Efficacy, safety, and economic impact of diazepam suppositories with as-needed acetaminophen for prevention of seizure recurrence during the same fever episode in children with suspected simple febrile seizures.

OBJECTIVE: This study was undertaken to evaluate the efficacy, safety, and economic impact of diazepam suppositories with as-needed acetaminophen in comparison with as-needed acetaminophen alone for prevention of seizure recurrence during the same fever episode in suspected pediatric simple febrile seizures (SFS). METHODS: This single-center, prospective, observational study was conducted from July 29, 2019 to February 15, 2021 at a children's hospital. Children aged 6 months to 60 months presenting to the emergency department with suspected SFS were included. Participants receiving both diazepam suppositories and as-needed acetaminophen were compared with those receiving as-needed acetaminophen alone. The primary outcome was seizure recurrence during the same fever episode. The secondary outcomes included the incidence of central nervous system (CNS) pathologies, adverse events, and medical costs. RESULTS: Of the 316 participants, 228 (72.2%) had their first febrile seizure. Diazepam (.3-.5 mg/kg for up to two doses) was administered to 88 of 316 patients (27.8%). The outcomes were available for 306 patients. The recurrence rate was 3.5% (3/85) in the patients receiving diazepam with as-needed acetaminophen and 12.2% (27/221) in the patients receiving as-needed acetaminophen alone (relative risk = .29, 95% confidence interval [CI] = .09-.93, p = .03). The adjusted odds ratio of diazepam administration against recurrence was .23 (95% CI = .07-.78, p = .02). None of the patients had a CNS pathology. No severe adverse events occurred, although mild ataxia was observed significantly more often in the patients receiving diazepam and as-needed acetaminophen (29.4% vs. 18.7%, p = .04). The median medical cost was US $199 (interquartile range [IQR] = 86-244) for the group receiving both medications and US $202 (IQR = 114-242) for the group receiving as-needed acetaminophen alone. SIGNIFICANCE: Compared with as-needed acetaminophen alone, diazepam with as-needed acetaminophen may reduce seizure recurrence more during the same fever episode without severe adverse events or additional costs in children with suspected SFS.

Mass testing and treatment for malaria followed by weekly fever screening, testing and treatment in Northern Senegal: feasibility, cost and impact.

BACKGROUND: Population-wide interventions using malaria testing and treatment might decrease the reservoir of Plasmodium falciparum infection and accelerate towards elimination. Questions remain about their effectiveness and evidence from different transmission settings is needed. METHODS: A pilot quasi-experimental study to evaluate a package of population-wide test and treat interventions was conducted in six health facility catchment areas (HFCA) in the districts of Kanel, Linguère, and Ranérou (Senegal). Seven adjacent HFCAs were selected as comparison. Villages within the intervention HFCAs were stratified according to the 2013 incidences of passively detected malaria cases, and those with an incidence ≥ 15 cases/1000/year were targeted for a mass test and treat (MTAT) in September 2014. All households were visited, all consenting individuals were tested with a rapid diagnostic test (RDT), and, if positive, treated with dihydroartemisinin-piperaquine. This was followed by weekly screening, testing and treatment of fever cases (PECADOM++) until the end of the transmission season in January 2015. Villages with lower incidence received only PECADOM++ or case investigation. To evaluate the impact of the interventions over that transmission season, the incidence of passively detected, RDT-confirmed malaria cases was compared between the intervention and comparison groups with a difference-in-difference analysis using negative binomial regression with random effects on HFCA. RESULTS: During MTAT, 89% (2225/2503) of households were visited and 86% (18,992/22,170) of individuals were tested, for a combined 77% effective coverage. Among those tested, 291 (1.5%) were RDT positive (range 0-10.8 by village), of whom 82% were < 20 years old and 70% were afebrile. During the PECADOM++ 40,002 visits were conducted to find 2784 individuals reporting fever, with an RDT positivity of 6.5% (170/2612). The combination of interventions resulted in an estimated 38% larger decrease in malaria case incidence in the intervention compared to the comparison group (adjusted incidence risk ratio = 0.62, 95% CI 0.45-0.84, p = 0.002). The cost of the MTAT was $14.3 per person. CONCLUSIONS: It was operationally feasible to conduct MTAT and PECADOM++ with high coverage, although PECADOM++ was not an efficient strategy to complement MTAT. The modest impact of the intervention package suggests a need for alternative or complementary strategies.

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.].

Evaluation of perioperative prophylaxis with fosfomycin tromethamine in ureteroscopic stone removal: an investigator-driven prospective, multicenter, randomized, controlled study.

PURPOSE: To compare efficacy, safety, and cost-effectiveness of fosfomycin tromethamine with other standard-of-care antibiotics in patients undergoing ureteroscopic lithotripsy. METHODS: This study was a prospective, multicenter, randomized, controlled trial. Eligible patients scheduled for ureteroscopic lithotripsy were randomly assigned to receive either fosfomycin (fosfomycin group, N = 101 patients) or standard-of-care antibiotic therapy as prophylaxis (control group, N = 115 patients). The incidence of infectious complications and adverse events was analyzed between the two groups, as well as the cost-benefit analysis. RESULTS: The incidence of infections following lithotripsy was 3.0% in the fosfomycin group and 6.1% in the control group (p > 0.05). Only asymptomatic bacteriuria was reported in fosfomycin group. In the control group was reported asymptomatic bacteriuria (3.5%), fever (0.9%), bacteremia (0.9%), and genitourinary infection (0.9%). The rate of adverse events was very low, with no adverse event reported in the fosfomycin group and only one in the control group (forearm phlebitis). The average cost per patient of antibiotic therapy with fosfomycin was 151.45 ± 8.62 yuan (22.7 ± 1.3 USD), significantly lower compared to the average cost per patient of antibiotics used in the control group 305.10 ± 245.95 yuan (45.7 ± 36.9 USD; p < 0.001). CONCLUSIONS: Two oral doses of 3 g fosfomycin tromethamine showed good efficacy and safety and low cost in perioperative prophylaxis of infections following ureteroscopic stone removal.

Travel burden associated with granulocyte colony-stimulating factor administration in a Medicare aged population: a geospatial analysis.

OBJECTIVE: Prophylaxis with granulocyte colony-stimulating factors (G-CSFs) is recommended for patients receiving myelosuppressive chemotherapy regimens with a high risk of febrile neutropenia (FN). G-CSFs should be administered starting the day after chemotherapy, necessitating return trips to the oncology clinic at the end of each cycle. We examined the travel burden related to prophylactic G-CSF injections after chemotherapy in the US. METHODS: We used 2012-2014 Medicare claims data to identify a national cohort of beneficiaries age 65+ with non-myeloid cancers who received both chemotherapy and prophylactic G-CSFs. Patient travel origin was based on residence ZIP code. Oncologist practice locations and hospital addresses were obtained from the Medicare Physician Compare and Hospital Compare websites and geocoded using the Google Maps Application Programming Interface (API). Driving distance and time to the care site from each patient ZIP code tabulation area (ZCTA) were calculated using Open Street Maps road networks. Geographic and socio-economic characteristics of each ZCTA from the US Census Bureau's American Community Survey were used to stratify and analyze travel estimates. RESULTS: The mean one-way driving distance to the G-CSF provider was 23.8 (SD 30.1) miles and the mean one-way driving time was 33.3 (SD 37.8) minutes. When stratified by population density, the mean one-way travel time varied from 12.1 (SD 10.1) minutes in Very Dense Urban areas to 76.7 (SD 72.1) minutes in Super Rural areas. About 48% of patients had one-way travel times of <20 minutes, but 19% of patients traveled ≥50 minutes one way for G-CSF prophylaxis. Patients in areas with above average concentrations of aged, poor or disabled residents were more likely to experience longer travel. CONCLUSIONS: Administration of G-CSF therapy after chemotherapy can present a significant travel burden for cancer patients. Technological improvements in the form and methods of drug delivery for G-CSFs might significantly reduce this travel burden.

A Cluster Randomized Controlled Evaluation of the Health Impact of a Novel Antimicrobial Hand Towel on the Health of Children Under 2 Years Old in Rural Communities in Nyanza Province, Kenya.

To assess the health impact of reusable, antimicrobial hand towels, we conducted a cluster randomized, yearlong field trial. At baseline, we surveyed mothers, and gave four towels plus hygiene education to intervention households and education alone to controls. At biweekly home visits, we asked about infections in children < 2 years old and tested post-handwashing hand rinse samples of 20% of mothers for Escherichia coli. At study's conclusion, we tested 50% of towels for E. coli. Baseline characteristics between 188 intervention and 181 control households were similar. Intervention and control children had similar rates of diarrhea (1.47 versus 1.48, P = 0.99), respiratory infections (1.38 versus 1.48, P = 0.92), skin infections (1.76 versus 1.79, P = 0.81), and subjective fever (2.62 versus 3.40, P = 0.04) per 100 person-visits. Post-handwashing hand contamination was similar; 67% of towels exhibited E. coli contamination. Antimicrobial hand towels became contaminated over time, did not improve hand hygiene, or prevent diarrhea, respiratory infections, or skin infections.

The use of a modified, oscillating positive expiratory pressure device reduced fever and length of hospital stay in patients after thoracic and upper abdominal surgery: a randomised trial.

QUESTION: Does the use of an oscillating positive expiratory pressure (PEP) device reduce postoperative pulmonary complications in thoracic and upper abdominal surgical patients? DESIGN: A multi-centre, parallel-group, randomised controlled trial with intention-to-treat analysis, blinding of some outcomes, and concealed allocation. PARTICIPANTS: A total of 203 adults after thoracic or upper abdominal surgery with general anaesthesia. INTERVENTION: Participants in the experimental group used an oscillating PEP device, thrice daily for 5 postoperative days. Both the experimental and control groups received standard medical postoperative management and early mobilisation. OUTCOME MEASURES: Fever, days of antibiotic therapy, length of hospital stay, white blood cell count, and possible adverse events were recorded for 28 days or until hospital discharge. RESULTS: The 99 participants in the experimental group and 104 in the control group were well matched at baseline and there was no loss to follow-up. Fever affected a significantly lower percentage of the experimental group (22%) than the control group (42%), with a RR of 0.56 (95% CI 0.36 to 0.87, NNT 6). Similarly, length of hospital stay was significantly shorter in the experimental group, at 10.7 days (SD 8.1), than in the control group, at 13.3 days (SD 11.1); the mean difference was 2.6 days (95% CI 0.4 to 4.8). The groups did not differ significantly in the need for antibiotic therapy, white blood cell count or total expense of treatment. CONCLUSION: In adults undergoing thoracic and upper abdominal surgery, postoperative use of an oscillating PEP device resulted in fewer cases of fever and shorter hospital stay. However, antibiotic therapy and total hospital expenses were not significantly reduced by this intervention. TRIAL REGISTRATION: NCT00816881.

Short-term effects of continuous subcutaneous insulin infusion therapy in perioperative patients with diabetes mellitus.

BACKGROUND: Hyperglycemia is common and hard to control in surgical patients with diabetes. We retrospectively investigated short-term effects of continuous subcutaneous insulin infusion (CSII) in perioperative patients with diabetes. PATIENTS AND METHODS: Perioperative patients with diabetes discharged between January 1, 2006 and January 1, 2012 were included. Glucose control and postoperative outcomes were compared between the patients using CSII or non-CSII insulin therapy. RESULTS: We identified 108 pairs of patients matched by propensity and surgical category who were using CSII therapy (CSII group) or non-CSII insulin therapy (control group). The CSII group had significantly lower fasting glucose levels (on the first postoperative day, 9.06±3.09 mmol/L vs. 11.05±4.19 mmol/L; P=0.003) and lower mean glucose levels (on the operation day, 9.93±2.65 mmol/L vs. 12.05±3.86 mmol/L; P=0.001). The CSII group also had a lower incidence of fever (on the first postoperative day, 30.4% vs. 53.2%; P=0.005). Furthermore, patients in the CSII group experienced significantly shorter postoperative intervals for suture removal (P=0.02) and hospital discharge (P=0.03). No significant difference in the total medical expenditure was observed between the two groups (P=0.47). We also made a comparison between the 30 pairs of patients who were using CSII or multiple daily insulin injection therapy but observed no significant difference between these two therapies in glucose control or postoperative outcomes. CONCLUSIONS: Compared with non-CSII insulin therapy, even short-term implementation of CSII can improve the postoperative control of glucose, reduce the incidence of postoperative fever, and shorten the time for suture removal and discharge in surgical patients with diabetes.

An innovative pay-for-performance (P4P) strategy for improving malaria management in rural Kenya: protocol for a cluster randomized controlled trial.

BACKGROUND: In high-resource settings, 'pay-for-performance' (P4P) programs have generated interest as a potential mechanism to improve health service delivery and accountability. However, there has been little or no experimental evidence to guide the development or assess the effectiveness of P4P incentive programs in developing countries. In the developing world, P4P programs are likely to rely, at least initially, on external funding from donors. Under these circumstances, the sustainability of such programs is in doubt and needs assessment. METHODS/DESIGN: We describe a cluster-randomized controlled trial underway in 18 health centers in western Kenya that is testing an innovative incentive strategy to improve management of an epidemiologically and economically important problem--diagnosis and treatment of malaria. The incentive scheme in this trial promotes adherence to Ministry of Health guidelines for laboratory confirmation of malaria before treatment, a priority area for the Ministry of Health. There are three important innovations that are unique to this study among those from other resource-constrained settings: the behavior being incentivized is quality of care rather than volume of service delivery; the incentives are applied at the facility-level rather than the individual level, thus benefiting facility infrastructure and performance overall; and the incentives are designed to be budget-neutral if effective. DISCUSSION: Linking appropriate case management for malaria to financial incentives has the potential to improve patient care and reduce wastage of expensive antimalarials. In our study facilities, on average only 25% of reported malaria cases were confirmed by laboratory diagnosis prior to the intervention, and the total treatment courses of antimalarials dispensed did not correspond to the number of cases reported. This study will demonstrate whether facility rather than individual incentives are compelling enough to improve case management, and whether these incentives lead to offsetting cost-savings as a result of reduced drug consumption. TRIAL REGISTRATION: ClinicalTrials.gov Registration Number NCT01809873.

A retrospective study of patients' out-of-pocket costs for granulocyte colony-stimulating factors.

OBJECTIVE: With rising healthcare costs, there is an increasing concern with the burden of out-of-pocket costs on cancer patients. This study examined patients' out-of-pocket expenditures for granulocyte colony-stimulating factors, pegfilgrastim and filgrastim, which are given to cancer patients receiving myelosuppressive chemotherapy and have been shown to decrease the incidence of febrile neutropenia. METHODS: Adult patients who received chemotherapy and granulocyte colony-stimulating factors in the outpatient setting in the United States between January 2007 and June 2010 were evaluated using medical and pharmacy claims data from two healthcare data sources, the MarketScan(®) Commercial and Medicare Supplemental Databases and the HealthCore Integrated Research Database(SM). The distribution of out-of-pocket costs for granulocyte colony-stimulating factors per patient and per administration was described for each quarter. Longitudinal analyses of out-of-pocket costs for granulocyte colony-stimulating factors were also performed for patients with continuous health plan eligibility during each calendar year from 2007 to 2009. RESULTS: The pattern of out-of-pocket expenditures for pegfilgrastim and filgrastim was generally consistent between the databases and over time. On average, about 65%-75% of patients had zero quarterly out-of-pocket costs for granulocyte colony-stimulating factors. Across the years, the mean quarterly out-of-pocket costs per patient were $100-$150 and $50-$80 for pegfilgrastim and filgrastim, respectively. The mean quarterly out-of-pocket costs for granulocyte colony-stimulating factors per administration were $40-$70 and $8-$10, respectively. CONCLUSION: In this retrospective analysis of medical and pharmacy claims data, most patients who received chemotherapy and granulocyte colony-stimulating factors in 2007 to 2010 had incurred no quarterly out-of-pocket costs associated with G-CSF use.

Comparison of short versus long term antibiotic prophylaxis in elective caesarean section at the Obafemi Awolowo University Teaching Hospitals Complex, Ile-Ife, Nigeria.

AIMS AND OBJECTIVES: This study was to determine any significant difference between the incidence of infectious morbidity with the use of a 24 hour antibiotics regimen compared to a 7-day course of antibiotics following elective caesarean section using a cheap and easily available combination of Ampicillin/Cloxacillin and Metronidazole. PATIENTS AND METHODS: Two hundred patients planned to have elective caesarean section for various indications and who satisfied the inclusion criteria were enrolled in the study in two groups of 100 patients each between the period of January to June 2010. Patients were randomized to receive either Ampiclox as 4 intravenous doses of 1g stat and 500 mg each 6 hourly and Metronidazole as 3 intravenous doses of 500 mg each 8 hourly both for 24 hours or same combination intravenously for 48 hours and subsequent oral use for 5 days. RESULTS: The mean maternal age, parity, gestational age and indication for caesarean section were similar in the two groups of participants. There was no statistical difference in the incidence of febrile morbidity (17%/18%, p=0.852), urinary tract infection (6%/4%, p=0.196), wound infection (4%/3%, p=0.056) and endometritis (3%/2%, p=0.367). The mean cost of antibiotics per patient (N730/$4.65) in the short term prophylaxis group was half that of the long term prophylaxis group (N1, 540/$9.81). CONCLUSION: There was no difference in the incidence of infection related morbidity when short term prophylactic antibiotics was used at elective caesarean section compared to long term prophylactic antibiotics.

Primary prophylaxis with granulocyte colony-stimulating factor (GCSF) reduces the incidence of febrile neutropenia in patients with non-Hodgkin lymphoma (NHL) receiving CHOP chemotherapy treatment without adversely affecting their quality of life: cost-benefit and quality of life analysis.

PURPOSE: Treatment of non-Hodgkin lymphoma (NHL) with cyclophosphamide, vincristine, doxorubicin and prednisone (CHOP) is known to be associated with a significant risk of febrile neutropenia (FN) of up to 50% [Osby et al. 2003 Blood 101(10): 3840-3848; Lyman and Delgado 2003 Cancer 98(11): 2402-2409]. This study sought to examine the impact of primary granulocyte colony-stimulating factor (GCSF) prophylaxis on the incidence of FN, quality of life and overall cost. METHODS: In this retrospective cohort study, a group of 65 consecutive patients who received CHOP chemotherapy for NHL between December 2006 and October 2009 was studied. Patients either received filgrastim (300 mcg, average of seven doses), pegylated filgrastim (6 mg, single dose), or no GCSF prophylaxis. In addition, 19 patients were asked to complete Functional Assessment of Cancer Therapy: General quality-of-life questionnaires. RESULTS: Overall, patients who received primary GCSF prophylaxis had significantly fewer FN compared to those who did not (5 vs. 60%, p < 0.0001; numbers needed to treat of 1.8; 95% confidence interval, 1.6-2.9). Cost-benefit analysis showed that the GCSF prophylaxis was associated with only a small increase in direct financial cost ($238 NZD [US$189] more to give primary GCSF prophylaxis per patient vs. no prophylaxis). The quality of life assessment showed that the patients' quality of life scores were similar to the published data from the validation study population (466 patients with mixed cancers) for Functional Assessment of Cancer Therapy. CONCLUSIONS: Our study shows that primary GCSF prophylaxis is effective in preventing FN in patients receiving CHOP chemotherapy for NHL without adversely affecting their quality of life, and is cost effective.

Pegfilgrastim: a review of the pharmacoeconomics for chemotherapy-induced neutropenia.

For oncology patients, febrile neutropenia (FN) can be a serious and costly toxicity of chemotherapy, often forcing a reduction in chemotherapy dose intensity and/or duration. Several therapeutic agents are used to reduce the occurrence of neutropenic episodes: granulocyte colony-stimulating factors (G-CSFs) and granulocyte-macrophage colony-stimulating factors. Appropriate administration of colony-stimulating factors reduces the risk of FN episodes and the costs associated with FN treatment. In the USA, the two most commonly used G-CSFs are filgrastim and the longer-acting pegfilgrastim. This pharmacoeconomic review of pegfilgrastim briefly considers some of the early research of G-CSFs, then focuses on the most recent comparative studies of pegfilgrastim against the backdrop of forthcoming US patent expiration for both products. The authors conclude with commentary on the market for pegfilgrastim in light of the growing debate surrounding the optimal selection of patients, treatment costs and future alternatives for the use of these agents in chemotherapy.

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.

Pharmacoeconomics of the myeloid growth factors: a critical and systematic review.

BACKGROUND: The pharmacoeconomics of the myeloid growth factors (MGFs) is an important topic that has received substantial attention in recent years. The use of the MGFs as primary prophylaxis to prevent febrile neutropenia (FN) has grown considerably over the past decade and professional guidelines regarding their use have broadened the settings in which these agents are indicated. Recent data also suggest a potential role for them in reducing infection-related and all-cause mortality. The cost and effectiveness of these agents will continue to gain visibility as companies pursue approval for biosimilar agents in the US, similar to their recent approval in Europe. OBJECTIVES: The objective of this paper is to review the available pharmacoeconomic literature on the MGFs, which is particularly timely in light of the recent passage of healthcare reform and the increasing focus on cost control. The cost of treating cancer in the US is rising faster than the already rapid increase in overall medical expenditure. The clinical utility and cost effectiveness of supportive care measures in oncology must therefore be weighed carefully. This review focuses on the use of different formulations of MGFs for primary and secondary prophylaxis of chemotherapy-induced neutropenia. METHODS: A MEDLINE search was performed to find studies that became available since the prior review of this topic was published in Pharmacoeconomics in 2003. RESULTS: Acceptable cost-minimization estimates for primary prophylaxis with the MGFs in patients receiving cancer chemotherapy have been provided by several studies in the US. Of the commonly used agents in the US, pegfilgrastim appears to be superior to the currently recommended dose and schedule of filgrastim in terms of cost minimization, and primary prophylaxis appears to be less costly than secondary prophylaxis. However, the cost benefits of primary prophylaxis in Europe are not as pronounced as in the US, due to the lower costs of medical care. Data continue to emerge suggesting a decreased risk of early mortality from averted infections as well as the possibility of a disease-specific mortality benefit through maintaining the relative dose intensity of chemotherapy with MGF support. CONCLUSION: This evidence will prove valuable in assessing the overall cost effectiveness and cost utility of the MGFs in patients receiving cancer chemotherapy.

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.

Clinical effects of leucoreduction of blood transfusions.

For many years filtration for removal of leucocytes from red blood cell (RBC) and platelet transfusions was applied for selected patients to prevent cytomegalovirus (CMV) (re)activation, HLA immunisation and recurrent febrile nonhaemolytic transfusion reactions (FNHTR ). Since the 1980s, there was also growing concern about cancer recurrence and postoperative infections. In this review we discuss the studies on possible benefits of leucoreduction. In 2001 the Dutch Health Council decided that all blood products should undergo leucoreduction by filtration, as a precautionary measure to reduce possible transmission of variant Creutzfeld-Jacob disease (vCJD). The incidences of transfusion-transmitted CMV infection, HLA immunisation and FN HTR are decreased by universal leucoreduction. However, transfusion-related immunomodulation with presumed negative effects on cancer immunosurveillance, postoperative infections or aggravating organ failure, investigated in randomised controlled trials, revealed no support for extended indications for leucoreduction. An exception was seen in cardiac surgery where leucoreduction reduced short-term mortality by approximately 50%. The exact mechanism(s) for this effect is (are) not known. Pro-inf lammatory cytokines induced by eucocytecontaining RBC transfusions in combination with the inflammatory response after cardiac surgery may aggravate morbidity and could lead to mortality. In this review we discuss the evidence for the benefits of universal leucoreduction. Based on the available evidence, reversal to the use of buffy-coat depleted RBCs and restricted indications for leucoreduction by filtration (extended with open-heart surgery) is a safe option.