Entry screening for severe acute respiratory syndrome (SARS) or influenza: policy evaluation.
Explore the source record for details and available documents.
Communicable Disease Control↗
Biomedical subjects
B S Cooper
Publications and source records attributed to B S Cooper.
Isolation measures in the hospital management of methicillin resistant Staphylococcus aureus (MRSA): systematic review of the literature.
OBJECTIVE: To evaluate the evidence for the effectiveness of isolation measures in reducing the incidence of methicillin resistant Staphylococcus aureus (MRSA) colonisation and infection in hospital inpatients. DESIGN: Systematic review of published articles. DATA SOURCES: Medline, Embase, CINAHL, Cochrane Library, System for Information on Grey Literature in Europe (SIGLE), and citation lists (1966-2000). REVIEW METHODS: Articles reporting MRSA related outcomes and describing an isolation policy were selected. No quality restrictions were imposed on studies using isolation wards or nurse cohorting. Other studies were included if they were prospective or employed planned comparisons of retrospective data. RESULTS: 46 studies were accepted; 18 used isolation wards, nine used nurse cohorting, and 19 used other isolation policies. Most were interrupted time series, with few planned formal prospective studies. All but one reported multiple interventions. Consideration of potential confounders, measures to prevent bias, and appropriate statistical analysis were mostly lacking. No conclusions could be drawn in a third of studies. Most others provided evidence consistent with a reduction of MRSA acquisition. Six long interrupted time series provided the strongest evidence. Four of these provided evidence that intensive control measures including patient isolation were effective in controlling MRSA. In two others, isolation wards failed to prevent endemic MRSA. CONCLUSION: Major methodological weaknesses and inadequate reporting in published research mean that many plausible alternative explanations for reductions in MRSA acquisition associated with interventions cannot be excluded. No well designed studies exist that allow the role of isolation measures alone to be assessed. None the less, there is evidence that concerted efforts that include isolation can reduce MRSA even in endemic settings. Current isolation measures recommended in national guidelines should continue to be applied until further research establishes otherwise.
Cross Infection↗
Methicillin-resistant Staphylococcus aureus in hospitals and the community: stealth dynamics and control catastrophes.
Methicillin-resistant Staphylococcus aureus (MRSA) represents a serious threat to the health of hospitalized patients. Attempts to reduce the spread of MRSA have largely depended on hospital hygiene and patient isolation. These measures have met with mixed success: although some countries have almost eliminated MRSA or remained largely free of the organism, others have seen substantial increases despite rigorous control policies. We use a mathematical model to show how these increases can be explained by considering both hospital and community reservoirs of MRSA colonization. We show how the timing of the intervention, the level of resource provision, and chance combine to determine whether control measures succeed or fail. We find that even control measures able to repeatedly prevent sustained outbreaks in the short-term can result in long-term control failure resulting from gradual increases in the community reservoir. If resources do not scale with MRSA prevalence, isolation policies can fail "catastrophically."
Community-Acquired Infections↗
Systematic review of isolation policies in the hospital management of methicillin-resistant Staphylococcus aureus: a review of the literature with epidemiological and economic modelling.
OBJECTIVE: To review the evidence for the effectiveness of different isolation policies and screening practices in reducing the incidence of methicillin-resistant Staphylococcus aureus (MRSA) colonisation and infection in hospital in-patients. To develop transmission models to study the effectiveness and cost-effectiveness of isolation policies in controlling MRSA. DATA SOURCES: MEDLINE, EMBASE, CINAHL, The Cochrane Library and SIGLE (1966-2000). Hand-searching key journals. No language restrictions. REVIEW METHODS: Key data were extracted from articles reporting MRSA-related outcomes and describing an isolation policy in a hospital with epidemic or endemic MRSA. No quality restrictions were imposed on studies using isolation wards (IW) or nurse cohorting (NC). Other studies were included if they were prospective or employed planned comparisons of retrospective data. Stochastic and deterministic models investigated long-term transmission dynamics, studying the effect of a fixed capacity IW, producing economic evaluations using local cost data. RESULTS: A total of 46 studies were accepted: 18 IWs, 9 NC, 19 other isolation policies. Most were interrupted time series, with few planned formal prospective studies. All but one reported multiple interventions. Consideration of potential confounders, measures to prevent bias, and appropriate statistical analysis were mostly lacking. No conclusions could be drawn in a third of studies. Most others provided evidence consistent with reduction of MRSA acquisition. Six long interrupted time series provided the strongest evidence. Four of these provided evidence that intensive control measures which included patient isolation were effective in controlling MRSA. In two others IW use failed to prevent endemic MRSA. There was no robust economic evaluation. Models showed that improving the detection rate or ensuring adequate isolation capacity reduced endemic levels, with substantial savings achievable. CONCLUSIONS: Major methodological weaknesses and inadequate reporting in published research mean that many plausible alternative explanations for reductions in MRSA acquisition associated with interventions cannot be excluded. No well-designed studies allow the role of isolation measures alone to be assessed. Nonetheless, there is evidence that concerted efforts that include isolation can reduce MRSA even when endemic. Little evidence was found to suggest that current isolation measures recommended in the UK are ineffective, and these should continue to be applied until further research establishes otherwise. The studies with the strongest evidence, together with the results of the modelling, provide testable hypotheses for future research. Guidelines to facilitate design of future research are produced.
Cost-Benefit Analysis↗
Pathogen population dynamics: the age of the strain.
Explore the source record for details and available documents.
Bacteria↗
Inhibition of apoptosis in cultured porcine granulosa cells by inhibitors of caspase and serine protease activity.
Protease inhibitors were used to test the hypothesis that caspases and other proteases were active during apoptosis in cultured porcine granulosa cells. Cells isolated from 3 to 6 mm follicles were cultured for 24 h in Dulbecco's modified Eagles medium: Hams F12 (1:11 containing 1% fetal bovine serum. Final inhibitor concentrations, added in 10 microL of dimethylsulfoxide, were 0, 1, 5, 25 and 125 microM. Cells with compromised plasma membrane integrity, identified by uptake ethidium homodimer, increased during culture in the absence of inhibitors from 37% to 43%. Apoptotic (A0) cells, identified by DNA fluorescence flow cytometry, increased (P < 0.05) from 1.7% to 29%. The serine protease inhibitor N-tosyl-L-phenylalanine chloromethyl ketone (TPCK) at 125 microM was lethal increasing (P < 0.05) cells with compromised membranes to 92%. In response to TPCK, A0 cells decreased from 55% to 1.2%; progesterone and estradiol production were decreased by 94% and 98%, respectively. The general caspase inhibitor, benzyloxycarbonyl-valinyl-alaninyl-aspartyl fluoro methylketone, decreased (P < 0.05) A0 cells linearly from 33% to 3 % between 0 and 125 microM without significant effect on steroidogenesis or on the percentage of cells with compromised plasma membranes. Other inhibitors only had a marginal effect on apoptosis; concentrations of > or = 1 microM decreased (P < 0.05) A0 cells from 29% to 18% to 21% and had no significant effect on membrane integrity or steroid production. We conclude that caspases are associated with apoptosis in cultured porcine granulosa cells. Death induced by TPCK was through a non-apoptotic mechanism.
Amino Acid Chloromethyl Ketones↗
Expression of resistance to tetracyclines in strains of methicillin-resistant Staphylococcus aureus.
A diverse collection of methicillin-resistant Staphylococcus aureus (MRSA) isolates resistant to tetracycline was screened by PCR for the presence of the resistance determinants tetK, tetL, tetM or tetO. Twenty-four of 66 isolates had tetM alone, 21 had tetK alone and 21 had both tetK and tetM (tetKM). All isolates were tetL- and tetO-negative. MICs of tetracycline, doxycycline and minocycline were evaluated for all isolates with or without preincubation in the presence of subinhibitory concentrations of tetracycline or minocycline. All isolates with one or more tetracycline resistance determinants were resistant to tetracycline 8 mg/L without induction of resistance. Some MRSA isolates of each of these three genotypes showed an unexpected lack of resistance to tetracyclines when the disc diffusion or agar dilution method was applied to uninduced cells. Resistance to tetracycline and doxycycline was greater (two- to four-fold) in tetK cells preincubated with tetracycline (tetK MRSA isolates were susceptible to minocycline </=0.25 mg/L under all conditions tested). For isolates with tetM alone, preincubation with tetracycline or minocycline gave up to a four-fold increase in the level of resistance to doxycycline and minocycline. Induction of doxycycline and minocycline resistance was clearly observed for tetKM isolates when cells were preincubated with minocycline. This study suggests that, despite the results of susceptibility testing, all tetracycline-resistant S. aureus isolates should be treated as resistant to doxycycline, and all tetM-positive isolates should be treated as resistant to all tetracyclines. A double disc diffusion method has been developed to identify inducible resistance to minocycline and to distinguish between tetK, tetM and tetKM isolates.
Genes, Bacterial↗
Preliminary analysis of the transmission dynamics of nosocomial infections: stochastic and management effects.
A simple mathematical model is developed for the spread of hand-borne nosocomial pathogens such as Staphylococcus aureus within a general medical-surgical ward. In contrast to previous models a stochastic approach is used. Computer simulations are used to explore the properties of the model, and the results are presented in terms of the pathogen's successful introduction rate, ward-level prevalence, and colonized patient-days, emphasizing the general effects of changes in management of patients and carers. Small changes in the transmissibility of the organism resulted in large changes in all three measures. Even small increases in the frequency of effective handwashes were enough to bring endemic organisms under control. Reducing the number of colonized patients admitted to the ward was also an effective control measure across a wide range of different situations. Increasing surveillance activities had little effect on the successful introduction rate but gave an almost linear reduction in colonized patient-days and ward-level prevalence. Shorter lengths of patient stay were accompanied by higher successful introduction rates, but had little effect on the other measures unless the mean time before detection of a colonized individual was large compared to the mean length of stay. We conclude that chance effects are likely to be amongst the most important factors in determining the course of an outbreak. Mathematical models can provide valuable insights into the non-linear interactions between a small number of processes, but for the very small populations found in hospital wards, a stochastic approach is essential.
Computer Simulation↗
Prescription drug coverage and spending for Medicare beneficiaries.
Outpatient prescription drug coverage is not a Medicare covered benefit. Debate continues in Congress and elsewhere on modernizing the Medicare benefit package, including proposals that would help the Nation's seniors pay for prescription drugs. Very little is known about which persons within the Medicare population have drug coverage from other sources. Using 1995 data from the Medicare Current Beneficiary Survey (MCBS), the authors present information on who has coverage by various sociodemographic categories. The data indicate higher-than-average levels of coverage for minority persons, beneficiaries eligible for Medicare because of disability, and those with higher incomes.
Adolescent↗
Follicle-stimulating hormone and insulin-like growth factor-I attenuate apoptosis in cultured porcine granulosa cells.
Thymocytes and granulosa cells (GC) were cultured up to 48 h to determine the effect of dexamethasone (DEX) on apoptosis in culture (in RPMI containing 10% fetal bovine serum [FBS] at 38 degrees C in a 5% CO2:95% air atmosphere). In experiment 2, GC were cultured for 24 h at a density of 0.5 x 10(6) cells/0.5 ml in Dulbecco's Modified Eagle's medium:Hams F-12 (1:1) containing 1% FBS to determine whether porcine FSH and insulin-like growth factor-I (IGF-I) attenuated apoptosis and to compare two methods of measuring apoptosis: 1) flow cytometry of dispersed cells for subdiploid DNA fluorescence and 2) densitometry of internucleosomal DNA fragments. The percentages of apoptotic (%A0) thymocytes and GC increased (p < 0.01) during 48 h of culture. Compared to no DEX, 0.1 or 1.0 microM DEX in thymocytes caused a 33% further increase (p < 0.01) in %A0 cells but had no effect in GC. In experiment 2, apoptosis, measured by %A0 GC and amount of internucleosomal fragments, decreased (p < 0.01) by 50% during culture in the presence of FSH (4 NIH-S1 mU/ml) or IGF-I (50 ng/ml); results from these techniques were correlated (r = 0.829, n = 44, p < or = 0.0001). We conclude that 1) porcine GC and thymocytes undergo spontaneous apoptosis in culture, 2) two methods of analyzing apoptosis were in excellent agreement, and 3) FSH and IGF-I attenuated spontaneous apoptosis in cultured porcine GC.
Animals↗
Development of an end-stage renal disease managed care demonstration.
At present, end-stage renal disease (ESRD) beneficiaries cannot enroll in health maintenance organizations (HMOs) or social health maintenance organizations (SHMOs), but HMO members who develop ESRD may remain enrolled, and the Health Care Financing Administration (HCFA) pays the HMO a state-specific, but otherwise unadjusted, capitation rate that is 95% of fee-for-service (FFS) costs. Thus, more than 6,000 ESRD beneficiaries were enrolled in HMOs in 1993, when Congress mandated an ESRD SHMO demonstration in which not only Medicare-covered services, but extra benefits were to be provided to Medicare beneficiaries, with the SHMO receiving a capitation rate based on 100% of FFS costs. The demonstration will test (1) the feasibility of year-round open enrollment of ESRD beneficiaries in HMOs; (2) a capitation system based on treatment status--dialysis, transplant, or functioning graft--and adjusted for age and whether diabetes was the cause of renal failure; (3) the effect of the additional benefits; and (4) whether managed care can improve ESRD quality outcomes. HCFA made demonstration awards in September 1996 to Kaiser-Permanente in Southern California; Health Options in Southern Florida; and Phoenix Healthcare in Central Tennessee. The sites are expected to have 1 year of planning and development before beginning the congressionally mandated 3 years of service delivery. There will be an independent evaluation.
Adult↗
Follicular Atresia, follicular fluid hormones, and circulating hormones during the midluteal phase of the estrous cycle in pigs.
The incidence of atresia, concentrations of follicular fluid steroids, and circulating concentrations of estradiol, FSH, and progesterone were investigated to determine whether there was any evidence for a wave of follicular activity or atresia between Days 7 and 15 of the estrous cycle in pigs, Cyclic pigs (gilts) were slaughtered on Days 7, 9, 11, 13, and 15 (4, 4, 4, 4, and 3 pigs per day), and 287 follicles > 2 mm were dissected from ovaries to recover follicular fluid and granulosa cells. Apoptotic (Ao) granulosa cells were those containing sub-diploid DNA fluorescence as determined by flow cytometry. follicles with > or = 10% Ao granulosa cells were classified as atretic, and those with < 10% Ao granulosa cells were designated nonatretic. The percentage of atretic follicles (AF) per pig was 35.5 +/- 4.7 (mean +/- SEM), and while the percentage of AF ranged from 12% to 73%, means did not differ significantly among days. Mean follicular estradiol concentration was higher (p < 0.05) in nonatretic follicles (NAF) than in AF; in NAF, the concentration decreased (p < 0.05) from 15 ng/ml on Day 7 to 2.5 ng/ml on Day 11 and then increased (p < 0.05) to 10 ng/ml on Day 15 of the cycle. Mean follicular progesterone concentration was higher (p < 0.05) in AF than in NAF, while follicular androstenedione concentration (20 +/- 1.5 ng/ml, overall mean +/- SEM) did not differ between AF and NAF. Mean plasma estradiol, FSH, and progesterone concentrations did not differ among days of the cycle or differ significantly during the last 42 h before slaughter. Plasma estradiol and FSH concentrations were not significantly correlated with percentage of AF or with follicular steroid concentrations. These results support the notion of continuous growth and atresia of ovarian follicles in pigs independent of changes in plasma FSH and follicular steroid concentration, without evidence for a dominant cohort of follicles during the luteal phase of the estrous cycle.
Animals↗
Thirty years of Medicare: impact on the covered population.
Explore the source record for details and available documents.
Aged↗
Atresia in follicles grown after ovulation in the pig: measurement of increased apoptosis in granulosa cells and reduced follicular fluid estradiol-17 beta.
The incidence of atresia in the first group of follicles grown after ovulation was investigated in the pig. At slaughter, 113 follicles 3-6 mm in diameter were dissected from the ovaries of four pregnant pigs per day on Days 5, 6, and 7 after the onset of estrus. Granulosa cells were isolated from each follicle. The percentage of granulosa cells containing sub-diploid amounts of DNA (%Ao cells), a measure of apoptosis, was determined for each follicle by DNA fluorescence flow cytometry of propidium iodide (PI) stained nuclei of ethanol-fixed cells. Granulosa cell DNA condition was used to classify follicles. Follicles with > or = 10% Ao cells (n = 33) were designated biochemically atretic (BA), and follicles with < 10% Ao cells (n = 80) were designated biochemically healthy (BH). Internucleosomal cleavage, also indicative of apoptosis, was determined by autoradiographic analysis of [32P]-3'-end-labeled DNA from granulosa cells. Densitometric analysis showed that optical density of [32P]-3'-end-labeled DNA fragments in the 0.18-20-kb size range was correlated with the %Ao cells (R > or = 0.90, N = 22, p < 0.001). The incidence of pigs with BA follicles was 2 of 4, 3 of 4, and 4 of 4 on Days 5, 6, and 7, respectively. The %BA follicles per pig (mean +/- SEM) increased (p < or = 0.01) between Days 5 and 7; values were 6.2 +/- 3.6, 28.1 +/- 13.5, and 50.0 +/- 7.1, respectively, on Days 5, 6, and 7.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Follicular atresia in pigs: measurement and physiology.
The physiological regulation of follicular atresia was investigated during the early luteal phase after ovulation and during altrenogest-synchronized preovulatory maturation in pigs (gilts). Apoptosis in dispersed granulosa cells was determined by flow cytometry. Apoptotic (A0) cells contain low, subdiploid amounts of DNA fluorescence. Follicles were classified biochemically as atretic or nonatretic based on the percentage of A0 (% A0) cells, atretic with > or = 10%, and nonatretic with < 10% A0 granulosa cells. The % A0 granulosa cells/follicle ranged from .02 to 89. Follicles containing debris in their isolated granulosa cells were classified as morphologically atretic. The morphological and biochemical criteria of atresia were in agreement for 224 of 248 follicles. Internucleosomal DNA cleavage, the hallmark of apoptosis, was determined by autoradiographic analysis of [32P]3'-end labeled DNA from granulosa cells. Densitometric analysis showed that optical density of [32P]3'-end labeled DNA fragments in the .18 to 20 kbp size range was correlated with the % A0 cells (R > .9, n = 22, P < .001). During altrenogest-synchronized preovulatory maturation, < 5% of large (> 6 mm in diameter) follicles were atretic. Among medium-sized follicles (3 to 6 mm) on d 1 and 3 of preovulatory maturation, only 17% were atretic, in contrast with d 5 when 87% were atretic. During the early luteal phase, atretic follicles/pig increased from 6% on d 5 to 50% on d 7 after estrus. Follicular fluid estradiol-17 beta concentration was greater (P < .001) in nonatretic than in atretic follicles on d 5 and 6 after estrus, but by d 7 estradiol-17 beta had decreased to a mean < 1 ng/mL in nonatretic and atretic follicles. The increase in apoptosis in granulosa cells and loss of estradiol-17 beta production in vivo indicated a high incidence of atresia among the first group of follicles grown after ovulation in pigs. These results indicate that apoptotic cell death was involved in degeneration of granulosa cells and atresia during two different stages of follicular development.
Animals↗
Flow cytometric determination of degraded deoxyribonucleic acid in granulosa cells to identify atretic follicles during preovulatory maturation in the pig.
Granulosa cells of individual follicles were analyzed by DNA fluorescence flow cytometry to determine how the percentage of cells with degraded DNA and the distribution of cells in the phases of the cell cycle (Go/G1, S1, G2/M) related to the incidence of morphological atresia and to changes in follicular steroid concentrations. Follicles were dissected from ovaries recovered at slaughter on Days 1, 3, 5, or 7 of altrenogest-synchronized preovulatory maturation. Twenty-one follicles with debris among their isolated granulosa cells were classified as morphologically atretic (MA); 92 follicles with debris-free granulosa cells were classified as morphologically healthy (MH). Granulosa cells were prepared for flow cytometry by fixation in 80% ethanol and staining with propidium iodide (PI) containing RNase. DNA fluorescence intensity was determined by use of the 488-nm line of an argon laser. A subpopulation of granulosa cells with degraded DNA (Ao cells), containing less fluorescence than the Go/G1 peak, was found in the DNA histogram of every follicle. The percentage of Ao cells ranged from 0.02 to 83.6% per follicle. The percentage of Ao cells was inversely related to the percentage of Go/G1 cells (r = -0.9611, p = 0.0001). The percentage of Ao cells (mean +/- SEM) was greater (p = 0.0001) in MA (45.9 +/- 6.3%) than in MH follicles (5.3 +/- 1.6%). Follicular estradiol-17 beta was less in MA than in MH follicles, but androstenedione or progesterone did not differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS)
Androstenedione↗
Changes in follicular estradiol-17 beta, progesterone and inhibin immunoactivity in healthy and atretic follicles during preovulatory maturation in the pig.
Follicular hormones, growth and granulosa cell gonadotropin sensitive adenylate cyclase activity were determined in healthy and atretic follicles during preovulatory maturation in pigs. Ovaries were recovered at slaughter which was 1, 3, 5 or 7 d after the last administration of a progesterone agonist (altrenogest). Plasma FSH decreased (P < .05) by 64% between days 1 and 3 and remained low through day 5. The number of large (> 5 mm) follicles increased from 2.7 on day 1 to 14.8 on day 3 and did not differ significantly among days 3, 5 and 7. The number of small (1-2 mm) and medium (3-5 mm) follicles decreased (P < or = .05) by 82% between days 3 and 5. Follicles first became estrogen-active (EA) (> or = 100 ng of estradiol-17 beta/ml of follicular fluid) on day 3, with 14.3% of medium and 73.8% of large follicles being EA. About 30% of small and 13% of medium follicles were morphologically atretic on days 1 and 3. However, by day 5, the proportion of atretic small and medium follicles had increased (P < or = .05) to 100 and 59%, respectively. Follicular fluid inhibin immunoactivity and estradiol-17 beta were lower (P < or = .05) and progesterone was greater (P < or = .05) in atretic than healthy follicles. Granulosa cells from large follicles produced (P < or = .05) more cAMP than cells from healthy or atretic small/medium follicles. Compared to control or pFSH treatment, pLH increased cAMP production by granulosa cells from large follicles on all days and from small/medium follicles on days 1 and 5; pLH had no effect on granulosa cells from atretic follicles. Compared to control, pFSH increased cAMP production in granulosa cells from healthy small/medium follicles only on day 1; no effect was detected in granulosa cells from large or atretic follicles on any day. We conclude that decreased secretion of FSH increased loss and atresia among non-ovulatory follicles. Atretic follicles were marked by loss of granulosa cell gonadotropin-sensitive adenylate cyclase activity and by low concentrations of estradiol-17 beta.
Animals↗
Expression of a bovine growth hormone transgene inhibits pregnant mare's serum gonadotropin-induced follicle maturation in prepuberal gilts.
Prepuberal gilts were injected with PMSG to determine whether expression of a bovine growth hormone (bGH) transgene inhibited preovulatory maturation of ovarian follicles. Seven transgenic (TG) gilts of line 3706, which expresses a mouse metallothionein-bGH transgene, and eight nontransgenic, control (C) gilts (128 to 147 d old) were injected with PMSG, 12.5 IU/kg BW, 72 h before necropsy. Surface ovarian follicles > or = 1 mm in diameter were counted, measured for diameter, and aspirated for fluid. Follicles were classified morphologically as healthy or atretic and those with follicular fluid estradiol-17 beta > or = 100 ng/mL were classified as estrogenactive (EA). The number of follicles per gilt was 64.3 +/- 6.1 (mean +/- SEM) and did not differ significantly between bGH-TG and C gilts. The PMSG treatment induced growth of large (> 5 mm) follicles in both bGH-TG and C gilts. However, compared with C gilts, bGH-TG gilts had fewer (P < .05) large follicles (5.9 +/- 1.5 vs 18.3 +/- 5.4), a lower proportion of EA large follicles (35 +/- 12.5 vs 69 +/- 13.2%), and in large follicles less (P < .05) estradiol-17 beta (86 +/- 17 vs 350 +/- 69 ng/mL) and androstenedione (300 +/- 33 vs 1,283 +/- 221 ng/mL). Follicular fluid progesterone and inhibin did not differ significantly between bGH-TG and C gilts. The incidence of atresia among small and medium follicles did not differ significantly between bGH-TG and C gilts.(ABSTRACT TRUNCATED AT 250 WORDS)
Androstenedione↗