Antimicrobial prescribing and infections in long-term care facilities (LTCF): a multilevel analysis of the HALT 2016 study, Ireland, 2017.

BackgroundThe 2016 point prevalence survey (PPS) of healthcare-associated infections (HAI) and antimicrobial use (AMU) in Irish long-term care facilities (LTCF) (HALT) showed a 9.8% AMU and 4.4% HAI prevalence, based on aggregated data analysis.AimOur aim was to identify institutional and resident risk factors of AMU and HAI.MethodsHALT 2016 gathered information using institutional and resident questionnaires, for residents who met the surveillance definition of active HAI and/or AMU, limiting analysis to the aggregated institutional level. In January 2017, we requested additional data on age, sex, urinary catheter use and disorientation of current residents from HALT 2016 LTCF and matched to 2016 HALT data.ResultsOf 224 HALT 2016 LTCF, 80 provided additional information on 3,816 residents; prevalence of AMU was 10.6% and HAI was 4.7%. Presence of a coordinating physician (Odds ratio (OR): 0.3; 95% confidence interval (CI): 0.2-0.6), antimicrobial stewardship committee (OR: 0.2; 95%; CI: 0.1-0.6), healthcare assistants (OR: 0.9; 95% CI: 0.9-1.0), antimicrobial consumption feedback (OR: 0.3; 95% CI: 0.1-0.6) and medical care by personal general practitioner (OR: 0.6; 95% CI: 0.7-1.0) were associated with less AMU and feedback on surveillance of infection prevention and control (IPC) practices (OR: 0.6; 95% CI: 0.3-1.0) with less HAI. AMU and HAI varied significantly between LTCF.ConclusionsMultilevel modelling identified significant inter-facility variation, as well as institutional factors associated with AMU and HAI. An antimicrobial stewardship committee linked with feedback on IPC and prescribing was associated with reduced AMU and HAI.

Permanent Childhood Hearing Impairment: Aetiological Evaluation of Infants identified through the Irish Newborn Hearing Screening Programme.

The Newborn Hearing Screening Programme (NHSP) was established in Cork University Maternity Hospital (CUMH) in April 2011. Between April 2011 and July 2014, 42 infants were identified with a Permanent Childhood Hearing Impairment (PCHI). Following this diagnosis, infants underwent a paediatric assessment according to recognised guidelines with the intention of identifying the underlying aetiology of the PCHI. The aim of this study was to assess the findings of this aetiological workup via retrospective chart review. PCHI data was obtained from the eSP database. This is a web based information system (eSP) used to track each baby through the screening and referral process A retrospective chart review of these patients was performed. Sixteen (38%) infants were diagnosed with a bilateral sensorineural hearing loss. Two infants had congenital CMV infection. A Connexin 26 gene mutation was detected in one infant. Two infants were diagnosed with Waardenburg syndrome, One with Pendred syndrome and one with Pfeiffer syndrome. Five babies underwent cochlear implantation. Through adherence to the recommended protocol a possible cause of PCHI may be determined. This study has identified areas of future improvement for this service in Ireland.

Increased risk of hip fracture associated with dually treated HIV/hepatitis B virus coinfection.

HIV and hepatitis B virus (HBV) infections are each associated with reduced bone mineral density, but it is unclear whether HIV/HBV coinfection is associated with an increased risk of fracture. We determined whether dually treated HIV/HBV patients had a higher incidence of hip fracture compared to treated HBV-monoinfected, antiretroviral therapy (ART)-treated HIV-monoinfected and HIV/HBV-uninfected patients. We conducted a cohort study among 4156 dually treated HIV/HBV-coinfected, 2053 treated HBV-monoinfected, 96,253 ART-treated HIV-monoinfected, and 746,794 randomly sampled uninfected persons within the US Medicaid populations of California, Florida, New York, Ohio and Pennsylvania (1999-2007). Coinfected patients were matched on propensity score to persons in each comparator cohort. Weighted survival models accounting for competing risks were used to estimate cumulative incidences and hazard ratios (HRs) with 95% confidence intervals (CIs) of incident hip fracture for dually treated coinfected patients compared to (i) HBV-monoinfected receiving nucleos(t)ide analogue or interferon alfa therapy, (ii) HIV-monoinfected on ART and (iii) uninfected persons. Dually treated coinfected patients had a higher cumulative incidence of hip fracture compared to ART-treated HIV-monoinfected (at 5 years: 1.70% vs 1.24%; adjusted HR, 1.37 [95% CI, 1.03-1.83]) and uninfected (at 5 years: 1.64% vs 1.22%; adjusted HR, 1.35 [95% CI, 1.03-1.84]) persons. The cumulative incidence of hip fracture was higher among coinfected than treated HBV-monoinfected patients (at 5 years: 0.70% vs 0.27%), but this difference was not statistically significant in competing risk analysis (adjusted HR, 2.62 [95% CI, 0.92-7.51]). Among Medicaid enrollees, the risk of hip fracture was higher among dually treated HIV/HBV-coinfected patients than ART-treated HIV-monoinfected and uninfected persons.

Temporal Trends in Hospitalisations for Heart Failure.

Heart failure (HF) is the most common cause for admission in patients over 65 and hospitalisations account for almost 1% of the health care budget in Ireland. A need to understand the epidemiological data in relation to hospitalisations for HF plays an important part in the planning and distribution of heart care services. The aim of this study was to analyse the temporal trends in hospitalisations for HF and look at potential areas for improvement. Cross sectional data was obtained from the Eurostat database. Data was extracted with the ICD 10 code for heart failure (1-50). The years 2002-2010 were analysed between the ages of 0-105. Between 2002 and 2010 there were 51369 admissions for HF in Irish hospitals. Of these, 54.7% were males and 87% were older than 65 years. The age standardised hospitalisation rates decreased from 157.5 per 100,000 to 127.2 per 100,000, a relative decrease of 19.2% (p = 0.02). There was an increase in HF hospitalizations for those aged > 85 from 17.9% to 26.7% (p = 0.001). There was no significant change in length of stay (12.0 days in 2002 and 12.4 days in 2010). This study of epidemiological surveillance data on Irish HF hospitalisations has shown a 19% reduction in hospitalisations between 2002 and 2010. Although this study shows an overall successful reduction in HF admission rates, the challenges remain in ensuring we manage the burden of those > 65 years, in particular those > 85 years.

The role of veterinarians and feed-store vendors in the prescription and use of antibiotics on small dairy farms in rural Peru.

This study aimed to describe and compare the role of veterinarians and feed-store vendors in the use of antibiotics on small dairy farms in Cajamarca, Peru, a major dairy-producing center characterized by small, rural farms with poor, mostly uneducated farmers. We used a purposive sampling strategy to recruit 12 veterinarians into 2 focus group discussions and supplemented these data with 8 semi-structured interviews with feed-store vendors. Participants reported that inappropriate antibiotic usage was widespread among their clients, which may prevent the efficient use of drugs on farms where animal disease can be devastating to the livelihood of the farmer. Participants also identified many barriers to appropriate prescribing and use, including availability of drugs, competition from other prescribers, economic constraints and habits of farmers, and limited farmer knowledge of drugs and disease. Veterinarians expressed mistrust toward nonprofessional prescribers, whereas feed-store vendors felt that veterinarians were important partners in promoting the health of their clients' animals.

Gender differences in PTSD severity and pain outcomes: baseline results from the LAMP trial.

Background: Post-traumatic stress disorder (PTSD) and chronic pain are highly prevalent comorbid conditions. Veterans dually burdened by PTSD and chronic pain experience more severe outcomes compared to either disorder alone. Few studies have enrolled enough women Veterans to test gender differences in pain outcomes [catastrophizing, intensity, interference] by the severity of PTSD. Aim: Examine gender differences in the association between PTSD symptoms and pain outcomes among Veterans enrolled in a chronic pain clinical trial. Methods: Participants were 421 men and 386 women Veterans with chronic pain who provided complete data on PTSD symptoms and pain outcomes. We used hierarchical linear regression models to examine gender differences in pain outcomes by PTSD symptoms. Results: Adjusted multivariable models indicated that PTSD symptoms were associated with higher levels of pain catastrophizing (0.57, 95% CI [0.51, 0.63]), pain intensity (0.30, 95% CI [0.24, 0.37]), and pain interference (0.46, 95% CI [0.39, 0.52]). No evidence suggesting differences in this association were found in either the crude or adjusted models (all interaction p-values<0.05). Conclusion: These findings may reflect the underlying mutual maintenance of these conditions whereby the sensation of pain could trigger PTSD symptoms, particularly if the trauma and pain are associated with the same event. Clinical implications and opportunities testing relevant treatments that may benefit both chronic pain and PTSD are discussed.

Prescriber adherence to pharmacokinetic monitoring service recommendations for aminoglycoside dosing and the risk of acute kidney injury.

OBJECTIVE: The importance of adherence to aminoglycoside dosing recommendations by a pharmacokinetic monitoring service for preventing acute kidney injury (AKI) is unknown. We aimed to examine the association between AKI and discordance in aminoglycoside dosing between physician orders and recommendations by a pharmacokinetic monitoring service. MATERIALS: We utilized 2000 - 2003 data from a large quaternary care academic medical center, including: hand-written pharmacokinetic monitoring service recommendations; computerized physician order entry inpatient medication orders; and electronic inpatient laboratory orders and results. METHODS: We conducted a case-control study, nested within users of intravenous aminoglycosides. Outcomes of interest were cases of AKI, as determined by changes in serum creatinine. Exposures of interest were discordances between pharmacokinetic monitoring service recommendations and physician orders in the past 2 days with regard to total daily aminoglycoside dose. RESULTS: Most patients received once-daily or less frequent aminoglycoside dosing. In 1,414 evaluable aminoglycoside courses, 220 patients developed AKI, for a cumulative incidence of 15.6%. We identified 690 controls, matched these to 220 cases, and found adjusted odds ratios of 0.72 (95% CI: 0.37 - 1.39) for overdose discordance and of 0.83 (0.51 - 1.34) for underdose discordance, suggesting that discordance in dosing is not associated with AKI. CONCLUSION: Non-adherence to dosing recommendations for aminoglycosides was not associated with risk of AKI in a setting primarily of once-daily aminoglycoside administration.

Complete thrombospondin mRNA sequence includes potential regulatory sites in the 3' untranslated region.

The nucleotide sequence of human thrombospondin (TS) mRNA has been determined from human fibroblast and endothelial cDNAs. The sequence of 5802 bp begins 110 bp upstream from the initiator codon and includes the entire 3' untranslated region (UTR) of the mRNA. The coding region (3510 bp) specifies a protein of 1170 amino acids with all of the known features of the TS subunit (Frazier, W. A. 1987. J. Cell Biol. 105:625-632). The long 3' UTR of 2166 nucleotides is extremely A/T-rich, particularly in the latter half. It contains 37 TATT or ATTT(A) sequences that have been suggested as mediators of the stability of mRNAs for cytokines, lymphokines, and oncogenes (Shaw, G., and R. Kamen. 1986. Cell. 46:659-667). Another unusual feature of the 3' UTR of TS mRNA is a stretch of 42 nucleotides of which 40 are thymidines (uridine in the mRNA) including an uninterrupted sequence of 26 thymidines. This region is flanked by two sets of direct repeats suggesting that it may be an insertion element of retrotranscriptional origin. Comparison of the 3' untranslated region of TS mRNA with the GenBank data base indicates the greatest degree of similarity with an alpha-interferon gene which contains a number of the TATT/ATTT consensus sites. The degree of similarity between the TS and interferon sequences is the same in regions of the interferon gene corresponding to its coding and noncoding regions suggesting that most of the TS 3' UTR may be derived from an interferon gene or pseudogene. The features of the TS mRNA 3' UTR provide a potential explanation for the rapid regulation of TS message observed in cultured cells in response to PDGF and suggest that TS is a member of a group of proteins which are intimately involved in the control of cell growth and differentiation.

Co-expression of the voltage-gated potassium channel Kv1.4 with transient receptor potential channels (TRPV1 and TRPV2) and the cannabinoid receptor CB1 in rat dorsal root ganglion neurons.

Potassium channels contribute to basic neuronal excitability and modulation. Here, we examined expression patterns of the voltage-gated potassium channel Kv1.4, the nociceptive transduction channels TRPV1 and TRPV2 as well as the putative anti-nociceptive cannabinoid receptor CB1 by immunofluorescence double-labelings in sections of rat dorsal root ganglia (DRGs). Kv1.4, TRPV1 and CB1 were each detected in about one third of neurons (35.7+/-0.5%, 29.4+/-1.1% and 36.4+/-0.5%, respectively, mean diameter 19.1+/-0.3 microm). TRPV2 was present in 4.4+/-0.4% of all neurons that were significantly larger in diameter (27.4+/-0.7 microm; P < 0.001). Antibody double-labeling revealed that the majority of Kv1.4-positive neurons co-expressed TRPV1 (73.9+/-1.5%) whereas none expressed TRPV2. The largest overlap was found with CB1 (93.1+/-0.1%). CB1 expression resembled that seen for Kv1.4 since the majority of neurons expressing CB1-protein also expressed TRPV1 (69.4+/-6.5%) but not TRPV2 (0.6+/-0.3%). When CB1-mRNA was detected using in situ hybridizations an additional subset of larger neurons was labeled including 82.4+/-17.7% of the TRPV2 expressing neurons. However, co-localization of Kv1.4 with CB1-mRNA (92%, mean diameter: 18.5 microm) was essentially the same as with CB1-protein. The almost complete overlap of CB1 and Kv1.4 in nociceptive DRG neurons suggests a functional synergistic action between Kv1.4 and CB1. The potassium channel may have two important roles in nociception. As the molecular basis of A-type current it could be involved in the control of repetitive discharges at peripheral terminals and as a downstream signal transduction site of CB1 in the control of presynaptic transmitter release at central terminals.

Pharmacoepidemiologic Methods for Studying the Health Effects of Drug-Drug Interactions.

A drug-drug interaction (DDI) occurs when one or more drugs affect the pharmacokinetics (the body's effect on the drug) and/or pharmacodynamics (the drug's effect on the body) of one or more other drugs. Pharmacoepidemiologic studies are the principal way of studying the health effects of potential DDIs. This article discusses aspects of pharmacoepidemiologic research designs that are particularly salient to the design and interpretation of pharmacoepidemiologic studies of DDIs.

Severe hypoglycemia in users of sulfonylurea antidiabetic agents and antihyperlipidemics.

Drug-drug interactions causing severe hypoglycemia due to antidiabetic drugs is a major clinical and public health problem. We assessed whether sulfonylurea use with a statin or fibrate was associated with severe hypoglycemia. We conducted cohort studies of users of glyburide, glipizide, and glimepiride plus a statin or fibrate within a Medicaid population. The outcome was a validated, diagnosis-based algorithm for severe hypoglycemia. Among 592,872 persons newly exposed to a sulfonylurea+antihyperlipidemic, the incidence of severe hypoglycemia was 5.8/100 person-years. Adjusted hazard ratios (HRs) for sulfonylurea+statins were consistent with no association. Most overall HRs for sulfonylurea+fibrate were elevated, with sulfonylurea-specific adjusted HRs as large as 1.50 (95% confidence interval (CI): 1.24-1.81) for glyburide+gemfibrozil, 1.37 (95% CI: 1.11-1.69) for glipizide+gemfibrozil, and 1.63 (95% CI: 1.29-2.06) for glimepiride+fenofibrate. Concomitant therapy with a sulfonylurea and fibrate is associated with an often delayed increased rate of severe hypoglycemia.

Successful Comparison of US Food and Drug Administration Sentinel Analysis Tools to Traditional Approaches in Quantifying a Known Drug-Adverse Event Association.

The US Food and Drug Administration's Sentinel system has developed the capability to conduct active safety surveillance of marketed medical products in a large network of electronic healthcare databases. We assessed the extent to which the newly developed, semiautomated Sentinel Propensity Score Matching (PSM) tool could produce the same results as a customized protocol-driven assessment, which found an adjusted hazard ratio (HR) of 3.04 (95% confidence interval [CI], 2.81-3.27) comparing angioedema in patients initiating angiotensin-converting enzyme (ACE) inhibitors vs. beta-blockers. Using data from 13 Data Partners between 1 January 2008, and 30 September 2013, the PSM tool identified 2,211,215 eligible ACE inhibitor and 1,673,682 eligible beta-blocker initiators. The tool produced an HR of 3.14 (95% CI, 2.86-3.44). This comparison provides initial evidence that Sentinel analytic tools can produce findings similar to those produced by a highly customized protocol-driven assessment.

Cholesterol biosynthesis and 3-hydroxy-3-methyl-glutaryl coenzyme A reductase in cultured glial and neuronal cells. Regulation by lipoprotein and by certain free sterols.

Regulation of cholesterol synthesis and, particularly, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase was studied in C-6 glial and neuroblastoma cells. Comparison of rates of incorporation of radioactivity from [14C]-acetate or [3H]mevalonate into digitonin-precipitable sterols indicated that HMG-CoA reductase is the major rate-limiting enzyme in cholesterol biosynthesis in both cell types. HMG-CoA reductase exhibited marked changes in enzymatic activity according to the lipoprotein content of the medium. However, significant differences were observed between the two cell types in the quantitative and temporal aspects of this regulation. Thus, in C-6 glial cells, when total serum lipoprotein was removed from the medium, reductase activity increased by 7-8-fold between 2 and 6 h later. After 24 h reductase activity in cells grown in lipoprotein-poor serum was 20-fold higher than in cells grown in regular serum. In neuroblastoma cells, under similar conditions, reductase activity did not increase at all until cells were in lipoprotein-poor serum for more then 6 h, and after 24 h, enzyme activity in cells grown in lipoprotein-poor serum was only approx. 3-fold higher than that in cells grown in regular serum. Addition of total serum lipoprotein caused a rapid decline in enzymatic activity in both cell types, with a t1/2 of 2-2.5 h; however, the onset of the decline was immediate in the glial cells but delayed 1-1.5 h in the neuronal cells. The critical regulatory component in the total lipoprotein fraction was shown to be contained in the low density lipoproteins for the reductase of both cell types. Regulation of reductase by free sterols was shown in both the glial and neuronal cells. However, effects were more marked and evolved more rapidly in the glial cells. The data thus provide important insight into the regulation of cholesterol synthesis in two cell types which are considered to be good models of neurons and glia of developing brain. The occurrence of more marked and more rapid regulation in the glial than in the neuronal cells is compatible with the important role glia play in brain lipid synthesis. The demonstration of dramatic regulation of HMG-CoA reductase by desmosterol, a sterol found in high concentration in brain early in development, may indicate a heretofore unrecognized role for this sterol in the regulation of cholesterol biosynthesis during maturation. 7-Ketocholesterol was shown to induce in C-6 glial cells a rate of decline of HMG-CoA reductase activity compatible with a t 1/2 of just 20 min. This extremely rapid rate of decline suggests that the effect involves an alteration in catalytic efficiency of the enzyme. The mechanism of this effect remains to be determined.

Regulation of cholesterol ester synthesis in cultured glial and neuronal cells. Relation to control of cholesterol synthesis.

Regulation of cholesterol ester synthesis was studied in cultured C-6 glial and neuroblastoma cells. Particular emphasis was placed on the relation of this regulation to control of cholesterol synthesis. The effectors studied were low density lipoprotein (LDL) and desmosterol. Distinct differences in regulation were observed between the glial and neuronal cells. In the neuronal cells cholesterol ester synthesis (from [14C]oleate) was not affected by even high concentrations of LDL or desmosterol. In contrast, cholesterol ester synthesis was stimulated as much as 12-fold in the glial cells after just 5 h exposure to LDL or desmosterol. Cholesterol synthesis (from [14C]acetate) was inhibited in a simultaneous and quantitatively similar manner. Suitable experiments indicated that alterations in pool sizes of intermediates did not contribute to the genesis of the observed responses and suggested that LDL and desmosterol produced their effects by stimulating esterification of primarily endogenous cholesterol. The data may have major implications concerning the controlling metabolic events prior to and at the onset of myelination.

Analysis of age-associated changes in collagen crosslinking in the skin and lung in monkeys and rats.

The present study was designed to address a specific question: can we define collagen aging in vivo in terms of alterations in collagen crosslinking? In order to assess the complete spectrum of change throughout life, tissues from rats, monkeys and (where available) humans were examined at ages ranging from fetal to old. Skin and lung were selected in order to include all of the crosslinks derived from lysyl oxidase-generated aldehydes that have been identified thus far, both reducible and nonreducible. Crosslinks analyzed included hydroxylysinonorleucine, dihydroxylysinorleucine, histidinohydroxymerodesmosine, hydroxypyridinium, lysyl pyridinium, and a deoxy analogue of hydroxypyridinium found in skin that differs structurally from lysyl pyridinium. Tissues from both a short-lived species (rats) and a long-lived species (monkeys) were analyzed to test further the hypothesis that changes in crosslinking are linked predominantly to biological age of the animal, rather than temporal aging. We found that biological aging seems to regulate certain predictable changes during the first part of the lifespan: the disappearance postnatally of dihydroxylysinonorleucine in skin, the rapid decrease in difunctional crosslink content in lung and skin during early growth and development, and the gradual rise in hydroxypyridinium and lysyl pyridinium in lung tissue. Changes in crosslinking were far less predictable during the second half of the lifespan. Although hydroxypridinium content continued to rise or reached a plateau in rat and monkey lungs, respectively, it showed a decrease in human lungs. The analogous trifunctional crosslink in skin, the so-called 'pyridinoline analogue', decreased dramatically in both rats and monkeys in later life. Our data suggest that caution must be taken in drawing inferences about human connective tissue aging from experiments performed in short-lived species such as rodents. Furthermore, the finding that there may be fewer total lysyl oxidase-derived crosslinks per collagen molecule in very old animals as compared with young animals suggests that we may need to expand our concepts of collagen crosslinking.

Risk of major complications from coronary angioplasty performed immediately after diagnostic coronary angiography: results from the Registry of the Society for Cardiac Angiography and Interventions.

OBJECTIVES: This study was designed to determine the risk of performing percutaneous transluminal coronary angioplasty (PTCA) at the time of diagnostic catheterization ("combined procedures"). BACKGROUND: Health care providers are under increasing pressure to combine diagnostic and interventional coronary procedures to reduce costs. However, the risk associated with combined procedures has not been rigorously assessed. METHODS: A multicenter cohort study of 35,700 patients undergoing elective PTCA from 1992 through 1995 was performed to determine the risk of major complications (myocardial infarction, emergency coronary artery bypass graft surgery or death) from combined relative to staged procedures (i.e., performing PTCA at a session subsequent to diagnostic catheterization). RESULTS: The risks of major complications from combined and staged procedures were 2.0% and 1.6%, respectively (unadjusted odds ratio [OR] 1.28, 95% confidence interval [CI] 1.05 to 1.57). After adjusting for clinical and angiographic differences and clustering by laboratory, the risk from combined procedures was not significantly elevated (multivariable OR 1.18, 95% CI 0.89 to 1.55). However, several subgroups of patients did have an increased risk from combined procedures: patients with multivessel disease (multivariable OR 1.64, 95% CI 1.13 to 2.39); women (multivariable OR 1.64, 95% CI 1.05 to 2.55); patients > 65 years old (multivariable OR 1.40, 5% CI 1.02 to 1.93); and patients undergoing multilesion PTCA (multivariable OR 1.53, 95% CI 1.06 to 2.21). The risk of combined relative to staged procedures decreased over the 4-year period (multivariable p = 0.029). CONCLUSIONS: Combining PTCA with diagnostic catheterization appears to be safe in many patients. However, several subgroups of patients may be at increased risk. Careful patient selection will most likely remain critical to ensuring the safety of combined procedures.

Lack of hepatotoxic effects of parenteral ketorolac in the hospital setting.

BACKGROUND: No large controlled studies to date have examined the hepatic safety of parenteral ketorolac, which is used to treat acutely ill hospitalized patients who may be at greatest risk of liver injury. OBJECTIVE: To measure the association between the use of parenteral ketorolac and subsequent liver injury. METHODS: A nonexperimental cohort study conducted in 35 hospitals in the greater Philadelphia, Pa, region examined 10,272 courses of parenteral ketorolac (the exposed group) and 10,247 courses of parenteral opioid (the comparison group). Liver injury was defined by a modified international consensus definition that relied exclusively on liver function tests. Proportional hazards regression was used to calculate the rate ratio and 95% confidence interval for the association between ketorolac exposure and the occurrence of liver injury, controlling for potentially confounding factors, and to explore the possible effects of duration and dose. RESULTS: The incidence of liver injury was 1.0% in the ketorolac group and 1.2% in the opioid group, yielding an unadjusted rate ratio of 0.77 (95% confidence interval, 0.59 1.01). Simultaneously adjusting for multiple potentially confounding factors did not change this result. There was no evidence for a duration-response relationship (P = .96) or a dose-response relationship (P = .23). We were unable to identify any subgroups that were susceptible to possible hepatotoxic effects of parenteral ketorolac. CONCLUSIONS: This study failed to find evidence of a hepatotoxic effect of parenteral ketorolac use in the hospital setting and provides strong evidence against the existence of a clinically meaningful association between exposure to parenteral ketorolac in the hospital setting and liver injury.

Automated measurement of ciliary beat frequency.

Measurements of ciliary beat frequency using video images are dependent on observer interpretation. To obtain objective estimates of ciliary beat frequency from video-image sequences, a computer-based method was developed. Regions of interest of video-image sequences were selected and digitized. Variations in numerical values representing light intensity resulting from cilia beating were extracted and analyzed using autocorrelation techniques. The ciliary beat frequencies obtained for 14 in vitro experiments on ciliated cells or epithelium from the frog palate (Rana catesbeiana) over the range of frequencies 2-25 Hz correlated well with independent observer measurements (r = 0.979). The addition of such computer-based methods to video observer-based systems allows more objective and efficient determinations of ciliary beat frequency.

Postmarketing drug surveillance: an epidemiologic approach.

Postmarketing surveillance refers to any means of gathering information about a product after it has been approved for public use. Postmarketing surveillance studies address assorted aspects of beneficial and detrimental adverse drug effects, including the existence of particular causal effects, frequency of and risk factors for certain outcomes, economic consequences of therapy, and characterization of drug use in clinical practice. The primary scientific discipline engaged in postmarketing studies is epidemiology. The principal epidemiologic study designs used in postmarketing surveillance studies are randomized trials, cohort studies, and case-control studies. Regardless of their design, all studies involving human subjects should be conducted by qualified investigators according to a written protocol that has been approved by an institutional review board. Promotional activities conducted under the guise of postmarketing studies are unacceptable.