Exploring the reasons for wanting a peer partner to be physically active among women living with and beyond a cancer diagnosis: a content analysis.

BACKGROUND: Initiating and maintaining exercise is challenging for women during and post-cancer treatment. Adopting a peer partner model to provide social support to be active may contribute to lasting behaviour change of both partners. Despite this, finding a "like peer" can be challenging. PURPOSE: To explore women's reasons for seeking an online exercise partner following a diagnosis with cancer (through  www.activematch.ca ). We also examined women's potential sociodemographic and cancer-related differences by reported reasons for wanting an exercise partner. METHODS: Individuals creating an ActiveMatch profile completed demographic and physical activity questions (N = 199, Mage(SD) = 51.9(10.8) years), including an open-ended question regarding their "reason for wanting an exercise partner". An inductive content analysis was completed focusing on the participants' peer exercise partner preferences. Additional chi-square tests were run to assess whether participants differed based on sociodemographic and cancer-related characteristics and their motivations to be active by category of "reason for wanting an exercise partner" endorsed in the open-ended question. RESULTS: The participants' reasons for wanting an exercise partner were coded into seven categories, with most participants highlighting the reasons of motivation (52.3%), social support (48.7%), and accountability and adherence (26.6%). Women < 50 years of age were more likely to report accountability and adherence-related preferences for a partner. Those reporting endorsing weight loss as their primary reason for becoming active were more likely to be categorized as wanting a peer partner for motivation. CONCLUSIONS: While finding a peer partner can be challenging, matching women living with and beyond a cancer diagnosis based on their reason for wanting an exercise partner, as well as their reasons for wanting to be active, may be important to build successful peer exercise partnerships.

Antimicrobial activity of a natural compound and analogs against multi-drug-resistant Gram-positive pathogens.

The increasing prevalence of methicillin-resistant Staphylococcus aureus (MRSA) has sparked global concern due to the dwindling availability of effective antibiotics. To increase our treatment options, researchers have investigated naturally occurring antimicrobial compounds and have identified MC21-A (C58), which has potent antimicrobial activity against MRSA. Recently, we have devised total synthesis schemes for C58 and its chloro-analog, C59. Here, we report that both compounds eradicate 90% of the 39 MRSA isolates tested [MIC90 and minimum bactericidal concentration (MBC90)] at lower or comparable concentrations compared to several standard-of-care (SoC) antimicrobials including daptomycin, vancomycin, and linezolid. Furthermore, a stable, water-soluble sodium salt of C59, C59Na, demonstrates antimicrobial activity comparable to C59. C59, unlike vancomycin, kills stationary-phase MRSA in a dose-dependent manner and completely eradicates MRSA biofilms. In contrast to vancomycin, exposing MRSA to sub-MIC concentrations of C59 does not result in the emergence of spontaneous resistance. Similarly, in a multi-step study, C59 demonstrates a low propensity of resistance acquisition when compared to SoC antimicrobials, such as linezolid and clindamycin. Our findings suggest C58, C59, and C59Na are non-toxic to mammalian cells at concentrations that exert antimicrobial activity; the lethal dose at median cell viability (LD50) is at least fivefold higher than the MBC90 in the two mammalian cell lines tested. A morphological examination of the effects of C59 on a MRSA isolate suggests the inhibition of the cell division process as a mechanism of action. Our results demonstrate the potential of this naturally occurring compound and its analogs as non-toxic next-generation antimicrobials to combat MRSA infections. IMPORTANCE: The rapid emergence of methicillin-resistant Staphylococcus aureus (MRSA) isolates has precipitated a critical need for novel antibiotics. We have developed a one-pot synthesis method for naturally occurring compounds such as MC21-A (C58) and its chloro-analog, C59. Our findings demonstrate that these compounds kill MRSA isolates at lower or comparable concentrations to standard-of-care (SoC) antimicrobials. C59 eradicates MRSA cells in biofilms, which are notoriously difficult to treat with SoC antibiotics. Additionally, the lack of resistance development observed with C59 treatment is a significant advantage when compared to currently available antibiotics. Furthermore, these compounds are non-toxic to mammalian cell lines at effective concentrations. Our findings indicate the potential of these compounds to treat MRSA infections and underscore the importance of exploring natural products for novel antibiotics. Further investigation will be essential to fully realize the therapeutic potential of these next-generation antimicrobials to address the critical issue of antimicrobial resistance.

Th1-like Treg cells are dressed to suppress anti-tumor immunity.

Mechanisms of Th1-like Treg suppression are unknown in cancer. Two studies in Immunity by Ayala et al. and Zagorulya et al. demonstrate that Th1-like Treg cells interact with type 1 dendritic cells in tumors and draining lymph nodes to potently suppress anti-tumor immunity.

Safety and efficacy of Vitamin C, Vitamin E, and selenium supplementation in the oncology setting: A systematic review.

OBJECTIVE: With rising rates of complementary and alternative medicine (CAM) use, the exploration of CAM integration into oncology treatments is becoming increasingly prevalent. Antioxidants have been proposed as potentially beneficial to prevent or treat cancer. However, evidence summaries are limited, and the United States Preventive Services Task Force has recently recommended the use of Vitamin C and E supplementation for cancer prevention. Thus, the objective of this systematic review is to evaluate the existing literature on the safety and efficacy of antioxidant supplementation in oncology patients. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, using prespecified search terms in PubMed and CINAHL. Two reviewers independently reviewed titles, abstracts, and full-text articles, with a third reviewer resolving conflicts, before the included articles underwent data extraction and quality appraisal. RESULTS: Twenty-four articles met the inclusion criteria. Of the included studies, nine evaluated selenium, eight evaluated Vitamin C, four evaluated Vitamin E, and three of these studies included a combination of two or more of these agents. The most frequently evaluated cancer types included colorectal cancer (n = 4), leukemias (n = 4), breast cancer (n = 3), and genitourinary cancers (n = 3). Most of the studies focused on the antioxidants' therapeutic efficacy (n = 15) or their use in protecting against chemotherapy- or radiation-induced side effects (n = 8), and one study evaluated the role of an antioxidant in protection against cancer. Findings were generally favorable among the studies, and adverse effects of supplementation were limited. Furthermore, the average score for all the included articles on the Mixed Methods Appraisal Tool was 4.2, indicating the high quality of the studies. CONCLUSIONS: Antioxidant supplements may provide benefits in reducing incidence or severity of treatment-induced side effects with limited risk for adverse effects. Large, randomized controlled trials are needed to confirm these findings among various cancer diagnoses and stages. Healthcare providers should understand the safety and efficacy of these therapies to address questions that arise in caring for those with cancer.

Environmental context predicts state fluctuations in negative symptoms in youth at clinical high risk for psychosis.

BACKGROUND: Negative symptoms (avolition, anhedonia, asociality) are a prevalent symptom in those across the psychosis-spectrum and also occur at subclinical levels in the general population. Recent work has begun to examine how environmental contexts (e.g. locations) influence negative symptoms. However, limited work has evaluated how environments may contribute to negative symptoms among youth at clinical high risk for psychosis (CHR). The current study uses Ecological Momentary Assessment to assess how four environmental contexts (locations, activities, social interactions, social interaction method) impact state fluctuations in negative symptoms in CHR and healthy control (CN) participants. METHODS: CHR youth (n = 116) and CN (n = 61) completed 8 daily surveys for 6 days assessing negative symptoms and contexts. RESULTS: Mixed-effects modeling demonstrated that negative symptoms largely varied across contexts in both groups. CHR participants had higher negative symptoms than CN participants in most contexts, but groups had similar symptom reductions during recreational activities and phone call interactions. Among CHR participants, negative symptoms were elevated in several contexts, including studying/working, commuting, eating, running errands, and being at home. CONCLUSIONS: Results demonstrate that negative symptoms dynamically change across some contexts in CHR participants. Negative symptoms were more intact in some contexts, while other contexts, notably some used to promote functional recovery, may exacerbate negative symptoms in CHR. Findings suggest that environmental factors should be considered when understanding state fluctuations in negative symptoms among those at CHR participants.

In the right place at the right time: tissue-resident memory T cells in immunity to cancer.

Tissue-resident memory (Trm) cells have recently emerged as essential components of the immune response to cancer. Here, we highlight new studies that demonstrate how CD8+ Trm cells are ideally suited to accumulate in tumors and associated tissues, to recognize a wide range of tumor antigens (Ags), and to persist as durable memory. We discuss compelling evidence that Trm cells maintain potent recall function and serve as principal mediators of immune checkpoint blockade (ICB) therapeutic efficacy in patients. Finally, we propose that Trm and circulating memory T-cell compartments together form a formidable barrier against metastatic cancer. These studies affirm Trm cells as potent, durable, and necessary mediators of cancer immunity.

Negative symptoms in schizophrenia differ across environmental contexts in daily life.

A recent environmental theory of negative symptoms posits that environmental contexts (e.g., location, social partner) play a significant-yet often unaccounted for-role in negative symptoms of schizophrenia (SZ). "Gold-standard" clinical rating scales offer limited precision for evaluating how contexts impact symptoms. To overcome some of these limitations, Ecological Momentary Assessment (EMA) was used to determine whether there were state fluctuations in experiential negative symptoms (anhedonia, avolition, and asociality) in SZ across contexts (locations, activities, social interaction partner, social interaction method). Outpatients with SZ (n = 52) and healthy controls (CN: n = 55) completed 8 daily EMA surveys for 6 days assessing negative symptom domains (anhedonia, avolition, and asociality) and contexts. Multilevel modeling demonstrated that negative symptoms varied across location, activity, social interaction partner, and social interaction method. For the majority of contexts, SZ and CN did not report significantly different levels of negative symptoms, with SZ only reporting higher negative symptoms than CN while eating, resting, interacting with a significant other, or being at home. Further, there were several contexts where negative symptoms were similarly reduced (e.g., recreation, most social interactions) or elevated (e.g., using the computer, working, running errands) in each group. Results demonstrate that experiential negative symptoms dynamically change across contexts in SZ. Some contexts may "normalize" experiential negative symptoms in SZ, while other contexts, notably some used to promote functional recovery, may increase experiential negative symptoms.

A Cross-Sectional Analysis of Military Physician Residency Websites.

INTRODUCTION: Medical physician residency program websites often serve as the first contact for any prospective applicant. No analysis of military residency program websites has yet been conducted, in contrast to their civilian counterparts. This study evaluated all military residency programs certified by the Accreditation Council for Graduate Medical Education (ACGME) 2021-2022 to determine program website comprehensiveness and accessibility and identify areas for improvement. MATERIALS AND METHODS: A list of military residency programs in the USA was compiled using Defense Health Agency Graduate Medical Education resources together with the ACGME database. A total of 15 objective website criteria covering education and recruitment content were assessed by two independent evaluators. Accessibility was also scored. Programs' website scores were compared by geographic location, specialty affiliation, type of institution partnership, and program size. Analysis was performed with descriptive statistics and comparison via an unpaired t-test or Kruskal-Wallis analysis, as appropriate. RESULTS: A total of 124 military residency program websites were evaluated with a range of scores from 0 to 15 out of 15 possible points. Six programs had no identifiable website. All three services were represented with 43% joint-service programs. Content concerning physician education and development was more widely available than content directed toward the recruitment of applicants. The number of residency program websites reporting each content criterion varied greatly, but overall, no single service had a significantly higher score across their residencies' websites. Significant variation occurred among individual specialties (P < .05) but there was no significant difference in surgical and nonsurgical specialties. Civilian-associated programs (18 programs, 14.5%) were associated with significantly greater website comprehensiveness scored best on informatics measures for recruitment and performed 64% better than military-only programs overall. CONCLUSIONS: Program information in an accessible website platform allows prospective applicants to gain comprehensive perspectives of programs during the application process without reliance on personal visits and audition rotations. Limitations to in-person experiences, such as those caused by reductions in travel and concern for student safety during the global pandemic caused by the SARS-CoV-2 virus, may be alleviated by accessible virtual information. Our results indicate that there is opportunity for all military residency programs to improve their websites and better recruit applicants through understanding their audience and optimizing their reach online.

Myocarditis Following COVID-19 Vaccination: A Systematic Review of Case Reports.

Introduction: COVID-19, the infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), often presents with a spectrum of symptoms at varying levels of severity, ranging from asymptomatic patients to those with fatal complications, such as myocarditis. With increased availability of COVID-19 vaccines, the awareness of possible side effects has expanded as reports surface. This study reviewed cases of myocarditis following COVID-19 vaccination and with existing literature on COVID-19 infection-induced myocarditis to compare clinical courses and analyze possible mechanisms of action. Methods: A systematic review of literature was conducted to identify published case reports (as of February 3, 2022) pertaining to the development of myocarditis following COVID-19 vaccination with either Pfizer or Moderna for an in-depth analysis. Additional subgroup analyses were conducted based on age, past medical history, vaccine manufacturer, and dose number. Results: There were 53 eligible case reports that were included in this study. Patients were mostly male with a median age of 24 years, and the most reported symptom upon presentation was chest pain. Seventy percent of the cases involved the Pfizer vaccine with a majority of myocarditis developing subsequent to second dose. Resolution of symptoms was achieved in all but one patient. Clinical severity, as measured primarily by left ventricular ejection fraction, appeared to be worse among adult patients than pediatric, as well as for patients with comorbidities. Conclusion: This study revealed an observable association between COVID-19 vaccines and myocarditis. However, the clinical course and prognosis seem favorable and less prevalent than those conferred from natural infection.

Characterizing the relationship between peak assistance torque and metabolic cost reduction during running with ankle exoskeletons.

BACKGROUND: Reducing the energy cost of running with exoskeletons could improve enjoyment, reduce fatigue, and encourage participation among novice and ageing runners. Previously, tethered ankle exoskeleton emulators with offboard motors were used to greatly reduce the energy cost of running with powered ankle plantarflexion assistance. Through a process known as "human-in-the-loop optimization", the timing and magnitude of assistance torque was optimized to maximally reduce metabolic cost. However, to achieve the maximum net benefit in energy cost outside of the laboratory environment, it is also necessary to consider the tradeoff between the magnitude of device assistance and the metabolic penalty of carrying a heavier, more powerful exoskeleton. METHODS: In this study, tethered ankle exoskeleton emulators were used to characterize the effect of peak assistance torque on metabolic cost during running. Three recreational runners participated in human-in-the-loop optimization at four fixed peak assistance torque levels to obtain their energetically optimal assistance timing parameters at each level. RESULTS: We found that the relationship between metabolic rate and peak assistance torque was nearly linear but with diminishing returns at higher torque magnitudes, which is well-approximated by an asymptotic exponential function. At the highest assistance torque magnitude of 0.8 Nm/kg, participants' net metabolic rate was 24.8 ± 2.3% (p = 4e-6) lower than running in the unpowered devices. Optimized timing of peak assistance torque was as late as allowed during stance (80% of stance) and optimized timing of torque removal was at toe-off (100% of stance); similar assistance timing was preferred across participants and torque magnitudes. CONCLUSIONS: These results allow exoskeleton designers to predict the energy cost savings for candidate devices with different assistance torque capabilities, thus informing the design of portable ankle exoskeletons that maximize net metabolic benefit.

Resident memory CD8+ T cells in regional lymph nodes mediate immunity to metastatic melanoma.

The nature of the anti-tumor immune response changes as primary tumors progress and metastasize. We investigated the role of resident memory (Trm) and circulating memory (Tcirm) cells in anti-tumor responses at metastatic locations using a mouse model of melanoma-associated vitiligo. We found that the transcriptional characteristics of tumor-specific CD8+ T cells were defined by the tissue of occupancy. Parabiosis revealed that tumor-specific Trm and Tcirm compartments persisted throughout visceral organs, but Trm cells dominated lymph nodes (LNs). Single-cell RNA-sequencing profiles of Trm cells in LN and skin were distinct, and T cell clonotypes that occupied both tissues were overwhelmingly maintained as Trm in LNs. Whereas Tcirm cells prevented melanoma growth in the lungs, Trm afforded long-lived protection against melanoma seeding in LNs. Expanded Trm populations were also present in melanoma-involved LNs from patients, and their transcriptional signature predicted better survival. Thus, tumor-specific Trm cells persist in LNs, restricting metastatic cancer.

A Multicenter Evaluation of Ceftolozane/Tazobactam Treatment Outcomes in Immunocompromised Patients With Multidrug-Resistant Pseudomonas aeruginosa Infections.

BACKGROUND: Real-world data assessing outcomes of immunocompromised patients treated with ceftolozane/tazobactam (C/T) are limited. This study evaluated treatment and clinical outcomes of immunocompromised patients receiving C/T for multidrug-resistant (MDR) Pseudomonas aeruginosa. METHODS: This was a 14-center retrospective cohort study of adult immunocompromised inpatients treated for ≥24 hours with C/T for MDR P. aeruginosa infections. Patients were defined as immunocompromised if they had a history of previous solid organ transplant (SOT), disease that increased susceptibility to infection, or received immunosuppressive therapies. The primary outcomes were all-cause 30-day mortality and clinical cure. RESULTS: Sixty-nine patients were included; 84% received immunosuppressive agents, 68% had a history of SOT, and 29% had diseases increasing susceptibility to infection. The mean patient age was 57 ± 14 years, and the median (interquartile range) patient Acute Physiology and Chronic Health Evaluation II and Charlson Comorbidity Index scores were 18 (13) and 5 (4), respectively, with 46% receiving intensive care unit care at C/T initiation. The most frequent infection sources were respiratory (56%) and wound (11%). All-cause 30-day mortality was 19% (n = 13), with clinical cure achieved in 47 (68%) patients. Clinical cure was numerically higher (75% vs 30%) in pneumonia patients who received 3-g pneumonia regimens vs 1.5-g regimens. CONCLUSIONS: Of 69 immunocompromised patients treated with C/T for MDR P. aeruginosa, clinical cure was achieved in 68% and mortality was 19%, consistent with other reports on a cross-section of patient populations. C/T represents a promising agent for treatment of P. aeruginosa resistant to traditional antipseudomonal agents in this high-risk population.

Intrinsic "Turn-On" Aptasensor Detection of Ochratoxin A Using Energy-Transfer Fluorescence.

Ochratoxin A (OTA) is an intrinsically fluorescent phenolic mycotoxin that contaminates a wide range of food products and is a serious health threat to animals and humans. An OTA binding aptamer (OTABA) that folds into an antiparallel G-quadruplex (GQ) in the absence and presence of target OTA has been incorporated into a vast variety of aptasensor platforms for OTA detection. The development of a simple, aptamer-based approach would allow for detection of the toxin without the use of complex analytical instrumentation, which has been the gold standard for OTA detection thus far. However, to date, none of the aptasensor platforms have utilized the natural fluorescence of the phenolic toxin for detection. Herein, we report that OTA binding to OTABA involves π-stacking interactions that lead to GQ-to-toxin energy transfer (ET), which affords a "turn-on" fluorescence self-signaling platform in which the emission of the aptamer-target complex is enhanced in comparison to the free toxin alone. Selective excitation of the GQ-OTA complex at 256 nm leads to a 4-fold enhancement in OTA fluorescence. The GQ-OTA ET detection platform boasts a limit of detection ∼2 ng/mL, which is comparable to a previously demonstrated fluorescence resonance energy transfer immunoassay platform for OTA detection, and displays excellent OTA selectivity and recovery from red wine samples.

Novel N-1 substituted fluoroquinolones inhibit human topoisomerase I activity and exhibit anti-proliferative activity.

Fluoroquinolone-class agents selectively target the bacterial type IIA topoisomerases DNA gyrase and topoisomerase IV, with a few exceptions that target eukaryotic type IIA topoisomerases. Fluoroquinolones bind and stabilize type IIA topoisomerase-DNA covalent complexes that contain a double-strand break. This unique mode of action is referred to as 'topoisomerase poisoning'. We discovered that two novel fluoroquinolones having aryl functionality at the N-1 position, UITT-3-217 (217) and UITT-3-227 (227), could inhibit the catalytic activity of human topoisomerase II without stabilizing topoisomerase-DNA complexes, i.e., without poisoning it. Surprisingly, these compounds are more effective in inhibiting the catalytic activities of human and bacterial topoisomerase I. The National Cancer Institute's 60 human tumor cell lines screen revealed significant anti-proliferative activities with 217 and 227 against the majority of 60 cancer cell lines. A proof of concept in vivo efficacy study using an HT-29 xenograft model of human colorectal cancer showed that 217 could inhibit the proliferation of human colorectal cancer cells to a degree comparable to fluorouracil in mice. Although 227 also exhibited anti-proliferative activity, it was not as effective as 217 in this xenograft model. These novel fluoroquinolones may serve as promising lead compounds for the development of new anticancer drugs.

Assessing the significance of Ruditapes philippinarum as a sentinel for sediment pollution: bioaccumulation and biomarker responses.

The present study assessed whether the bivalve Ruditapes philippinarum may be appropriately deployed as a bioindicator in monitoring transitional environments, in terms of bioaccumulation potential and biomarker responses. The concentrations of trace metals, PAHs and PCBs were determined in sediments and clam tissue, and biomarkers were estimated at various levels of biological complexity (i.e. metallothioneins, lipofuscins, survival-in-air and reburrowing behaviour). Sediments and clams were collected biannually in 2004 and 2005 at eight sites within Venice lagoon, which were influenced differently by natural and anthropogenic impacts. Results highlighted that the broad variations of pollutant concentrations in sediments were not consistent either with the body residuals or with the biomarker responses. Consequently, on the basis of the observed weak responsiveness and sensitivity to anthropogenic stressors we suggest a more cautious use for R. philippinarum as sentinel organism, at least in estuarine sediments in the north Adriatic transitional areas.

Fludarabine, Cyclophosphamide and Rituximab: an effective chemoimmunotherapy combination with high remission rates for chronic lymphocytic leukaemia.

BACKGROUND: Combined Fludarabine and Cyclophosphamide is now standard first-line therapy in chronic lymphocytic leukaemia (CLL) and the addition of Rituximab improves outcome. METHODS: We adopted a modified Fludarabine, Cyclophosphamide and Rituximab (FCR) protocol in treating 39 patients (median age 57 years) with progressive or advanced CLL. Depending on CR, treatment was given for four or six cycles. RESULT: Twenty-six patients were treatment naïve and 13 were pre-treated. Twelve patients had progressive Binet stage A, 16 stage B and 11 stage C disease. The overall response rate (ORR) was 100%, with 75% achieving CR. Neutropenia was the major toxicity in 71/187 (38%) of the cycles. There were five deaths, two from infection and three from progressive disease. Twenty-six of 31 patients have maintained their post-treatment disease status for a median of 17 months (2-41). CONCLUSION: We conclude that FCR is a feasible, well-tolerated and effective treatment for patients with CLL.

Enhanced metaboreflex sensitivity in hypertensive humans.

The exercise pressor reflex (EPR) is composed of the mechanoreflex and the metaboreflex and has been shown to be overactive in spontaneously hypertensive rats. The aim of the present study was to isolate the metaboreflex using post-exercise ischemia (PEI) and examine the BP response in normotensive (NTN) and hypertensive (HTN) humans. We hypothesize that the post-exercise ischemia-induced maintenance of BP will be greater in HTN when compared to NTN adults. A total of 15 NTN (65 +/- 1 years) and 12 HTN (64 +/- 1 years) adults were recruited. Beat-to-beat mean arterial pressure (MAP) was measured non-invasively (Finometer). Dynamic handgrip exercise (DHE) was performed for 3 min followed by 2 min of PEI. An unpaired t test was used to examine differences between groups. As compared to resting baseline values, the change in MAP during PEI was greater in HTN than NTN subjects (HTN: Delta = 12 +/- 3 mmHg, NTN: Delta = 6 +/- 1 mmHg, P < 0.05). These data suggest that HTN humans have enhanced metaboreflex sensitivity.

Excising basal cell carcinomas: comparing the performance of general practitioners, hospital skin specialists and other hospital specialists.

BACKGROUND: General practitioners (GPs) are not encouraged to excise basal cell carcinomas (BCCs). Despite this, as many of 10% of BCCs may be excised by GPs. GPs may be able to have a greater role in the diagnosis and management of BCC, but much needs to be learnt before this can be advocated. OBJECTIVE: To compare the practice of GPs, skin specialists (dermatologists and plastic surgeons) and other hospital specialists in excising BCCs. METHODS: A retrospective analysis of all BCCs excised in the Grampian region between 1 January and 31 December 2005 was carried out In total, 1087 reports were rated for source, quality of clinical information provided and extent of excision. RESULTS: GPs perform significantly less well than skin specialists when diagnosing and excising BCCs, but appear equal in diagnostic skill and better at excision than other hospital specialists. Non-specialized GPs appear to perform as well as GPs with special interest (GPwSI) in adequately excising BCCs. In 18.7% of all cases, the information supplied to the pathologist with the biopsy sample was inadequate to draw a conclusion. CONCLUSIONS: GPs compare unfavourably with skin specialists in diagnosing and excising BCCs. The performance of nonspecialized GPs does not appear to differ markedly from that of GPwSI. There is considerable room to optimize current GP performance, particularly with lesions of the head and neck, and it may be that novel approaches to GP training are required to achieve this. Structured request forms may improve the quality of clinical information provided when skin biopsies are submitted for pathological examination.

Secondary prevention clinics for coronary heart disease: a 10-year follow-up of a randomised controlled trial in primary care.

OBJECTIVES: To evaluate the effects of nurse-led secondary prevention clinics for coronary heart disease (CHD) in primary care on total mortality and coronary event rates after 10 years. DESIGN: Follow-up of a randomised controlled trial by review of national datasets. SETTING: Stratified random sample of 19 general practices in northeast Scotland. PARTICIPANTS: Original study cohort of 1343 patients, aged <80 years, with a working diagnosis of CHD, but without dementia or terminal illness and not housebound. INTERVENTION: Nurse-led secondary prevention clinics promoted medical and lifestyle aspects of secondary prevention and offered regular follow-up for 1 year, MAIN OUTCOME MEASURES: Total mortality and coronary events (non-fatal myocardial infarctions (MIs) and coronary deaths). RESULTS: Mean (SD) follow-up was at 10.2 (0.19) years. No significant differences in total mortality or coronary events were found at 10 years. 254 patients in the intervention group and 277 patients in the control group had died: cumulative death rates were 38% and 41%, respectively (p = 0.177). 196 coronary events occurred in the intervention group and 195 in the control group: cumulative event rates were 29.1% and 29.1%, respectively (p = 0.994). When Kaplan-Meier survival analysis, adjusted for age, sex and general practice, was used, proportional hazard ratios were 0.88 (0.74 to 1.04) for total mortality and 0.96 (0.79 to 1.18) for coronary death or non-fatal MI. No significant differences in the distribution of cause of death classifications was found at either 4 or 10 years. CONCLUSIONS: After 10 years, differences between groups were no longer significant. Total mortality survival curves for the intervention and control groups had not converged, but the coronary event survival curves had. Possibly, therefore, the earlier that secondary prevention is optimised, the less likely a subsequent coronary event is to prove fatal.