Incidence and preventability of adverse drug events in nursing homes.

PURPOSE: Adverse drug events, especially those that may have been preventable, are among the most serious concerns about medication use in nursing homes. We studied the incidence and preventability of adverse drug events and potential adverse drug events in nursing homes. METHODS: We performed a cohort study of all long-term care residents of 18 community-based nursing homes in Massachusetts during a 12-month observation period. Potential drug-related incidents were detected by stimulated self-report by nursing home staff and by periodic review of the records of nursing home residents by trained nurse and pharmacist investigators. Each incident was classified by 2 independent physician-reviewers, using a structured implicit review process, by whether or not it constituted an adverse drug event or potential adverse drug event (those that may have caused harm, but did not because of chance or because they were detected), by the severity of the event (significant, serious, life-threatening, or fatal), and by whether it was preventable. Examples of significant events included nonurticarial rashes, falls without associated fracture, hemorrhage not requiring transfusion or hospitalization, and oversedation; examples of serious events included urticaria, falls with fracture, hemorrhage requiring transfusion or hospitalization, and delirium. RESULTS: During 28,839 nursing home resident-months of observation in the 18 participating nursing homes, 546 adverse drug events (1.89 per 100 resident-months) and 188 potential adverse drug events (0.65 per 100 resident-months) were identified. Of the adverse drug events, 1 was fatal, 31 (6%) were life-threatening, 206 (38%) were serious, and 308 (56%) were significant. Overall, 51% of the adverse drug events were judged to be preventable, including 171 (72%) of the 238 fatal, life-threatening, or serious events and 105 (34%) of the 308 significant events (P < 0.001). Errors resulting in preventable adverse drug events occurred most often at the stages of ordering and monitoring; errors in transcription, dispensing, and administration were less commonly identified. Psychoactive medications (antipsychotics, antidepressants, and sedatives/hypnotics) and anticoagulants were the most common medications associated with preventable adverse drug events. Neuropsychiatric events were the most common types of preventable adverse drug events. CONCLUSIONS: Adverse drug events are common and often preventable in nursing homes. More serious adverse drug events are more likely to be preventable. Prevention strategies should target the ordering and monitoring stages of pharmaceutical care.

The ability of strains of Klebsiella aerogenes to survive on the hands.

The ability of Klebsiella aerogenes strains isolated from outbreaks of infection, from sporadic infections and from the environment to survive on hands were compared. Considered as groups, the outbreak strains survived best and the environmental strains least well. The possible importance of these observations in relation to outbreaks of Klebsiella infection in hospitals and to heterogeneity of pathogenic potential and transmissibility in Klebsiella aerogenes is discussed.

A comparison of the properties of Klebsiella strains isolated from different sources.

The ability to form gas in lactose bile-salt broth at 44.5 degrees C (the "faecal coliform" or FC test), growth in nutrient broth at 10 degrees C, indole production and pectin liquefaction were studied in 480 strains of Klebsiella isolated from human and animal infections, from various sites in the hospital environment and hospital food, and from river water and flowers. A positive FC response was correlated inversely with the ability to grow at 10 degrees C. Most strains of human and animal clinical origin were FC positive, whereas strains from water and flowers were mainly FC negative. The frequency of a positive FC response in strains from the hospital environment fell between these two extremes. The production of indole and liquefaction of pectin by klebsiellas was correlated directly with the ability to grow at 10 degrees C and a negative FC response. Nearly all of the strains could be allocated to one of four groups on the basis of these tests. The capsular serotype, bacteriocine-inhibition patterns and antibiotic sensitivities of the strains were examined. No correlation was evident between the first two properties and klebsiellas from any particular source. Strains of clinical origin were more often resistant to five or more antibiotics than were strains from the hospital environment, which in turn showed a greater frequency of antibiotic resistance than did strains from river water and flowers.

Learning from failure in health care: frequent opportunities, pervasive barriers.

The notion that hospitals and medical practices should learn from failures, both their own and others', has obvious appeal. Yet, healthcare organisations that systematically and effectively learn from the failures that occur in the care delivery process, especially from small mistakes and problems rather than from consequential adverse events, are rare. This article explores pervasive barriers embedded in healthcare's organisational systems that make shared or organisational learning from failure difficult and then recommends strategies for overcoming these barriers to learning from failure, emphasising the critical role of leadership. Firstly, leaders must create a compelling vision that motivates and communicates urgency for change; secondly, leaders must work to create an environment of psychological safety that fosters open reporting, active questioning, and frequent sharing of insights and concerns; and thirdly, case study research on one hospital's organisational learning initiative suggests that leaders can empower and support team learning throughout their organisations as a way of identifying, analysing, and removing hazards that threaten patient safety.

Leading organisational learning in health care.

As healthcare organisations seek to enhance safety and quality in a changing environment, organisational learning practices can help to improve existing skills and knowledge and provide opportunities to discover better ways of working together. Leadership at executive, middle management, and local levels is needed to create a sense of shared purpose. This shared vision should help to build effective relationships, facilitate connections between action and reflection, and strengthen the desirable elements of the healthcare culture while modifying outdated assumptions, procedures, and structures.

A mathematical model for bacterial inactivation.

The first order kinetic model, the Buchanan model and Cerf's model, can model a linear survival curve, a survival curve with a shoulder and a survival curve with a tailing, respectively. However, they are not suitable for fitting a sigmoidal survival curve. The three models were integrated into a new model that was capable of fitting the four most commonly observed survival curves: linear curves, curves with a shoulder, curves with a tailing (biphasic curves) and sigmoidal curves. The new model was compared with the Whiting-Buchanan model using the survival curves of Staphylococcus aureus. The goodness-of-fit of the proposed model is practically as good as that of the Whiting-Buchanan model. Compared with the Whiting-Buchanan model, the proposed model has a more mechanistic background. Since for non-linear survival curves, such as biphasic and sigmoidal curves, the t(m-D) value (the time required for an m-log-cycle reduction of microorganisms under a given condition) cannot be estimated accurately by the existing or traditional method, a new method is also proposed to predict accurately the t(m-D) value for non-linear survival curves.

Reproductive cycles and pregnancy in interspecific sheep<==>goat chimaeras.

The objectives of the current study were to determine whether interspecific sheep<==>goat chimaeras exhibited reproductive cycles of their component species and were capable of maintaining ovine and caprine pregnancies to term. All chimaeras had oestrous cycles and several exhibited characteristics of both ewes and does, including short, 6-7-day cycles. Sixteen caprine pregnancies were confirmed in eight sheep<==>goat and one hybrid<==>sheep chimaera from 21 embryo transfers; of these, six appeared normal by ultrasonographic examination during Weeks 5 or 6, but none progressed beyond Week 8. Three apparent pseudopregnancies developed in two animals. In contrast, eight of 11 pregnancies in chimaeras resulted in term ovine offspring after transfer of ovine embryos or natural matings with rams. By comparison, interspecific (caprine or hybrid) pregnancies in ewes were lost in Week 4 (n = 8) or Weeks 5-6 (n = 2). First interspecific (ovine or hybrid) pregnancies in does were maintained longer (Weeks 6-12, n = 7) than second interspecific pregnancies (Weeks 4-5, n = 5) (P < 0.05) or interspecific pregnancies in ewes (P < 0.05). The results suggest that abnormal fetomaternal interactions during the early stages of implantation are responsible for termination of caprine pregnancies in the ovine or chimaeric uterus, whereas ovine conceptuses are able to implant successfully in the chimaeric uterus. All chimaeras were fertile, since each carried at least one ovine pregnancy to term following natural matings with rams.

Inter- and intraspecific placentae in sheep, goats and sheep-goat chimaeras.

These studies compared inter- and intraspecific placentae during implantation and at full-term in sheep, goats and interspecific sheep-goat chimaeras. Histological sections prepared from intra- and interspecific day-26, 32 and 36 placentae in ewes and does indicated an altered ability of the trophoblast to invade the maternal caruncle in interspecific pregnancies. Two sheep-in-goat pregnancies were less, and two goat-in-sheep pregnancies were more, invasive than homologous pregnancies. Caprine pregnancies in chimaeras generally terminated before timed samples could be obtained, but biopsy samples collected at laparotomy between days 42 and 48 demonstrated both normal and abnormal placentation in chimaeras after breedings to rams. In six of 11 full-term fetal placentae from ovine pregnancies in chimaeras, there was abnormal retention of maternal caruncular tissue to the extent that macroscopic lesions were visible on the surface of the fetal cotyledons. Histological observations indicated that proliferation of maternal septa and hyalinization of maternal vessels had occurred at the expense of the fetal villi. Overall, the results suggested that the physiological events that regulate implantation are different in the two species, despite anatomical similarities between the ovine and caprine placenta. The caprine conceptus is likely to be rejected in the ovine or chimaeric uterus because of its over-invasiveness in the early stages of implantation, whereas the ovine conceptus can survive in the potentially chimaeric uterus.

Survival analysis for evaluation of corneal ulcer healing times in calves with naturally acquired infectious bovine keratoconjunctivitis.

A clinical trial examining the efficacy of 2 drugs for treatment of a natural epizootic of infectious bovine keratoconjunctivitis was performed. The study was conducted in 103 grazing Hereford calves during the summer of 1985. The calves were prospectively and randomly assigned to 1 of 3 groups at the beginning of the study on June 17, and were examined 3 times weekly thereafter until the final observation on August 6. Calves in group 1 (n = 34) were not treated and were used as controls. Calves of group 2 (n = 34) with corneal ulcers were treated with a long-acting oxytetracycline formulation (OTC group). The parenteral treatment was repeated in 72 hours. Affected calves of group 3 (n = 35) were treated topically with furazolidone spray when they developed new corneal ulcers, or when existing lesions worsened during subsequent examination periods (NFZ group). Healing times of the corneal ulcers were reported in 3 ways: the combined times for ulcers present in both eyes of a calf simultaneously (method A), independent times of each ulcer on a calf (method B), and time of the first ulcer for each calf (method C). Censored healing times were examined as left censored (ulcer present at the beginning of the study), right censored (ulcer not healed at the end of the study), or uncensored (true) healing times. The effect that the treatments had on healing times were investigated by use of notched box and whisker plots, life tables, and Cox regression models. The analysis indicated that treatment of calves with either antimicrobial reduced the healing time of corneal ulcers, compared with untreated controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of fecal samples collected per rectum and off the ground for estimation of environmental contamination attributable to beef cattle.

OBJECTIVES: To determine whether sampling feces off the ground replicates prevalence estimates for specific pathogens obtained from fecal samples collected per rectum of adult cows, and to determine characteristics of feces on the ground (fecal pats) that are associated with subsequent identification of Campylobacter spp, Cryptosporidium parvum, and Giardia duodenalis. ANIMALS: A random sample of adult beef cattle from 25 herds located throughout California. PROCEDURE: 1,115 rectal and ground fecal samples were obtained. Samples were submitted for culture of Campylobacter spp and examined, using a direct fluorescent antibody assay, to detect C parvum oocysts and G duodenalis cysts. Characteristics of fecal pats, such as volume and consistency, were recorded. RESULTS: Prevalence of Campylobacter spp was 5.0% (20/401) for rectal fecal samples, which was significantly greater than prevalence determined for ground fecal samples (2/402; 0.5%). Most isolates were C jejuni subsp jejuni. Prevalence of C parvum was higher in rectal fecal samples (6/557; 1.1%) than in ground fecal samples (1/558; 0.2%), but this difference was not significant. Prevalence of G duodenalis did not differ for rectal (36/557; 6.5%) versus ground (26/558; 4.7%) fecal samples. CONCLUSIONS AND CLINICAL RELEVANCE: Evaluation of ground fecal samples may not accurately indicate the prevalence of Campylobacter spp or C parvum in cattle but may reflect prevalence of G duodenalis. Differences in prevalence estimates between the 2 methods suggest inactivation of pathogens in feces after cattle have defecated. Prevalence estimates generated by evaluation of ground fecal samples, however, may more accurately estimate environmental pathogen burden.

Topically applied furazolidone or parenterally administered oxytetracycline for the treatment of infectious bovine keratoconjunctivitis.

The effectiveness of topically applied furazolidone (FZ) or parenterally administered oxytetracycline (OTC) for treatment of infectious bovine keratoconjunctivitis was determined in a field study. Between June 13 and Aug 6, 1985, a study was conducted on a ranch in northern California. Eyes of Hereford calves (n = 103) were examined 3 times each week for 7 weeks. After daily examinations on June 13 and 14, calves were allotted randomly to 3 groups. On June 17, calves (that had corneal ulcers) of groups 1 (n = 35) and 2 (n = 35) were treated with OTC and FZ, respectively. Treatments were administered again only if new ulcers were observed, if an existing ulcer worsened, or if a healed ulcer recurred. Calves of group 3 remained untreated (controls). Corneal ulcers developed in 35 of the FZ-treated calves, in 33 of the OTC-treated calves, and in 33 of the untreated calves. Corneal perforations were observed in 3 untreated and 2 FZ-treated calves but were not observed in any OTC-treated calves. Panophthalmitis developed in one eye of an untreated calf. Corneal ulcers in the OTC-treated calves were smaller and healed more rapidly than did corneal ulcers in calves of the other groups. By the 22nd day of the study (July 3), the number of OTC-treated calves with corneal ulcers was less than that of the other 2 groups. Calves of the OTC treatment group had the fewest multiple corneal ulcer recurrences, but calves of all 3 groups had a similar number of single corneal ulcer recurrences.(ABSTRACT TRUNCATED AT 250 WORDS)

Mycobacterium bovis in California dairies: a case series of 2002-2013 outbreaks.

From 2002 to 2013, bovine tuberculosis (bTB) caused by Mycobacterium bovis (M. bovis) has been detected on numerous dairies in California. In total, twelve herds had bTB detected and are included in the case series which describes these recent outbreaks and discusses potential pathways of introduction. Epidemiological investigations to determine the initial source of bTB in each herd included obtaining data on likely pathways of pathogen introduction. Pathways included purchasing cattle, use of heifer-raising operations, commingling of cattle at greater risk of exposure to infected cattle with cattle destined for California dairies, contact with infected wildlife, exposure to humans with bTB infections, community and neighboring herds and others. Epidemiologic and molecular typing data confirmed the source of infection in 3 herds and probable sources of infection in 2 herds. In the 7 remaining herds described in this case series an epidemiologic link to a source could not be determined and molecular typing results did not associate M. bovis isolates acquired from these herds with another specific U.S. herd or U.S.-born animal. Preventing new introductions of M. bovis onto California dairies will require rigorous epidemiologic investigation of all the potential pathways of introduction discussed here. The root cause(s) of bTB on California dairies is certainly multifactorial with complex interactions of herd management practices, importation of cattle at greater risk of exposure to infected cattle, and the potential of human M. bovis exposure. The extensive use of molecular typing has improved epidemiologists' ability to narrow the scope of potential sources.

Antigenic variation in Klebsiella.

The serological reactions of klebsiella strains repeatedly isolated from four patients were examined. Variations in capsular antigens of strains from the same patient were mainly restricted to slight changes in the titre of quellung reactions and occasionally differences in cross-reactions were noted. In one case a strain reacted more strongly with a heterologous antiserum than with homologous antiserum after it had been resident in the bowel of a patient for five weeks. No significant antigenic variation was observed when multiple colonies from the same klebsiella culture were tested.

The development and assessment of a bacteriocin typing method for Klebsiella.

Klebsiellas are generally typed by the method of capsular serotyping but, although this is a reliable method, it is time consuming, requires the production of a large number of antisera and is not generally available. For this reason another method for typing klebsiellas was sought. A bacteriocin typing method involving mitomycin C induction was developed and the cultural conditions giving optimum klebecin production and the best methods of testing the sensitivity of the organisms to klebecins were determined. Of 190 klebsiella strains screened for bacteriocinogeny, only 68 (35.8%) produced klebecin and after calculation of similarity values by computer analysis, a typing set of 15 producers was selected. This typing set allowed over 96% of klebsiella strains to be typed and tests of the reproducibility of the method and the variability of typing patterns in natural populations of klebsiella indicated that results of acceptable accuracy could be obtained, while retaining good discrimination if two or more differences were required between patterns before they were regarded as distinct. A complete set of capsular antisera were prepared, enabling the results obtained from klebecin typing to be compared with those from serotyping. There was generally close agreement between the results from the two typing methods and greater discrimination was obtained between similar strains when the two methods were combined. Klebecin typing and serotyping revealed relationships between strains from five outbreaks of infection, and strains of the same serotype from different hospitals could frequently be distinguished by their klebecin typing patterns.

An Arabidopsis homologue of bacterial RecA that complements an E. coli recA deletion is targeted to plant mitochondria.

Homologous recombination results in the exchange and rearrangement of DNA, and thus generates genetic variation in living organisms. RecA is known to function in all bacteria as the central enzyme catalyzing strand transfer and has functional homologues in eukaryotes. Most of our knowledge of homologous recombination in eukaryotes is limited to processes in the nucleus. The mitochondrial genomes of higher plants contain repeated sequences that are known to undergo frequent rearrangements and recombination events. However, very little is known about the proteins involved or the biochemical mechanisms of DNA recombination in plant mitochondria. We provide here the first report of an Arabidopsis thaliana homologue of Escherichia coli RecA that is targeted to mitochondria. The mt recA gene has a putative mitochondrial presequence identified from the A. thaliana genome database. This nuclear gene encodes a predicted product that shows highest sequence homology to chloroplast RecA and RecA proteins from proteobacteria. When fused to the GFP coding sequence, the predicted presequence was able to target the fusion protein to isolated mitochondria but not to chloroplasts. The mitochondrion-specific localization of the mt recA gene product was confirmed by Western analysis using polyclonal antibodies raised against a synthetic peptide from a unique region of the mature mtRecA. The Arabidopsis mt recA gene partially complemented a recA deletion in E. coli, enhancing survival after exposure to DNA-damaging agents. These results suggest a possible role for mt recA in homologous recombination and/or repair in Arabidopsis mitochondria.

The fate of Salmonella enteritidis PT4 in home-made mayonnaise prepared with citric acid.

The fate of Salmonella enteritidis PT4 in home-made mayonnaise prepared with citric acid solution (citric acid concentration of > or = 4.98% (w/v)) was investigated. It was found that pH of mayonnaise is closely related to the ratio of egg yolk to citric acid, and the inactivation rate of the micro-organisms increases as the ratio decreases and/or incubation temperature increases. To achieve Salm. enteritidis PT4-free home-made mayonnaise prepared with pure lemon juice (citric acid concentration > or = 5% (w/v)), it is recommended that the pH should be 3.30 or below, or, in practice, at least 20 ml pure lemon juice per fresh egg yolk should be used. For the use of 20-35 ml pure lemon juice per egg yolk, the product should be held at 22 degrees C or over for at least 72 h and for the use of over 35 ml pure lemon juice per egg yolk, for at least 48 h before consumption or refrigeration.

Corynebacterium pyogenes mastitis outbreak in inbred heifers in a California dairy.

An outbreak of Corynebacterium pyogenes mastitis ("Summer Mastitis") was observed in a group of 96 heifers. The outbreak affected 8 animals, of which 7 were too young for breeding. The disease incidence was highest in calves 2 to 4 months old. Cases were observed over an initial estimated 14 day period with a further case being detected 14 days subsequently. Corynebacterium pyogenes mastitis has not been reported in calves this age. Factors postulated to influence the outbreak include the presence of large numbers of flies, intersucking of calves, and possible viral disease.

Maternal serum reactivity to species-specific antigens in sheep-goat interspecific pregnancy.

Three models were used to test the hypothesis that interspecific pregnancy failure between the sheep and goat is due to a species-specific, maternal antibody response. Interspecific pregnancies were established in ewes and does, sheep in equilibrium goat chimeric conceptuses produced by injection of ovine blastocysts were transferred to ovine recipients, and ovine and caprine pregnancies were established in interspecific chimeras. Complement-mediated lymphocytotoxic and hemolytic assays were used to monitor onset and titer of antibodies. Sera from 3 of 8 injection-chimera recipients reacted with all caprine peripheral blood lymphocytes (PBL) and red blood cells (RBC) tested (n = 18). Sera from 3 of 6 ewes and 7 of 7 does also were pancytotoxic to PBL of the other species (n greater than or equal to 20). Absorptions with xenogeneic RBC generally removed the reactivity. The data were consistent with responses to species-specific, monomorphic antigens expressed on PBL and RBC, and probably trophoblast. The response preceded or coincided with interspecific pregnancy failure in does, but not in ewes. Accordingly, no xenoreactivity was observed in chimera sera but caprine pregnancies were resorbed (n = 16) and ovine pregnancies developed to term (n = 11). The data did not support the hypothesis that failure of caprine pregnancy in ewes or chimeras is due to a species-specific, maternal antibody response. In contrast, a maternal, cytotoxic antibody response to species-specific antigen(s) may contribute to failure of hybrid or ovine pregnancy in does.