Strategic management and public policy

Making strategic decisions that ensure a productive fit between the internal situation and external environment of a healthcare entity--sometimes, even decisions that ensure its survival--is a great challenge. The author suggests that hospitals must adopt specific strategies to anticipate and respond appropriately to changes in policy.     

Production and characterization of a monoclonal antibody reactive with a specific neoantigenic determinant (comprising B beta 54-118) in degradation products of fibrin and of fibrinogen

Balb/c mice were immunized with a mixture of fibrin degradation products (XDPs) prepared by complete lysis of a human blood clot by tissue-type plasminogen activator and purified by immunoaffinity chromatography. Spleen cells of the mice were fused with P3 X 63 Ag 8653 myeloma cells. A clone (FDP 14) was selected that produces monoclonal antibodies (MoAbs) of the IgG1 kappa type that react with a neoantigenic determinant exposed in these XDPs, but not in intact fibrinogen or in fibrin monomers. Furthermore, the MoAb is reactive with some pure, individual degradation products of fibrinogen (fragments X, Y, E, and the N-terminal disulphide knot) and with the fibrinogen B beta-chain but not with A alpha- and gamma-chains or with fragments D, FCB-2 and FCB-3. Comparison of the known primary structures of these fibrinogen fragments indicates that the stretch B beta 54-118 comprises at least an important part of the epitope recognized by FDP-14. Apparently, this stretch contributes importantly to a neoantigenic determinant that is not functional in intact fibrinogen and fibrin monomer and that can be made functional by reduction of fibrinogen, or by digestion with plasmin or CNBr.     

Spondylometaphyseal dysplasia, corner fracture type: a heritable condition associated with coxa vara

The authors present the radiographic features of a previously incompletely delineated bone dysplasia, which they call spondylometaphyseal dysplasia, corner fracture type. This is a dominant heritable condition associated with short stature and developmental coxa vara. The progressive hip deformity usually causes significant disability requiring surgical correction. Developmental coxa vara, simulated corner fractures of long tubular bones, and vertebral body abnormalities result in a diagnostic constellation. Knowledge of these distinctive radiologic features allows accurate diagnosis, which in turn should lead to appropriate genetic counseling and possibly to earlier, more efficacious surgical treatment of the coxa vara.     

Effacement of the fetal cisterna magna in association with myelomeningocele

The cisterna magna is effaced in association with myelomeningocele. The authors retrospectively investigated the size of the fetal cisterna magna as a predictor of fetal myelomeningocele in 67 pregnant women (17-38 menstrual weeks) referred for prenatal sonography because of an elevated serum alpha-fetoprotein level (n = 61) or a suspicion of fetal ventriculomegaly on previously obtained sonograms (n = 6). Twenty fetuses had myelomeningocele, 14 had isolated ventriculomegaly, and 33 were normal. A normal-sized cisterna magna (range, 4-9 mm in depth) was present in all normal fetuses. In 19 of 20 fetuses with myelomeningocele, the views of the posterior fossa were adequate, and in each of these the cisterna magna was effaced (n = 18) or very small (n = 1). The cisterna magna was effaced in five of 13 (38%) fetuses with isolated ventriculomegaly in whom the posterior fossa was adequately imaged. Although effacement of the cisterna magna is a nonspecific finding, the high negative predictive value of this sign is useful during routine screening of the fetal neural axis.     

Comparing MDI and DPI Aerosol Deposition Using In Vitro Experiments and a New Stochastic Individual Path (SIP) Model of the Conducting Airways

Pharmaceutical Research - Deposition characteristics of MDI and DPI aerosols were compared throughout the conducting airways for the first time using a combination of in vitro experiments and a...     

Characterization of Respiratory Drug Delivery with Enhanced Condensational Growth using an Individual Path Model of the Entire Tracheobronchial Airways

The objective of this study was to evaluate the delivery of inhaled pharmaceutical aerosols using an enhanced condensational growth (ECG) approach in an airway model extending from the oral cavity to the end of the tracheobronchial (TB) region. The geometry consisted of an elliptical mouth-throat (MT) model, the upper TB airways extending to bifurcation B3, and a subsequent individual path model entering the right lower lobe of the lung. Submicrometer monodisperse aerosols with diameters of 560 and 900 nm were delivered to the mouth inlet under control (25 °C with subsaturated air) or ECG (39 or 42 °C with saturated air) conditions. Flow fields and droplet characteristics were simulated using a computational fluid dynamics model that was previously demonstrated to accurately predict aerosol size growth and deposition. Results indicated that both the control and ECG delivery cases produced very little deposition in the MT and upper TB model (approximately 1%). Under ECG delivery conditions, large size increases of the aerosol droplets were observed resulting in mass median aerodynamic diameters of 2.4–3.3 μm exiting B5. This increase in aerosol size produced an order of magnitude increase in aerosol deposition within the TB airways compared with the controls, with TB deposition efficiencies of approximately 32–46% for ECG conditions. Estimates of downstream pulmonary deposition indicted near full lung retention of the aerosol during ECG delivery. Furthermore, targeting the region of TB deposition by controlling the inlet temperature conditions and initial aerosol size also appeared possible.     

Effect of menstrual cycle phase on dopamine D2 receptor availability in female cynomolgus monkeys

Sex differences have been reported in a variety of affective and neurodegenerative disorders that involve dysfunctional dopamine (DA) neurotransmission. In addition, there is evidence for differences in sensitivity to the abuse-related effects of psychostimulants across the menstrual cycle which may result from effects of ovarian hormones on DA function. The goal of the present study was to extend previous work examining menstrual cycle-related changes in DA D2 receptor availability in humans to drug-naive female cynomolgus monkeys (n=7) using the selective D2-like receptor ligand [(18)F]fluoroclebopride (FCP) and a high-resolution microPET P4 scanner. Menstrual cycle phase was characterized by daily vaginal swabs and measurements of serum progesterone levels. PET studies were conducted once during the luteal phase and once during the follicular phase. Regions of interest in the caudate nucleus, putamen, and cerebellum were defined on coregistered MRIs. Distribution volumes were calculated for FCP in each structure and the distribution volume ratio (DVR) for both brain regions relative to the cerebellum was used as a measure of D2 receptor availability. FCP DVRs were significantly higher in the luteal phase compared to the follicular phase in both the caudate nucleus (11.7% difference, p=0.02) and putamen (11.6% difference, p=0.03). These findings extend earlier work in humans and suggest that changes in DA receptor availability may be involved in the variation in symptoms of various neuropsychiatric disorders across the menstrual cycle, including differences in sensitivity to the abuse-related effects of stimulants.     

Transient Absorption of Inhaled Vapors into a Multilayer Mucus–Tissue–Blood System

Previous studies have approximated the absorption of vapors into the walls of the respiratory tract as a steady state process. However, non-dimensional analysis indicates that the absorption of vapors in the conducting airways is time-dependent over the timescale of a breathing cycle. The objective of this study was to evaluate the mass transport of sample chemical species through a simple multilayer system composed of mucus, tissue, and blood components on a transient basis. Individual multilayer models were considered that represent the wall dimensions of the nasal extrathoracic (ET₂), bronchial (BB), and bronchiolar (bb) airways. Sample vapors considered were acetaldehyde and benzene, which are highly soluble and moderately soluble in mucus, respectively. To determine absorption, mass transport was calculated based on an existing analytical steady state solution, a new analytical transient solution, and a numerical transient solution. Results indicated that concentrations within the mucus and tissue layers were highly time dependent in the ET₂ and BB regions and moderately time dependent in the bb airways over the timescale of an inhalation cycle, which is approximately 1–2 s. Fluxes of vapors into the tissue and blood varied with time for approximately 6–8 s in the BB region and 0.6–0.8 s in the bb model. The associated transient blood uptake of acetaldehyde and benzene in the upper ET₂ and BB regions varied from steady state values by a factor of approximately 30 after 1 s. Under similar conditions, transient uptake in the bb model varied from steady state conditions by a factor of approximately 1.3. Surprisingly, inclusion of chemical reactions in the mucus and tissue modified the transient uptake predictions only for very large values of reaction rate coefficients (K > 100 min⁻¹). In summary, transient effects significantly impact the absorption of vapors into the walls of the upper respiratory tract (ET₂ and BB regions) and may largely diminish the effects of chemical reactions over the timescale of an inhalation cycle. Furthermore, the transient analytical solution that was developed provides the basis for an improved boundary condition in future CFD simulations of air-phase transport and wall absorption.     

Paediatric use of intensive care

OBJECTIVES--To determine the number of children from a defined population who use intensive care facilities, to analyse bed occupancy data for those children, and to estimate the number of intensive care beds required to satisfy this demand throughout the year. DESIGN--Examination of admission data books from intensive care units within the four Birmingham health authorities and the neighbouring health authorities. RESULTS--Two hundred and ninety seven children resident within the four Birmingham health authorities used intensive care facilities in a calendar year. One hundred and forty one (47%) of these were admitted for specialist paediatric services. Of the remaining 156, 106 (68%) were cared for in adult intensive care units, 46 (29%) in a paediatric intensive care unit and four (3%) in a special care baby unit. Use of intensive care varied from none to 11 patients each day, and was lowest in the summer and highest during the winter months. During periods of peak demand, one in 19,000 (5.3/100,000) children were using intensive care facilities. CONCLUSIONS--These data provide a population based minimum need for paediatric intensive care beds. They are higher than previous estimates and do not include provision for children from outside Birmingham, or for those denied intensive care due to bed shortages. These factors and the marked seasonal variation in demand need to be considered when planning intensive care services for children if bed shortages are to be avoided.