Systematic development and validation of a predictive model for major postoperative complications in the Peri-operative Quality Improvement Project (PQIP) dataset.

Complications are common following major surgery and are associated with increased use of healthcare resources, disability and mortality. Continued reliance on mortality estimates risks harming patients and health systems, but existing tools for predicting complications are unwieldy and inaccurate. We aimed to systematically construct an accurate pre-operative model for predicting major postoperative complications; compare its performance against existing tools; and identify sources of inaccuracy in predictive models more generally. Complete patient records from the UK Peri-operative Quality Improvement Programme dataset were analysed. Major complications were defined as Clavien-Dindo grade ≥ 2 for novel models. In a 75% train:25% test split cohort, we developed a pipeline of increasingly complex models, prioritising pre-operative predictors using Least Absolute Shrinkage and Selection Operators (LASSO). We defined the best model in the training cohort by the lowest Akaike's information criterion, balancing accuracy and simplicity. Of the 24,983 included cases, 6389 (25.6%) patients developed major complications. Potentially modifiable risk factors (pain, reduced mobility and smoking) were retained. The best-performing model was highly complex, specifying individual hospital complication rates and 11 patient covariates. This novel model showed substantially superior performance over generic and specific prediction models and scores. We have developed a novel complications model with good internal accuracy, re-prioritised predictor variables and identified hospital-level variation as an important, but overlooked, source of inaccuracy in existing tools. The complexity of the best-performing model does, however, highlight the need for a step-change in clinical risk prediction to automate the delivery of informative risk estimates in clinical systems.

Behavioral and genetic architecture of fear conditioning and related phenotypes.

Contextual fear conditioning is a form of Pavlovian learning during which an organism learns to fear previously neutral stimuli following their close temporal presentation with an aversive stimulus. In mouse models, freezing behavior is typically used to quantify learned fear. This dependent variable is the sum of multiple processes, including associative/configural learning, fear and anxiety, and general activity. To explore phenotypic constructs underlying contextual fear conditioning and correlated behaviors, as well as factors that may contribute to individual differences in learning and mental health, we tested BXD recombinant inbred strains previously found to show extreme contextual fear conditioning phenotypes and BXD parental strains, C57BL/6J and DBA/2J, in a series of tests including locomotor, anxiety, contextual/cued fear conditioning and non-associative hippocampus-dependent learning behaviors. Hippocampal expression of two previously identified candidate genes for contextual fear conditioning was also quantified. Behavioral and gene expression data were analyzed using exploratory factor analysis (EFA), which suggested five unique constructs representing activity/anxiety/exploration, associative fear learning, anxiety, post-shock freezing, and open field activity phenotypes. Associative fear learning and expression of one candidate gene, Hacd4, clusteredas a construct withinthefactor analysis. Post-shock freezingduring fear conditioning and expression of candidate gene Ptprd emerged as another unique construct, highlighting theindependenceof freezing after footshock from other fear conditioning variables in the current dataset.EFA results additionally suggest shared phenotypic variance in adaptive murine behaviors related to anxiety, general activity, and exploration. These findings inform understanding of fear learning and underlying biological mechanisms that may interact to produce individual differences in fear- and learning-related behaviors in mice.

Development and internal validation of a model for postoperative morbidity in adults undergoing major elective colorectal surgery: the peri-operative quality improvement programme (PQIP) colorectal risk model.

Over 1.5 million major surgical procedures take place in the UK NHS each year and approximately 25% of patients develop at least one complication. The most widely used risk-adjustment model for postoperative morbidity in the UK is the physiological and operative severity score for the enumeration of mortality and morbidity. However, this model was derived more than 30 years ago and now overestimates the risk of morbidity. In addition, contemporary definitions of some model predictors are markedly different compared with when the tool was developed. A second model used in clinical practice is the American College of Surgeons National Surgical Quality Improvement Programme risk model; this provides a risk estimate for a range of postoperative complications. This model, widely used in North America, is not open source and therefore cannot be applied to patient populations in other settings. Data from a prospective multicentre clinical dataset of 118 NHS hospitals (the peri-operative quality improvement programme) were used to develop a bespoke risk-adjustment model for postoperative morbidity. Patients aged ≥ 18 years who underwent colorectal surgery were eligible for inclusion. Postoperative morbidity was defined using the postoperative morbidity survey at postoperative day 7. Thirty-one candidate variables were considered for inclusion in the model. Death or morbidity occurred by postoperative day 7 in 3098 out of 11,646 patients (26.6%). Twelve variables were incorporated into the final model, including (among others): Rockwood clinical frailty scale; body mass index; and index of multiple deprivation quintile. The C-statistic was 0.672 (95%CI 0.660-0.684), with a bootstrap optimism corrected C-statistic of 0.666 at internal validation. The model demonstrated good calibration across the range of morbidity estimates with a mean slope gradient of predicted risk of 0.959 (95%CI 0.894-1.024) with an index-corrected intercept of -0.038 (95%CI -0.112-0.036) at internal validation. Our model provides parsimonious case-mix adjustment to quantify risk of morbidity on postoperative day 7 for a UK population of patients undergoing major colorectal surgery. Despite the C-statistic of < 0.7, our model outperformed existing risk-models in widespread use. We therefore recommend application in case-mix adjustment, where incorporation into a continuous monitoring tool such as the variable life adjusted display or exponentially-weighted moving average-chart could support high-level monitoring and quality improvement of risk-adjusted outcome at the population level.

Obstetric anaesthesia over the next 10 years: Africa and Middle East.

Maternal and neonatal health outcomes vary within Africa and the Middle East. Despite substantial improvements over the past 20 years, there are persisting inequities in access to, and the quality of, obstetric anaesthetic care. These are most noticeable in Sub-Saharan Africa which has only 3% of the world's healthcare workforce but approximately two-thirds of global maternal deaths. Improvements are being made by: improving access; increasing numbers of trained staff; delivering accessible training; gathering data; conducting research and quality improvement activities; using innovative technologies; and forming productive collaborations. Further improvements will be needed to cope with increasing demand, the impacts of climate change and potential future pandemics.

A learning health systems approach to improving the quality of care for patients in South Asia.

Poor quality of care is a leading cause of excess morbidity and mortality in low- and middle- income countries (LMICs). Improving the quality of healthcare is complex, and requires an interdisciplinary team equipped with the skills to design, implement and analyse setting-relevant improvement interventions. Such capacity is limited in many LMICs. However, training for healthcare workers in quality improvement (QI) methodology without buy-in from multidisciplinary stakeholders and without identifying setting-specific priorities is unlikely to be successful. The Care Quality Improvement Network (CQIN) was established between Network for Improving Critical care Systems and Training (NICST) and University College London Centre for Perioperative Medicine, with the aim of building capacity for research and QI. A two-day international workshop, in collaboration with the College of Surgeons of Sri Lanka, was conducted to address the above deficits. Innovatively, the CQIN adopts a learning health systems (LHS) approach to improving care by leveraging information captured through the NICST electronic multi-centre acute and critical care surveillance platform. Fifty-two delegates from across the CQIN representing clinical, civic and academic healthcare stakeholders from six countries attended the workshop. Mapping of care processes enabled identification of barriers and drivers to the delivery of care and facilitated the selection of feasible QI methods and matrices. Six projects, reflecting key priorities for improving the delivery of acute care in Asia, were collaboratively developed: improving assessment of postoperative pain; optimising sedation in critical care; refining referral of deteriorating patients; reducing surgical site infection after caesarean section; reducing surgical site infection after elective general surgery; and improving provision of timely electrocardiogram recording for patients presenting with signs of acute myocardial infarction. Future project implementation and evaluation will be supported with resources and expertise from the CQIN partners. This LHS approach to building capacity for QI may be of interest to others seeing to improve care in LMICs.

The information-loss model: a mathematical theory of age-related cognitive slowing.

A model of cognitive slowing is proposed with the following assumption: Information is lost during processing, processing occurs in discrete steps with step duration inversely related to the amount of information currently available, and the effect of aging is to increase the proportion of information lost per step. This model correctly predicts a positively accelerated relation between latencies of older and younger adults and provides a unified account of the effects of task complexity, practice, speed-accuracy tradeoffs, and fluctuations in individual performance. Strong support for the thesis that cognitive slowing is global, and not localized in specific age-sensitive components, is provided by the fact that the model accurately predicts the latencies of older adults on the basis of those of younger adults, without regard to the nature of the task, across a latency range of nearly 2 orders of magnitude.

Acute hemodynamic effects of endralazine: a new vasodilator for chronic refractory congestive heart failure.

Invasive hemodynamic measurements were made in 10 supine patients with chronic refractory congestive heart failure (CHF) due to ischemic heart disease or cardiomyopathy before and after oral administration of a new arteriolar vasodilator, endralazine. In 9 patients, a 10 mg dose of endralazine produced maximal increases in cardiac and stroke volume indexes of 56 and 41%, respectively, with a 45% reduction in total systemic resistance. After a 5 mg dose of endralazine, cardiac index increased maximally by 38% and stroke volume index by 34%, with a 31% decrease in total systemic resistance. Mean arterial pressure decreased 11 +/- 4 mm Hg (mean +/- standard error of mean) with the 5 mg dose and 17 +/- 5 mm Hg after the 10 mg dose. There were no significant changes in the right atrial, pulmonary arterial, or pulmonary capillary wedge pressures. After administration of a single dose of endralazine, statistically significant hemodynamic changes were observed from 1 to 8 hours with peak responses at 3 to 4 hours. These observations suggest that endralazine has hemodynamic properties similar to those of its structural analog, hydralazine. However, endralazine metabolism is largely independent of the patients' acetylator status, and no cases of systemic lupus erythematosus have been reported after long-term oral administration. These findings suggest that endralazine may be an efficacious drug that is potentially safer than hydralazine in the treatment of chronic CHF.

Long-term beneficial effects of endralazine, a new arteriolar vasodilator at rest and during exercise capacity in chronic congestive heart failure.

Hemodynamic measurements were made at rest and during submaximal and maximal exercise in 12 patients with chronic congestive heart failure before and after oral endralazine (EN). After acute assessment, patients received endralazine, twice daily, for a mean of 2.8 months, when hemodynamic measurements were repeated. The drug was withdrawn for 3 to 4 days and subsequently reintroduced. Three patients with greatly elevated pulmonary wedge pressures were assessed after 30 mg of isosorbide dinitrate, which was also chronically administered. Resting mean cardiac and stroke volume indexes increased by 44 and 33%, respectively (p less than 0.01), with concomitant reduction of the systemic resistance. This improvement was maintained on a long-term basis in 8 of the 11 surviving patients. Withdrawal and subsequent reintroduction of EN confirmed that there was worsening of left ventricular dysfunction in the other 3 subjects. Chronic but not acute therapy produced a modest reduction in wedge pressure. At maximal exercise, cardiac and stroke volume indexes increased by 29 and 18%, respectively (p less than 0.01), after EN; the duration of exercise increased in 7 of the 10 subjects after acute therapy and this was maintained on a long-term basis. Mean creatinine clearance increased by 34% (p less than 0.01). The results confirm that EN produces acute and long-term hemodynamic and functional improvement without tolerance in congestive heart failure.

A poisonous plant file in TOXLINE.

A file has been added to TOXLINE on the subject of the toxicology of poisonous plants. It contains 2508 records, each of which comprises the full reference, key words, Chemical Abstracts Service Registry Number and abstract when available. A controlled vocabulary was constructed for the indexing and can be obtained from the National Technical Information Service. Searches can be made for several different data elements including authors; year; significant textwords of the title or abstract; journal or book; document type such as review or case report; geographic place at the level of continent, nation and state/province; plant species at the level of family, genus and species; plant parts involved; animal species affected including humans; type of harmful effects including major signs and lesions and chemicals.

Variations in mechanical sampling: their causes and effects.

Three characteristics of a sample of AutoAnalyzer Sampler II modules have been measured: eccentricity of the cam, eccentricity of the spindle driving the cam, and the lengths of the chords of the cam lobes. Imprecision in timing may make a significant contribution to analytical error.

Subsequent infection among adolescent African-American males attending a sexually transmitted disease clinic.

PURPOSE: To identify predictors of subsequent infection among a sample of 15- to 19-year-old African-American males attending an urban sexually transmitted disease (STD) clinic in the Midwest. METHODS: During a 14-month period, 562 youth participated in a brief STD prevention intervention designed to promote condom use. They completed self-administered questionnaires (baseline, posttest, 30-day and 6-month) on their sexual and condom use behavior in the past month. Infection data (baseline, 5 years before, and 12 months after baseline) were obtained from clinic and state surveillance records. Logistic regression was used to predict infection within 6 and 12 months of the baseline visit. RESULTS: Within 12 months of the baseline, 31.3% were treated for an infection, of whom 1.4% returned within 30 days, an additional 17.1% within 6 months, and the remaining 12.8% within the last 6 months. The 12-month rate was 1.6-1.7 times higher than the rates reported for older STD clinic attendees. Subsequent infection was positively associated with age at first intercourse, number of children fathered, infection prior to and at the index visit, exchange of sex for drugs in the past year, and perceived risk of infection within the year; it was negatively associated with frequency of condom use with one's steady partner. CONCLUSIONS: Sexually transmitted disease clinic staff routinely obtain information from young African-American males that can be used to identify individuals who are most likely to become reinfected. Because repeaters account for a disproportionate number of infections, prevention efforts tailored to their needs would have a corresponding impact on STD rates.

Public health and food safety: a historical association.

Since the initial passage in 1906 of the first Pure Food and Drug Act and the Meat Inspection Act, public health, as measured by mortality trends, has greatly improved. These acts have been amended several times, and other laws dealing with safety of foods and drinks have been enacted. Food- and beverage-transmitted infectious diseases that were so devastating after the Civil War have been controlled. Nutritional deficiencies such as pellagra are almost nonexistent. Mass episodes of poisoning of food by chemical contaminants that have plagued some other countries have not occurred in the United States. Other factors such as refrigeration and improved transportation have helped, but it is probable that food safety regulatory activities have contributed to the saving of the 1.8 million Americans who would die each year if the public health advances since 1900 had not been made. Effective use of information was a key factor in the improvement in public health. Now, as then, effective information systems are needed.

The impact of a culturally appropriate STD/AIDS education intervention on black male adolescents' sexual and condom use behavior.

A culturally appropriate, theoretically based videotape was developed to promote condom use among African American males, ages 15 to 19, attending a municipal sexually transmitted disease (STD) clinic. The videotape's impacts were compared to those achieved by an African American health educator who delivered the same messages during a face-to-face session and by standard care. Data were obtained on participants' (N = 562) condom use knowledge, self-efficacy, and intentions; sexual and condom use behaviors; and perceived risk of infection. At posttest, "videotape" and "health educator" participants demonstrated greater condom use knowledge; "health educator" participants indicated greater self-efficacy and stronger condom use intentions with steady partners. At 6 months, participants in all conditions reported more partners and acts of vaginal intercourse (past month); however, they were more likely to report consistent condom use with steady partners (18% vs. 53%) and casual partners (26% vs. 50%). Perceived risk of infection was lower at the posttest and declined during the study period.

Infrared photographic measurement of pupillary effects of dichlorvos in Beagles.

Dichlorvos was given orally to Beagles at dose rates of 13.4, 27, and 40.5 mg/kg of body weight. Pupillary response to a single strobe flash was observed by using infrared cinematography. In dogs given the two larger dosages, the pupil contracted to a smaller size than it had been before treatment (base line) and recovered more slowly to base-line diameter.

Heptachlor residue accumulation and depletion in broiler chickens.

Broiler chickens were fed heptachlor in concentrations of 0, 0.01, 0.03, 0.1, and 0.3 mg/kg of the ration for the first 8 weeks of life. There were no adverse effects on health or performance. Residue concentrations in adipose tissue increased rapidly for 1 to 2 weeks and then tended to plateau at concentrations about five times greater than those in the rations. Birds exposed only during the 7th week of life stored 25% as much residue as did the chickens exposed in the 1st week, but the former also ate only 63% as much feed. Fat extracted from liver and muscle contained more residue than did fat extracted from adipose tissue. The ratio of the concentration of heptachlor to its epoxide metabolite was higher in muscle fat than in heptic or abdominal fat. Residue concentrations depleted by about half in the first 4 weeks after cessation of exposure.

Experimental hexachlorophene intoxication in young swine.

Hexachlorophene (HCP) intoxication in swine was studied as a possible model of HCP poisoning in human beings. Swine were topically or orally given HCP each day, and observations were made on central nervous system function, hematologic measurements, serum chemical analyses, necropsy, microscopic examination of tissues, and concentrations of HCP residues in blood and tissue. Intoxication was observed in orally exposed swine, but the syndrome was not consistently produced in topically exposed swine. Signs and microscopic lesions were all related to dysfunction of the central nervous system, e.g., incoordination, paresis, and status spongiosus. Occurrence of signs and lesions, mortality rates, and concentrations of HCP residue were positively correlated with the dosage of HCP given.

Model-based evaluation of HIV prevention interventions.

The ultimate goal of HIV prevention interventions is to reduce the spread of HIV; however, the effectiveness of these programs is seldom assessed directly. Although direct measurement of an intervention's impact via HIV seroincidence monitoring is usually unfeasible, mathematical models can be used to estimate the number of infections averted by the intervention. This article describes three model-based summary measures of sexually transmitted HIV risk and discusses their relevance to HIV program evaluation in general economic efficiency analyses in particular. The calculation of these measures is demonstrated with an illustrative application to previously published data from an HIV prevention intervention for gay men.

Lessons learned from a mentoring program for teenage mothers.

PURPOSE: This study evaluated a mentoring program designed to decrease the risk of repeat pregnancy among unmarried primiparous teens, ages 12-19. METHODS: Adolescents (n = 110) completed a battery that assessed sexual/contraceptive behavior; psychological adjustment; and attitudes towards school. Teens were then randomly assigned to a mentor or control group, and reassessed at 6, 12, 18, and 24 months. Mentored teens received social support and assistance dealing with community agencies from mentors who were trained community volunteers. RESULTS AND CONCLUSIONS: At baseline, mentor and control teens had similar sexual histories, school achievement profiles (percentage enrolled, cumulative grade point average), and anticipated being the same age when they had a second child. At 24 months (n = 81), most mentor and control teens were making progress in school. Fifty percent had graduated or had advanced two grades; 10 of the 16 graduating teens were seeking additional education. However, the mentoring program did not significantly impact repeat pregnancy rates. At 33 months, 66.0% of the mentored teens and 68.8% of the control teens had experienced a repeat pregnancy. Thirty-six percent of teens had one repeat pregnancy; 24% had two or more pregnancies. Sixty-two percent of the pregnancies with known resolution (89) resulted in live births; 26% were aborted. In providing this mentoring program, several important lessons were learned.