The role of education in antimicrobial stewardship.

The role of antimicrobial stewardship programmes (ASPs) has expanded in health systems. ASP interventions often contain an educational component; however, current guidelines suggest that educational interventions should not be used alone but to support other stewardship interventions. Such interventions are most commonly directed towards prescribers (often general practice physicians) with few studies offering education towards other healthcare providers such as pharmacists, nurses, or even members of the stewardship team. Educational interventions are offered most frequently, but not exclusively, with concomitant stewardship interventions such as prospective audit and feedback. Such strategies appear to positively impact prescribing behaviours, but it is not possible to isolate the effect of education from other interventions. Common educational methods include one-time seminars and online e-learning modules, but unique strategies such as social media platforms, educational video games and problem-based learning modules have also been employed. Education directed towards patients often occurs in conjunction with education of local prescribers and wider community-based efforts to impact prescribing. Such studies evaluating patient education often include passive educational leaflets and focus most often on appropriate treatment of upper respiratory tract infections. Educational interventions appear to be an integral component of other interventions of ASPs; however, there is a paucity of evidence to support use as a stand-alone intervention outside of regional public health interventions. Future studies should focus on efficacy of educational interventions including providing education to non-prescribers and disease states beyond upper respiratory tract infections to demonstrate a broader role for education in ASP activities.

Comparative in vivo activity of gemifloxacin in a rat model of respiratory tract infection.

The in vivo efficacy of the novel quinolone gemifloxacin (SB-265805) was examined in a rat respiratory tract infection (RTI) model against four strains of Streptococcus pneumoniae and two strains of Haemophilus influenzae with varying susceptibilities to standard antimicrobial agents. Animals were infected intrabronchially to produce pneumonia and therapy with oral gemifloxacin, amoxycillin-clavulanate, ciprofloxacin, cefuroxime, azithromycin, trovafloxacin, grepafloxacin or levofloxacin was started 24 h after infection. The doses administered were chosen to approximate in the rat the serum or tissue concentrations measured in humans following therapeutic dosing. Therapy continued once- or twice-daily for 3 days, and approximately 17 h after the end of therapy the lungs were excised for bacterial enumeration. Following infection with strains of S. pneumoniae, gemifloxacin produced a 3-5 log reduction in bacterial numbers compared with untreated animals. Gemifloxacin was as effective as amoxycillin- clavulanate, and was as potent or more potent than all other comparators. Notably, the quinolone agents trovafloxacin, ciprofloxacin, grepafloxacin and levofloxacin were significantly less effective (P < 0.01) than gemifloxacin: these agents reduced bacterial numbers by < or =3 log compared with untreated animals. Gemifloxacin produced a marked response against H. influenzae infection, reducing bacterial numbers significantly (P < 0.01) compared with untreated controls. Gemifloxacin was significantly more potent than cefuroxime and azithromycin. None of the other comparator agents was more potent than gemifloxacin. The excellent efficacy seen in these experimental models of RTI with S. pneumoniae and H. influenzae confirms the in vitro activity of gemifloxacin against these organisms. This indicates that gemifloxacin may be of significant benefit in the treatment of RTI.

Comparative efficacy of gemifloxacin in experimental models of pyelonephritis and wound infection.

Gemifloxacin (SB-265805) is a potent, novel fluoroquinolone with broad-spectrum antimicrobial activity. In this study, the efficacy of gemifloxacin was studied in experimental models of Gram-negative pyelonephritis (caused by Escherichia coli or Proteus mirabilis) and Gram-positive wound infection resulting from Streptococcus pyogenes, Staphylococcus epidermidis or Staphylococcus aureus. Gemifloxacin activity against these pathogens was compared with those of amoxycillin-clavulanate, ciprofloxacin, cefuroxime, azithromycin, trovafloxacin, grepafloxacin, levofloxacin and tosufloxacin. Oral treatment was initiated 1 h after infection and continued once or twice daily for 3 days. Around 17 h after the end of treatment, animals were killed and the infected kidneys or the skin around the wound site were excised for the enumeration of viable bacteria. In the pyelonephritis model (either microorganism), gemifloxacin reduced bacterial numbers significantly (P < 0.01) compared with no treatment. No comparator agent had a greater effect than gemifloxacin. Notably, grepafloxacin and azithromycin were significantly less effective (P < 0.01) than gemifloxacin against E. coli pyelonephritis, and amoxycillin-clavulanate, azithromycin and trovafloxacin were inferior (P < 0.01) against P. mirabilis infection. In the S. pyogenes wound infection model, gemifloxacin, amoxycillin-clavulanate, cefuroxime and azithromycin reduced bacterial numbers significantly compared with controls (P < 0.01). Results for the comparator quinolones were not significantly different from untreated controls (P > 0.05). Gemifloxacin was also effective against staphylococcal infection, as were grepafloxacin and levofloxacin, while ciprofloxacin, trovafloxacin and tosufloxacin were significantly less effective against these pathogens than gemifloxacin (P < 0.01). No comparator agent had greater activity than gemifloxacin against S. pyogenes or S. aureus infections. These data demonstrate the potential benefit of gemifloxacin in the treatment of Gram-negative urinary tract infection and Gram-positive skin and soft tissue infection.

Adjunctive cognitive-behavioral therapy for rapid-cycling bipolar disorder: an empirical case study.

A basic biopsychosocial model of episode onset in rapid-cycling bipolar disorder is presented with a special emphasis on cognitive and other psychosocial contributors. A three-pronged, face-valid, cognitive-behavioral treatment protocol meant to supplement medications is deduced from the available research literature. The concrete treatment components focus on prevention of mood cycles, early detection of cycle onset, and mood restabilization during cycles. The treatment protocol was pilot tested on a rapid-cycling bipolar patient who first received pharmacotherapy only followed by pharmacotherapy plus adjunctive cognitive-behavioral therapy (CBT). Detailed treatment measures were collected before, during, and after treatment. A comparison of Beck Depression Inventory and Young Mania Scale scores in pharmacotherapy versus pharmacotherapy plus CBT conditions suggest the addition of CBT produces significant clinical gains. Scores on the Beck Anxiety Inventory and Hopelessness Scale provide further support for the CBT treatment model. These preliminary results suggest cognitive-behavioral or similarly structured psychosocial treatment models could greatly enhance the medical treatment of rapid-cycling bipolar patients and warrants further controlled investigation.

A prospective study of hyperactive boys with conduct problems and normal boys: adolescent and adult criminality.

OBJECTIVE: To examine the relationship between attention deficit disorder with hyperactivity in childhood and criminality in adolescence and adulthood in 89 hyperactive and 87 normal control subjects. METHOD: In this prospective study, adolescent follow-up intervals ranged from 13 to 21 years and adult follow-up ranged from 18 to 23 years. The official arrest records for all subjects were obtained. RESULTS: Hyperactive subjects had significantly higher juvenile (46% versus 11%) and adult (21% versus 1%) arrest rates. Juvenile and adult incarceration rates were also significantly higher. Childhood conduct problems predicted later criminality, and serious antisocial behavior in adolescence predicted adult criminality. CONCLUSIONS: Hyperactive children are at risk for both juvenile and adult criminality. The risk for becoming an adult offender is associated with conduct problems in childhood and serious antisocial behavior (repeat offending) in adolescence. Hyperactive children who do not have conduct problems are not at increased risk for later criminality.

Selective immunomodulatory activity of SK&F 106615, a macrophage-targeting antiarthritic compound, on antibody and cellular responses in rats and mice.

The azaspiranes are novel immunomodulators which are effective in a variety of animal models of autoimmune disease and transplantation. The compounds appear to target macrophages and alter their functional activity. One of these compounds, SK&F 106615 (N,N-diethyl-8,8-dipropyl-2-azaspiro[4.5]decane-2-propanamine++ + dihydrochloride), is now in phase II clinical trials for rheumatoid arthritis. As many drugs/compounds effective in autoimmune disease and transplantation are overtly immunosuppressive, we designed studies to show that SK&F 106615 has selective immunomodulatory effects and that it does not perform in a manner characteristic of classical immunosuppressive agents on immune function. SK&F 106615 inhibited mouse and rat spleen cell and rat peripheral blood mononuclear cell proliferation in vitro with an IC50 of 500 nM. In vivo, treatment of C57BL/6 mice (15 mg/kg/day, i.p.) or rats (20 mg/kg/day, p.o.) for 2 weeks had no effects on specific antibody synthesis to ovalbumin (OVA) compared to rapamycin (RAP) which completely suppressed the antibody response. Compared to cyclosporin A (CsA), FK 506 and RAP which suppressed the antibody (plaque forming) response to particulate (sheep red blood cells) antigen in a dose responsive manner, SK&F 106615 administered at a dose of 50 mg/kg was inactive. There was an inhibition of the proliferative response of lymph node cells from treated mice and rats to mitogen and antigen in ex vivo assays. SK&F 106615, but not RAP, induced cells in the spleens of mice that could inhibit normal spleen cell proliferation in a co-culture assay. Thus, a selective immunomodulatory effect can be shown for SK&F 106615 in the absence of generalized immunosuppression.

Law school performance predicted by explanatory style.

The explanatory styles of 387 law students were assessed prior to law school using the Attributional Style Questionnaire (ASQ). Longitudinal performance measures were collected throughout law school and related to each student's initial explanatory style. In contrast to studies with undergraduates, students who made stable, global, and internal attributions for negative events combined with the converse attributions for success (typically called pessimists) outperformed more optimistic students on measures of grade point averages and law journal success. We discuss the limitations of current attributional research methodologies and suggest the prudent and cautious perspective necessary for law or skill-based professions may account for our findings.

Credentialing physicians for new technology: the physician's learning curve must not harm the patient.

Laparoscopic Cholecystectomy (L.C.) offers advantages that are realized only when patient safety is assured. In November 1990, The Department of Surgery at The New York Hospital Medical Center of Queens initiated a program to introduce this new technology to surgeons who had not performed the operation previously. A preceptorship program was initiated, accompanied by contemporaneous quality assurance review. This is the experience of 15 general surgeons who performed their first 400 L.C.s from November 1990 through March 1993. There were no deaths and only one common bile duct injury (0.25%).

Prediction of antisocial behavior in attention-deficit hyperactivity disorder boys from aggression/defiance scores.

OBJECTIVE: To predict teen-age arrests from measures of childhood defiance in attention-deficit hyperactivity disorder (ADHD) boys. METHOD: Defiance ratings that were independent of hyperactivity were obtained on two groups of ADHD boys. Official arrest data obtained on all subjects 9 years later were used as the outcome measure. RESULTS: ADHD boys with high defiance ratings had significantly higher felony offender rates than did boys with low ratings. However, the ADHD boys with low ratings had significantly higher felony offender rates than did normal control boys. CONCLUSIONS: Clinicians and parents should be alerted to the fact that minor antisocial features in ADHD boys, such as defiance, signal an increased risk for later serious antisocial behavior. However, they should not be misled by the absence of defiance in ADHD boys to think that these boys are not at risk for serious antisocial behavior (arrests for serious criminal behavior) later in life.

Preferential neural processing of attended stimuli in attention-deficit hyperactivity disorder and normal boys.

Event-related auditory and visual potentials were recorded from 36 attention-deficit hyperactivity disorder (ADHD) and 35 normal 6-year-old subjects engaged in a two-choice discrimination task. When normal subjects attended to stimuli in a given modality, enhanced negative (N2) and positive (P3b) responses (as compared with responses to nonattended stimuli) were found for auditory and visual target stimuli. In contrast, when ADHD subjects attended, little or no enhanced negative responses were found in either modality, and enhanced positive P3b responses were found only in response to visual target stimuli. Auditory N1, N2, and P3b and visual N2 amplitudes to attended target stimuli were significantly reduced in ADHD subjects as compared with normal subjects. No between-group differences were found for responses to nonattended stimuli. Both amplitude and latency abnormalities indicate that ADHD boys suffer from deficient preferential processing of attended stimuli. P3b and N2 abnormalities found here suggest deficiencies in two independent cognitive processes thought to be crucial to what we perceive, learn, and remember.

Ontogeny of selective attention effects on event-related potentials in attention-deficit hyperactivity disorder and normal boys.

A longitudinal study of young attention-deficit hyperactivity disorder (ADHD) boys has found clear evidence for developmental abnormalities in event-related potential (ERP) waves that reflect cognitive processes associated with selective attentional tasks. Boys alternated attention to auditory or visual modalities in a train of stimuli, in an attempt to detect target stimuli in the attended modality. Results suggest that ADHD boys' attentional difficulties are due to insufficient facilitation of responses to the attended stimuli and not to an inability to block ignored stimuli. Abnormalities in ERPs reflecting cognitive processes associated with both interchannel selection mechanisms (processing negativity) and intrachannel selection mechanisms (P3b) were found. The degree of abnormality in the P3b responses to target stimuli in ADHD boys (lower than normal boys) was found to increase with age. It is suggested that the abnormally low P36 response to attended target stimuli found in ADHD boys may be due in part to insufficient LC noradrenergic activity normally triggered by attended task-relevant or novel stimuli.

Longitudinal study of AERPs in hyperactive and normal children: relationship to antisocial behavior.

Changes in AERP measures from childhood to adolescence were studied in 2 subgroups of hyperactive children (25 non-delinquent and 9 delinquent) and 1 group of 34 non-delinquent normal children. The 3 groups were selected on the basis of official delinquency measures obtained 8 years after their initial evaluations. All subjects were studied using the same AERP paradigm at both points in time. The major finding was that the non-delinquent hyperactive subjects were found to have abnormal maturational changes as reflected by AERP measures while the delinquent hyperactive subjects were found to have normal maturational changes in these same measures. This suggests that these 2 hyperactive groups are on a different developmental course and that they may represent different clinical entities. Results of the comparison of cross-sectional data in childhood and again in adolescence were consistent with the concept of 2 distinct subgroups.

Thymectomy for myasthenia gravis: 14-year experience.

Forty-eight consecutive patients with myasthenia gravis (MG) attended by generalized weakness were treated by complete thymectomy, performed transsternally in 46 patients and through a left thoracotomy in two with thymomas. There were no operative deaths. A 12-year-old child with fulminating MG died of acute pneumonia shortly after hospital discharge. Of the remaining 47 evaluable patients, thymectomy resulted in complete remission in six, marked improvement with a reduced need for medication in 20, and mild improvement on the same dosage of medication in 18. Neither the age of the patient, nor the histopathology of the excised thymus, nor the postoperative change in acetylcholine receptor antibody titer were found to have a significant influence on the response to thymectomy. If the ten patients who were 20 years of age or younger were excluded, the patients with a shorter duration of MG achieved a better response to operation. The authors conclude that thymectomy is effective treatment for MG, regardless of the age of the patient or the type of thymic pathology.

A cross-sectional and longitudinal study of age effects of electrophysiological measures in hyperactive and normal children.

Longitudinal and cross-sectional event-related potential, EEG power spectral, and skin conductance level data were obtained from 138 hyperactive and 60 normal boys. A age-by-diagnosis interaction was found for several measures in the cross-sectional data and for all three types of measures in the longitudinal data. These findings emphasize the importance of age in electrophysiological studies of young children and strongly suggest an abnormal maturational process in hyperactive children.

Childhood brain function differences in delinquent and non-delinquent hyperactive boys.

Childhood electrophysiological and clinical measures were obtained in 110 hyperactive (HA) and 76 normal children, who were later followed up as adolescents. Official arrest data were obtained on all subjects and used to measure outcome. The usual interpretation, that the presence of a brain function abnormality suggests a poor prognosis, does not apply to the clinical EEG, EEG spectral and ERP measures obtained on these HA boys. In fact, the converse was found to be true, that is EEG and ERP abnormalities were associated with a good outcome, while normal values of these measures were associated with a poor outcome. Data were presented that suggest that there may be two distinct subgroups of HA boys. The first group was characterized by abnormalities in childhood brain function, abnormal changes in brain function with age, less antisocial and hyperactive behavior in childhood, and absence of delinquency in adolescence. The second group was characterized by normal childhood brain function, normal changes in brain function with age, more antisocial and hyperactive behavior in childhood, and teenage delinquency. Childhood EEG and ERP measures were found to be significantly different in these delinquent and non-delinquent HA groups, while social, familial and cognitive attributes were not. The N2 amplitude of the AERP in delinquent hyperactive (DHA) boys was found to be significantly larger than in the non-delinquent hyperactive (NDHA) boys. This N2 amplitude may prove clinically useful in selecting HA boys for delinquency prevention programs.