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The marriage of older men to younger women is common across cultures. On one hand, husband-older marriage may serve the interests of both sexes, a conclusion broadly consistent with reported gender differences in mate preferences. On the other hand, men alone may benefit from such marriages at a cost to women if seniority enables men to exert dominance in conflicts of interest. Indeed, in public health large spousal age gaps are generally deemed “pathological”, both as a cause and consequence of gender inequalities harmful to women. We investigate these alternative models of spousal age gap using data from a cross-sectional survey of women in Mwanza, northwestern Tanzania (n = 993). Consistent with the notion that spousal age gaps are a product of sexual conflict, women typically married with a larger age gap than stated ideals. However, adjusting for potential confounds, spousal age gap was not associated with fertility or the risk of divorce. Furthermore, women's mental health and autonomy in household decision-making was higher in husband-older marriages compared to rare cases of same-age or wife-older marriage. Beyond this comparison, the magnitude of spousal age gaps was unrelated to either measure of women's wellbeing among the overwhelming majority of marriages where the husband was older. Together these findings suggest husband-older marriage does not influence marital stability, relatively large spousal age gaps are neither especially costly nor beneficial to women, and that alternative sociodemographic factors are more important in driving variation in women's wellbeing and reproductive success in this context. Our results support neither a model of mutual benefits, nor a pathological conceptualization of spousal age gaps. We conclude by both encouraging evolutionary human scientists to engage more fully with models of sexual conflict in future studies of marriage and mating, and suggesting that public health scholars consider more neutral interpretations of spousal age differences.

To determine the frequency, impact, and factors associated with self-reported neurobehavioural disability (NBD) in individuals with stroke. A secondary aim was to examine the course of self-reported NBD over time and associations with outcomes.Eighty-seven participants admitted for inpatient rehabilitation post-stroke completed the St Andrew's-Swansea Neurobehavioural Outcome Scale. Demographic and stroke details and measures of functional disability, cognitive impairment, mood, and self-rated impact of NBD symptoms were completed. Twenty-seven participants and 19 close-others were reassessed three to six months following discharge.Overall reporting of neurobehavioural problems was infrequent. The domains of interpersonal and cognitive difficulties were the most commonly identified but were still only reported occasionally. However, even mild NBD was significantly correlated with negative impact. Greater self-reported NBD was significantly correlated with greater functional dependence, anxiety, and depression during inpatient rehabilitation. Self-reports of NBD remained stable over time and, at follow-up, was significantly correlated with depressive symptoms both in participants with stroke and close-others.In survivors of stroke, self-report of NBD is associated with poor outcomes in function, anxiety, and depression. These findings highlight the importance of routine and comprehensive assessment and intervention to manage NBD following stroke.IMPLICATIONS FOR REHABILITATIONDespite relatively infrequent self-reporting, presence of NBD remained stable across a six month follow-up period following rehabilitation which highlights the potential persistent nature of these difficulties.Even mild levels of self-reported NBD were associated with emotional distress in both stroke survivors and their significant others indicating a need for relevant interventions to support long-term outcomes.Routine screening for the presence of NBD is recommended to facilitate early detection and intervention to optimise post-stroke recovery.

Background The proposition that a pregnancy is 40 weeks or 280 days in duration is attributed to the German obstetrician Franz Naegele (1778-1851). His rule adds nine months and seven days to the first day of the last menstrual period. The expected date of confinement from this formula is approximately right in the majority of cases. However, the idea that this rule can apply to every pregnant female - young or old, nulliparous or multigravida, Caucasian, Asian, African, or Indigenous - stretches credulity. In addition, many women regard the 40-week date as a deadline, which if crossed, may then place the baby under stress. Forty weeks is such a simple, round, convenient figure that it has proved difficult to challenge, despite criticism. Nonetheless, what might have been an appropriate formula in Germany in the 19th century deserves to be revisited in the 21st. Aims To review the length of pregnancy, in the light of current technology, in particular ultrasound scanning, and assisted reproductive techniques. Material and methods A Medline search was performed for variables on the length of pregnancy, the expected date of confinement, and prolonged pregnancy. Results A number of factors were found to significantly influence the length of a pregnancy, including ethnicity, height, variations in the menstrual cycle, the timing of ovulation, parity and maternal weight. Conclusions Naegele's rule should be considered as a guideline for the expected date of confinement, and not a definite date.

Despite evidence of the efficacy of telerehabilitation post-stroke, uptake has lagged behind the development of available technology, slowed by low confidence in user experience. We aimed to explore the issue of acceptability by characterizing the experience of telerehabilitation for service providers and consumers of a memory rehabilitation program. Semi-structured interviews were conducted with nine clinicians (

Malaria in pregnancy remains a major problem of public health concern in Sub-Saharan Africa due to its endemicity and the diverse consequences on both the mother and the baby. Much attention, therefore, is needed to fully understand the epidemiology of the disease and to mitigate the devastating outcomes. The present study aimed at investigating malaria in pregnancy, its adverse effects on pregnant women and the impact on birthweight of babies. A total of 222 pregnant women gave their consent and were recruited into the study during their routine Antenatal care visits. This study employed a combination of cross-sectional and longitudinal cohort study designs. For 122 women in the cross-sectional arm, blood samples and data were obtained once, whilst 100 women in the longitudinal cohort arm were followed up from recruitment until delivery. Demographic information, obstetric history and risk factors were obtained by administering questionnaires. About 1.0 ml of venous blood was drawn to determine malaria parasitaemia and anaemia status of the participants. The birthweights of the babies were also taken at delivery. The prevalence of malaria and anaemia was 19.8% and 27.0% respectively at registration for all 222 participants. All infections wereP. falciparummalaria. One hundred and forty-six (65.8%) of participants had ITN but only 72 (32.4%) used it the previous night. Young age and rural settings were risk factors for malaria. Young age and malaria positive pregnant women had increased risk of anaemia. In the follow-up group which ended with 54 participants, the overall prevalence of malaria and anaemia were 18.7% and 32.4% respectively. Fifty-two (96.3%) of pregnant women attended ANC ≥ 4 times and 55.6% took ≥ 3 doses of SP. There were two cases of miscarriage. Low birthweight occurred in 5.6% of babies. Both malaria and anaemia during pregnancy had no significant impact on birthweight of the babies. Although few of the babies had low birthweight, this number can be further reduced when pregnant women attend ANC and take SP at the recommended number of times.

Purpose: To investigate the level of agreement of neurobehavioral disability following stroke.Methods: Stroke patients and nurses were recruited from an inpatient neurorehabilitation facility. In t...

Rehabilitation of memory remains an unmet need for many stroke survivors. Telehealth methods may provide a solution, however evidence supporting the efficacy of remotely-delivered therapy is needed. A non-concurrent multiple baseline design was used with randomized onset of intervention across five individuals with chronic stroke-related memory complaints. A six-week compensatory memory skills programme was delivered individually via internet videoconferencing. Target behaviours of frequencies of self-reported lapses of everyday and prospective memory were measured weekly across baseline, intervention, and follow-up phases. A secondary outcome of functional goal attainment was measured once per phase, with participants setting two personal rehabilitation goals. Data were analysed visually and statistically. Improvements in memory functioning were statistically significant on at least one measure of target behaviour for four out of five participants at intervention or follow-up. Visual evidence of level change indicated at least modest improvements for all participants by follow-up. All participants attained at least one functional goal by follow-up. High rates of treatment adherence and participant satisfaction were observed. Technological issues were minimal and did not impact content delivery or engagement. These results provide preliminary support for the efficacy of a telehealth-delivered rehabilitation programme in improving memory function and achieving memory-related goals for stroke survivors.

Objective:Rehabilitation of memory after stroke remains an unmet need. Telehealth delivery may overcome barriers to accessing rehabilitation services.Method:We conducted a non-randomized intervention trial to investigate feasibility and effectiveness of individual telehealth (internet videoconferencing) and face-to-face delivery methods for a six-week compensatory memory rehabilitation program. Supplementary analyses investigated non-inferiority to an existing group-based intervention, and the role of booster sessions in maintaining functional gains. The primary outcome measure was functional attainment of participants’ goals. Secondary measures included subjective reports of lapses in everyday memory and prospective memory, reported use of internal and external memory strategies, and objective measures of memory functioning.Results:Forty-six stroke survivors were allocated to telehealth and face-to-face intervention delivery conditions. Feasibility of delivery methods was supported, and participants in both conditions demonstrated treatment-related improvements in goal attainment, and key subjective outcomes of everyday memory, and prospective memory. Gains on these measures were maintained at six-week follow-up. Short-term gains in use of internal strategies were also seen. Non-inferiority to group-based delivery was established only on the primary measure for the telehealth delivery condition. Booster sessions were associated with greater maintenance of gains on subjective measures of everyday memory and prospective memory.Conclusions:This exploratory study supports the feasibility and potential effectiveness of telehealth options for remote delivery of compensatory memory skills training after a stroke. These results are also encouraging of a role for booster sessions in prolonging functional gains over time.

The rapid rise in opioid use has recently contributed to several pressing concerns, including an unprecedented number of fatal overdoses, a marked increase in treatment admissions, a spike in emergency department visits, and a significant proportion of adults who test positive for opioids at the time of arrest. The majority of arrestees who test positive for opioids after being booked into jail also report prior engagement with a substance use treatment program, highlighting the need to address posttreatment substance use and involvement in the criminal justice system. The current study was conducted to untangle the posttreatment substance use–arrest relationship and better understand how one may influence the other. Analyses conducted with 396 adults, drawn from a nationwide sample of patients seeking treatment for opioid use disorder, demonstrated that posttreatment arrest increased the likelihood of substance use, but the evidence suggested that this relationship was not reciprocal. These results have significant implications for criminal justice practices with regard to using alternatives to arrest as methods to minimize posttreatment substance use.

Copyright © The Author(s) 2017. Objectives: To evaluate the impact of adding a mobile health (mHealth) decision support system for antibiotic prescribing to an established antimicrobial stewardship programme(ASP). Methods: In August 2011, the antimicrobial prescribing policy was converted into a mobile application (app). A segmented regression analysis of interrupted time series was used to assess the impact of the app on prescribing indicators, using data (2008-14) from a biannual point prevalence survey of medical and surgical wards. There were six data points pre-implementation and six data points post-implementation. Results: There was an increase in compliance with policy (e.g. compliance with empirical therapy or expert advice) in the two specialties of medicine (6.48%, 95% CI = -1.25 to 14.20) and surgery (6.63%, 95% CI = 0.15-13.10) in the implementation period, with a significant sudden change in level in surgery (P,0.05). There was an increase, though not significant, in medicine (15.20%, 95% CI = -17.81 to 48.22) and surgery (35.97%, 95% CI = -3.72 to 75.66) in the percentage of prescriptions that had a stop/review date documented. The documentation of indication decreased in both medicine (-16.25%, 95% CI = -42.52 to 10.01) and surgery (-14.62%, 95% CI = -42.88 to 13.63). Conclusions: Introducing the app into an existing ASP had a significant impact on the compliance with policy in surgery, and a positive, but not significant, effect on documentation of stop/review date in both specialties. The negative effect on the third indicator may reflect a high level of compliance pre-intervention, due to existing ASP efforts. The broader value of providing an antimicrobial policy on a digital platform, e.g. the reach and access to the policy, should be measured using indicators more sensitive to mHealth interventions. The research was partially funded by the National Institute for Health Research (NIHR) Health Protection Research Unit (HPRU) in Healthcare Associated Infections and Antimicrobial Resistance at Imperial College London in partnership with PHE and the NIHR Imperial Patient Safety Translational Research Centre. This work was also supported by the National Institute for Health Research Biomedical Research Centre Funding Scheme at Imperial College, the National Centre for Infection Prevention and Management (CIPM) funded by the United Kingdom Clinical Research Council and the Showcase Hospitals Fund.

Between-match recovery time, and acute and chronic workloads likely affect subsequent match-injury risk in elite rugby league players.Workloads of 28 players throughout two seasons were calculated during short (7 days), and long (≥7 days) between-match recovery times. 'Acute' workloads (1 week) greater than 'chronic' workloads (4-week rolling average acute workload) resulted in acute:chronic workload ratios above 1.No difference was found between the match-injury risk of short and long between-match recovery periods (7.5±2.5% vs 6.8±2.5%). When players had a short recovery between matches, high chronic workloads (18.9-22.0 km) were associated with a smaller risk of match injury than chronic workloads18.9 km (relative risk (RR) range 0.27-0.32 (CI 0.08 to 0.92); likelihood range 90-95%, likely). Players who had shorter recovery and acute:chronic workload ratios ≥1.6, were 3.4-5.8 times likely to sustain a match injury than players with lower acute:chronic workload ratios (RR range 3.41-5.80 (CI 1.17 to 19.2); likelihood range 96-99%, very likely). Acute:chronic workload ratios between 1.2 and 1.6 during short between-match recovery times demonstrated a greater risk of match injury than ratios between 1.0 and 1.2 (RR=2.88 (CI 0.97 to 8.55); likelihood=92%, likely).Contrary to the philosophy that high workloads and shorter recovery equate to increased injury risk, our data suggest that high and very-high chronic workloads may protect against match injury following shorter between-match recovery periods. Acute:chronic workload ratios ∼1.5 are associated with a greater risk of match injury than lower acute:chonic workload ratios. Importantly, workloads can be manipulated to decrease the match-injury risk associated with shorter recovery time between matches.

Background Identifying asymptomatic reservoirs of malaria parasites using index cases as entry points into the community is potentially a cost-effective way towards achieving malaria elimination. Methods Within 1 year, 1430 confirmed malaria cases were identified in Marani hospital, western Kenya. Fifty cases were followed up, and 108 index case household members and 612 neighbours within a 100 m radius were screened. As controls, samples were collected from 510 individuals matched with index cases and located at a distance of ≥ 500 m from them. Infections were diagnosed by microscopy and PCR while simultaneously collecting malaria vectors indoor using pyrethrum spray catches. Results In the index case and neighbour households, the prevalence of infection was approximately twice as high as in control households (by PCR: index cases households: 28.9%, neighbours: 25.3%, matched controls: 12.9%). In index case households, the indoor vector density (Anopheles gambiae and Anopheles funestus) was higher (0.46 female/house/night) than in neighbouring (0.31 f/h/n) and control houses (0.29 f/h/n). Conclusions Screening index case households and neighbours approximately doubles the chance to detect asymptomatic infections compared to randomly selected households. However, even if all cases were followed up, only a small proportion (˂ 10%) of the asymptomatic reservoir in the population would have been identified. Control programmes need to weigh the increased chance to find cases around index cases vs. the logistical challenges to target this subgroup within the population.

Early switch (ES) from intravenous (IV) to oral antibiotic therapy programmes is increasingly included as a component of hospital antimicrobial stewardship initiatives that aim to optimize antimicrobial therapy while limiting toxicity and resistance. In terms of prioritizing the most cost-effective stewardship interventions, ES has been seen as a ‘low-hanging fruit’, which refers to selecting the most obtainable targets rather than confronting more complicated issues. Administration of highly bioavailable oral antibiotics should be considered for nearly all non-critically ill patients and has been recommended as an effective and safe strategy for over two decades. However, to accrue the most benefit from ES, it should be combined with an early discharge (ED) plan, protocol, or care pathway. Benefits of this combined approach include improved patient comfort and mobility, reduced incidence of IV-line-related adverse effects, reduced IV antimicrobial preparation time, decreased hospital stays, reduced antimicrobial purchasing and administration costs, decreased patient deconditioning, and shortened recovery times. Results from published studies document decreases in healthcare resource use and costs following implementation of ES programmes, which in most studies facilitate the opportunity for ED and ED programmes. Barriers to the implementation of these programmes include clinician misconceptions, practical considerations, organizational factors, and a striking lack of awareness of IV to oral switch guidance. These and other barriers will need to be addressed to maximize the effectiveness of ES and ED programmes. As national antimicrobial stewardship programmes dictate the inclusion of ES and ED programmes within healthcare facilities, programmes must be developed and success must be documented.

Suboptimal antibiotic penetration into soft tissues can occur in patients with poor circulation due to peripheral vascular disease (PVD) or diabetes. We conducted a real-world analysis of antibiotic treatment, hospital resource use and clinical outcomes in patients with PVD and/or diabetes receiving linezolid or vancomycin for the treatment of methicillin-resistant Staphylococcus aureus complicated skin and soft-tissue infections (MRSA cSSTIs) across Europe. This subgroup analysis evaluated data obtained from a retrospective, observational medical chart review study that captured patient data from 12 European countries. Data were obtained from the medical records of patients ≥ 18 years of age, hospitalized with an MRSA cSSTI between 1 July 2010 and 30 June 2011 and discharged alive by 31 July 2011. Hospital length of stay and length of treatment were compared between the treatment groups using inverse probability of treatment weights to adjust for clinical and demographic differences. A total of 485 patients had PVD or diabetes and received treatment with either vancomycin (n = 258) or linezolid (n = 227). After adjustment, patients treated with linezolid compared with vancomycin respectively had significantly shorter hospital stays (17.9 ± 13.6 vs. 22.6 ± 13.6 days; p

We aimed to characterize real-world dosing of weight-based intravenous (IV) antibiotic therapy in patients hospitalized for methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft-tissue infections (cSSTIs). This was a subgroup analysis of a retrospective chart review that captured data from 12 European countries. The study included patients ≥18 years old, hospitalized with an MRSA cSSTI between 1 July 2010 and 30 June 2011 and discharged alive by 31 July 2011. Patients treated with IV vancomycin, teicoplanin or daptomycin at any stage during hospitalization were included in this analysis. Analyses were conducted at the regimen level (dosing in mg/kg or in mg, frequency, and total daily dose (TDD)), with potentially multiple regimens per patient, and the patient level, categorizing patients into low, standard (labelled) and high dosing groups according to their initial MRSA-targeted regimen. Among the 1502 patients in the parent study, 998 patients contributed a total of 1050 daptomycin, teicoplanin or vancomycin regimens. Across all regimens, the mean initial TDDs were 6.3 ± 1.9 mg/kg for daptomycin, 10.5 ± 4.9 mg/kg for teicoplanin and 28.5 ± 11.5 mg/kg for vancomycin. A total of 789 patients received first-line therapy with one of the above antibiotics. The majority of patients receiving first-line teicoplanin and daptomycin (96% and 80%, respectively) received higher than labelled cSSTI doses, whereas vancomycin doses were lower than labelled doses in >40% of patients. These real-world data reveal significant deviation from labelled antibiotic dosing in 12 European countries and the potential for suboptimal outcomes in patients with MRSA cSSTIs.

Aim To determine the incidence and clinical features of laparoscopic gynaecological deaths in Australia. Materials and Methods Gynaecological laparoscopic mortality data were obtained from the National Coronial Information Systems (NCIS) and Australian State Coroners Courts, for the period July 1 2000 to December 31 2012. Results Eighteen deaths were identified, providing a mortality rate of approximately 1 per 70,000 laparoscopic procedures. The commonest cause of death was from bowel perforation, most of which were unrecognised during the operation. Conclusion Gynaecologists should be trained to recognise and manage the rare event of laparoscopic perforation of a viscus or a blood vessel.

Objective To investigate a topical local anesthesia technique as a means to prevent and/or diminish pain in mice in a laboratory setting associated with tail vein injections performed by personnel in training. Study design Prospective, randomized experimental trial. Animals Thirty six adult female, 23–28 g CD-1 mice from an in-house training colony. They were acclimated to routine training and handling classes. Methods Eutectic mixture of local anesthetics (EMLA) cream (2.5% lidocaine/2.5% prilocaine) or a bland ointment control (n = 18) was applied on the tail prior to intravenous injection. The injections were performed by novices, who had never attempted the procedure, and experienced personnel. All participants were blinded to treatment groups. Three injection attempts were allowed per animal. The mice were observed and scored by blinded evaluators for behavioral and physiological changes, including respiratory rate, vocalization, tail flick, and escape behaviors, during and after the injection. Results This study demonstrates that aversive behaviors induced by lateral tail vein injection were not changed by the preemptive application of EMLA cream. The aversive behaviors associated with lateral tail vein injection were significantly affected by the number of injection attempts and the individual's experience level. Conclusions and clinical relevance Topical EMLA cream did not reduce signs of aversive reaction to tail vein injection and thus we did not find support for its use in mouse training programs for tail vein injections.

An update to the American Cancer Society (ACS) guideline regarding screening for the early detection of cervical precancerous lesions and cancer is presented. The guidelines are based on a systematic evidence review, contributions from 6 working groups, and a recent symposium cosponsored by the ACS, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology, which was attended by 25 organizations. The new screening recommendations address age-appropriate screening strategies, including the use of cytology and high-risk human papillomavirus (HPV) testing, follow-up (eg, the management of screen positives and screening intervals for screen negatives) of women after screening, the age at which to exit screening, future considerations regarding HPV testing alone as a primary screening approach, and screening strategies for women vaccinated against HPV16 and HPV18 infections. CA Cancer J Clin 2012;62:147-172. V C

We have developed an efficient, streamlined, cost-effective approach to obtain Investigational New Drug (IND) approvals from the Food and Drug Administration (FDA) for positron emission tomography (PET) imaging probes (while the FDA uses the terminology PET drugs, we are using “PET imaging probes,” “PET probes,” or “probes” as the descriptive terms). The required application and supporting data for the INDs were collected in a collaborative effort involving appropriate scientific disciplines. This path to INDs was successfully used to translate three [18 F]fluoro-arabinofuranosylcytosine (FAC) analog PET probes to phase 1 clinical trials. In doing this, a mechanism has been established to fulfill the FDA regulatory requirements for translating promising PET imaging probes from preclinical research into human clinical trials in an efficient and cost-effective manner. Electronic supplementary material The online version of this article (doi:10.1007/s11307-014-0735-2) contains supplementary material, which is available to authorized users.

Polycyclic aromatic hydrocarbons (PAH) such as benzo[a]pyrene (BaP) are ubiquitous environmental pollutants found in tobacco smoke, air pollution, and grilled foods. Prenatal exposure to BaP causes premature reproductive senescence in mice, and other PAHs are transplacental ovarian carcinogens. Glutathione (GSH) is critical for detoxification of the reactive metabolites of PAHs. Therefore, we hypothesized that mice that are genetically deficient in GSH synthesis, due to deletion of the modifier subunit of glutamate cysteine ligase (Gclm), the rate-limiting enzyme in GSH synthesis, have increased destruction of oogonia, premature ovarian failure, and ovarian tumorigenesis after transplacental BaP exposure compared with Gclm+/+ females. Gclm+/− female and male mice were mated, and dams were treated with 0, 2, or 10 mg/kg/d BaP in sesame oil by gavage from gestational days 7 to 16. Compared with oil-treated F1 females of the same genotype, Gclm−/− prenatally BaP-treated females had significantly greater decrements in offspring production than Gclm+/+ BaP-treated females. Similarly, we observed significant BaP dose × Gclm genotype interactions on ovarian follicle counts and ovarian tumor multiplicity at 7.5 months of age, with Gclm−/− females having greater decrements in follicle numbers and more ovarian tumors in response to prenatal BaP exposure than Gclm+/+ females. The ovarian tumors were positive for the epithelial marker cytokeratin. Our results show that prenatal exposure of females to BaP causes premature ovarian failure and ovarian tumorigenesis and that embryonic GSH deficiency due to deletion of Gclm increases sensitivity to these transplacental ovarian effects of BaP. Cancer Res; 73(2); 908–17. ©2012 AACR.

Author(s): Khan, Michelle J; Massad, L Stewart; Kinney, Walter; Gold, Michael A; Mayeaux, EJ; Darragh, Teresa M; Castle, Philip E; Chelmow, David; Lawson, Herschel W; Huh, Warner K | Abstract: ObjectiveVaginal cancer is an uncommon cancer of the lower genital tract, and standardized screening is not recommended. Risk factors for vaginal cancer include a history of other lower genital tract neoplasia or cancer, smoking, immunosuppression, and exposure to diethylstilbestrol in utero. Although cervical cancer screening after total hysterectomy for benign disease is not recommended, many women inappropriately undergo vaginal cytology and/or human papillomavirus (HPV) tests, and clinicians are faced with managing their abnormal results. Our objectives were to review the literature on vaginal cytology and high-risk HPV (hrHPV) testing and to develop guidance for the management of abnormal vaginal screening tests.Materials and methodsAn electronic search of the PubMed database through 2015 was performed. Articles describing vaginal cytology or vaginal hrHPV testing were reviewed, and diagnostic accuracy of these tests when available was noted.ResultsThe available literature was too limited to develop evidence-based recommendations for managing abnormal vaginal cytology and hrHPV screening tests. However, the data did show that (1) the risk of vaginal cancer in women after hysterectomy is extremely low, justifying the recommendation against routine screening, and (2) in women for whom surveillance is recommended, e.g., women posttreatment for cervical precancer or cancer, hrHPV testing may be useful in identification of vaginal cancer precursors.ConclusionsVaginal cancer is rare, and asymptomatic low-risk women should not be screened. An algorithm based on expert opinion is proposed for managing women with abnormal vaginal test results.

To assess the impact of an infection team review of patients receiving antibiotics in six hospitals across the UK and to establish the suitability of these patients for continued care in the community.An evaluation audit tool was used to assess all patients on antibiotic treatment on acute wards on a given day. Clinical and antibiotic use data were collected by an infection team (doctor, nurse and antibiotic pharmacist). Assessments were made of the requirement for continuing antibiotic treatment, route and duration [including intravenous (iv)/oral switch] and of the suitability of the patients for discharge from hospital and their requirement for community support.Of 1356 patients reviewed, 429 (32%) were on systemic antibiotics, comprising 165 (38%) on iv ± oral antibiotics and 264 (62%) on oral antibiotics alone. Ninety-nine (23%) patients (including 26 on iv antibiotics) had their antibiotics stopped immediately on clinical grounds. The other 330 (77%) patients (including 139 on iv antibiotics) needed to continue antibiotics, although 47 (34%) could be switched to oral. Eighty-nine (21%) patients were considered eligible for discharge, comprising 10 who would have required outpatient parenteral antibiotic therapy (OPAT), 55 who were suitable for oral outpatient treatment and 24 who had their antibiotics stopped.Infection team review had a significant impact on antimicrobial use, facilitating iv to oral switch and a reduction in the volume of antibiotic use, possibly reducing the risk of healthcare-associated complications and infections. It identified many patients who could potentially have been managed in the community with appropriate resources, saving 481 bed-days. The health economics are reported in a companion paper.

In 2000, the Term Breech Trial was published, and its authors recommended cesarean section as the safest mode of delivery for breech-presenting babies. Criticisms of the trial were raised at the time, which the authors dismissed. Since then, maternal deaths have been recorded among women undergoing cesarean sections for breech presentations. Accordingly, those initial criticisms deserve to be revisited.

Neurotensin receptor-1 (NTR-1) is overexpressed in colon cancers and colon cancer cell lines. Signaling through this receptor stimulates proliferation of colonocyte-derived cell lines and promotes inflammation and mucosal healing in animal models of colitis. Given the causal role of this signaling pathway in mediating colitis and the importance of inflammation in cancer development, we tested the effects of NTR-1 in mouse models of inflammation-associated and sporadic colon cancer using NTR-1-deficient (Ntsr1(-) (/-)) and wild-type (Ntsr1(+/+)) mice. In mice treated with azoxymethane (AOM) to model sporadic cancer, NTR-1 had a significant effect on tumor development with Ntsr1(+/+) mice developing over twofold more tumors than Ntsr1(-) (/-) mice (p = 0.04). There was no effect of NTR-1 on the number of aberrant crypt foci or tumor size, suggesting that NT/NTR-1 signaling promotes the conversion of precancerous cells to adenomas. Interestingly, NTR-1 status did not affect tumor development in an inflammation-associated cancer model where mice were treated with AOM followed by two cycles of 5% dextran sulfate sodium (DSS). In addition, colonic molecular and histopathologic analyses were performed shortly after a single cycle of DSS. NTR-1 status did not affect colonic myeloperoxidase activity or histopathologic scores for damage and inflammation. However, Ntsr1(-) (/-) mice were more resistant to DSS-induced mortality (p = 0.01) and had over twofold higher colonic expression levels of Il6 and Cxcl2 (p < 0.04), cytokines known to promote tumor development. These results represent the first direct demonstration that targeted disruption of the Ntsr1 gene reduces susceptibility to colon tumorigenesis.

Objectives/Hypothesis: To evaluate the patterns of failure, survival, and functional outcomes for patients treated with transoral robotic surgery (TORS) and compare these results with those from a cohort of patients treated with concurrent chemoradiation (CRT). Study Design: Prospective non-randomized case control study. Methods: Between April 2007 and April 2009, 30 patients with head and neck squamous cell carcinoma were treated with primary TORS and adjuvant therapy as indicated on an institutional review board–approved protocol. Patients were evaluated before treatment, after treatment, and at subsequent 3-month intervals after completing treatment to determine their disease and head and neck–specific functional status using the Performance Status Scale for Head and Neck Cancer and the Functional Oral Intake Score (FOIS). Functional scores were compared to a matched group of head and neck patients treated with primary CRT. Results: The TORS patient population included 73% stage III-IV and 23% nonsmokers. The median follow-up was 20.4 months (range, 12.8–39.6 months). The 18-month locoregional control, distant control, disease-free survival, and overall survival were 91%, 93%, 78%, and 90%, respectively. Compared to the primary CRT group, TORS was associated with better short-term eating ability (72 vs. 43, P = .008), diet (43 vs. 25, P = .01), and FOIS (5.5 vs. 3.3, P < .001) at 2 weeks after completion of treatment. In contrast to TORS patients who returned to baseline, the CRT group continued to have decreased diet (P = .03) and FOIS (P = .02) at 12 months. Conclusions: Our early experience in treating selected head and neck cancers with TORS is associated with excellent oncologic and functional outcomes that compare favorably to primary CRT.

To systematically review and analyse evidence for cholesterol-lowering efficacy of at least 4 weeks of add-on ezetimibe vs doubling statin dose, in adults with primary hypercholesterolaemia.MEDLINE, EMBASE and Cochrane databases were searched to identify randomised controlled trials of ezetimibe-statin combination vs statin titration (January 1993 - March 2010). Studies were selected using predefined criteria. Two reviewers conducted screening of articles, critical appraisal and data extraction; a third reviewer resolved disagreements. The difference between treatments was analysed for four co-primary outcomes: mean percentage change from baseline in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and total cholesterol (TC); and proportion of patients achieving LDL-C treatment goal. Data were combined by two sets of direct comparison fixed and random effects meta-analysis: (1) compared data in the same treatment period between groups; (2) compared the incremental change in lipid levels of add-on ezetimibe vs doubling statin dose. Heterogeneity was assessed using the I(2) statistic.Thirteen studies including 5080 patients were included in the meta-analyses. Data on simvastatin, atorvastatin and rosuvastatin were analysed. Results for primary and secondary outcomes were in favour of the ezetimibe-statin combination. A significantly greater percentage reduction in LDL-C levels was achieved in patients treated with ezetimibe-statin vs statin monotherapy (weighted mean difference [WMD]: -14.1% [-16.1, -12.1], p 0.001). Reduction in LDL-C levels attributed to add-on ezetimibe was significantly greater than that for statin dose doubling (WMD: -15.3% [-19.1, -11.4], p 0.001). Achievement of LDL-C goal favoured add-on ezetimibe over statin titration and was statistically significant (odds ratio: LDL-C treatment goal 2.45 [1.95, 3.08], p = 0.007).Meta-analyses were restricted by the limited number of studies with similar trial design and method of statin titration. Results indicate that add-on ezetimibe is significantly more effective in reducing LDL-C levels than doubling statin dose, enabling more patients to achieve LDL-C goal.

To describe the methodology in developing an antimicrobial self-assessment toolkit (ASAT).The ASAT was developed through a National Pharmacy Reference Group using an evidence-based approach of published information and national reports to identify criteria for inclusion. These were subdivided into domains that addressed: 1) Antimicrobial management within the Trust-structures and lines of responsibility and accountability-high-level notification to the Board. 2) Operational delivery of an antimicrobial strategy-operational standards of good antimicrobial stewardship. 3) Risk assessment for antimicrobial chemotherapy. 4) Clinical governance assurance. 5) Education and training-training needs and delivery of education and training for all who issue, prescribe and administer antimicrobials. 6) Antimicrobial pharmacist-systems in place for ensuring their optimum use. 7) Patients, Carers and the Public-information needs of patients, carers and the public.A web-based toolkit was developed using information from national reports and guidance on antimicrobial stewardship. The toolkit offers a checklist for hospitals to self-assess their organizations' levels of antimicrobial stewardship.The ASAT offers a web-enabled, version-controlled instrument for the assessment of antimicrobial stewardship in acute hospitals. It may offer a sensitive instrument to assess longitudinal progress on antimicrobial stewardship in an individual institution or act as a benchmark with similar organizations. Further work is ongoing to evaluate and further refine the ASAT.

Transgenic mouse models of human cancers represent one of the most promising approaches to elucidate clinically relevant mechanisms of action and provide insights into the treatment efficacy of new antitumor drugs. The use of Trp53 transgenic mice (Trp53 knockout [Trp53(-/-)] mice) for these kinds of studies is, so far, restricted by limitations in detecting developing tumors and the lack of noninvasive tools for monitoring tumor growth, progression, and treatment response.We hypothesized that quantitative small-animal PET with (18)F-FDG was able to detect the onset and location of tumor development, follow tumor progression, and monitor response to chemotherapy. To test these hypotheses, C57BL/6J Trp53(-/-) mice underwent longitudinal small-animal PET during lymphoma development and gemcitabine treatment. Trp53 wild-type (Trp53(+/+)) mice were used as controls, and histology after full necropsy served as the gold standard.In Trp53(+/+) mice, the thymic standardized uptake value (SUV) did not exceed 1.0 g/mL, with decreasing (18)F-FDG uptake over time. Conversely, all Trp53(-/-) mice that developed thymic lymphoma showed increasing thymic glucose metabolism, with a mean SUV doubling time of 9.0 wk (range, 6.0-17.5 wk). Using an SUV of 3.0 g/mL as a criterion provided a sensitivity of 78% and a specificity of 100% for the detection of thymic lymphoma. Treatment monitoring with (18)F-FDG PET correctly identified all histologic responses and relapses to gemcitabine.(18)F-FDG small-animal PET can be used to visualize onset and progression of thymic lymphomas in Trp53(-/-) mice and monitor response to chemotherapy. Thus, (18)F-FDG small-animal PET provides an in vivo means to assess intervention studies in the Trp53 transgenic mouse model.

The social and health sciences have often emphasised the negative impacts of large sibship size and late birth order on childhood. For example, it is now well established that, other things being equal, children in large families and/or with many older siblings, receive lower allocations of care time from both parents, are more likely to grow up in conditions of economic hardship, and, as a likely consequence, exhibit relatively poor educational and physical health outcomes. Few researchers have, however, quantitatively assessed how siblings may influence indicators of mental health, where it is conceivable that social interactions with siblings may have a positive influence. Here, using data from a large British cohort survey (the Avon Longitudinal Study of Parents and Children), we explored the effects of sibling configuration on the Strengths and Difficulties Questionnaire, as a multidimensional index for mental health problems. We demonstrate a significant socio-economic gradient in mental health between the ages of three and nine years, but little evidence for negative effects of large sibship size. Rerunning this analysis to examine birth order, a much clearer pattern emerged; the presence of older siblings was associated with relatively good mental health, while the presence of younger siblings was associated with relatively poor mental health. This suggests that being born into a large family, providing the child is not joined by subsequent siblings, may carry important benefits unconsidered by past research. We discuss possible interpretations of this pattern and the wider implications for understanding the family context of child development.

To quantify repeat Pap testing and colposcopic biopsies among women in the National Breast and Cervical Cancer Early Detection Program between 2003 and 2006 (N=955,494).Rates of repeat Pap testing (two tests within 9 months) and colposcopic biopsies were estimated along with 95% confidence intervals (CIs). Odds ratios and 95% CIs for receipt of colposcopic biopsy compared with repeat Pap testing were estimated from multivariable logistic regression models. Finally, we estimated positive predictive values and 95% CIs of cervical intraepithelial neoplasia (CIN) 2 or worse (CIN 3, carcinoma in situ, invasive cancer) for two strategies: 1) repeat Pap testing followed by colposcopic biopsy and 2) colposcopic biopsy alone.There were 39,583 and 53,880 women with repeat Pap testing and colposcopic biopsy, respectively, from 2003 to 2006. Overall, age-standardized rates of repeat Pap testing and colposcopic biopsies were 37.2 per 1,000 women and 39.3 per 1,000 women, respectively. Younger women, Hispanic women, and African-American women were more likely to receive colposcopic biopsies compared with repeat Pap tests. Positive predictive values of colposcopic biopsy were highest after abnormal Pap test results (27% after a result of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion, 70% after a result of high-grade squamous intraepithelial lesion/squamous cell cancer).Colposcopic biopsies are common among young women after being screened for cervical cancer and, except among those with the most severe Pap test results, may not be efficient in detecting serious disease. These results conflict with current recommendations for less aggressive follow-up for most young women.II.

We developed the 'Pragmatic Proxy Protocol' (PPP) to estimate the prevalence of hospital-acquired infection (HAI) by integrating our existing pharmacy serial point prevalence studies of anti-infective prescribing practices with electronic data on microbiological and radiographic markers of infection. Our method was evaluated against the standard Hospital Infection Society/Infection Control Nurses Association Protocol (HIP). In the non-surgical patients, PPP has a sensitivity of 1.00 [confidence interval (CI): 0.70-1.00] and specificity of 0.97 (CI: 0.93-0.99). PPP suggests that for non-surgical patients, the prevalence of HAI using HIP could be underestimated by 42%. PPP takes about two-thirds of the time of HIP (75 vs 106 h) and is at least one-third cheaper. It could easily be adapted to advances in electronic reporting and, with the development of Anti-infective Care Bundles, would increase its sensitivity for the detection of HAI in surgical patients. PPP could be used to increase the frequency of routine HAI surveillance to determine the overall burden of infection and assess the efficacy of intervention strategies in a timely manner allowing rapid, direct feedback and engagement with clinicians.

Background Life history theory and resource dilution models of the family suggest that siblings may present a threat to healthy development because they compete for resources that parents have available to invest in individual offspring. Using data from a large cohort study of contemporary British families (ALSPAC), we test this hypothesis using childhood growth trajectories as a biomarker for health status. Methods Incorporating time-varying measures of changing family structure and socio-economic environment, this study represents the first true longitudinal analysis of family configuration effects on human growth. Using separate multi-variate multi-level models we estimate the effect of sibling number and sibling age and sex on height from birth to 10 years. Results Adjusting for family level socio-economic factors, the presence of siblings is associated with deficits in height across the study period. At the largest comparison, we estimate that compared with only children, children with four siblings have a reduced birth length by � 8.7 mm (95% confidence interval (CI): � 14.8 to � 2.6) and a reduced rate of growth by � 2.3 mm per year (95% CI: � 3.8 to � 0.8), leading to a deficit of 31.5 mm by age 10. Older siblings are associated with larger lasting negative consequences on height than younger siblings. We find no difference in the height of children in relation to the sex of siblings. Conclusions Even in the relatively wealthy, well-nourished conditions of modern Western society, children are not buffered from the health costs of reduced parental investment. Later-born children appear worst affected by within family resource division.

In 1970, Drs. Said and Mutt isolated a novel peptide from porcine intestinal extracts with powerful vasoactive properties, and named it vasoactive intestinal peptide (VIP). Since then, the biological actions of VIP in the gut as well as its signal transduction pathways have been extensively studied. A variety of in vitro and in vivo studies have indicated that VIP, expressed in intrinsic non-adrenergic non-cholinergic (NANC) neurons, is a potent regulator of gastrointestinal (GI) motility, water absorption and ion flux, mucus secretion and immune homeostasis. These VIP actions are believed to be mediated mainly by interactions with highly expressed VPAC(1) receptors and the production of nitric oxide (NO). Furthermore, VIP has been implicated in numerous physiopathological conditions affecting the human gut, including pancreatic endocrine tumors secreting VIP (VIPomas), insulin-dependent diabetes, Hirschsprung's disease, and inflammatory bowel syndromes such as Crohn's disease and ulcerative colitis. To further understand the physiological roles of VIP on the GI tract, we have begun to analyze the anatomical and physiological phenotype of C57BL/6 mice lacking the VIP gene. Herein, we demonstrate that the overall intestinal morphology and light microscopic structure is significantly altered in VIP(-/-) mice. Macroscopically there is an overall increase in weight, and decrease in length of the bowel compared to wild type (WT) controls. Microscopically, the phenotype was characterized by thickening of smooth muscle layers, increased villi length, and higher abundance of goblet cells. Alcian blue staining indicated that the latter cells were deficient in mucus secretion in VIP(-/-) mice. The differences became more pronounced from the duodenum to the distal jejunum or ileum of the small bowel but, became much less apparent or absent in the colon with the exception of mucus secretion defects. Further examination of the small intestine revealed larger axonal trunks and unusual unstained patches in myenteric plexus. Physiologically, the VIP(-/-) mice showed an impairment in intestinal transit. Moreover, unlike WT C57BL/6 mice, a significant percentage of VIP(-/-) mice died in the first postnatal year with overt stenosis of the gut.

Aim Investigate whether acute workload (1 week total distance) and chronic workload (4-week average acute workload) predict injury in elite rugby league players. Methods Data were collected from 53 elite players over two rugby league seasons. The 'acute:chronic workload ratio' was calculated by dividing acute workload by chronic workload. A value of greater than 1 represented an acute workload greater than chronic workload. All workload data were classified into discrete ranges by z-scores. Results Compared with all other ratios, a very-high acute:chronic workload ratio (2.11) demonstrated the greatest risk of injury in the current week (16.7% injury risk) and subsequent week (11.8% injury risk). High chronic workload (>16 095 m) combined with a veryhigh 2-week average acute:chronic workload ratio (1.54) was associated with the greatest risk of injury (28.6% injury risk). High chronic workload combined with a moderate workload ratio (1.02-1.18) had a smaller risk of injury than low chronic workload combined with several workload ratios (relative risk range from 0.3 to 0.7×/1.4 to 4.4; likelihood range=88-94%, likely). Considering acute and chronic workloads in isolation (ie, not as ratios) did not consistently predict injury risk. Conclusions Higher workloads can have either positive or negative influences on injury risk in elite rugby league players. Specifically, compared with players who have a low chronic workload, players with a high chronic workload are more resistant to injury with moderate-low through moderate-high (0.85-1.35) acute:chronic workload ratios and less resistant to injury when subjected to 'spikes' in acute workload, that is, very-high acute:chronic workload ratios 1.5.

Blood coagulation exists to halt excessive blood loss. It is paradoxical that surgery and trauma simultaneously represent major risk factors for both hemorrhagic and thrombotic complications. A summary of the available evidence used to guide contemporary approaches to perioperative care will be reviewed.Although the advent of factor-specific products has safely allowed for intervention on patients with congenital hemostatic defects, the presence of an increasingly complex surgical population (chronic liver disease, traumatic injuries, and requirements for chronic anticoagulation) has renewed concerns about hemorrhagic risks. However, the past three decades of clinical sciences have supported a re-emphasis on the prevention of venous thromboembolism (VTE), a major cause of morbidity and mortality in hospitalized surgical patients. There is now an abundance of data confirming the robust risk:benefit ratio of antithrombotic prophylaxis in the vast majority of surgical patients, regardless of their medical comorbidities.Perioperative hemorrhage is a natural risk of any surgical intervention and deserves careful evaluation and prompt intervention. However, in order to support ongoing efforts in the prevention of medical errors, the application of evidence-based guidelines for the prophylaxis of VTE in surgical patients must become a standard part of daily practice.

Objective To describe the results of breast cancer screening among low-income and uninsured women in the only national organized screening program in the US, the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). Methods We analyzed mammography and diagnostic follow-up data for 789,647 women who received their first mammogram in the NBCCEDP and 454,754 subsequent mammograms among these women. We calculated the rate of mammograms with abnormal findings, diagnostic follow-up, biopsy, and cancers detected per 1000 mammograms by age and racial or ethnic groups. Positive Predictive Values (PPVs) were estimated for abnormal mammograms and biopsy. Results Nearly 64% of the women screened in the program were from 50 to 64 years of age and about 46% were members of racial or ethnic minority groups. Women aged 40 to 49 years had the highest rates of abnormal mammograms and of diagnostic follow-up. However, cancer detection rates were highest in women aged 60 to 64 years. In addition, the PPVs for both abnormal mammograms and biopsy were highest in the oldest age group. Conclusions Cancer detection rates and PPVs for both abnormal mammograms and biopsy were highest in women aged 50 years or more. These results support the programs focus on screening women aged 50 and older for breast cancer.

OBJECTIVE Annual cervical cancer screening in women with many prior normal Pap tests is common despite limited evidence on the cost-effectiveness of this strategy. We estimated the cost-effectiveness of screening women with 3 or more prior normal tests compared with screening those with no prior tests. METHODS We used a validated cost-effectiveness model in conjunction with data on the prevalence of biopsy-proven cervical neoplasia in women enrolled in the Centers for Disease Control and Prevention National Breast and Cervical Cancer Early Detection Program. Women were grouped according to age at the final Program Pap test (aged < 30, 30-44, 45-59, and 60-65 years) and by screening history (0, 1, 2, and 3+ consecutive prior normal Program tests) to estimate cost per life-year and quality-adjusted life-year associated with annual, biennial, and triennial screening. RESULTS For women aged 30-44 years with no prior tests, incremental cost-effectiveness ratios ranged from 20,533 US dollars for screening triennially (compared with no further screening) to 331,837 US dollars for screening annually (compared with biennially) per life-year saved. Among same-aged women with 3 or more prior normal Program tests, incremental cost-effectiveness ratios for the same measures ranged from 60,029 US dollars to 709,067 US dollars per life-year saved. Inclusion of the most conservative utility estimates resulted in incremental cost-effectiveness ratios in excess of 100,000 US dollars per quality-adjusted life-year saved associated with annual screening of same-aged women with 3 or more prior normal tests compared with biennial screening. CONCLUSION As the number of prior normal Pap tests increases, the costs per life-year saved increase substantially. Resources should be prioritized for screening those never or rarely screened women. LEVEL OF EVIDENCE II-2.

In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology or cotesting (cytology in combination with high-risk human papillomavirus [hrHPV] testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective U.S.-based registration study. Thirteen experts, including representatives from the Society of Gynecologic Oncology, the American Society for Colposcopy and Cervical Pathology, the American College of Obstetricians and Gynecologists, the American Cancer Society, the American Society of Cytopathology, the College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the U.S. Food and Drug Administration (FDA) for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for health care providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

The National Breast and Cervical Cancer Early Detection Program (NBCCEDP), administered by the Centers for Disease Control and Prevention (CDC), provides breast and cervical cancer screening to low-income women who are uninsured or underinsured. For women with three consecutive annual Pap tests with normal findings, the NBCCEDP supports extending the screening interval to every 3 years. Thirteen telephone focus groups were conducted with physician providers in 17 states and the District of Columbia to investigate familiarity with NBCCEDP's triennial Pap test policy, the Pap test intervals actually used, and the factors influencing screening interval selection. No participants were familiar with NBCCEDP's triennial Pap test policy, and none reported routinely extending the screening interval after three consecutive annual Pap tests with normal findings. Two patterns of screening interval use were reported: annual screeners continued performing yearly Pap tests, and selective extended screeners offered an extended interval to select patients. Annual and selective extended screeners reported that both unique and common factors influenced the screening intervals they used. The NBCCEDP has established its cancer screening priorities to focus limited resources on the goal of providing services to eligible women who have rarely or never been screened. Increased efforts are needed to educate physicians about the science supporting an extended Pap screening interval and overcome the barriers associated with its adoption.

Antibiotic resistance presents a major public health challenge at local, national and international levels. At a local level, the challenge is to tackle the antibiotic stewardship agenda, within the clinical governance framework, across all professional groups and specialities. This paper presents the response to this challenge in a large multi‐site NHS trust. The approach focuses around a multi‐disciplinary antibiotic steering group, in which a dedicated infectious diseases pharmacist plays a key role. Proposes seven key elements for a successful antibiotic stewardship programme and discuss examples of local action. These elements are: strong leadership; dedicated individuals with responsibility for leading on antibiotic use; integration into pre‐existing trust structures; harnessing existing resources to deliver change; obtaining local data on prescribing patterns and resistance; communication; and education and training. All pillars of clinical governance are supported by the multi‐disciplinary approach described.

OBJECTIVE To describe results of cervical cytology screening among low-income and uninsured women in the National Breast and Cervical Cancer Early Detection Program. METHODS We analyzed data from 750,591 women who received their first Papanicolaou (Pap) test in the program between July 1995 and March 2001. RESULTS Nearly 85% of the women were aged 40 years or older. Almost half were members of racial or ethnic minority groups. Overall, the percentage of abnormal Pap test results decreased with increasing age. The rates of cervical intraepithelial neoplasia (CIN) were highest in the younger age groups but the rate of invasive cancer increased with age. White women had the highest age-adjusted percentage of abnormal Pap test results and the highest rate of biopsy-confirmed CIN 2 or worse. CONCLUSIONS In this nationwide screening program, only 7% of all biopsy-confirmed high-grade cervical lesions (CIN 2 or worse) were invasive cancer. This underscores the success of Pap screening in identifying preinvasive disease and preventing cancer. LEVEL OF EVIDENCE II-3

Using a highly sensitive membrane permeability assay, a viral infection was discovered in the lungs of virus antibody free (VAF) Swiss-Webster mice purchased for respiratory toxicology studies. The assay is based on the uptake of a charged fluorescent compound by cells lacking an intact plasma membrane. Lungs from 74% of the untreated animals from a single vendor tested positive for injury in this assay. High-resolution histopathologic analysis of 1-μm epoxy resin sections from affected animals identified increased peribronchiolar lymphocytic infiltration and markers of epithelial cell injury. Viral particles were directly observed to be budding from the membranes of infiltrating lymphocytic cells by transmission electron microscopy. Standard histological analysis of paraffin-embedded tissues from lungs of the same mice failed to detect obvious pathology. Serological analyses failed to detect the presence of a virus in the affected mice. Therefore, we conclude that (1) a pathogenic condition was present in the respiratory systems of mice judged pathogen free by standard methodologies, (2) the observed condition produced a pattern of injury comparable to those caused by pulmonary toxicants, (3) high-resolution histopathology and advanced imaging techniques can increase the potential for detection of pathological conditions, and (4) apparently healthy animals can have unrecognized infections with the potential for confounding respiratory toxicology studies.

Background: Although clinical breast examinations (CBEs) provide important opportunities to detect breast cancer, little is known about factors that affect cancer detection during CBEs performed in community settings. To evaluate several potential factors, we analyzed data from 1,056,153 cancer screening records reported to the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). Methods: Using case-series methods, we compared 2159 cancers missed during CBEs with 3161 cancers detected during CBEs. Cancers missed during CBE were found by mammography and confirmed by biopsy or fine needle aspiration. Results: After controling for cancer stage, tumor size, and breast symptoms at time of CBE, we found that patient age and CBE history were significantly associated with the likelihood of cancer detection. Compared to women 50–59, women 40–49 were more likely to have their cancer detected during CBE (odds ratio (OR) = 1.84, 95% confidence interval (95% CI) 1.47–2.29), while women 70 and older were less likely to have it detected (OR = 0.74, 95% CI: 0.55–1.00). Among women receiving their first NBCCEDP-funded CBE, 67.5% had their cancer detected by CBE. Among women receiving their second or third CBE, the values were 59.3 and 48.8%, respectively. In an adjusted logistic model, a significant inverse relationship was observed between number of prior CBEs and percent of cancers detected in the index CBE (OR = 0.79, 95% CI: 0.72–0.88). Conclusions: Among women diagnosed with breast cancer, older women and those who have had multiple CBEs were more likely to have their cancer missed during CBE.

Understanding cellular repair mechanisms in vivo has been advanced through the use of well-defined injury and repair models and their application to knockout and transgenic animals, primarily mice generated in a variety of background strains. However, little is known concerning the effect that mouse strain itself has on the interpretation and comparability of observations when the strain used for genetic manipulation is not the strain used to develop the model. We compared acute bronchiolar injury and repair in three strains of mice used in knockout mouse development (C57BL/6, 129/TerSv, and 129/SvEv) to the model strain (Swiss Webster) after treatment with the same dose of naphthalene and sacrificed at 1, 2, 4, 7, and 14 days after treatment. Extent of Clara cell toxicity and exfoliation was identical in the distal airways of all strains. There were significant strain-related differences in ciliated cell squamation, initiation and duration of proliferation, epithelial differentiation, and time to completion of epithelial repair. We conclude that ciliated cells play a prominent role in repair of distal airway injury, but that all phases of the repair process differ by strain. In addition, our findings reinforce that control animals must be of the same strain, ideally litter mates, when transgenic or knockout mice are used for the study of airway repair processes and mechanisms.