Performance Assessment of the Universal Vital Assessment Score vs Other Illness Severity Scores for Predicting Risk of In-Hospital Death Among Adult Febrile Inpatients in Northern Tanzania, 2016-2019.

Importance: Severity scores are used to improve triage of hospitalized patients in high-income settings, but the scores may not translate well to low- and middle-income settings such as sub-Saharan Africa. Objective: To assess the performance of the Universal Vital Assessment (UVA) score, derived in 2017, compared with other illness severity scores for predicting in-hospital mortality among adults with febrile illness in northern Tanzania. Design, Setting, and Participants: This prognostic study used clinical data collected for the duration of hospitalization among patients with febrile illness admitted to Kilimanjaro Christian Medical Centre or Mawenzi Regional Referral Hospital in Moshi, Tanzania, from September 2016 through May 2019. All adult and pediatric patients with a history of fever within 72 hours or a tympanic temperature of 38.0 °C or higher at screening were eligible for enrollment. Of 3761 eligible participants, 1132 (30.1%) were enrolled in the parent study; of those, 597 adults 18 years or older were included in this analysis. Data were analyzed from December 2019 to September 2021. Exposures: Modified Early Warning Score (MEWS), National Early Warning Score (NEWS), quick Sequential Organ Failure Assessment (qSOFA), Systemic Inflammatory Response Syndrome (SIRS) assessment, and UVA. Main Outcomes and Measures: The main outcome was in-hospital mortality during the same hospitalization as the participant's enrollment. Crude risk ratios and 95% CIs for in-hospital death were calculated using log-binomial risk regression for proposed score cutoffs for each of the illness severity scores. The area under the receiver operating characteristic curve (AUROC) for estimating the risk of in-hospital death was calculated for each score. Results: Among 597 participants, the median age was 43 years (IQR, 31-56 years); 300 participants (50.3%) were female, 198 (33.2%) were HIV-infected, and in-hospital death occurred in 55 (9.2%). By higher risk score strata for each score, compared with lower risk strata, risk ratios for in-hospital death were 3.7 (95% CI, 2.2-6.2) for a MEWS of 5 or higher; 2.7 (95% CI, 0.9-7.8) for a NEWS of 5 or 6; 9.6 (95% CI, 4.2-22.2) for a NEWS of 7 or higher; 4.8 (95% CI, 1.2-20.2) for a qSOFA score of 1; 15.4 (95% CI, 3.8-63.1) for a qSOFA score of 2 or higher; 2.5 (95% CI, 1.2-5.2) for a SIRS score of 2 or higher; 9.1 (95% CI, 2.7-30.3) for a UVA score of 2 to 4; and 30.6 (95% CI, 9.6-97.8) for a UVA score of 5 or higher. The AUROCs, using all ordinal values, were 0.85 (95% CI, 0.80-0.90) for the UVA score, 0.81 (95% CI, 0.75-0.87) for the NEWS, 0.75 (95% CI, 0.69-0.82) for the MEWS, 0.73 (95% CI, 0.67-0.79) for the qSOFA score, and 0.63 (95% CI, 0.56-0.71) for the SIRS score. The AUROC for the UVA score was significantly greater than that for all other scores (P < .05 for all comparisons) except for NEWS (P = .08). Conclusions and Relevance: This prognostic study found that the NEWS and the UVA score performed favorably compared with other illness severity scores in predicting in-hospital mortality among a hospitalized cohort of adults with febrile illness in northern Tanzania. Given its reliance on readily available clinical data, the UVA score may have utility in the triage and prognostication of patients admitted to the hospital with febrile illness in low- to middle-income settings such as sub-Saharan Africa.

Pediatric emergency care in a low-income country: Characteristics and outcomes of presentations to a tertiary-care emergency department in Mozambique.

BACKGROUND: An effective pediatric emergency care (PEC) system is key to reduce pediatric mortality in low-income countries. While data on pediatric emergencies from these countries can drive the development and adjustment of such a system, they are very scant, especially from Africa. We aimed to describe the characteristics and outcomes of presentations to a tertiary-care Pediatric Emergency Department (PED) in Mozambique. METHODS: We retrospectively reviewed PED presentations to the "Hospital Central da Beira" between April 2017 and March 2018. Multivariable logistic regression was used to identify predictors of hospitalization and death. RESULTS: We retrieved 24,844 presentations. The median age was 3 years (IQR 1-7 years), and 92% lived in the urban area. Complaints were injury-related in 33% of cases and medical in 67%. Data on presenting complaints (retrieved from hospital paper-based registries) were available for 14,204 (57.2%) records. Of these, respiratory diseases (29.3%), fever (26.7%), and gastrointestinal disorders (14.2%) were the most common. Overall, 4,997 (20.1%) encounters resulted in hospitalization. Mortality in the PED was 1.6% (62% ≤4 hours from arrival) and was the highest in neonates (16%; 89% ≤4 hours from arrival). A younger age, especially younger than 28 days, living in the extra-urban area and being referred to the PED by a health care provider were all significantly associated with both hospitalization and death in the PED at the multivariable analysis. CONCLUSIONS: Injuries were a common presentation to a referral PED in Mozambique. Hospitalization rate and mortality in the PED were high, with neonates being the most vulnerable. Optimization of data registration will be key to obtain more accurate data to learn from and guide the development of PEC in Mozambique. Our data can help build an effective PEC system tailored to the local needs.

The cost-effectiveness of empirical antibiotic treatments for high-risk febrile neutropenic patients: A decision analytic model.

PURPOSE: Febrile neutropenia has a significant clinical and economic impact on cancer patients. This study evaluates the cost-effectiveness of different current empiric antibiotic treatments. METHODS: A decision analytic model was constructed to compare the use of cefepime, meropenem, imipenem/cilastatin, and piperacillin/tazobactam for treatment of high-risk patients. The analysis was performed from the perspective of U.S.-based hospitals. The time horizon was defined to be a single febrile neutropenia episode. Cost-effectiveness was determined by calculating costs and deaths averted. Cost-effectiveness acceptability curves for various willingness-to-pay thresholds (WTP), were used to address the uncertainty in cost-effectiveness. RESULTS: The base-case analysis results showed that treatments were equally effective but differed mainly in their cost. In increasing order: treatment with imipenem/cilastatin cost $52,647, cefepime $57,270, piperacillin/tazobactam $57,277, and meropenem $63,778. In the probabilistic analysis, mean costs were $52,554 (CI: $52,242-$52,866) for imipenem/cilastatin, $57,272 (CI: $56,951-$57,593) for cefepime, $57,294 (CI: $56,978-$57,611) for piperacillin/tazobactam, and $63,690 (CI: $63,370-$64,009) for meropenem. Furthermore, with a WTP set at $0 to $50,000, imipenem/cilastatin was cost-effective in 66.2% to 66.3% of simulations compared to all other high-risk options. DISCUSSION: Imipenem/cilastatin is a cost-effective strategy and results in considerable health care cost-savings at various WTP thresholds. Cost-effectiveness analyses can be used to differentiate the treatments of febrile neutropenia in high-risk patients.

Vehicular Hyperthermia-A Highly Preventable and Potentially Fatal Problem.

A child dying of heat injury due to being left unattended in a motor vehicle is a needless tragedy. Each year in the United States an average of 38 children mostly younger than age 2 years die of vehicular hyperthermia, frequently the result of a parental lapse of attention and not intentional neglect. Serious illness results quickly from exposure to rising heat within the passenger compartment, even on days when the temperature is fairly moderate. Prevention is paramount in addressing this problem and can best be accomplished by a combination of technological means, such as passive warning systems, laws that make leaving a child in a car alone illegal, and public education campaigns. [Pediatr Ann. 2018;47(3):e88-e90.].

Pre-hospital ambulance care of patients following a suspected seizure: A cross sectional study.

PURPOSE: We aimed to investigate the characteristics of patients presenting to the ambulance service with suspected seizures, the costs of managing these patients and the factors which predicted transport to hospital. METHODS: We employed a cross-sectional design using routine clinical data from a UK regional ambulance service. Logistic regression was used to identify predictors of transport to hospital from ambulance response times, demographics, clinical (physiological) findings and treatments. RESULTS: There were 177,715 emergency incidents recorded in 2011/12 of which 2.9% (5139/177,715) were classified as seizures by ambulance call handlers and 2.7% (4884/177,715) by paramedics on the scene. Suspected seizures were the seventh most common call type. The annual cost of managing these incidents was £890,148. Clinical and physiological variables were normal for most patients. 59.3% (2894/4884) of patients were transported to hospital. 1/4884 (0.02%) patient died. Administration of diazepam, insertion of an airway and pyrexia perfectly predicted transport to hospital, tachycardia had a modest association, but other variables were only weak predictors of transport to hospital. CONCLUSIONS: This study shows that most patients after a suspected seizure are not acutely unwell but nevertheless most patients are transported to hospital. Further research is required to determine which factors are important in decisions to transport to hospital and to create evidence-based tools to help paramedics identify patients who could be safely managed without transport to hospital.

Assessment of risk factors for post-rewarming "rebound hyperthermia" in cardiac arrest patients undergoing therapeutic hypothermia.

INTRODUCTION: The outcomes associated with therapeutic hypothermia (TH) after cardiac arrest, while overwhelmingly positive, may be associated with adverse events. The incidence of post-rewarming rebound hyperthermia (RH) has been relatively unstudied and may worsen survival and neurologic outcome. The purpose of this study was to determine the incidence and risk factors associated with RH as well as its relationship to mortality, neurologic morbidity, and hospital length of stay (LOS). METHODS: A retrospective, observational study was performed of adult patients who underwent therapeutic hypothermia after an out-of-hospital cardiac arrest. Data describing 17 potential risk factors for RH were collected. The primary outcome was the incidence of RH while the secondary outcomes were mortality, discharge neurologic status, and LOS. RESULTS: 141 patients were included. All 17 risk factors for RH were analyzed and no potential risk factors were found to be significant at a univariate level. 40.4% of patients without RH experienced any cause of death during the initial hospitalization compared to 64.3% patients who experienced RH (OR: 2.66; 95% CI: 1.26-5.61; p=0.011). The presence of RH is not associated with an increase in LOS (10.67 days vs. 9.45 days; absolute risk increase=-1.21 days, 95% CI: -1.84 to 4.27; p=0.434). RH is associated with increased neurologic morbidity (p=0.011). CONCLUSIONS: While no potential risk factors for RH were identified, RH is a marker for increased mortality and worsened neurologic morbidity in cardiac arrest patients who have underwent TH.

Primary prophylactic colony-stimulating factors for the prevention of chemotherapy-induced febrile neutropenia in breast cancer patients.

BACKGROUND: High-dose or dose-intensive cytotoxic chemotherapy often causes myelosuppression and severe neutropenia among cancer patients. Severe neutropenia accompanied by fever, named febrile neutropenia (FN), is the most serious manifestation of neutropenia usually requiring hospitalization and intravenous antibiotics. FN and neutropenia can lead to chemotherapy treatment delays or dose reductions, which potentially compromises the effectiveness of cancer treatment and prospects for a cure. Granulocyte-macrophage (GM) and granulocyte colony-stimulating factors (G-CSFs) are administered during chemotherapy in order to prevent or reduce the incidence or the duration of FN and neutropenia. OBJECTIVES: To assess the effect of prophylactic colony-stimulating factors (CSFs) in reducing the incidence and duration of FN, and all-cause and infection-related mortality during chemotherapy in patients with breast cancer. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, HEALTHSTAR, International Health Technology Assessment, SOMED, AMED and BIOSIS up to 8 August 2011. We also searched three Chinese databases (VIP, CNKI, CBM), the metaRegister of Controlled Trials, ClinicalTrials.gov, the World Health Organization's International Clinical Trials Registry Platform (WHO ICTRP) and OpenGrey.eu up to August 2011. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing CSFs (any dose) with placebo or no treatment in patients with breast cancer at any stage, at risk of developing FN while undergoing any type of chemotherapy. DATA COLLECTION AND ANALYSIS: We used pooled risk ratios (RR) with 95% confidence intervals (CIs) for binary outcomes. At least two review authors independently extracted data and assessed the risk of bias of the included studies. Trial authors were contacted for further details when information was unclear. MAIN RESULTS: We included eight RCTs involving 2156 participants with different stages of breast cancer and chemotherapy regimens. The trials were carried out between 1995 and 2008 and judged as being at least at moderate risk of bias. The strength of the evidence was weak for the majority of outcomes, which was mostly because of the small numbers of evaluable patients, varying definitions, as well as unclear measurements of the trials' outcomes and uncertain influences of supportive treatments on them. In most trials, the chemotherapy regimens had a risk of FN that was below the threshold at which current guidelines recommend routine primary prophylaxis with CSFs. Using CSFs significantly reduced the proportion of patients with FN (RR 0.27; 95% CI 0.11 to 0.70; number needed to treat for an additional beneficial outcome (NNTB) 12) but there was substantial heterogeneity which can be explained by possible differential effects of G-CSFs and GM-CSFs and different definitions of FN. A significant reduction in early mortality was observed in CSF-treated patients compared to placebo or no treatment (RR 0.32; 95% CI 0.13 to 0.77; NNTB 79). This finding was based on 23 fatal events in 2143 patients; wherein 19 of these 23 events occurred in one study and 17 events were attributed to progression of the disease by the study authors. For infection-related mortality, there were no significant differences between CSF and control groups (RR 0.14; 95% CI 0.02 to 1.29). In CSF-treated patients, the risk for hospitalization was significantly reduced (RR 0.14; 95% CI 0.06 to 0.30; NNTB 13), as well as the use of intravenous antibiotics (RR 0.35; 95% CI 0.22 to 0.55; NNTB 18). The risks of severe neutropenia, infection or not maintaining the scheduled dose of chemotherapy did not differ between CSF-treated and control groups. CSFs frequently led to bone pain (RR 5.88; 95% CI 2.54 to 13.60; number needed to treat for an additional harmful outcome (NNTH) 3) and injection-site reactions (RR 3.59; 95% CI 2.33 to 5.53; NNTH 3). AUTHORS' CONCLUSIONS: In patients with breast cancer receiving chemotherapy, CSFs have shown evidence of benefit in the prevention of FN. There is evidence, though less reliable, of a decrease of all-cause mortality during chemotherapy and a reduced need for hospital care. No reliable evidence was found for a reduction of infection-related mortality, a higher dose intensity of chemotherapy with CSFs or diminished rates of severe neutropenia and infections. The majority of adverse events reported from CSF use were bone pain and injection-site reactions but no conclusions could be drawn regarding late-term side effects.

Thermal protection of the newborn in resource-limited environments.

Appropriate thermal protection of the newborn prevents hypothermia and its associated burden of morbidity and mortality. Yet, current global birth practices tend to not adequately address this challenge. Here, we discuss the pathophysiology of hypothermia in the newborn, its prevention and therapeutic options with particular attention to resource-limited environments. Newborns are equipped with sophisticated mechanisms of body temperature regulation. Neonatal thermoregulation is a critical function for newborn survival, regulated in the hypothalamus and mediated by endocrine pathways. Hypothermia activates cellular metabolism through shivering and non-shivering thermogenesis. In newborns, optimal temperature ranges are narrow and thermoregulatory mechanisms easily overwhelmed, particularly in premature and low-birth weight infants. Hyperthermia most commonly is associated with dehydration and potentially sepsis. The lack of thermal protection promptly leads to hypothermia, which is associated with detrimental metabolic and other pathophysiological processes. Simple thermal protection strategies are feasible at community and institutional levels in resource-limited environments. Appropriate interventions include skin-to-skin care, breastfeeding and protective clothing or devices. Due to poor provider training and limited awareness of the problem, appropriate thermal care of the newborn is often neglected in many settings. Education and appropriate devices might foster improved hypothermia management through mothers, birth attendants and health care workers. Integration of relatively simple thermal protection interventions into existing mother and child health programs can effectively prevent newborn hypothermia even in resource-limited environments.

Assessment of the safety and feasibility of administering anti-pyretic therapy in critically ill adults: study protocol of a randomized trial.

BACKGROUND: Fever is one of the most commonly observed abnormal signs in patients with critical illness. However, there is a paucity of evidence to guide the management of febrile patients without acute brain injury and little is known about the biologic response to treatment of fever. As such, observational studies suggest that the treatment of fever is inconsistent. This pilot clinical trial will assess the safety and feasibility of treating febrile critically ill adult patients with an aggressive versus a permissive temperature control strategy. The biologic response to these two different temperature control strategies will also be assessed through analysis of a panel of inflammatory mediators. FINDINGS: The study population will include febrile adult patients admitted to one of two general medical-surgical intensive care units (ICUs) in Calgary, Alberta, Canada. Patients will be randomized to either an aggressive or permissive fever treatment strategy. The aggressive group will receive acetaminophen 650 mg enterally every 6 hours upon reaching a temperature ≥ 38.3 °C and external cooling will be initiated for temperatures ≥ 39.5 °C, whereas the permissive group will receive acetaminophen 650 mg every 6 hours upon reaching a temperature ≥ 40.0 °C and external cooling for temperatures ≥ 40.5 °C. The study will take place over 12 months with the goal of enrolling 120 patients. The primary outcome will be 28-day mortality after study enrolment, with secondary outcomes that will include markers of feasibility (e.g. the enrolment rate, and the number of protocol violations), and levels of select inflammatory and anti-inflammatory mediators. DISCUSSION: Results from this study will lead to a better understanding of the inflammatory effects of anti-pyretic therapy and will evaluate the feasibility of a future clinical trial to establish the best treatment of fever observed in nearly one half of patients admitted to adult ICUs. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01173367.

Assessment of an alternative meropenem dosing strategy compared with imipenem-cilastatin or traditional meropenem dosing after cefepime failure or intolerance in adults with neutropenic fever.

STUDY OBJECTIVE: To compare clinical outcomes of patients receiving an alternative dosage of meropenem with those of patients receiving imipenem-cilastatin or the traditional dosage of meropenem after failure of or intolerance to cefepime for treatment of febrile neutropenia. DESIGN: Retrospective, single-center cohort study. SETTING: 1250-bed urban academic medical center. PATIENTS: One hundred twenty-seven adults with neutropenic fever who received either imipenem-cilastatin or meropenem; imipenem-cilastatin was the preferred carbapenem until September 1, 2006, after which meropenem became the formulary carbapenem. MEASUREMENTS AND MAIN RESULTS: Of the 127 patients, 40 received imipenem-cilastatin 500 mg every 6 hours between September 1, 2005, and August 31, 2006; 87 patients received meropenem between September 1, 2006, and August 31, 2007: 29 received a traditional dosage of meropenem 1 g every 8 hours, and 58 received an alternative dosage of meropenem 500 mg every 6 hours. Primary outcomes of time to defervescence (median 3 vs 2 vs 3 days), need for additional antibiotics (20% vs 17% vs 14%), and time to receipt of additional antibiotics (median 5 vs 2 vs 1 days) were not significantly different among the imipenem-cilastatin, traditionally dosed meropenem, and alternatively dosed meropenem groups, respectively. In addition, significant differences in secondary outcomes, which were treatment duration (median 10 vs 8 vs 8 days), seizure rate (0% vs 0% vs 0%), in-hospital mortality (5% vs 7% vs 7%), and 30-day mortality (13% vs 7% vs 14%), were not identified among the three groups, respectively. CONCLUSION: The alternative meropenem dosage of 500 mg every 6 hours yielded similar patient outcomes, including time to defervescence, need for additional antibiotics, duration of therapy, and mortality, when compared with the traditional meropenem dosage and imipenem-cilastatin in adults with febrile neutropenia. In addition, no adverse effects on clinical outcomes were observed with the alternative dosage of meropenem.

Malaria treatment: no place like home.

If the United Nations Millennium Development Goals are to be met, there is a need to improve access to effective antimalarial treatment where the burden of malaria is highest. Health facilities are often bypassed by communities, and inappropriate and poor-quality self-medication is common. The home management of malaria (HMM) strategy has been shown to have an effect on malaria morbidity and mortality in the chloroquine era, but several evidence gaps remain to be filled to confirm its value in the era of artemisinin-based combination therapies. Nevertheless, if a substantial reduction of the malaria burden is to be achieved, access to effective medicines has to be vastly improved, and in most of sub-Saharan Africa, this will have to be through HMM.

Factors influencing in-hospital length of stay and mortality in cancer patients suffering from febrile neutropenia.

INTRODUCTION: Febrile neutropenia (FN) is a major complication of chemotherapy, costly in terms of morbidity, mortality and associated financial expenditure. The present study was conducted with the goal of highlighting FN as a serious problem in Pakistan, with the longer term objective of improved cancer survival, reduction in length of stay (LOS) in hospital, morbidity, mortality and costs in our existing developing country scenario. METHODS: A cross-sectional descriptive study was conducted on patients, > or =18 years, admitted with FN as a consequence of chemotherapy at a referral hospital in Karachi from 1st September 2006 to 30th April 2007. RESULTS: A total of 80 patients [43 (53.8%) males and 37 (46.2%) females] were selected. The mean age was 47.4 (SD +/-16.6; range 18-79) years. Sixty eight patients (86%) were < or = 65 years, 50% were < or = 50 years. Overall, inhospital mortality was 11%; 4% for patients on granulocyte colony stimulating factor (G-CSF) prophylaxis as against 20% for those without. The cause of death was either pneumonia or septic shock. Mean LOS was 7.53 (SD +/-3.8; range 2-17) days. Hematological malignancies, older age, severity of dehydration, pneumonia and culture positivity were significantly associated with LOS and death. Those above 50 years of age were 1.5 times as likely to be hospitalized longer and > three times as likely to die. Bacteremia conferred a 5-fold and pneumonia an 8-fold increase in the risk of death. CONCLUSION: The results of this study indicate that age, vital instability, dehydration, high creatinine, culture positivity and hematological malignancies are high risk factors in chemotherapy induced FN. Identification of FN risk factors with poor outcomes may help in devising protocols for modified dosage or including GCFs initially. This may help reduce the cost of cancer care as well as mortality and morbidity. Prospective studies of FN in multiple centers in Pakistan may be beneficial in evaluating these risk factors further.

A comparison of florfenicol and tulathromycine for the treatment of undifferentiated fever in feedlot calves.

The purpose of this study was to compare the relative cost-effectiveness of florfenicol with that of tulathromycin for treatment of undifferentiated fever (UF) in feedlot calves at ultra-high risk of developing UF that receive metaphylactic tulathromycin on arrival at the feedlot. Calves that received therapeutic florfenicol had lower overall mortality (P=.045) and bovine respiratory disease mortality (P=.050) compared with calves that received therapeutic tulathromycin, but no significant differences were detected in feedlot performance, carcass characteristics, or other animal health variables. There was a net advantage of Can$41.19/treated animal in the florfenicol group versus the tulathromycin group. This study demonstrates that it is more cost-effective to use florfenicol than tulathromycin for the initial treatment of UF in feedlot calves at ultra-high risk of developing UF that receive on-arrival metaphylactic tulathromycin.

The impact of hyperthermia and infection on acute ischemic stroke patients in the intensive care unit.

INTRODUCTION: Despite the recognized deleterious effects of hyperthermia on critically ill neurological patients, few investigations have studied hyperthermia after an ischemic stroke in the intensive care unit (ICU) setting. METHODS: Acute ischemic stroke patients admitted to the ICU were assigned to one of three groups: normothermia, mild hyperthermia (MH), or severe hyperthermia (SH). The etiology of hyperthermia was further divided into infectious and non-infectious groups. RESULTS: Among the 150 patients included in the study, MH and SH were observed in 15 and 40 patients, respectively. Hyperthermia and the Glasgow coma scale (GCS) score were independently related to in-hospital mortality and increased length of stay in the ICU (ILOS, > or =4 days). DISCUSSION: Infection (39 patients) was more prevalent in the SH group than in the MH group and was associated with greater ILOS. CONCLUSIONS: Monitoring and managing infection and reducing body temperature may be important factors for determining the outcomes of patients with acute ischemic stroke admitted to the ICU.

Therapeutic use of granulocyte colony-stimulating factors for established febrile neutropenia: effect on costs from a hospital perspective.

BACKGROUND: The prophylactic use of granulocyte colony-stimulating factors (G-CSFs) reduces the severity and duration of neutropenia and reduces the incidence of febrile neutropenia after cancer chemotherapy. However, the use of G-CSFs, particularly filgrastim, to treat established neutropenia remains controversial. A recent meta-analysis of randomised controlled trials (RCTs) evaluating G-CSF treatment for established febrile neutropenia demonstrated a reduction in prolonged hospitalisations. Because more than one-third of patients in the analysis were hospitalised for at least 10 days, this finding has broad pharmacoeconomic and clinical significance. This analysis presents the potential cost implications of G-CSF treatment for established neutropenia among hospitalised patients. METHODS: Direct medical costs ($US, year 2003 values) related to hospitalisation for established neutropenia were modelled using a hospital perspective and according to two treatment options: (i) no use of G-CSF during the neutropenic episode (control); and (ii) addition of daily G-CSF until neutrophil recovery. Within each option, we modelled the probability of a long stay (>or=10 days) and patient survival. The model used three data sets: discharge data from a consortium of academic medical institutions, drug cost data (filgrastim) from Federal payers, and estimates of G-CSF efficacy derived from a meta-analysis of RCTs of treatment in patients with established febrile neutropenia. The lowest expected total cost was predicted for both treatment options; sensitivity analyses and Monte Carlo simulations were used to evaluate the robustness of the model. RESULTS: The G-CSF arm produced the lowest expected cost, and predicted net estimated savings of $US1046 per neutropenic episode compared with the control strategy. G-CSF was less expensive than the control for most reasonable estimates of cost per day and all lengths of stay (LOS) >or=10 days. G-CSF was the least costly strategy for 73.5% of 10,000 Monte Carlo iterations, while the no-G-CSF control strategy predicted savings in 26.5% of iterations. CONCLUSIONS: This pharmacoeconomic model suggests that therapeutic use of G-CSF should be considered for patients with established neutropenia in order to reduce overall hospital cost. G-CSF treatment may offer substantial potential savings for hospitalised patients with established neutropenia over a wide range of model assumptions. Therapeutic G-CSF use among patients hospitalised for established neutropenia may complement the recommended prophylactic use of these agents for the prevention of neutropenic episodes.

Acetaminophen and diphenhydramine premedication for allergic and febrile nonhemolytic transfusion reactions: good prophylaxis or bad practice?

Febrile nonhemolytic and allergic reactions are the most common transfusion reactions, but usually do not cause significant morbidity. In an attempt to prevent these reactions, US physicians prescribe acetaminophen or diphenhydramine premedication before more than 50% of blood component transfusions. Acetaminophen and diphenhydramine are effective therapies for fever and allergy, respectively, so their use in transfusion has some biologic rationale. However, these medications also have potential toxicity, particularly in ill patients, and in the studies performed to date, they have failed to prevent transfusion reactions. Whether the benefits of routine prophylaxis with acetaminophen and diphenhydramine outweigh their risks and cost requires reexamination, particularly in light of the low reaction rates reported at many institutions even when premedication is not prescribed.

Mortality and adverse health events in newly admitted nursing home residents with and without dementia.

OBJECTIVES: To evaluate the association between dementia and mortality, adverse health events, and discharge disposition of newly admitted nursing home residents. It was hypothesized that residents with dementia would die at a higher rate and develop more adverse health events (e.g., infections, fevers, pressure ulcers, falls) than residents without dementia because of communication and self-care difficulties. DESIGN: An expert clinician panel diagnosed an admission cohort from a stratified random sample of 59 Maryland nursing homes, between 1992 and 1995. The cohort was followed for up to 2 years or until discharge. SETTING: Fifty-nine Maryland nursing homes. PARTICIPANTS: Two thousand one hundred fifty-three newly admitted residents aged 65 and older not having resided in a nursing home for 8 or more days in the previous year. MEASUREMENTS: Mortality, infection, fever, pressure ulcers, fractures, and discharge home. RESULTS: Residents with dementia had significantly lower overall rates of infection (relative risk (RR)=0.77, 95% confidence interval (CI)=0.70-0.85) and mortality (RR=0.61, 95% CI=0.53-0.71) than those without dementia, whereas rates of fever, pressure ulcers, and fractures were similar for the two groups. These results persisted when rates were adjusted for demographic characteristics, comorbid conditions, and functional status. During the first 90 days of the nursing home stay, residents with dementia had significantly lower rates of mortality if not admitted for rehabilitative care under a Medicare qualifying stay (RR=0.25, 95% CI=0.14-0.45), were less often discharged home (RR=0.33, 95% CI=0.28-0.38), and tended to have lower fever rates (RR=0.78, 95% CI=0.63-0.96) than residents without dementia. CONCLUSION: Newly admitted nursing home residents with dementia have a profile of health events that is distinct from that of residents without dementia, indicating that the two groups have different long-term care needs. Results suggest that further investigation of whether residents with dementia can be well managed in alternative residential settings would be valuable.

An evaluation of the relative efficacy of a new formulation of oxytetracycline for the treatment of undifferentiated fever in feedlot calves in western Canada.

A field trial was performed under commercial feedlot conditions in western Canada to compare the efficacy of a new formulation of long-acting oxytetracycline (LA 30) to a standard long-acting oxytetracycline formulation (LA 20) and florfenicol (FLOR) for the treatment of undifferentiated fever (UF) in calves that received metaphylactic tilmicosin upon arrival at the feed-lot. Seven hundred and ninety-seven recently weaned, auction market derived, crossbred, beef calves suffering from UF were allocated to 1 of 3 experimental groups as follows: LA 30, which received intramuscular long-acting oxytetracycline (300 mg/mL formulation) at the rate of 30 mg/kg body weight (BW) at the time of allocation; LA 20, which received intramuscular long-acting oxytetracycline (200 mg/mL formulation) at the rate of 20 mg/kg BW at the time of allocation; or FLOR, which received intramuscular florfenicol administered at the rate of 20 mg/kg BW at the time of allocation and again 48 hours later. Two hundred and sixty-six animals were allocated to the LA 30 group, 265 animals were allocated to the LA 20 group, and 266 animals were allocated to the FLOR group. The relative efficacy of the LA 30 group, as compared with the LA 20 and FLOR groups, was assessed by comparing relapse, chronicity, wastage, and mortality rates. The overall mortality (RR = 0.50) rate in the LA 30 group was significantly (P < 0.05) lower than in the LA 20 group. However, the overall chronicity (RR = 2.56) and overall wastage (RR = 6.97) rates of the LA 30 group were significantly (P < 0.05) higher than in the LA 20 group. There were no significant (P > or = 0.05) differences in UF relapse rates or cause specific mortality rates between the LA 30 and LA 20 groups. In the economic analysis, there was an advantage of $28.59 CDN per animal in the LA 30 group compared with the LA 20 group. The overall chronicity (RR = 2.25) and overall wastage (RR = 2.80) rates of the LA 30 group were significantly (P < 0.05) higher than the FLOR group. There were no significant (P > or = 0.05) differences in UF relapse rates, overall mortality rates, or cause specific mortality rates between the LA 30 and FLOR groups. In the economic analysis, there was an advantage of $12.90 CDN per animal in the LA 30 group compared with the FLOR group. In summary, the results of this study indicate that it is more cost-effective to use a new formulation of long-acting oxytetracycline (300 mg/mL formulation administered at a rate of 30 mg/kg BW) than a standard long-acting oxytetracycline formulation (200 mg/mL formulation administered at a rate of 20 mg/kg BW) or florfenicol for the treatment of UF in feedlot calves that have previously received metaphylactic tilmicosin upon arrival at the feedlot.

Determinants of mortality among children in the urban slums of Dhaka city, Bangladesh.

The growing slum population in the developing world is an increasing challenge for local health authorities. Little is known of the patterns of disease occurrence including treatment types offered in this population. The paper describes reported child mortality and its determinants, including the main diseases affecting children and treatments, in the slum population of Dhaka city, Bangladesh. 1500 households in three slum communities were included in a cross-sectional survey. Reported death rates in the households per 1000 children (0-107 months) within the last year from the interview were 20.5 for boys and 27.0 for girls. More girls than boys died in infancy (age < 12 months). The most frequent reported causes of deaths were tetanus in infancy and diarrhoea among children aged < or = 12 months. Vaccination coverage (DPT, polio, measles and BCG) was 73% for children < 3 years of age. The results showed that gender difference in mortality may have been influenced by the patterns of treatment received during sickness and the choice of treatment was determined by the financial ability of the households. Household income, children's vaccinations, TT immunization of mothers and personal cleanliness appeared to be significantly associated with child mortality. Despite the relatively high vaccination coverage for this population, child mortality remained alarmingly high, indicating that socioeconomic and environmental conditions must be improved to substantially reduce morbidity and mortality in this population.

1983 Henderson Award Lecture. Thermal homeostasis in old age.

The relationships of homeostasis to the physiologic and socioeconomic concomitants of aging are presented. Neurohumoral control of body temperature may become deranged in old age as a result of changes in the intrinsic regulatory system. Drugs and stressful climatic temperatures can have deleterious effects. Sensitivity of the elderly to environmental temperature changes is diminished, and their resources to control environmental temperatures are likely to be limited, leaving them more vulnerable than the young to hypothermia and hyperthermia.