An investigation of routes to cancer diagnosis in 10 international jurisdictions, as part of the International Cancer Benchmarking Partnership: survey development and implementation.

OBJECTIVES: This paper describes the methods used in the International Cancer Benchmarking Partnership Module 4 Survey (ICBPM4) which examines time intervals and routes to cancer diagnosis in 10 jurisdictions. We present the study design with defining and measuring time intervals, identifying patients with cancer, questionnaire development, data management and analyses. DESIGN AND SETTING: Recruitment of participants to the ICBPM4 survey is based on cancer registries in each jurisdiction. Questionnaires draw on previous instruments and have been through a process of cognitive testing and piloting in three jurisdictions followed by standardised translation and adaptation. Data analysis focuses on comparing differences in time intervals and routes to diagnosis in the jurisdictions. PARTICIPANTS: Our target is 200 patients with symptomatic breast, lung, colorectal and ovarian cancer in each jurisdiction. Patients are approached directly or via their primary care physician (PCP). Patients' PCPs and cancer treatment specialists (CTSs) are surveyed, and 'data rules' are applied to combine and reconcile conflicting information. Where CTS information is unavailable, audit information is sought from treatment records and databases. MAIN OUTCOMES: Reliability testing of the patient questionnaire showed that agreement was complete (κ=1) in four items and substantial (κ=0.8, 95% CI 0.333 to 1) in one item. The identification of eligible patients is sufficient to meet the targets for breast, lung and colorectal cancer. Initial patient and PCP survey response rates from the UK and Sweden are comparable with similar published surveys. Data collection was completed in early 2016 for all cancer types. CONCLUSION: An international questionnaire-based survey of patients with cancer, PCPs and CTSs has been developed and launched in 10 jurisdictions. ICBPM4 will help to further understand international differences in cancer survival by comparing time intervals and routes to cancer diagnosis.

Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial.

BACKGROUND: Ovarian cancer has a poor prognosis, with just 40% of patients surviving 5 years. We designed this trial to establish the effect of early detection by screening on ovarian cancer mortality. METHODS: In this randomised controlled trial, we recruited postmenopausal women aged 50-74 years from 13 centres in National Health Service Trusts in England, Wales, and Northern Ireland. Exclusion criteria were previous bilateral oophorectomy or ovarian malignancy, increased risk of familial ovarian cancer, and active non-ovarian malignancy. The trial management system confirmed eligibility and randomly allocated participants in blocks of 32 using computer-generated random numbers to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening, in a 1:1:2 ratio. The primary outcome was death due to ovarian cancer by Dec 31, 2014, comparing MMS and USS separately with no screening, ascertained by an outcomes committee masked to randomisation group. All analyses were by modified intention to screen, excluding the small number of women we discovered after randomisation to have a bilateral oophorectomy, have ovarian cancer, or had exited the registry before recruitment. Investigators and participants were aware of screening type. This trial is registered with ClinicalTrials.gov, number NCT00058032. FINDINGS: Between June 1, 2001, and Oct 21, 2005, we randomly allocated 202,638 women: 50,640 (25·0%) to MMS, 50,639 (25·0%) to USS, and 101,359 (50·0%) to no screening. 202,546 (>99·9%) women were eligible for analysis: 50,624 (>99·9%) women in the MMS group, 50,623 (>99·9%) in the USS group, and 101,299 (>99·9%) in the no screening group. Screening ended on Dec 31, 2011, and included 345,570 MMS and 327,775 USS annual screening episodes. At a median follow-up of 11·1 years (IQR 10·0-12·0), we diagnosed ovarian cancer in 1282 (0·6%) women: 338 (0·7%) in the MMS group, 314 (0·6%) in the USS group, and 630 (0·6%) in the no screening group. Of these women, 148 (0·29%) women in the MMS group, 154 (0·30%) in the USS group, and 347 (0·34%) in the no screening group had died of ovarian cancer. The primary analysis using a Cox proportional hazards model gave a mortality reduction over years 0-14 of 15% (95% CI -3 to 30; p=0·10) with MMS and 11% (-7 to 27; p=0·21) with USS. The Royston-Parmar flexible parametric model showed that in the MMS group, this mortality effect was made up of 8% (-20 to 31) in years 0-7 and 23% (1-46) in years 7-14, and in the USS group, of 2% (-27 to 26) in years 0-7 and 21% (-2 to 42) in years 7-14. A prespecified analysis of death from ovarian cancer of MMS versus no screening with exclusion of prevalent cases showed significantly different death rates (p=0·021), with an overall average mortality reduction of 20% (-2 to 40) and a reduction of 8% (-27 to 43) in years 0-7 and 28% (-3 to 49) in years 7-14 in favour of MMS. INTERPRETATION: Although the mortality reduction was not significant in the primary analysis, we noted a significant mortality reduction with MMS when prevalent cases were excluded. We noted encouraging evidence of a mortality reduction in years 7-14, but further follow-up is needed before firm conclusions can be reached on the efficacy and cost-effectiveness of ovarian cancer screening. FUNDING: Medical Research Council, Cancer Research UK, Department of Health, The Eve Appeal.

Invasive mucormycosis and aspergillosis in a healthy 22-year-old battle casualty: case report.

BACKGROUND: Invasive mucormycosis or aspergillosis is a life-threatening infection. The disease typically occurs in immunocompromised patients (e.g., those with diabetes mellitus or burns) but is rarely serious in otherwise-healthy young trauma patients. METHODS: Case report and literature review. RESULTS: A previously-healthy 22-year-old United States Marine who sustained large soft tissue injuries in support of Operation Enduring Freedom underwent multiple operations in theater to stabilize his wounds. He was evacuated first to Landstuhl Regional Medical Center in Germany and thence to the National Naval Medical Center in Maryland, where appropriate antifungal therapies were initiated and wide débridements were undertaken without success. His clinical status deteriorated, and he died. Tissue examination revealed systemic invasive mucormycosis and aspergillosis. CONCLUSION: The suspicion of invasive fungal infections must be tested early if intervention is to be curative.

Emergent management of postpartum hemorrhage for the general and acute care surgeon.

BACKGROUND: Postpartum hemorrhage is one of the rare occasions when a general or acute care surgeon may be emergently called to labor and delivery, a situation in which time is limited and the stakes high. Unfortunately, there is generally a paucity of exposure and information available to surgeons regarding this topic: obstetric training is rarely found in contemporary surgical residency curricula and is omitted nearly completely from general and acute care surgery literature and continuing medical education. METHODS: The purpose of this manuscript is to serve as a topic specific review for surgeons and to present a surgeon oriented management algorithm. Medline and Ovid databases were utilized in a comprehensive literature review regarding the management of postpartum hemorrhage and a management algorithm for surgeons developed based upon a collaborative panel of general, acute care, trauma and obstetrical surgeons' review of the literature and expert opinion. RESULTS: A stepwise approach for surgeons of the medical and surgical interventions utilized to manage and treat postpartum hemorrhage is presented and organized into a basic algorithm. CONCLUSION: The manuscript should promote and facilitate a more educated, systematic and effective surgeon response and participation in the management of postpartum hemorrhage.

Transforming an academic military treatment facility into a trauma center: lessons learned from Operation Iraqi Freedom.

BACKGROUND: To manage the influx of patients with predominately extremity injuries from Operation Iraqi Freedom (OIF), our center was required to transform from a nontrauma academic hospital to a trauma hospital by using a multidisciplinary approach. STUDY DESIGN: A retrospective chart review was performed of casualties from OIF who were received over 14 months. RESULTS: A total of 313 casualties were received. The average number of admissions was 16 per month, except during November 2004, when there were 88 admissions over 7 days. The mean ISS for all patients was 14.1 +/- 10.3. A total of 113 patients (36%) required admission to the intensive care unit for an average of 7.5 +/- 5.2 days. The mean interval between injury and arrival in the continental United States was 6.5 +/- 4.6 days. Most casualties suffered multisystem trauma, with extremity injuries predominating. The multidisciplinary approach to casualty care consisted of several meetings a week and included everyone involved in caring for these combat casualties. CONCLUSIONS: A multidisciplinary approach transformed an existing medical center into a trauma receiving hospital capable of managing and maintaining a surge in patient admissions resulting in minimal morbidity and mortality. This model further supports a multidisciplinary approach to trauma care and could serve as a guideline for transforming existing medical centers into trauma receiving hospitals to deal with patient overflow in the event of future civilian mass casualties.

Warfare-related complex abdominal wall reconstruction using a bioprosthetic regenerate template and negative pressure therapy.

Warfare-related torso/abdominal wounds are often unique and complex and can pose a significant reconstructive challenge. The objective of this manuscript is to report the unique and successful management of a complex warfare-related abdominal wound. A dermal regenerate template in combination with negative pressure wound therapy was used to reconstitute lateral abdominal wall integrity after radical debridement and control of a necrotizing soft tissue infection of the torso. Adjunctive continuous negative pressure (vacuum assisted closure) therapy was used to provide external coverage and encourage the formation of granulation tissue. With this combination therapy, torso wound size decreased in surface area by 82% and the underlying musculofascial defect decreased by 64%. Neovascularization of a 55-cm(2) acellular dermal graft was achieved as evidenced by surface granulation and complete survival of a partial-thickness skin graft. In our patient with a complex war injury, advanced tissue replacement techniques and negative pressure wound therapy resulted in a decreased abdominal wall defect, a restoration of abdominal wall integrity/domain, and allowed for concurrent surgical treatment of complex intra-abdominal injuries.

Effect of Body Mass Index on pregnancy outcomes in nulliparous women delivering singleton babies.

BACKGROUND: The increasing prevalence of obesity in young women is a major public health concern. These trends have a major impact on pregnancy outcomes in these women, which have been documented by several researchers. In a population based cohort study, using routinely collected data, this paper examines the effect of increasing Body Mass Index (BMI) on pregnancy outcomes in nulliparous women delivering singleton babies. METHODS: This was a retrospective cohort study, based on all nulliparous women delivering singleton babies in Aberdeen between 1976 and 2005. Women were categorized into five groups--underweight (BMI < 20 Kg/m2), normal (BMI 20-24.9 Kg/m2) overweight (BMI 25-29.9 Kg/m2), obese (BMI 30-34.9 Kg/m2) and morbidly obese (BMI > 35 Kg/m2). Obstetric and perinatal outcomes were compared by univariate and multivariate analyses. RESULTS: In comparison with women of BMI 20-24.9, morbidly obese women faced the highest risk of pre-eclampsia {OR 7.2 (95% CI 4.7, 11.2)} and underweight women the lowest {OR 0.6 (95% CI 0.5, 0.7)}. Induced labour was highest in the morbidly obese {OR 1.8 (95% CI 1.3, 2.5)} and lowest in underweight women {OR 0.8 (95% CI 0.8, 0.9)}. Emergency Caesarean section rates were highest in the morbidly obese {OR 2.8 (95% CI 2.0, 3.9)}, and comparable in women with normal and low BMI. Obese women were more likely to have postpartum haemorrhage {OR 1.5 (95% CI 1.3, 1.7)} and preterm delivery (< 33 weeks) {OR 2.0 (95% CI 1.3, 2.9)}. Birthweights less than 2,500 g were more common in underweight women {OR 1.7 (95% OR 1.2, 2.0)}. The highest risk of birth weights > 4,000 g was in the morbidly obese {OR 2.1 (95% CI 1.3, 3.2)} and the lowest in underweight women {OR 0.5 (95% CI 0.4, 0.6)}. CONCLUSION: Increasing BMI is associated with increased incidence of pre-eclampsia, gestational hypertension, macrosomia, induction of labour and caesarean delivery; while underweight women had better pregnancy outcomes than women with normal BMI.

Assessment of patient management skills and clinical skills of practising doctors using computer-based case simulations and standardised patients.

CONTEXT: Standardised assessments of practising doctors are receiving growing support, but theoretical and logistical issues pose serious obstacles. OBJECTIVES: To obtain reference performance levels from experienced doctors on computer-based case simulation (CCS) and standardised patient-based (SP) methods, and to evaluate the utility of these methods in diagnostic assessment. SETTING AND PARTICIPANTS: The study was carried out at a military tertiary care facility and involved 54 residents and credentialed staff from the emergency medicine, general surgery and internal medicine departments. MAIN OUTCOME MEASURES: Doctors completed 8 CCS and 8 SP cases targeted at doctors entering the profession. Standardised patient performances were compared to archived Year 4 medical student data. RESULTS: While staff doctors and residents performed well on both CCS and SP cases, a wide range of scores was exhibited on all cases. There were no significant differences between the scores of participants from differing specialties or of varying experience. Among participants who completed both CCS and SP testing (n = 44), a moderate positive correlation between CCS and SP checklist scores was observed. There was a negative correlation between doctor experience and SP checklist scores. Whereas the time students spent with SPs varied little with clinical task, doctors appeared to spend more time on communication/counselling cases than on cases involving acute/chronic medical problems. CONCLUSION: Computer-based case simulations and standardised patient-based assessments may be useful as part of a multimodal programme to evaluate practising doctors. Additional study is needed on SP standard setting and scoring methods. Establishing empirical likelihoods for a range of performances on assessments of this character should receive priority.

Distribution and care of shipboard blast injuries (USS Cole DDG-67).

On October 12, 2000, the destroyer USS Cole was anchored in a foreign port and was severely damaged by explosives in a small craft adjacent to the ship at the port side waterline. Seventeen crew members were killed in the incident. The wounded were evacuated to several medical facilities for their initial care and then to the military hospital in Landstuhl, Germany, and subsequently to the Charette Health Care Center (Naval Medical Center) in Portsmouth, Virginia. There were 35 surviving patients who had sustained 81 total injuries associated with the explosion. The distribution of the injuries included orthopedic, ophthalmologic, soft tissue, otolaryngologic, burns, inhalation, and other miscellaneous injuries. Twenty-seven of the patients were discharged after 24-hour observation. This article reviews the distribution of injuries found in the fatalities and the wounded crew members and the subsequent care required to prepare the military medical community for potential future incidents of this type.

Parietal foramina with cleidocranial dysplasia is caused by mutation in MSX2.

The combination of skull defects in the form of enlarged parietal foramina (PFM) and deficient ossification of the clavicles is known as parietal foramina with cleidocranial dysplasia (PFMCCD). It is considered to be distinct from classical cleidocranial dysplasia (CCD) and is listed as a separate OMIM entry (168550). So far, only two families have been reported and the molecular basis of the disorder is unknown. We present a third family with PFMCCD, comprising four affected individuals in three generations, and demonstrate that a heterozygous tetranucleotide duplication in the MSX2 homeobox gene (505_508dupATTG) segregates with the phenotype. PFMCCD is indeed aetiologically distinct from CCD, which is caused by mutations in the RUNX2 gene, but allelic with isolated PFM, in which MSX2 mutations were previously identified. Our observations highlight the role of MSX2 in clavicular development and the importance of radiological examination of the clavicles in subjects with PFM.