Effectiveness of nurse-led services for people with chronic disease in achieving an outcome of continuity of care at the primary-secondary healthcare interface: A quantitative systematic review.

BACKGROUND: Globally, chronic disease is a leading cause of illness, disability and death and an important driver of health system utilization and spending. Continuity of care is a significant component of quality healthcare. However, an association between nurse-led services, interventions, patient outcomes and continuity of care at the primary and secondary interface as an outcome, has not been established for people with chronic disease. OBJECTIVE: To identify the effectiveness of nurse-led services for people with chronic disease in achieving an outcome of continuity of care at the primary-secondary healthcare interface. DESIGN: Quantitative systematic review. DATA SOURCES: Systematic searches of Medline, Cochrane, Embase, Emcare, JBI and Scopus databases were conducted of studies published between 1946 and May 2019 using the search terms "nurse", "continuity of care" and "chronic disease". REVIEW METHODS: Quality of the included studies was assessed using the Cochrane risk of bias tool for randomized controlled trials and Joanna Briggs Institute quality appraisal checklists. A second reviewer screened 10% of full text articles and all articles in critical appraisal. Studies were excluded from the review if they were of poor methodological quality or the description of the effect of the nurse-led service was inadequately reported. RESULTS: Fourteen studies were included in the review (n=4,090 participants). All studies incorporated recognized continuity of care interventions. The nurse-led services were associated with fewer hospitalizations, reduced by 2-8.9% and re-admissions reduced by 14.8-51% (n=886). Reporting of positive patient experiences and improvement in symptoms and lifestyle was also evident. An association of nurse-led services with improved continuity of care between primary and secondary health services as an outcome per se could not be concluded. CONCLUSION: Nurse-led services for adults provide coordinated interventions that support continuity of care for people with chronic disease in both the primary and secondary healthcare settings that are associated with reduced hospitalizations or readmissions and patient satisfaction. However, the limited use of validated continuity of care outcome measurement tools precluded establishing correlations between interventions, patient outcomes and continuity of care as a specific outcome.

Medication use and potentially high-risk prescribing in older patients hospitalized for diabetes: a missed opportunity to improve care?

AIMS: To examine the appropriateness of medicine use and potentially high-risk prescribing before and after hospitalization for diabetes. METHODS: A retrospective cohort study of patients hospitalized for diabetes was conducted using administrative data from the Australian Government Department of Veterans' Affairs for the period between 1 January 2012 and 31 December 2012. The appropriateness of medicine use and potentially high-risk prescribing, including hyper-polypharmacy and associated treatment conflicts, were examined for the 120-day periods before and after hospitalization. RESULTS: A total of 876 patients were hospitalized for a diabetes-related complication. Of these, 25% were not dispensed an antidiabetic medicine 4 months before hospitalization and 25% had not had their HbA1c levels measured in the preceding 6 months. The use of antidiabetic medicines increased to 85% after hospitalization, with a 25.6% relative increase (95% CI 10.9-42.1) in the proportion of those dispensed insulin. The prevalence of high-risk prescribing before hospital admission was high; 70% had > 10 medicines dispensed, a third had at least one treatment conflict and half were dispensed a potentially inappropriate medicine. The use of long-acting sulphonylureas and corticosteroids had relative decreases of 46.0% (95% CI 17.0-64.9) and 29.9% (95% CI 8.8-46.0), respectively. Few changes in other high-risk prescribing patterns were observed after discharge. CONCLUSIONS: This study has identified poor medication-related care and, in particular, high-risk-prescribing in people subsequently hospitalized for diabetes. While diabetes medicine use improved after hospitalization, there was little change in potentially inappropriate medicine use, which suggests that an opportunity to improve medication use in this older vulnerable population has been missed.

Effect of a general practitioner management plan on health outcomes and hospitalisations in older patients with diabetes.

BACKGROUND: Little is known about the impact of a general practitioner management plan (GPMP) on health outcomes of patients with diabetes. AIM: To examine the impact of a GPMP on the risk of hospitalisation for diabetes. METHODS: A retrospective study using administrative data from the Australian Government Department of Veterans' Affairs was conducted (1 July 2006 to 30 June 2014) of diabetes patients either exposed or unexposed to a GPMP. The primary end-point was the risk of first hospitalisation for a diabetes-related complication and was assessed using Cox proportional hazard regression models with death as a competing risk. Secondary end-points included rates of receiving guideline care for diabetes, with differences assessed using Poisson regression analyses. RESULTS: A total of 16 214 patients with diabetes were included; 8091 had a GPMP, and 8123 did not. After 1 year, 545 (6.7%) patients with a GPMP and 634 (7.8%) of patients without a GPMP were hospitalised for a diabetes complication. There was a 22% reduction in the risk of being hospitalised for a diabetes complication (adjusted hazard ratio (HR) 0.78, 95% confidence interval (CI) 0.69-0.87, P < 0.0001) for those who received a GPMP by comparison to those who did not. Increased rates of diabetes guideline care, HbA1c claims (adjusted HR 1.29, 95% CI 1.25-1.33) and microalbuminura claims (adjusted HR 1.65, 95% CI 1.58-1.72) were observed after a GPMP. CONCLUSION: Provision of a GPMP in older patients with diabetes resulted in improved health outcomes, delaying the risk of hospitalisation at 12 months for diabetes complications. GPMP should be included as part of routine primary care for older patients with diabetes.

Anti-seizure prophylaxis in critically ill patients with traumatic brain injury in an intensive care unit.

The objectives of this prospective observational study were to determine the proportion of patients with traumatic brain injury who received effective anti-seizure prophylaxis. The study was conducted in a tertiary level ICU of a major trauma referral centre between February 2012 and August 2013. A total of 2361 patients were admitted to the ICU in this study period, of whom125 patients (index) with traumatic head injury were included in this study. The patients had a mean age of 45 years (SD=19), a mean score on the Glasgow Coma Scale of 9 (SD=4), a mean injury severity score of 27 (SD=13) and a mean APACHE III score of 55 (SD=27). Only 13.6 % (17 of 125) of patients were given anti-seizure prophylaxis and phenytoin levels were measured in 9.6% (12 of 125). Although all 12 patients achieved an effective concentration for phenytoin therapy (>40 µmol/l) after the loading dose, no patient had their target concentration consistently maintained in the recommended therapeutic range (40 to 80 µmol/l) throughout the seven-day monitoring period. There was wide fluctuation in phenytoin levels in the patients in this study. Twenty-two (18%) of the index patients had post-traumatic seizures, indicating a high prevalence for this study. Poor compliance with guidelines could possibly explain this phenomenon. Future studies are needed to look at the dosing and monitoring of phenytoin and/or alternative anti-seizure prophylaxis in patients with traumatic brain injury.

Efficacy and safety of beloranib for weight loss in obese adults: a randomized controlled trial.

AIM: To assess the efficacy, safety and tolerability of beloranib treatment for obesity. METHODS: This phase II, double-blind, randomized study investigated the effects of beloranib suspension (0.6, 1.2 and 2.4 mg) or placebo, administered subcutaneously, for 12 weeks in 147 participants (primarily white women) with obesity. No diet or exercise advice was administered. RESULTS: At week 12, beloranib resulted in dose-dependent progressive weight loss of -5.5 ± 0.5, -6.9 ± 0.6 and -10.9 ± 1.1 kg for the 0.6, 1.2 and 2.4 mg beloranib doses, respectively, compared with -0.4 ± 0.4 kg with placebo (all p < 0.0001 vs placebo). Weight loss with beloranib was associated with corresponding reductions in waist circumference and body fat mass, as well as improvements in lipids, high-sensitivity C-reactive protein and blood pressure. Sleep disturbance and gastrointestinal adverse events were more common with beloranib than with placebo; these were generally mild to moderate, transient and dose-related, and led to more early study withdrawals in participants in the group with the highest dose of beloranib. CONCLUSIONS: In this 12-week phase II study, beloranib produced clinically and statistically significant weight loss and corresponding improvements in cardiometabolic risk factors. Beloranib appeared safe, and the 0.6 and 1.2 mg doses were generally well tolerated. The 2.4 mg dose was associated with increased sleep latency and mild to moderate gastrointestinal adverse events over the first month of treatment. These findings represent a novel mechanism for producing clinically meaningful weight loss.

Hospitalization for drug-induced hepatotoxicity: linking Y-codes with pharmaceutical claims data to identify implicated medicines.

WHAT IS KNOWN AND OBJECTIVE: Hospital admissions associated with an adverse drug reaction are often coded to the International Classification of Diseases external cause Y-codes, denoting the medicine class deemed to cause the adverse drug reaction. Matching hospital data with outpatient dispensing data has the potential to identify the specific causative medicines but the ability to identify the causative medicines in this way has not been previously assessed. This study aimed to determine the proportion of Y-coded hospitalizations for drug-induced hepatotoxicity that could be matched with a potential causative medicine from outpatient dispensing data. METHODS: A retrospective cohort study was undertaken from 1 Jan 2005 to 30 June 2012 using data from the Australian Government Department of Veterans' Affairs of all admissions coded to drug-induced hepatotoxicity. Medicine use in the 6 months prior to hospitalization was examined to identify the probable causative medicines. RESULTS AND DISCUSSION: Thirty five admissions were identified for 31 patients. All admissions were preceded by use of medicines known to cause hepatotoxicity. Twenty four admissions had a Y-code recorded, of which 19 admissions had at least one Y-code specifying the causative medicine class (22 Y-codes). Of the 22 Y-codes, 95% could be successfully matched with a medicine from the same class that had been dispensed in the 6 months prior to admission. Further, 92% were preceded by use of multiple hepatotoxic medicines. WHAT IS NEW AND CONCLUSION: Results of our study demonstrate that hospital administrative data can be linked to prescription dispensing data to identify specific medicines suspected of causing the adverse drug reaction.

General practitioner management plans delaying time to next potentially preventable hospitalisation for patients with heart failure.

BACKGROUND: Several studies have shown that the Australian Medicare-funded chronic disease management programme can lead to improvements in care processes. No study has examined the impact on long-term health outcomes. AIMS: This retrospective cohort study assessed the association between provision of a general practitioner management plan and time to next potentially preventable hospitalisation for older patients with heart failure. METHODS: We used the Australian Government Department of Veterans' Affairs (DVA) claims database and compared patients exposed to a general practitioner management plan with those who did not receive the service. Kaplan-Meier analysis and Cox proportional hazards models were used to compare time until next potentially preventable hospitalisation for heart failure between the exposed and unexposed groups. RESULTS: There were 1993 patients exposed to a general practitioner management plan and 3986 unexposed patients. Adjusted results showed a 23% reduction in the rate of potentially preventable hospitalisation for heart failure at any time (adjusted hazard ratio, 0.77; 95% confidence interval, 0.64 to 0.92; P = 0.0051) among those with a general practitioner management plan compared with the unexposed patients. Within one year, 8.6% of the exposed group compared with 10.7% of the unexposed group had a potentially preventable hospitalisation for heart failure. CONCLUSIONS: A general practitioner management plan is associated with delayed time to next potentially preventable hospitalisation for heart failure.

Impact of a compulsory final year medical student curriculum on junior doctor prescribing.

BACKGROUND: Attendance at face-to-face sessions and completion of online components of the National Prescribing Curriculum was made compulsory for final year medical students at the University of Adelaide in 2010. AIMS: To determine the impact of a compulsory prescribing curriculum for final year medical students on their prescribing competencies at the start of clinical practice. Graduates' attitudes to their medical school training in prescribing were also surveyed. METHODS: Two cohorts of medical graduates from the University of Adelaide who commenced medical practice in 2010 and 2011 were required to complete a prescribing task using the National Inpatient Medication Chart (NIMC) at orientation and after 6 months of clinical practice. The main outcome measure was a performance in a scenario-based prescribing test, as determined by test scores and overall safety of prescriptions at orientation and 6 months of clinical practice. RESULTS: There was a small difference in the average total score for the prescribing task between the 2010 and 2011 cohorts at orientation (P = 0.0007). The 2011 cohort had a higher number of safer charts at commencement of practice. We found no difference between the 2010 and 2011 cohorts in attitudes towards their undergraduate pharmacology education, and new graduates feel poorly prepared. CONCLUSION: Medical graduates who are required to complete a practically oriented prescribing curriculum in final year perform slightly better on a prescribing assessment at commencement of practice. More work on preparing graduates for this complex task before graduation is needed.

Anaemia in chronic heart failure: more awareness is required.

AIMS: To determine the characteristics of anaemic patients, how well anaemia is investigated and its contributing factors in patients with chronic heart failure (CHF). METHODS: Retrospective analysis of longitudinal data collected during routine management of patients admitted with CHF at an Australian tertiary hospital. One thousand and twenty-one patients admitted with CHF between 1997 and 2005 were included. Anaemia was defined as a haemoglobin concentration <110 g/L. Data were compared between anaemic and non-anaemic patients. RESULTS: The prevalence of anaemia among patients with CHF was 20.3% in our study. These patients were more likely to be older, female, and have a higher prevalence of chronic renal failure and peripheral vascular disease. Despite previous studies reporting a higher mortality rate among CHF patients with anaemia, only 60% of patients had basic investigations for anaemia (i.e. iron studies, vitamin B12, folate and thyroid function testing). The cause of anaemia is usually multifactorial with 63.8% of patients having at least two factors contributing to their anaemia. Chronic renal failure, iron deficiency and anaemia of chronic disease were the most common contributors. These factors were not predicted based on abnormalities in mean corpuscular volume. Patients with anaemia had a longer length of stay in hospital. CONCLUSIONS: Anaemia in patients with CHF is common but not well investigated. The aetiology of anaemia is usually multifactorial and not easily predicted. Patients with anaemia and CHF have poorer outcomes. There needs to be more awareness among clinicians about the importance of investigating and treating anaemia in patients with CHF.

Aspirin for primary prevention: do potential benefits outweigh the risks?

The role of aspirin for primary prevention in healthy individuals has been the subject of clinical trials for more than a quarter of a century. Because of this evidence, or sometimes despite it, many individuals self-administer aspirin to prevent cardiovascular events. This article reviews the published work for aspirin in primary prevention of cardiovascular and malignant diseases and considers whether aspirin would be approved by regulatory authorities for this use if it were to be marketed for this indication today.

What we have here is a failure to communicate! Improving communication between tertiary to primary care for chronic heart failure patients.

BACKGROUND: The aims of this study were to determine the documentation of pharmacotherapy optimization goals in the discharge letters of patients with the principal diagnosis of chronic heart failure. METHODS: A retrospective practice audit of 212 patients discharged to the care of their local general practitioner from general medical units of a large tertiary hospital. Details of recommendations regarding ongoing pharmacological and non-pharmacological management were reviewed. The doses of medications on discharge were noted and whether they met current guidelines recommending titration of angiotensin-converting enzyme inhibitors and beta-blockers. Ongoing arrangements for specialist follow up were also reviewed. RESULTS: The mean age of patients whose letters were reviewed was 78.4 years (standard deviation +/- 8.6); 50% were men. Patients had an overall median of six comorbidities and eight regular medications on discharge. Mean length of stay for each admission was 6 days. Discharge letters were posted a median of 4 days after discharge, with 25% not posted at 10 days. No discharge letter was sent in 9.4% (20) of the cases. Only six (2.8%) letters had any recommendations regarding future titration of angiotensin-converting enzyme inhibitors and 6.6% (14) for beta-blockers. Recommendations for future non-pharmacological management, for example, diuretic action plans, regular weight monitoring and exercise plans were not found in the letters in this audit. CONCLUSION: Hospital discharge is an opportunity to communicate management plans for treatment optimization effectively, and while this opportunity is spurned, implementation gaps in the management of cardiac failure will probably remain.

Results of a phase IIa clinical trial of an anti-inflammatory molecule, chaperonin 10, in multiple sclerosis.

BACKGROUND: Chaperonin 10 (Cpn10) is a mitochondrial molecule involved in protein folding. The aim of this study was to determine the safety profile of Cpn10 in patients with multiple sclerosis (MS). METHODS: A total of 50 patients with relapse-remitting or secondary progressive MS were intravenously administered 5 mg or 10 mg of Cpn10 weekly for 12 weeks in a double-blind, randomized, placebo controlled, phase II trial. Clinical reviews, including Expanded Disability Status Scale and magnetic resonance imaging (MRI) with Gadolinium, were undertaken every 4 weeks. Stimulation of patient peripheral blood mononuclear cells with lipopolysaccharide ex vivo was used to measure the in vivo activity of Cpn10. RESULTS: No significant differences in the frequency of adverse events were seen between treatment and placebo arms. Leukocytes from both groups of Cpn10-treated patients produced significantly lower levels of critical proinflammatory cytokines. A trend toward improvement in new Gadolinium-enhancing lesions on MRI was observed, but this difference was not statistically significant. No differences in clinical outcome measures were seen. CONCLUSIONS: Cpn10 is safe and well tolerated when administered to patients with MS for 3 months, however, a further extended phase II study primarily focused on efficacy is warranted.

Helicobacter pylori-induced peptic ulcer disease is associated with inadequate regulatory T cell responses.

BACKGROUND AND AIMS: Helicobacter pylori infection is the major cause of peptic ulceration and gastric adenocarcinoma. To address the hypothesis that the human acquired immune response to H. pylori influences pathogenesis, we characterised the gastric T helper (Th) and regulatory T cell (Treg) response of infected patients. METHODS: The human gastric CD4(+) T cell response of 28 donors who were infected with H. pylori and 44 who were not infected was analysed using flow cytometry. The T cell associated mucosal cytokine response was analysed by real-time polymerase chain reaction assay of samples from 38 infected and 22 uninfected donors. Recombinant interleukin 10 (IL10) was added to co-cultures of H. pylori and AGS cells and its suppressive effects upon inflammatory responses were measured. RESULTS: We found that the H. pylori-specific response consists of both T helper 1 and 2 subsets with high levels of IL10-secreting Tregs. People with peptic ulcer disease had a 2.4-fold reduced CD4(+)CD25(hi)IL10(+) Treg response (p = 0.05) but increased Th1 and Th2 responses (Th1: 3.2-fold, p = 0.038; Th2: 6.1-fold, p = 0.029) compared to those without ulcers. In vitro studies showed that IL10 inhibited IL8 expression and activation of nuclear factor kappa B induced by H. pylori in gastric epithelial cells, and enhanced H. pylori growth in a bacterial-cell co-culture model. CONCLUSIONS: Together our data suggest that H. pylori induces a regulatory T cell response, possibly contributing to its peaceful coexistence with the human host, and that ulcers occur when this regulatory response is inadequate.

Pharmacists' role in the post-discharge management of patients with heart failure: a literature review.

BACKGROUND AND OBJECTIVE: The incidence of heart failure is increasing in developed countries. In the aged population, heart failure is a common cause of hospitalization and hospital readmission, which in conjunction with post-discharge care, impose a significant cost burden. Inappropriate medication management and drug-related problems have been identified as major contributors to hospital readmissions. In order to enhance the care and clinical outcomes, and reduce treatment costs, heart failure disease management programmes (DMPs) have been developed. It is recommended that these programmes adopt a multi-disciplinary approach, and pharmacists, with their understanding and knowledge of medication management, can play a vital role in the post-discharge care of heart failure patients. The aim of this literature review was to assess the role of pharmacists in the provision of post-charge services for heart failure patients. METHOD: An extensive literature search was undertaken to identify published studies and review articles evaluating the benefits of an enhanced medication management service for patients with heart failure post-discharge. RESULTS: Seven studies were identified evaluating 'outpatient' or 'post-discharge' pharmacy services for patients with heart failure. In three studies, services were delivered prior to discharge with either subsequent telephone or home visit follow-up. Three studies involved the role of a pharmacist in a specialist heart failure outpatient clinic. One study focused on a home-based intervention. In six of these studies, positive outcomes, such as decreases in unplanned hospital readmissions, death rates and greater compliance and medication knowledge were demonstrated. One study did not show any difference in the number of hospitalizations between intervention and control groups. The quality of evidence of the randomized controlled trials was assessed using the Jadad scoring method. None of the studies achieved a score of more than 2, out of a maximum of 5, indicating the potential for bias. DISCUSSION: The DMPs carried out by pharmacists have contributed to positive patient outcomes, which has highlighted the value of extending the traditional roles of pharmacists from the provision of professional guidance to the delivery of continuity of care through a more holistic and direct approach. CONCLUSION: This review has demonstrated the effectiveness of pharmacists' interventions to reduce the morbidity and mortality associated with heart failure. However, there is an on-going need for the development and evaluation of pharmacy services for these patients.

Evaluation of BioStar FLU OIA assay for rapid detection of influenza A and B viruses in respiratory specimens.

BACKGROUND: Demand for the rapid diagnosis of influenza infections has increased with the advent of the availability of neuraminidase antiviral therapy for influenza A and B. Several rapid assays that detect both influenza A and B are now available. OBJECTIVES: In this study we compared the performance of the BioStar FLU OIA assay to Bartels Viral Respiratory Screening and Identification Kit (Bartels Inc., Issaquah, WA), and cell culture. STUDY DESIGN: A total of 145 patient specimens for influenza virus detection submitted in either viral transport medium or in sterile containers were evaluated by the three methods. Specimen types included nasal washings, nasal swabs, sputum, throat swabs, and bronchial alveolar lavage (BAL) fluids. RESULTS: Fifty six positive specimens were identified based on culture and/or DFA. Of these, 30 specimens were positive by the OIA assay for an overall sensitivity of 54%. The OIA assay detected 48% (n = 21) of the 44 culture positive specimens and 81% (n = 29) of the 36 DFA positive specimens. Eighty six of the 89 culture/DFA negative samples were negative by the OIA assay (97% specificity). Analysis of the OIA assay sensitivity from samples submitted in M4 transport medium or in sterile containers revealed that M4 transport medium does not reduce the sensitivity of the OIA assay. Fifteen of the 27 positive samples submitted in M4 transport medium were positive by the OIA assay (56% sensitivity) compared to 15 of 29 positive samples transported in sterile containers (52% sensitivity). Twelve specimens were either culture and/or DFA positive for viruses other than influenza, but negative by the OIA assay, suggesting that there was no cross reactivity of the OIA assay with the other virus types recovered in this study. CONCLUSIONS: The overall excellent specificity of the BioStar FLU OIA allows for treatment of positive patients for influenza, however, a negative result should be confirmed by DFA and culture.

Evaluation of the dose-response relationship for intra-nasal oxymetazoline hydrochloride in normal adults.

OBJECTIVES: To evaluate the dose-response relationship of increasing doses of oxymetazoline compared with placebo in normal subjects, and to determine the sensitivities of rhinomanometry, acoustic rhinometry and symptoms in discriminating between differing doses of oxymetazoline in normal subjects. METHODS: The study had a randomized, double-blind, placebo-controlled, parallel group, dose-response design. One hundred and twenty-five healthy volunteers with no nasal obstruction were randomized to administration of a single intra-nasal dose of oxymetazoline (6.25 microg, 12.5 microg, 25 microg or 50 microg) or placebo to each nasal cavity. Nasal airway resistance (NAR) was measured by active posterior rhinomanometry. Total minimum cross-sectional area (tMCA) and volume (tVOL) were measured by acoustic rhinometry. Symptoms of congestion (CON) were assessed on a visual analogue scale. RESULTS: The two highest doses of oxymetazoline produced a significant decrease in NAR compared with placebo (P = 0.015) but not between placebo and 12.5 microg or 6.25 microg. There was a dose-response relationship for tVOL, which increased significantly after all doses compared with placebo (P < 0. 001) and showed differences between 6.25-microg and 25-microg (P < 0. 014) and 12.5-microg and 50-microg (P < 0.05) doses. tMCA increased compared with placebo after all treatments (P = 0.028), but there were no significant differences between any of the active doses. There were no significant changes in CON after any treatments compared with placebo. CONCLUSIONS: tVOL shows a clear dose-response relationship for the range of doses of oxymetazoline administered. tVOL provides a sensitive and discriminatory measure of small nasal changes after low doses of oxymetazoline. NAR is able to discriminate between doses, but is less sensitive than tVOL and tMCA, requiring a higher threshold dose before significant changes are seen in nasal patency.

The nasal airways response in normal subjects to oxymetazoline spray: randomized double-blind placebo-controlled trial.

AIMS: The effects of a single dose of oxymetazoline nasal spray on nasal patency have been compared with placebo using three separate measuring systems in normal subjects. METHODS: The study was a placebo-controlled, randomised double-blind crossover trial. Subjects without ear, nose or throat disease and with resting nasal airways resistance >0.15 Pa s cm-3 were selected so that a fall in airways resistance could be detected. Nasal airways resistance (NAR) was measured by NR6-2 rhinomanometer. Acoustic rhinometry (SR-2000 rhinometer) provided the sum of the minimum cross-sectional areas (tMCA) and volume (tVOL) of the left and right nasal cavities. Symptoms of congestion were assessed on a visual analogue scale (CON, range 0-100). Measurements were made for 60 min before and for 120 min after bilateral administration of oxymetazoline nasal spray (0.9 mg) or placebo (0.9% saline). Crossover occurred 7-21 days later. Results for all measures were analysed as change from average baseline value by trapezoidal AUC, and statistical significance was tested by 2-way anova. RESULTS: NAR, tMCA, tVOL and CON did not change after placebo, but NAR and CON fell and tMCA and tVOL increased significantly at all timepoints after oxymetazoline. NAR_AUC, tVOL_AUC, tMCA_AUC were significantly different between placebo and oxymetazoline (P<0.001) as was CON_AUC (P=0.012). The day-to-day intraindividual repeatability of baseline NAR tMCA and tVOL was <10%. CONCLUSIONS: Normal subjects can be used to detect the effects of nasally vasoactive drugs with a variety of complementary systems, with the advantages of easy subject recruitment and low variability.

[Plasmodium falciparum travels by train from Ethiopia to Djibouti]. / Plasmodium falciparum voyage en train d'Ethiopie a Djibouti.

To investigate the role of the Djibouti-Ethiopian railway as a potential vehicle for inter-regional spread of malaria vectors and malaria parasites, we performed a double-sided study, both entomological and parasitological, during November 1989, at the frontier post of Guelile where the trains from Ethiopia enter the Republic of Djibouti. No malaria-transmitting mosquitoes were collected either from the daily passenger train or from the weekly vegetables train. One hundred and five passengers entering Djibouti by train from Ethiopia had a thick film examined for malaria parasites. Five smears were positive for Plasmodium falciparum, among them two showed gametocytes. We conclude that the railway may be an effective route for the propagation of the human malaria parasite between Ethiopia and Djibouti. Indeed, passengers infected abroad could import plasmodia into Djibouti and thus become the index cases for local malaria outbreaks, in case the climatic and entomological prerequisites essential for sustaining malaria transmission are present.