Age comparison of treatment adherence with antipsychotic medications among individuals with bipolar disorder

BACKGROUND: Few studies have evaluated medication adherence among older vs younger individuals with bipolar disorder (BPD). We compared adherence with antipsychotic medication among older (age 60 and older) and younger individuals using a large case registry (n = 73,964). METHODS: Adherence was evaluated using the medication possession ratio (MPR) for patients receiving antipsychotic medication. RESULTS: Twenty six thousand five hundred and thirty younger individuals (mean age 46.9) and 6,461 older individuals (mean age 69.2) were prescribed antipsychotic medication. Among older individuals, 61.0% (n = 3,350) were fully adherent, while 19.0% (n = 1,043) were partially adherent and 20.0% (n = 1,098) were non-adherent. Among younger individuals, 49.5% (n = 10,644) were fully adherent, while 21.8% (n = 4,680) were partially adherent, and 28.7% (n = 6,170) were non-adherent. As with younger patients, comorbid substance abuse and homelessness predicted non-adherence among older patients with BPD. CONCLUSION: Older individuals with BPD were more adherent with antipsychotic medications compared to younger individuals. However, a substantial proportion (approximately 39%) of older patients with BPD still have difficulties with adherence.     

Risk indicators and psychopathology in traumatised children and adolescents with a history of sexual abuse

PURPOSE: Childhood sexual abuse (CSA) is widespread amongst South African (SA) children, yet data on risk factors and psychiatric consequences are limited and mixed. METHODS: Traumatised children and adolescents referred to our Youth Stress Clinic were interviewed to obtain demographic, sexual abuse, lifetime trauma and psychiatric histories. RESULTS: Data for 94 participants (59 female, 35 male; mean age 14.25 [8.25-19] years) exposed to at least one lifetime trauma were analysed. Sexual abuse was reported in 53% of participants (42.56% females, 10.63% males) with 64% of violations committed by perpetrators known to them. Multinomial logistic regression analysis revealed female gender (P=0.002) and single-parent families (P=0.01) to be significant predictors of CSA (62.5%). CSA did not predict exposure to other traumas. Sexually abused children had significantly higher physical and emotional abuse subscale scores and total CTQ scores than non-abused children. Depression (33%, X(2)=10.89, P=0.001) and PTSD (63.8%, X(2)=4.79, P=0.034) were the most prevalent psychological consequences of trauma and both were significantly associated with CSA. CONCLUSIONS: High rates of CSA predicted high rates of PTSD in this traumatised sample. Associations we found appear consistent with international studies of CSA and, should be used to focus future social awareness, prevention and treatment strategies in developing countries.     

Timing of antibiotics in febrile children meeting sepsis criteria at a paediatric emergency department

Objective

Delay in antibiotic administration in paediatric sepsis is associated with increased mortality and prolonged organ dysfunction. This pre-intervention study evaluated performance in paediatric sepsis management.

Methods

Retrospective cohort study of febrile children admitted through the ED at The Children's Hospital at Westmead, Sydney, between 1 May and 31 July 2017. Participants were children aged 29 days to 60 months excluding children with simple febrile seizures, neonates and children who had received intravenous antibiotics elsewhere. We assessed the timing of antibiotic administration in children meeting local sepsis guidelines. We conducted a survey of clinicians in ED in 2018 to describe contributing factors.

Results

There were 160 febrile children admitted and 144 presentations were included in the analysis. Male 53% (n = 76); median age 20.1 months (interquartile range [IQR] 3.9–37 months). Thirty-seven (26%) febrile children met local sepsis criteria. The median time from triage to first dose of intravenous antibiotic was 109 min (IQR 62–183 min). Delay (>60 min) occurred in 26 (76%) children. Reported reasons contributing to delay included high patient load, long waiting times, difficult intravenous access, delayed prescribing, inadequate staffing and difficulty distinguishing between a viral infection and serious bacterial infection.

Conclusion

There was frequent delay in administering antibiotics in children meeting local sepsis criteria, more commonly in young infants. Reasons contributing to delay were specific to young children along with departmental factors that will require addressing through targeted quality improvement interventions.     

Screening for alcoholism

Alcoholism is one of the largest public health problems of the nation and is a significant cofactor in such ubiquitous diseases as hypertension, developmental abnormalities, heart failure, liver failure, and many other conditions. The cost to the nation's health is immense. One strategy for reducing morbidity and cost has been to establish methods for screening in order to increase recognition rates leading to increased rates of therapeutic intervention. In this article, the rationale for two methods of alcohol screening, brief interviews and biological markers of excessive drinking, the relevant statistical issues bearing on this problem, and the current research on screening exams are reviewed and summarized. Finally, some of the newer approaches toward alcoholism screening as well as the consequences to the medical care system should alcohol screening eventuate on a large scale are briefly described.     

EMS providers do not accurately note motor-vehicle crash patients with positive serum alcohol concentrations

INTRODUCTION: Alcohol use is associated with many motor-vehicle crashes and may increase the severity of injury. Because alcohol use also may mask injury, prehospital emergency care providers (PHECPs) may make inaccurate assessments. To assess and triage crash victims accurately, PHECPs must identify recent alcohol use. STUDY OBJECTIVE: This study examines the accuracy of PHECPs in identifying motor-vehicle crash victims who had positive serum alcohol concentrations. DESIGN: Retrospective cohort study. POPULATION: Included in the study were motor-vehicle crash victims more than 17 years of age who were conveyed directly to a university medical center emergency department by ground ambulance (n = 372). TIME PERIOD: 15 July 1990 to 15 July 1991. METHODS: Data sources included ambulance report forms and hospital records. Variables that were abstracted included the Revised Trauma Score (RTS), the PHECPs' impression of alcohol use, and serum alcohol concentrations. Sensitivity, specificity, predictive-value positive, predictive-value negative, and 0.95 confidence intervals (0.95 CI) were calculated for the PHECPs' ability to identify patients with a serum alcohol concentration > 0. The relationship between the RTS and the impressions of alcohol use was analyzed with chi-square testing: a p-value of < 0.05 was considered statistically significant. CONCLUSION: This study suggests that PHECPs cannot accurately identify crash victims with positive serum alcohol concentrations. Selection bias and retrospective design are significant limitations of this study. Future studies should develop and evaluate methods to improve PHECPs' accuracy in assessing alcohol use in motor-vehicle crash victims.     

Heterotypic adherence between human B-lymphoblastic and pre-B- lymphoblastic cells and marrow stromal cells is a biphasic event: integrin very late antigen-4 alpha mediates only the early phase of the heterotypic adhesion

Heterotypic adherence between marrow stromal cells (MSC) and lymphoblastic cells is essential for normal lymphopoiesis and malignant lymphoblastic development. However, the detailed molecular mechanisms by which this heterotypic adherence occurs are poorly understood. The cell-cell interactions between a B-lymphoblastic cell line (UTMB-460) and a pre-B-cell line (NALM-6) with MSC were chosen as models to investigate potential mechanisms and adhesion molecules involved in the apposition between normal and malignant lymphoblastic cells and MSC. A parallel-flow detachment assay (PFDA) and a 51Cr detachment assay, coupled with monoclonal antibody (MoAb) blocking experiments, were used to quantify the attachment of lymphoblastic cells to confluent monolayers of MSC. The apposition between MSC and B-lymphoblastic cells (UTMB-460 cells) was investigated for variable time periods, ranging from 1 minute to 4 hours. Results from the temporal study suggest that the heterotypic adherence of the B-lymphoblastic cells to MSC is a biphasic event and the interactions occur rapidly (< or = 1 minute) after the two cells come into contact. More specifically, the early phase of adherence (< or = 15 minutes) solely involves very late antigen-4 alpha (VLA-4 alpha)/vascular cell adhesion molecule 1 (VCAM- 1) interactions, as evidenced by the nearly complete inhibition (93%) of UTMB-460 cell adherence in the presence of anti-VLA-4 alpha. The late phase (> or = 30 minutes) proceeds despite the continuous presence of anti-VLA-4 alpha. In addition, the late-phase adherence is not affected by MoAbs to LFA-1, CD44, VCAM-1, E-selectin, or L-selectin, which suggests the possible involvement of other adhesion molecules. Adherence of pre-B-lymphoblastic cells (NALM-6) to MSC is also biphasic. Integrin VLA-4 is again a major player in the early phase of pre-B-lymphoblastic cell/MSC interactions. The early phase of adherence may be important in homing of the malignant lymphoblastic cells to the MSC and the late phase in retention of malignant lymphoblastic cells in the bone marrow.     

Interleukin-3 treatment of rhesus monkeys leads to increased production of histamine-releasing cells that express interleukin-3 receptors at high levels

To understand the hematopoietic and nonhematopoietic responses to interleukin-3 (IL-3), expression of cell-surface IL-3 receptors (IL-3R) was examined on bone marrow (BM) cells and peripheral blood (PB) cells of rhesus monkeys during the course of in vivo IL-3 treatment. Whereas IL-3R expression is low in untreated monkeys, IL-3 administration led to a gradual increase in both low- and high-affinity binding sites for IL-3. This increase reflected the total number of cells expressing IL- 3Rs, as detected by flow cytometry using biotinylated IL-3. Most of these IL-3R+ cells in both BM and PB could be characterized as basophilic granulocytes that contained high levels of histamine. In contrast to the effect on these differentiated cells, IL-3 administration did not significantly alter the low level IL-3R expression on immature, CD34+ cells. Further flow cytometric analysis using biotinylated growth factors showed that the IL-3R+ basophils also expressed receptors for granulocyte-macrophage colony-stimulating factor (GM-CSF), but not for IL-6 or Kit ligand. These findings indicated that the IL-3R+ cells included neither monocytes, which express GM-CSFRs and IL-6Rs abundantly, nor mast cells, which express c- kit. By combining flow cytometric and Scatchard data, it was calculated that the basophils contain as many as 1 to 2 x 10(3) high-affinity IL- 3Rs and 15 to 30 x 10(3) low-affinity sites. The finding that in vivo IL-3 treatment leads to the production of large numbers of cells that express high levels of IL-3R and are capable of producing histamine provides an explanation for the often severe allergic reactions that occur during prolonged IL-3 administration. It also indicates that IL- 3, in addition to its direct effects on hematopoietic cells, may also stimulate hematopoiesis through the release of secondary mediators such as histamine by IL-3-responsive mature cells.     

Experimental transmission of West Nile virus by Culex nigripalpus from Honduras

As a result of concerns regarding the geographic spread of West Nile virus (WNV) to Central America, we evaluated the potential for Honduran Culex nigripalpus Theobald to transmit this virus. We tested individual mosquitoes captured in Olancho Province, Honduras, in September 2003. Mosquitoes were allowed to feed on 2- to 4- day-old chickens previously inoculated with a New York strain (Crow 397-99) of WNV. Infection rates in Cx. nigripalpus ranged from 81%-96% after feeding on chickens with viremias between 10(6.3) and 10(7.4) plaque-forming units per milliliter. Development of a disseminated infection was directly correlated with holding time after the infectious blood meal as 68% (19/28) of the mosquitoes tested 20 days after the infectious blood meal had a disseminated infection as compared to 38% (15/40) of the mosquitoes tested 14 days after feeding on the same viremic chickens (viremia = 10(6.97.4)). Nearly all (4/5) Cx. nigripalpus with a disseminated infection that fed on susceptible chickens transmitted virus by bite. In addition, 8 (57%) of 14 Cx. nigripalpus with a disseminated infection transmitted virus when tested by a capillary tube feeding assay. Based on its efficiency of viral transmission in this study and its role in the transmission of the closely related St. Louis encephalitis virus in the southeastern United States, Cx. nigripalpus should be considered a potentially important vector of WNV in Honduras and the rest of Central America.     

Infusible platelet membrane microvesicles: a potential transfusion substitute for platelets

BACKGROUND: Several substitutes for intact, viable platelets have been used for transfusion, both to people and in animal models, with varied success. Infusible platelet membrane (IPM) is prepared from human platelets. IPM retains the glycoprotein (GP)lb receptor and has platelet factor 3 activity (procoagulant activity). However, factor V, serotonin, a cytoplasmic marker enzyme (purine nucleotide phosphorylase), GPIIb/IIIa complex, and HLA class I and II antigens are all absent in IPM. STUDY DESIGN AND METHODS: IPM is prepared from outdated platelets. The platelets were disrupted by freezing and thawing; they were washed and heated to inactivate possible viral contaminants, and then the sonicated membrane microvesicle fraction was separated and lyophilized. The hemostatic activity of IPM was measured by its ability to reduce the prolonged bleeding time in thrombocytopenic rabbits. RESULTS: Administration of IPM at a dose of 2 mg per kg results in a substantial reduction in the bleeding time. In a series of 23 experiments, a median preinjection bleeding time of 15 minutes was reduced to 6 minutes within 4 hours after IPM administration. Administration of IPM did show a mild enhancement in the thrombogenicity index, as measured in the Wessler rabbit model. This enhancement is, however, not significant, as a thrombogenicity index value of up to 0.6 is clinically acceptable. CONCLUSION: IPM may have clinical potential as a substitute for platelets in the treatment of bleeding due to thrombocytopenia.     

Primary care-based intervention to reduce at-risk drinking in older adults: a randomized controlled trial

Aims To examine whether a multi‐faceted intervention among older at‐risk drinking primary care patients reduced at‐risk drinking and alcohol consumption at 3 and 12 months. Design Randomized controlled trial. Setting Three primary care sites in southern California. Participants Six hundred and thirty‐one adults aged ≥ 55 years who were at‐risk drinkers identified by the Comorbidity Alcohol Risk Evaluation Tool (CARET) were assigned randomly between October 2004 and April 2007 during an office visit to receive a booklet on healthy behaviors or an intervention including a personalized report, booklet on alcohol and aging, drinking diary, advice from the primary care provider and telephone counseling from a health educator at 2, 4 and 8 weeks. Measurements The primary outcome was the proportion of participants meeting at‐risk criteria, and secondary outcomes were number of drinks in past 7 days, heavy drinking (four or more drinks in a day) in the past 7 days and risk score. Findings At 3 months, relative to controls, fewer intervention group participants were at‐risk drinkers [odds ratio (OR) 0.41; 95% confidence interval (CI) 0.22–0.75]; they reported drinking fewer drinks in the past 7 days [rate ratio (RR) 0.79; 95% CI 0.70–0.90], less heavy drinking (OR 0.46; 95% CI 0.22–0.99) and had lower risk scores (RR 0.77 95% CI 0.63–0.94). At 12 months, only the difference in number of drinks remained statistically significant (RR 0.87; 95% CI 0.76–0.99). Conclusions A multi‐faceted intervention among older at‐risk drinkers in primary care does not reduce the proportions of at‐risk or heavy drinkers, but does reduce amount of drinking at 12 months.