A comparison of health care and blood supply system structures.

There is great diversity in the practice of blood banking and transfusion medicine between countries. We sought to relate this to the variety of health care and blood supply systems in different countries. Questionnaires were completed by respondents from 15 countries selected from among those with higher Human Development Indices. These data were reviewed searching for correlations with blood banking and transfusion medicine practices. Wide varieties of health care and blood supply schemes were documented. There was no apparent relationship between their structure and organization nor their financing arrangements and their proclivity for the implementation of new methods or approaches such as pathogen inactivation and universal leucoreduction. The costs of the operation of the blood supply system as represented by their product fees and the rate of collection of red cells could also not be associated with the factors examined. The diversity of practice evident across developed countries is not explicable solely through their health care and blood supply system structures. Other factors are likely involved but are not easy to define or measure.

Inventory management.

A critical aspect of blood transfusion is the timely provision of high quality blood products. This task remains a significant challenge for many blood services and blood systems reflecting the difficulty of balancing the recruitment of sufficient donors, the optimal utilization of the donor's gift, the increasing safety related restrictions on blood donation, a growing menu of specialized blood products and an ever-growing imperative to increase the efficiency of blood product provision from a cost perspective. As our industry now faces questions about our standard practices including whether or not the age of blood has a negative impact on recipients, it is timely to take a look at our collective inventory management practices. This International Forum represents an effort to get a snap shot of inventory management practices around the world, and to understand the range of different products provided for patients. In addition to sharing current inventory management practices, this Forum is intended to foster an exchange of ideas around where we see our field moving with respect to various issues including specialty products, new technologies, and reducing recipient risk from blood transfusion products.

Hospital cost and efficiency: do hospital size and ownership type really matter?

The primary research question this study addresses is, do size and ownership type make a difference in the efficiency and cost results of hospitals in Washington State? A further question is, what factors might explain such differences? The data source is the hospital financial data reports Washington hospitals submit to the Washington Department of Health. The sample was restricted to not-for-profit and government-owned hospitals, given that these ownership types are predominant in Washington State, and there are only two investor-owned hospitals. The measures of efficiency and cost represent the generally accepted financial indicators derived from the healthcare financial management literature. Cost and efficiency in these hospitals are analyzed using five efficiency ratios and five cost measures. The results are significant for five of the ten measures studied. Measured by occupancy percentage, small and large not-for-profit hospitals appear to achieve higher efficiency levels than government-owned hospitals do, but the larger hospitals of both ownership types report greater efficiency than that achieved by smaller hospitals. In terms of costs, small, not-for-profit hospitals report comparable costs to those of the largest hospitals, likely because 70 percent of the small not-for-profits are critical access hospitals. These findings deserve further study on a regional or national level. A more scientific study of the efficiency and cost of hospitals by size and ownership type would be important to control for case mix, scope of services, and payer mix. Such studies can generate important findings about the relationship of hospital size and ownership type to efficiency and cost. Conducted on a national level, such studies would provide policymakers with the empirical data they need to make decisions regarding the types of hospitals to encourage or discourage in the future.

Selective vitrification of euploid oocytes markedly improves survival, fertilization and pregnancy-generating potential.

Enthusiasm for oocyte cryopreservation has been limited by poor pregnancy rates per thawed metaphase II (MII) oocytes (<4%) and low implantation rates per embryos. The reasons relate to technical limitations in the freezing process, and the fact that <40% of oocytes are euploid and unable to produce 'competent' embryos. Comparative genomic hybridization was performed on the first polar body (PB-1) of 323 MII oocytes retrieved from 16 donors. Of these, 111 were euploid, and were vitrified. Seventy-five of 78 vitrified oocytes (96%) survived warming and were fertilized using intracytoplasmic sperm injection. Thirty-one (41%) subsequently developed into expanded blastocysts, of which no more than two were subsequently transferred per uterus to 16 out of 19 prospective embryo recipients. Twelve of 19 (63%) recipients produced 17 healthy babies (eight singletons, three twins, and one set of triplets) One twin pregnancy miscarried in the late first trimester The birth rate per transfer of a maximum of two blastocysts to 16 recipients was 75%. The implantation rate per vitrified euploid oocyte was 27%. This study showed a six-fold improvement in pregnancy rate per cryopreserved oocyte over previous reports and a marked improvement in implantation rate. If independently validated, this approach could open the door to commercial egg cryobanking, significantly expanding women's reproductive choices.

The early indicators of financial failure: a study of bankrupt and solvent health systems.

This article presents a series of pertinent predictors of financial failure based on analysis of solvent and bankrupt health systems to identify which financial measures show the clearest distinction between success and failure. Early warning signals are evident from the longitudinal analysis as early as five years before bankruptcy. The data source includes seven years of annual statements filed with the Securities and Exchange Commission by 13 health systems before they filed bankruptcy. Comparative data were compiled from five solvent health systems for the same seven-year period. Seven financial solvency ratios are included in this study, including four cash liquidity measures, two leverage measures, and one efficiency measure. The results show distinct financial trends between solvent and bankrupt health systems, in particular for the operating-cash-flow-related measures, namely Ratio 1: Operating Cash Flow Percentage Change, from prior to current period; Ratio 2: Operating Cash Flow to Net Revenues; and Ratio 4: Cash Flow to Total Liabilities, indicating sensitivity in the hospital industry to cash flow management. The high dependence on credit from third-party payers is cited as a reason for this; thus, there is a great need for cash to fund operations. Five managerial policy implications are provided to help health system managers avoid financial solvency problems in the future.

Response to cotrimoxazole in the management of childhood pneumonia in first-level health care facilities.

BACKGROUND: Reports of high levels of antimicrobial resistance to cotrimoxazole in children with non-severe pneumonia (NSP) have prompted calls for a change to amoxicillin in the therapeutic guidelines at the first-level health care facility (FLHF). FLHFs lack data about the use of World Health Organization (WHO) acute respiratory infection (ARI) standard case management (SCM). OBJECTIVE: To apply ARI SCM guidelines at the FLHF, assess clinical outcome of NSP with oral cotrimoxazole and determine the risk factors influencing treatment outcome. DESIGN: Health care workers (HCWs) at 14 health centres managed children aged 2-59 months with NSP according to ARI SCM guidelines. The primary outcome was treatment failure, including change of antibiotic therapy and loss to follow-up. RESULTS: Of 949 children enrolled, 110 (11.6%) failed therapy with oral cotrimoxazole. Clinical failure was significantly higher among children presenting with a fast respiratory rate of > or = 15 breaths/min above normal for age and wheezing on examination. CONCLUSIONS: To treat children with NSP at the FLHF, oral cotrimoxazole is an acceptable treatment choice in view of the efficacy, cost and ease of use. In children with wheezing and signs of pneumonia, the decision to use antibiotic therapy should be made after a trial of bronchodilator therapy.

Diabetic nephropathy in hypertransfused patients with beta-thalassemia. The role of oxidative stress.

OBJECTIVE: Pathogenesis of diabetes-related microvascular complications involving oxidative damage by free radicals has been demonstrated. Free radical generation has been shown to derive largely from iron. Our objectives, therefore, were to determine if there is an increased incidence and/or an accelerated course of nephropathy in patients with diabetes, secondary to transfusional hemochromatosis, and to examine whether free radical activity contributes to the development of this complication. RESEARCH DESIGN AND METHODS: We evaluated nine patients with homozygous beta-thalassemia, complicated by clinically overt diabetes, for diabetic nephropathy over a 7-year period. Lipid peroxidation was quantified by measuring the presence of 20 saturated and unsaturated aldehydes, and results were compared with five normotensive type 1 diabetic patients without iron overload. RESULTS: Nephropathy developed in five of nine patients (55%) after a mean duration of overt diabetes of 3.6 +/- 2.0 years. Three patients showed evidence of progressive microalbuminuria over a 7-year period (24.7-46.2, 52.2-430.1, and 17.7-54.3 micrograms/min, respectively). Two patients with borderline microalbuminuria (19.9 and 14.5 micrograms/min, respectively) demonstrated stable albumin excretion rates over the follow-up period. Total aldehyde concentration was significantly higher in beta-thalassemia diabetic patients, compared with nonthalassemic diabetic control subjects (8,106 +/- 1,280 vs. 4,594 +/- 247 nmol/l; P < 0.0001). The three patients with progressive microalbuminuria demonstrated significantly higher total aldehyde concentration, compared with the other beta-thalassemia diabetic patients with stable albumin excretion (9,428 +/- 337 vs. 7,445 +/- 1,003 nmol/l; P < 0.01). Serum vitamin E concentrations were significantly lower in beta-thalassemia patients with diabetes, compared with diabetic patients without iron overload (12.1 +/- 6.0 vs. 25.9 +/- 11.4 mumol/l; P = 0.02). Serum vitamin C concentrations did not differ between the two groups. Multiple regression analysis demonstrated total aldehyde concentration to be the most significant predictor for the development of microalbuminuria (P = 0.01), followed by the duration of diabetes (P = 0.02) and glycemic control (P = 0.02). CONCLUSIONS: Early development and an accelerated course of diabetic nephropathy in iron-loaded patients with beta-thalassemia are observed. These findings may be attributed to high oxidative stress in these patients, which is secondary to iron-derived free radicals and to the patients' diminished antioxidant reserves.

Reliability of amniotic fluid surfactant measurements.

A proficiency study designed to assess interlaboratory precision of amniotic fluid surfactant measurements is presented. A total of 31 laboratories participated in the study. The assays includes lecithin/sphingomyelin (L/S) ratio test, the measurement of phosphatidyl glycerol (PG), and the Lumadex-FSI test. L/S ratio values varied from "1.3" to over "5.0" on aliquots derived from the same pool. With only three exceptions, all PG values read as "positive." The interlaboratory agreement for the Lumadex-FSI assay was excellent. With the exception of two values of "46," all the other values were with "47" or "48."

Myelodysplastic syndrome with prolonged reticulocyte survival mimicking hemolytic disease.

A patient with myelodysplastic syndrome (refractory anemia) with marked and persistent reticulocytosis is presented. A referring diagnosis of hemolytic disease had been made. However, the 51Cr red cell survival was normal (T1/2 24 days). Reticulocyte morphology, red cell creatine content, and in vitro reticulocyte survival studies have suggested that the reticulocytosis arose as a consequence of delayed maturation of the reticulocytes. Two patients with myelodysplastic syndrome and delayed reticulocyte maturation have previously been described; in both patients, however, red cell survival was also shortened. Anemia with reticulocytosis, mimicking hemolytic disease, may be an unusual presentation of myelodysplastic syndrome.

Assessment of fetal pulmonary maturity by the Lumadex Foam Stability Index Test.

The authors describe the operational features and performance characteristics of a new commercial kit designed to measure the amount and functionality of amniotic fluid surfactant. This kit, the Lumadex-FSI Test, is based upon the manual foam stability index test. The test requires no more than 3.0 ml of centrifuged amniotic fluid. Initial experience based on 172 specimens, including 19 cases of neonatal respiratory distress syndrome (RDS), revealed the Lumadex-FSI Test to have excellent discriminating ability in predicting the likelihood of RDS. In 18 of 19 cases in which RDS was noted, the foam stability index was 46 or less. A foam stability index of 47 or above was associated in 133 of 134 cases with fetal pulmonary maturity. Based upon contamination studies with maternal serum and meconium, the authors observed that a 1% contamination with blood, or 4% contamination with meconium, would artifactually increase the Lumadex-FSI value. The Lumadex-FSI Test demonstrated a clinical reliability similar to that of the manual foam stability index procedure, in addition to making the test simpler, faster, and more accessible to the clinician, in whose hands this test will have unique input into the management of high-risk pregnancies.

Evaluation of the small third-trimester fetus using the foam stability index test.

The diagnostic effectiveness of the lecithin:sphingomyelin (L:S) ratio was compared with that of the quantitative amniotic fluid foam stability index (FSI) test in the prenatal evaluation of pregnancies associated with fetuses appropriately grown for gestational age (AGA) and with intrauterine growth retardation (IUGR). In 27 such pregnancies, both the L:S ratio assay and the FSI test were performed on amniotic fluid specimens collected within 72 hours of delivery. Of the 27 low birth weight (LBW) neonates studied, 15 were small for gestational age (SGA) but did not have idiopathic respiratory distress syndrome (IRDS), whereas of 12 AGA neonates, 9 had IRDS. The 15 IUGR cases were characterized by FSI values varying from 0.47 to 0.55, whereas the 12 AGA cases had values varying from 0.42 to 0.48. Thus, the FSI showed excellent differentiation between these 2 entities. The L:S ratio ranged from 1.1 to 3.4 in cases associated with IUGR and from 1.0 to 2.4 in AGA cases, showing a high degree of overlap. The combination of an L:S ratio of less than 1.5 and an FSI value of less than 0.47 consistently identified the fetus who would have IRDS.

Clinical evaluation of the quantitative foam stability index test.

The foam stability index (FSI) test for amniotic fluid is a quantitative test that uses ethanol as the antifoaming reagent; it presents values in terms of the highest ethanol volume fraction that will permit stable foam to occur. In this study the authors report on FSI tests results in terms of neonatal outcome in a total of 208 pregnancies in which fluids were obtained within 3 days of delivery. The authors noted a total of 27 cases of hyaline membrane disease (HMD) in their population. All 27 had FSI values of 0.47 or less, whereas 119 of the 181 patients without HMD had FSI values of 0.48 or above. The risk of HMD's occurring was calculated for 4 groups of FSI values. They were as follows: 1) FSI values less than or equal to 0.43 (62%); 2) FSI values of 0.44 and 0.45 (23%); 3) FSI values of 0.46 and 0.47% (14%); and 4) FSI values greater than 0.48 (0%). Comparable evaluations of the lecithin:sphingomyelin (L:S) ratio procedure performed on the same specimens revealed no apparently improved diagnostic reliability. In addition, in several cases of intrauterine growth retardation with normal neonatal respiratory status in which the L:S ratios were less than 1.5, the FSI test correctly predicted fetal lung maturity (FSI greater than or equal to 0.48). The authors conclude that the FSI test has sufficient diagnostic reliability to be considered as a sensitive and specific assay of fetal pulmonary maturation.

Identifying the small-for-gestational-age fetus on the basis of enhanced surfactant production.

The clinical utility of concurrent measurements of the fetal biparietal diameter, as measured by ultrasonography and fetal pulmonary maturity, as assessed by the amniotic fluid consisted of 57 cases in which pregnancy produced a low birth weight neonate (less than 2500 g). The combination of a small fetal biparietal diameter (less than 8.5 cm) and a mature foam stability index value (0.47 or greater) was associated with small-for-gestational-age neonates in 16 of 19 cases. In addition, the occurrence of an immature foam stability index value (less than 0.47) and a fetal biparietal diameter of less than 8.5 cm was associated with appropriate-for-gestational-age newborns in 16 of 16 cases. The discriminating ability of the foam stability index test in identifying the small-for-gestational-age infant was lost when the fetal biparietal diameter was 8.5 cm or more. Of clinical note was the fact that 14 cases in which the neonatal respiratory distress syndrome occurred were all associated with appropriate-for-gestational-age infants and foam stability index values of less than 0.47 (ie, immature). The results of this study suggest a potentially important clinical role for the concurrent measurement of fetal biparietal diameter and performance of the amniotic fluid foam stability index test in the prenatal evaluation of the high-risk, small, third-trimester fetus.

Assessing fetal lung maturation by the foam stability index test.

An assay has been developed and evaluated that quantifies the surface tension lowering ability of amniotic fluid surfactant. The formation of stable foam following vigorous shaking of amniotic fluid was evaluated by the addition of various amounts of dipalmitoyl lecithin in a solution of ethanol and saline and by fine adjustments of the ethanol volume fraction in the final assay mixture. The foam stability index (FSI) for a particular sample of amniotic fluid was defined as the highest ethanol volume fraction that would permit the formation of stable foam after vigorously shaking a mixture of ethanol and amniotic fluid. The assay is referred to as the FSI test. We report the FSI values in amniotic fluid specimens from 59 patients obtained within 72 hours of delivery. The L/S ratio was measured in 50 of the same 59 specimens. We observed 6 cases of neonatal hyaline membrane disease (HMD) and 2 cases of transient tachypnea of the newborn (TTNB) in this study. No cases of HMD or TTNB occurred with FSI values of greater than 0.47, while 2 cases of HMD were recorded in association with L/S ratios of 2.5 and 2.8, respectively. The potential clinical value of the FSI test is discussed.

In vitro fertilization and embryo transfer: two-year experience.

Between February 1983 and January 1985, 206 laparoscopies were performed on 172 women following controlled ovarian hyperstimulation with human menopausal gonadotropin (hMG) and human chorionic gonadotropin (hCG). Sixty-four clinical pregnancies advanced beyond the sixth week of gestation and were confirmed by ultrasound; and 37.2% of the patients conceived after in vitro fertilization and embryo transfer. The clinical pregnancy rate was 31.1% when based on the number of laparoscopies performed and 33.9% when based on the number of embryo transfers. There were 12 multiple pregnancies (18.8%), 11 miscarriages (17.2%), and one ectopic (tubal) pregnancy (1.6%). The most important factors contributing toward the success of this program were the establishment of specific criteria for patient selection, rigid adherence to clinical and laboratory protocols, and the maintenance of strict quality control.

Eliminating the risk of life-endangering complications following overstimulation with menotropin fertility agents: a report on women undergoing in vitro fertilization and embryo transfer.

OBJECTIVE: To evaluate a new method for preventing the life-endangering complications associated with inadvertent menotropin-induced severe ovarian hyperstimulation in patients undergoing in vitro fertilization and embryo transfer (IVF-ET). METHODS: Seventeen women each underwent a single cycle of controlled ovarian hyperstimulation with menotropins in preparation for IVF-ET. The indications for IVF-ET were tubal occlusion in nine, endometriosis in six, and unexplained infertility in two. The peak plasma estradiol (E2) concentration before hCG administration was greater than 6000 pg/mL and more than 30 ovarian follicles were detected by transvaginal ultrasound. Thus, life-endangering complications associated with severe ovarian hyperstimulation syndrome were highly likely to occur following hCG administration. Rather than cancel the cycle of treatment, menotropin therapy was discontinued and hCG administration was deferred for a number of days until the plasma E2 concentration fell below 3000 pg/mL ("prolonged coasting"), whereupon hCG was administered and egg retrievals and ETs were duly performed. RESULTS: None of the women developed severe ovarian hyperstimulation syndrome. There were six viable pregnancies (35.2%), which proceeded normally. CONCLUSION: This study indicates that "prolonged coasting" prevents severe ovarian hyperstimulation syndrome in severely overstimulated women undergoing IVF-ET, without necessitating cycle cancellation.

Deletion of the long arm of chromosome 5 in essential thrombocythemia.

A 51-year-old woman with no history of prior chemotherapy or radiation therapy was diagnosed with essential thrombocythemia (ET) according to the diagnostic criteria established by the Polycythemia Vera Study Group (PVSG). Cytogenetic analysis of bone marrow metaphases revealed both normal female karyotype and a single clonal abnormality, 46,XX,del(5)(q22q35). While chromosomal abnormalities have been reported in ET, their incidence is very low, and no specific abnormality has been found. Many of the reported cases of ET with chromosomal aberrations, including 5q-, do not meet the diagnostic criteria proposed by the PVSG, and may represent one of the other myeloproliferative disorders or a myelodysplastic syndrome. Furthermore, it is important to distinguish the 5q- syndrome, which may present with thrombocytosis and megakaryocytic hyperplasia, from ET. Our patient appears to be the first example of untreated ET clearly meeting the PVSG criteria in which 5q- was the only clonal abnormality seen at diagnosis.

N-methyl-D-aspartate receptors mediate responses of rat dorsal horn neurones to hindlimb ischemia.

We have investigated the role of NMDA receptors in the rat dorsal horn in mediating neuronal responses to noxious hindlimb ischemia, induced by acute occlusion of the femoral artery, as well as in the hyperalgesia evident when noxious mechanical stimuli were applied to the ischemic limb. Two specific NMDA antagonists, D-2-amino-5-phosphonovalerate (APV) and ketamine hydrochloride were applied intrathecally directly on to the spinal cord, in enflurane-anaesthetised rats. Both APV (1 microM and 100 microM) and ketamine (1 mM and 100 mM) inhibited the increase of dorsal horn neuronal firing rate induced by ischemia, but did not alter the neuronal response to noxious pinching or innocuous brushing of the receptive field. Both agents, however, abolished the hyperalgesia to noxious pinching induced by ischemia. Our results support the hypothesis that the excitatory amino acids are involved in the transmission of nociceptive information in the spinal dorsal horn, and also favour a central mechanism for hyperalgesia at the spinal level, possibly also mediated by the NMDA receptor.

Inadequate cervical mucus--a cause of "idiopathic" infertility.

The purpose of this study was to investigate and treat a group of patients referred for "idiopathic" infertility in whom no apparent cause for infertility, apart from inadequate cervical mucus, was found. Hormone investigations revealed that these patients could be divided into two groups: those with low sex steroid profiles despite apparent ovulation, and a second group with normal sex steroid profiles. All patients were treated with ovulation-inducing agents in an attempt to produce "controlled" ovarian hyperstimulation and an improved cervical mucus. Four of six patients conceived. The rationale behind the use of ovulation-inducing agents in this situation is discussed.

PIP: This study investigated and treated 6 women ages 24-37 years with unexplained infertility. Pretreatment investigations included basal body treatment recording, serial estradiol and progesterone assays, thyroid and adrenal function tests, cervical swab for culture, assessment of cervical mucus, a postcoital test prior to or during midcycle, laparoscopy and dye hydrotubation during the follicular phase of the cycle, and endometrial biopsy. The only abnormal features detected were the cervical mucus findings and sex steriods profiles. The cervical mucus was scant or absent at midcycle in 4 patients. All patients were treated with human menopausal gonadotropin (HMG) from day 3 of the menstrual cycle until an estradiol level of 1000-1500 pg/ml was achieved, at which point a single injection of 10,000 U of human chorionic gonadotropin (HCG) was administered. Clomiphene citrate was given to patients who did not respond to this regimen. 4 of the patients (including 1 treated with HMG alone and 3 treated with clomiphene and HMG) conceived during the treatment period. Cervical mucus improved in both quantity and quality and the postcoital tests became strongly positive, showing more than 20 motile sperm/high power field. These results suggest that treatment with ovulation-inducing agents can correct both poor follicular development and inadequate cervical stimulation in women with idiopathic infertility. HMG or a combination of clamiphene citrate and HMG is preferred to clamiphene citrate alone because the latter regimen may have an adverse effect on cervical mucus.