sucrose and sucrose plus liposomal lidocaine groups did not differ (mean difference: -5 [95% CI: -13 to 4]; P = .3). Local skin reactions were not observed, and the incidence of spitting up did not differ between sucrose-exposed and non-sucrose-exposed infants (1.4% vs 2.7%, respectively; P = .22). The mean (SD) plasma lidocaine level was 44.6 (55.3) ng/mL., Conclusions: Sucrose was more effective than liposomal lidocaine for reducing pain during venipuncture in newborns. The addition of liposomal lidocaine to sucrose did not confer any additional benefit to sucrose alone. There was no evidence of harm from liposomal lidocaine or sucrose.

There is a need to identify a primary measure of infant pain that can be used to assess pain in infants undergoing vaccine injections in order to facilitate vaccine outcomes research. The aim of the present study was to determine the reliability, validity and practicality of 3 measures of acute pain in infants; the Modified Behavioural Pain Scale (MBPS), Neonatal Infant Pain Scale (NIPS), and Face Legs Activity Cry Consolability Scale (FLACC). Five raters rated pain from videotapes in 120 infants aged 2-6 months undergoing vaccine injections that participated in a randomized controlled trial designed to compare pain responses between two vaccines, DPTaP-Hib vaccine and PCV vaccine. Inter-rater reliability coefficients for baseline and vaccine injections were all greater than 0.85. Cronbach's alpha ranged from 0.83 to 0.94. Construct validity was demonstrated for all measures by vaccine injection scores that were higher (p<0.001) than baseline scores and by PCV scores that were higher than DPTaP-Hib scores. Concurrent validity was demonstrated by bi-variate correlation coefficients that ranged from 0.84 to 0.92. Intra-rater reliability coefficients for scores obtained after a single viewing (simulating real time assessment) versus multiple viewings were ≥ 0.96. All measures demonstrated a significant difference in pain scores between the more painful (PCV) and less painful (DPTaP-Hib) vaccine for scores obtained after a single viewing. The majority of raters (4 out of 5) preferred the MBPS. Together, these results provide preliminary support for the MBPS as the primary outcome of pain during vaccine injections in infants., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Research indicates that life events involving goal attainment and goal striving trigger hypomania/mania and that negative life events trigger bipolar depression. These findings are consistent with the behavioral approach system (BAS) dysregulation model of bipolar disorders, which suggests that individuals with bipolar disorders are hypersensitive to cues signaling opportunity for reward and cues signaling failure and loss of rewards. However, no studies to date have investigated whether individuals with bipolar spectrum disorders experience increased rates of these BAS-relevant life events, which would place them at double risk for developing bipolar episodes. The present study found that individuals with bipolar II disorder and cyclothymia experience increased rates of BAS-activating and BAS-deactivating, but not goal-attainment, life events. Finally, for bipolar spectrum individuals only, BAS-activating events predicted BAS-deactivating events' rates., (Copyright 2010 APA, all rights reserved)

Although immunization injections are the most common painful medical procedures, pain-relieving interventions are not routinely used. In this randomized controlled trial, we compared the effectiveness of topical anesthesia using liposomal lidocaine to: (1) vapocoolant spray using a proprietary blend of 1,1,1,3,3-pentafluoropropane and 1,1,1,2-tetrafluoroethane; (2) nurse-administered tactile stimulation; or (3) self-directed distraction by means of reading a magazine. Liposomal lidocaine was more effective (p

Objective: To evaluate the effectiveness of different pain-relieving interventions to reduce pain from immunization in adults., Data Sources: MEDLINE (1950 to October Week 3 2008) PsycINFO (1967 to December Week 1 2008), CINAHL (1982 to October Week 4 2008), EMBASE (1980 to 2008 Week 43) and the Cochrane Central Register of Controlled Trials (3rd Quarter 2008)., Review Methods: Databases were searched for trials of pharmacological, behavioural, physical or operator-dependant techniques to reduce pain from immunization in adults. The primary outcome was pain as assessed by visual analogue scale or other numeric rating scale., Results: Six studies representing 853 participants were identified. One study evaluating pharmacological interventions (lidocaine-prilocaine) found them to be effective in reducing pain from immunization. Similarly, two studies evaluating physical pain relieving techniques, either skin cooling interventions (Fluori-Methane) or tactile stimulation (manual pressure at the site of injection) found them to reduce pain. One study of jet injectors found them to be more painful than conventional needle and syringe. Neither freezing needles nor warming vaccines was found to be effective in reducing pain. No studies investigated psychological interventions or oral analgesics (acetaminophen and ibuprofen)., Conclusion: There was limited evidence to support the use of lidocaine-prilocaine, Fluori-Methane and manual pressure for reducing immunization pain in adults. There was limited evidence of more pain with jet injectors compared to needle and syringe. Due to limited data, we recommend further investigation of methods to reduce immunization pain in adults, primarily psychological and physical techniques., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Bipolar disorders and substance use disorders (SUDs) show high co-occurrence. One explanation for this co-occurrence may be common personality vulnerabilities involved in both. The authors tested whether high behavioral approach system (BAS) sensitivity and impulsiveness are shared personality vulnerabilities in bipolar spectrum disorders and substance use problems and their co-occurrence in a longitudinal study of 132 individuals on the bipolar spectrum and 153 control participants. At Time 1, participants completed the Behavioral Inhibition System/BAS Scales and the Impulsive Nonconformity Scale. Substance use problems were assessed via the Michigan Alcoholism Screening Test and the Drug Abuse Screening Test at 4-month intervals for 1 year. Participants with bipolar disorder had higher rates of lifetime SUDs and substance use problems during the follow-up, relative to control participants. In line with hypotheses, higher BAS sensitivity and impulsiveness predicted bipolar status and increased substance use problems prospectively. BAS total, BAS Fun Seeking, and impulsiveness mediated the association between bipolar spectrum status and prospective substance use problems, with impulsiveness as the most important mediator. High BAS sensitivity and impulsiveness may represent shared personality vulnerabilities for both disorders and may partially account for their co-occurrence., ((c) 2009 APA, all rights reserved).)

The authors examined concurrent and prospective associations of behavioral approach system (BAS)-relevant and non-BAS-relevant cognitive styles with bipolar spectrum disorders. Controlling for depressive and hypomanic/manic symptoms, 195 individuals with bipolar spectrum disorders scored higher than 194 demographically similar normal controls on BAS sensitivity and BAS-relevant cognitive dimensions of performance concerns, autonomy, and self-criticism, but not on behavioral inhibition system sensitivity and non-BAS-relevant dimensions of approval seeking, sociotropy, and dependency. Moreover, group differences on autonomy fully mediated the association between higher BAS sensitivity and bipolar status. In addition, only BAS-related cognitive dimensions predicted the likelihood of onset of depressive and hypomanic/manic episodes among the bipolar individuals over a 3.2-year follow-up, controlling for initial symptoms and past history of mood episodes. Higher autonomy and self-criticism predicted a greater likelihood of hypomanic/manic episodes, and higher autonomy predicted a lower likelihood of major depressive episodes. In addition, autonomy mediated the associations between BAS sensitivity and prospective hypomanic/manic episodes. These findings suggest that individuals with bipolar spectrum disorders may exhibit a unique profile of BAS-relevant cognitive styles that influence the course of their mood episodes.

Background: Neonatal blood, obtained from a heel stick and stored dry on paper cards, has been the standard for birth defects screening for 50 years. Such dried blood samples are used, primarily, for analysis of small-molecule analytes. More recently, the DNA complement of such dried blood cards has been used for targeted genetic testing, such as for single nucleotide polymorphism in cystic fibrosis. Expansion of such testing to include polygenic traits, and perhaps whole genome scanning, has been discussed as a formal possibility. However, until now the amount of DNA that might be obtained from such dried blood cards has been limiting, due to inefficient DNA recovery technology., Results: A new technology is employed for efficient DNA release from a standard neonatal blood card. Using standard Guthrie cards, stored an average of ten years post-collection, about 1/40th of the air-dried neonatal blood specimen (two 3 mm punches) was processed to obtain DNA that was sufficient in mass and quality for direct use in microarray-based whole genome scanning. Using that same DNA release technology, it is also shown that approximately 1/250th of the original purified DNA (about 1 ng) could be subjected to whole genome amplification, thus yielding an additional microgram of amplified DNA product. That amplified DNA product was then used in microarray analysis and yielded statistical concordance of 99% or greater to the primary, unamplified DNA sample., Conclusion: Together, these data suggest that DNA obtained from less than 10% of a standard neonatal blood specimen, stored dry for several years on a Guthrie card, can support a program of genome-wide neonatal genetic testing.

Objective: To determine the safety of morphine for procedural pain management in nonintubated infants in the neonatal intensive care unit., Methods: Retrospective cohort study comparing nonintubated infants undergoing central line placement who received morphine during the procedure with a sex and age-matched group who did not receive morphine. The incidence of clinically significant respiratory depression and hypotension, defined as requiring intervention (ie, bag/mask ventilation, increased ventilatory support, and naloxone reversal for respiratory depression and saline volume expansion and inotropes for hypotension), were compared between groups using chi test., Results: There were no differences (P>0.05) between morphine (N=43) and no morphine (N=43) groups in gestational age [34.2 (4.6) vs. 34.6 (3.8) wk; P=0.63], postnatal age [13.7 (22.6) vs. 12.3 (15) wk; P=0.73], and weight [2.3 kg (0.9) for both groups]. Five (11.6%) morphine-treated infants experienced respiratory depression compared with none (0%) in the no morphine group (P=0.02); removal of 2 overdosed infants in the morphine group reduced the incidence to 7.3%, which was not significantly different from 0% in the no morphine group (P=0.07). There were no cases of hypotension., Conclusions: Morphine administration was associated with respiratory depression but not hypotension when administered to nonintubated infants undergoing central line placement. Morphine should be used with caution in this population.

Objectives: Research has found that bipolar spectrum disorders are associated with Behavioral Approach System (BAS) hypersensitivity and both unipolar and bipolar depression are associated with high Behavioral Inhibition System (BIS) sensitivity, but prospective studies of these relationships are lacking. We tested whether BAS and BIS sensitivities prospectively predicted the time to new onsets of major depressive and hypomanic and manic episodes in bipolar spectrum individuals., Methods: We followed 136 bipolar II or cyclothymic and 157 demographically matched normal control individuals prospectively for an average of 33 months. Participants completed the BIS/BAS scales and symptom measures at Time 1 and semi-structured diagnostic interviews every four months of follow-up., Results: The bipolar spectrum group exhibited higher Time 1 BAS, but not BIS, scores than the normal controls, controlling for Time 1 symptoms. Among bipolar spectrum participants, high BAS sensitivity prospectively predicted a shorter time to onset of hypomanic and manic episodes, whereas high BIS sensitivity predicted less survival time to major depressive episodes, controlling for initial symptoms., Conclusions: Consistent with the BAS hypersensitivity model of bipolar disorder, a highly responsive BAS provides vulnerability to onsets of (hypo)manic episodes. In addition, a highly sensitive BIS increases risk for major depressive episodes.

Aim: Research indicates that bipolar disorder is characterized by both high levels of impairment and high levels of achievement. A critical, and yet largely unexamined question, is: what psychological mechanisms promote high accomplishment (and low impairment) among bipolar spectrum individuals? The aim of this study was to examine this question. The Authors also conceptually explore how the answer to this question can enhance the development of intervention and prevention strategies for adolescents with a bipolar spectrum condition., Methods: Academic transcript data were obtained for 120 college students who had either a bipolar spectrum disorder (N=54) or no major psychopathology (N=66)., Results: Bipolar spectrum individuals obtained a lower cumulative grade point average (GPA, t=-2.9, P=0.005) and dropped more classes (t=2.1, P=or<0.04) than normal controls. The findings also have relevance to the behavioral approach system (BAS) dysregulation theory of bipolar disorder, as well as research on impulsivity among bipolar individuals. Specifically, follow-up analyses revealed that bipolar individuals exhibiting a combination of high BAS drive and low impulsivity earned higher GPAs than the remaining bipolar individuals. Thus, high BAS sensitivity, when paired with low impulsivity, may not be impairing and may contribute to the high achievement sometimes observed among bipolar individuals., Conclusion: Such information is important for the development of prevention and intervention programs designed adolescents that lower risk for bipolar impairment without decreasing achievement.

The association between personality disturbance and depression has been noted consistently. Prospective tests of personality's impact on the course of depression, however, are lacking. In a sample of 159 undergraduates who experienced at least one prospective depressive episode, dimensional scores for clusters B and C personality disturbance were examined as prospective predictors of four indicators of the course of depression: severity, episode duration, symptomatic chronicity and number of episodes. Cluster C personality disturbance, characterized by anxious and fearful features, predicted depression chronicity. Cluster B, characterized by dramatic, emotional and/or erratic features, predicted severity and duration of depression. The findings are discussed in terms of the possible mechanisms underlying the effects of clusters B and C, as well as implications for future research.

On the basis of the behavioral approach system (BAS) dysregulation theory of bipolar disorder, this study examined the relation between occurrence of a BAS activation-relevant life event--goal striving--and onset of hypomanic and depressive episodes and symptoms. In particular, the authors examined the relation between preparing for and completing final exams (a goal-striving event) and onset of bipolar spectrum episodes and symptoms in college students with bipolar II disorder or cyclothymia (i.e., "soft" bipolar spectrum conditions). One hundred fifty-nine individuals with either a bipolar spectrum disorder (n=68) or no major affective psychopathology (controls; n=91) were further classified on the basis of whether they were college students (i.e., completed final exams). Consistent with the BAS dysregulation theory, preparing for and completing final exams was associated with an increase in hypomanic but not depressive episodes and symptoms in individuals with a soft bipolar spectrum diagnosis. Furthermore, self-reported BAS sensitivity moderated the presence of certain hypomanic symptoms during final exams., ((c) 2007 APA, all rights reserved.)

Background: Negative cognitive styles have been shown to prospectively predict depression onset and recurrence. Research has also begun to suggest that cognitive styles may be associated with the course of depression as well. This study examined whether cognitive risk for depression onset also predicts the course of depression in a prospective design., Methods: One hundred fifty-nine initially nondepressed participants from the Temple-Wisconsin Cognitive Vulnerability to Depression Project who experienced a depressive episode while in the study were followed prospectively for 2.5 years. Four indicators of the course of depression were assessed from diagnostic interviews and questionnaires administered every 6 weeks: the number, severity and duration of episodes and the chronicity of the depression experienced., Results: Cognitive high-risk participants experienced more episodes of depression, more severe episodes, and more chronic courses than low-risk participants. There were no risk group differences observed for the duration of episodes., Limitations: This study's sample was chosen to include individuals with high and low cognitive vulnerability to depression, potentially limiting the generalizability of the findings to other individuals. Also, the study included some participants with a past history of depression., Conclusions: Negative cognitive styles predict a worse course of depression as well as rendering an individual prone to depression onset. This highlights that the cognitive factors impacting depression's course overlap, at least partly, with those that initiate depression. Thus, knowledge of a depressed individual's cognitive styles could aid in prognosis and treatment planning.

Do negative cognitive styles provide similar vulnerability to first onsets versus recurrences of depressive disorders, and are these associations specific to depression? The authors followed for 2.5 years prospectively college freshmen (N = 347) with no initial psychiatric disorders at high-risk (HR) versus low-risk (LR) for depression on the basis of their cognitive styles. HR participants had odds of major, minor, and hopelessness depression that were 3.5-6.8 times greater than the odds for LR individuals. Negative cognitive styles were similarly predictive of first onsets and recurrences of major depression and hopelessness depression but predicted first onsets of minor depression more strongly than recurrences. The risk groups did not differ in incidence of anxiety disorders not comorbid with depression or other disorders, but HR participants were more likely to have an onset of anxiety comorbid with depression., (2006 APA, all rights reserved)