Instructions: Given the medical questions below, return the medical difficulty/complexity of each question, please select among the following options:

1. Low: a PCP or general physician can answer this question without consulting a specialist.
2. Moderate: a PCP or general physician can answer this question in consultation with a specialist, and a single specialist can answer this question.
3. High: A team of multi-departmental specialists can answer this question, which requires specialists consulting to another department (Requires team effort to treat the case).

Question 1: Does immediate breast reconstruction compromise the delivery of adjuvant chemotherapy? Immediate breast reconstruction (IBR) provides psychological benefit to many early breast cancer patients however concerns persist regarding its potential impact on chemotherapy delivery. We investigated the association between IBR, complications and adjuvant chemotherapy delivery. Retrospective analysis of patients in an academic breast service, who underwent mastectomy, with or without reconstruction, and received adjuvant chemotherapy. Comparisons were made between 107 patients who received IBR and 113 who received mastectomy alone. Those receiving IBR were on average younger, with lower body mass index (BMI) and better prognoses. Overall complication rates were comparable (mastectomy alone: 45.1% versus IBR: 35.5%, p = 0.2). There was more return to surgery in the IBR group with 11.5% of tissue expanders requiring removal, whilst more seromas occurred in the mastectomy group. There was no significant difference in the median time to chemotherapy.

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Question 2: Treadmill training post stroke: are there any secondary benefits? To explore the secondary benefits of treadmill training for people in the chronic stage of recovery from stroke. Modified random assignment, matched-pair control group design with repeated measures. Outpatient stroke centre. Twenty individuals post first stroke who acknowledged walking slower than pre stroke. Participants matched by side of hemiparesis and motor impairment. Twelve 20-minute sessions of walking on a treadmill or weekly phone call. Depression (Beck Depression Index), mobility and social participation (Stroke Impact Scale 3.0 subscales) were assessed initially, at the end of 12 treatments (four weeks) and six weeks later. No significant difference was found between groups for any dependent measure. The ANOVA to investigate main effects in each group found no significant findings in the control group; however in the treatment group significant improvements over time for depression (P = 0.005, P<0.001), mobility (P = 0.008) and social participation (P = 0.004) were demonstrated.

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Question 3: Risk stratification in emergency surgical patients: is the APACHE II score a reliable marker of physiological impairment? The APACHE II (Acute Physiology and Chronic Health Evaluation II) score used as an intensive care unit (ICU) admission score in emergency surgical patients is not independent of the effects of treatment and might lead to considerable bias in the comparability of defined groups of patients and in the evaluation of treatment policies. Postoperative monitoring with the APACHE II score is clinically irrelevant. Inception cohort study. Secondary referral center. Eighty-five consecutive emergency surgical patients admitted to the surgical ICU in 1999. The APACHE II score was calculated before surgery; after admission to the ICU; and on postoperative days 3, 7, and 10. APACHE II scores and predicted and observed mortality rates. The mean +/- SD APACHE II score of 24.2 +/- 8.3 at admission to the ICU was approximately 36% greater than the initial APACHE II score of 17.8 +/- 7.7, a difference that was highly statistically significant (P<.001). The overall mortality of 32% favorably corresponds with the predicted mortality of 34% according to the initial APACHE II score. However, the predicted mortality of 50% according to the APACHE II score at admission to the ICU was significantly different from the observed mortality rate (P =.02). In 40 long-term patients (>/=10 days in the ICU), the difference between the APACHE II scores of survivors and patients who died was statistically significant on day 10 (P =.04).

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Question 4: Can myometrial electrical activity identify patients in preterm labor? The objective of the study was to determine whether myometrial electrical activity can differentiate false from true preterm labor. Electrical uterine myography (EUM) was measured prospectively on 87 women, gestational age less than 35 weeks. The period between contractions, power of contraction peaks and movement of center of electrical activity (RMS), was used to develop an index score (1-5) for prediction of preterm delivery (PTD) within 14 days of the test. The score was compared with fetal fibronectin (fFN) and cervical length (CL). Patients delivering within 14 days from testing showed a higher index and mean RMS (P = .000). No patients with EUM index scores of 1-2 delivered in this time frame. Combining EUM with CL or fFN increased predictability. Logistic regression revealed that history of PTD and EUM index had 4- to 5-fold increased risk for PTD. Gestational age at testing, body mass index, fFN, and CL were nonsignificant contributors to PTD risk.

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Question 5: Do parents recall and understand children's weight status information after BMI screening? As parents of young children are often unaware their child is overweight, screening provides the opportunity to inform parents and provide the impetus for behaviour change. We aimed to determine if parents could recall and understand the information they received about their overweight child after weight screening. Randomised controlled trial of different methods of feedback. Participants were recruited through primary and secondary care but appointments took place at a University research clinic. 1093 children aged 4-8 years were screened. Only overweight children (n=271, 24.7%) are included in this study. Parents of overweight children were randomised to receive feedback regarding their child's weight using best practice care (BPC) or motivational interviewing (MI) at face-to-face interviews typically lasting 20-40 min. 244 (90%) parents participated in a follow-up interview 2 weeks later to assess recall and understanding of information from the feedback session. Interviews were audio-taped and transcribed verbatim before coding for amount and accuracy of recall. Scores were calculated for total recall and sub-categories of interest. Overall, 39% of the information was recalled (mean score 6.3 from possible score of 16). Parents given feedback via BPC recalled more than those in the MI group (difference in total score 0.48; 95% CI 0.05 to 0.92). Although 94% of parents were able to correctly recall their child's weight status, fewer than 10 parents could accurately describe what the measurements meant. Maternal education (0.81; 0.25 to 1.37) and parental ratings of how useful they found the information (0.19; 0.04 to 0.35) were significant predictors of recall score in multivariate analyses.

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Question 6: Are complex coronary lesions more frequent in patients with diabetes mellitus? Coronary atherosclerotic burden is excessive in diabetic patients. Diabetes mellitus (DM) is an independent predictor for both death and myocardial infarction. It is not known whether the prevalence of complex coronary lesions, such as bifurcation and ostial lesions, is different in diabetics from nondiabetics. The aim of present study was to investigate the prevalence of these lesions in patients with DM. One thousand fourteen consecutive patients (mean age 61.3+/-10.7 years) were investigated. Coronary angiograms were examined for bifurcation and ostial lesions using a digital quantitative system. Patients were classified as diabetic (n=281) or nondiabetic (n=733). Patient mean age, and rates of hypertension and hyperlipidemia were significantly higher in the diabetic group than in the nondiabetic group (P<0.0001), although smoking was significantly lower (P=0.001). Reasons for coronary angiography and treatment were comparable between the two groups. The prevalence of bifurcation lesions and ostial lesions was significantly greater in the diabetic group than in the nondiabetic group (9.8% versus 4.3% [P=0.001] and 38.4% versus 29.2% [P=0.003]in the diabetic group versus the nondiabetic group). The presence of DM and greater age were found to be independent predictors for bifurcation lesions (OR=2.27 [P=0.004] and OR=1.03 [P=0.01], for DM and age, respectively) and ostial lesions (OR=1.40 [P=0.027] and OR=1.02 [P=0.001], for DM and age, respectively) in multivariate analysis.

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Question 7: Are the GFRUP's recommendations for withholding or withdrawing treatments in critically ill children applicable? To evaluate feasibility of the guidelines of the Groupe Francophone de Réanimation et Urgence Pédiatriques (French-speaking group of paediatric intensive and emergency care; GFRUP) for limitation of treatments in the paediatric intensive care unit (PICU). A 2-year prospective survey. A 12-bed PICU at the Hôpital Jeanne de Flandre, Lille, France. Were included when limitation of treatments was expected. Of 967 children admitted, 55 were included with a 2-day median delay. They were younger than others (24 v 60 months), had a higher paediatric risk of mortality (PRISM) score (14 v 4), and a higher paediatric overall performance category (POPC) score at admission (2 v 1); all p<0.002. 34 (50% of total deaths) children died. A limitation decision was made without meeting for 7 children who died: 6 received do-not-resuscitate orders (DNROs) and 1 received withholding decision. Decision-making meetings were organised for 31 children, and the following decisions were made: 12 DNROs (6 deaths and 6 survivals), 4 withholding (1 death and 3 survivals), with 14 withdrawing (14 deaths) and 1 continuing treatment (survival). After limitation, 21 (31% of total deaths) children died and 10 survived (POPC score 4). 13 procedures were interrupted because of death and 11 because of clinical improvement (POPC score 4). Parents' opinions were obtained after 4 family conferences (for a total of 110 min), 3 days after inclusion. The first meeting was planned for 6 days after inclusion and held on the 7th day after inclusion; 80% of parents were immediately informed of the decision, which was implemented after half a day.

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Question 8: Is external palliative radiotherapy for gallbladder carcinoma effective? Gallbladder carcinoma is characterized by delayed diagnosis, ineffective treatment and poor prognosis. Surgical resection has been thought to be the treatment of choice, while the role of radiotherapy as adjuvant or palliative treatment has not been fully clarified in the literature. We present the case of a 45-year-old female, with unresectable gallbladder carcinoma, grade IV, histologically diagnosed during laparotomy. The patient was treated with palliative intent with percutaneous transhepatic biliary drainage. Furthermore, she received external radiotherapy by (60)Co, using a three-field technique (anterior-posterior and right lateral). The total dose was 3,000 cGy in 10 fractions, with 300 cGy per fraction, 5 days weekly. The patient showed clinico-laboratory improvement and was discharged with a permanent percutaneous transhepatic endoprosthesis. During follow-up (10 and 12 months postirradiation), abdominal CTs showed no local extension of the tumor, while the patient had a good performance status. So far, 1 year after the diagnosis of gallbladder cancer she is still alive.

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Question 9: Can continuous physical training counteract aging effect on myoelectric fatigue? To compare the myoelectric onset of muscle fatigue in physically active trained young skiers with respect to elderly skiers and to test whether continuous training can counteract the selective loss of type II muscle fibers usually observed with aging. An observational, cross-sectional study of the myoelectric onset of muscle fatigue in the left tibialis anterior muscles. Surface electromyography recorded with portable devices at a downhill ski rescue lodge in the Italian Alps. Fifty-four physically trained, active skiers (43 men, 11 women; age range, 24-85y). Questionnaire on physical activity and 2 sustained isometric voluntary contractions at 20% and 2 at 80% of the maximal voluntary contraction level. Isometric contractions and mean and median spectral frequencies calculated to monitor the myoelectric manifestations of muscle fatigue. Fatigue indices did not differ significantly between younger and older subjects and, thus, did not show a correlation between myoelectric manifestations of muscle fatigue and age in physically active subjects.

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Question 10: Does the sex of acute stroke patients influence the effectiveness of rt-PA? Women have been reported to show more frequent recanalization and better recovery after intravenous (IV) recombinant tissue plasminogen activator (rt-PA) treatment for acute stroke compared with men. To investigate this we studied a series of stroke patients receiving IV rt-PA and undergoing acute transcranial doppler (TCD) examination. Acute stroke patients received IV rt-PA and had acute TCD examination within 4 hours of symptom onset at 4 major stroke centers. TCD findings were interpreted using the Thrombolysis in Brain Ischemia (TIBI) flow grading system. The recanalization rates, and poor 3-month outcomes (modified Rankin scale>2) of men and women were compared using the chi-square test. Multiple regression analysis was used to assess sex as a predictor of recanalization and poor 3-month outcome after controlling for age, baseline NIH Stroke Scale (NIHSS), time to treatment, hypertension, and blood glucose. 369 patients had TCD examinations before or during IV rt-PA treatment. The 199 (53.9%) men and 170 (46.1%) women had mean ages of 67 ± 13 and 70 ± 14 years, respectively. The sexes did not differ significantly in baseline stroke severity, time to TCD examination, or time to thrombolysis. Of the men, 68 (34.2%) had complete recanalization, 58 (29.1%) had partial recanalization, and 73 (36.6%) had no recanalization. Of the women, 53 (31.2%) had complete recanalization, 46 (27%) had partial recanalization, and 71 (41.8%) had no recanalization (p = 0.6). Multiple regression analyses showed no difference between the sexes in recanalization rate, time to recanalization, or clinical outcome at 3 months.

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Question 11: Is endometrial polyp formation associated with increased expression of vascular endothelial growth factor and transforming growth factor-beta1? Endometrial polyp is a common cause of abnormal uterine bleeding, but the etiology and pathogenesis remain unclear. Vascular endothelial growth factor (VEGF) is angiogenic, related to thick walled vessels and transforming growth factor-beta1 (TGF-β1) is related to fibrotic tissue, which are characteristics of endometrial polyps. The primary objective of this study was to find out if endometrial polyp formation is associated with increased expression of VEGF or TGF-β1, or both. A secondary objective is to determine if the changes are related to steroid receptor expression. This prospective study compared VEGF and TGF-β1 expression of endometrial polyps and adjacent endometrial tissue in 70 premenopausal women. The comparison of results was separately made for endometrium specimens obtained in the proliferative and secretory phases. The results were correlated with the steroid receptors (estrogen receptor and progesterone receptor) expression. The score of VEGF in glandular cells of endometrial polyps was significantly higher than the score in adjacent endometrium, both in the proliferative phase (P<0.001) and the secretory phase (P=0.03); the score of VEGF in stromal cells of endometrial polyps was significantly higher than the score in adjacent endometrium only in proliferative phase (P=0.006). The score of TGF-β1 in glandular cells of endometrial polyps was significantly higher than the score in adjacent endometrium in proliferative phase (P=0.02); whereas the score of TGF-β1 in stromal cells of endometrial polyps was significantly higher than the score in adjacent endometrium, both in the proliferative phase (P=0.006) and the secretory phase (P=0.008). There was a significant correlation between the expression of steroid receptors and VEGF and TGF-β1 (Spearman's correlation P<0.001 and P<0.05, respectively).

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Question 12: Outcomes of severely injured adult trauma patients in an Australian health service: does trauma center level make a difference? Trauma centers are designated to provide systematized multidisciplinary care to injured patients. Effective trauma systems reduce patient mortality by facilitating the treatment of injured patients at appropriately resourced hospitals. Several U.S. studies report reduced mortality among patients admitted directly to a level I trauma center compared with those admitted to hospitals with less resources. It has yet to be shown whether there is an outcome benefit associated with the "level of hospital" initially treating severely injured trauma patients in Australia. This study was designed to determine whether the level of trauma center providing treatment impacts mortality and/or hospital length of stay. Outcomes were evaluated for severely injured trauma patients with an Injury Severity Score (ISS)>15 using NSW Institute of Trauma and Injury Management data from 2002-2007 for our regional health service. To assess the association between trauma centers and binary outcomes, a logistic regression model was used. To assess the association between trauma centers and continuous outcomes, a multivariable linear regression model was used. Sex, age, and ISS were included as covariates in all models. There were 1,986 trauma presentations during the 6-year period. Patients presenting to a level III trauma center had a significantly higher risk of death than those presenting to the level I center, regardless of age, sex, ISS, or prehospital time. Peer review of deaths at the level III center identified problems in care delivery in 15 cases associated with technical errors, delay in decision making, or errors of judgement.

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Question 13: Vaccine protection in the elderly: are Austrian seniors adequately protected by vaccinations? The aim of the study was to evaluate, if elderly persons are sufficiently protected against infectious diseases by vaccination. 300 elderly (>60 years) and 300 young (<35 years) persons from five Austrian cities were recruited according to the criteria of a field study. Antibody concentrations against tetanus, diphtheria, tickborne encephalitis and influenza were assessed by ELISA or by haemagglutination inhibition test. Disease and vaccination histories were recorded. The results of the study demonstrate that protection against infectious diseases was frequently insufficient in the elderly. This was partly due to the fact that old persons were not vaccinated according to recommended strategies. However, low antibody concentration and a short duration of protective humoral immunity were also observed in many elderly persons in spite of regular vaccination. This was not only the case in frail, but also in healthy elderlies.

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Question 14: Is amoxapine an atypical antipsychotic? All currently available atypical antipsychotics have, at clinically relevant doses: i) high serotonin (5-HT)2 occupancy; ii) greater 5-HT2 than dopamine (D)2 occupancy; and iii) a higher incidence of extrapyramidal side effects when their D2 occupancy exceeds 80%. A review of pharmacologic and behavioral data suggested that amoxapine should also conform to this profile; therefore, we undertook a positron-emission tomography (PET) study of its 5-HT2 and D2 occupancy. Seven healthy volunteers received 50-250 mg/day of amoxapine for 5 days and then had [11C]-raclopride and [18F]-setoperone PET scans. 5-HT2 receptors showed near saturation at doses of 100 mg/day and above. The D2 receptor occupancies showed a dose-dependent increase, never exceeding 80%; at all doses 5-HT2 occupancy exceeded D2 occupancy.

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Question 15: Are the arginine vasopressin V1a receptor microsatellites related to hypersexuality in children with a prepubertal and early adolescent bipolar disorder phenotype? To examine family-based transmission of the number of 5' flanking arginine vasopressin V1a receptor (AVPR1A) microsatellites, which include [(GATA)(14)] and complex [(CT)(4)-TT-(CT)(8)-(GT)(24)]repeats, in probands with a prepubertal and early adolescent bipolar disorder phenotype (PEA-BP). Preferential transmission of the number of AVPR1A microsatellite repeats to hypersexual and uninhibited people-seeking probands was hypothesized, based on reports from preclinical work in the literature. Probands were 83 participants in an ongoing controlled study of PEA-BP. The PEA-BP phenotype was defined by DSM-IV mania with at least one of the cardinal symptoms of mania (elation and/or grandiosity) to avoid diagnosing mania only by symptoms that overlapped with those for attention-deficit hyperactivity disorder (ADHD). Comprehensive assessment of the probands included separate Washington University in St. Louis Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) interviews of parents about their children and of children about themselves. Hypersexuality and uninhibited people-seeking were assessed from the corresponding WASH-U-KSADS items. Microsatellite genotyping of the AVPR1A repeats was conducted using fluorescently labeled primers and detected by laser-induced fluorescence. Alleles were determined with the assistance of semi-automated allele-calling software. There were 32 complete, biological trios (28 informative families) for the GATA repeat and 34 complete, biological trios (30 informative families) for the complex repeat. Data were analyzed using case-control and family-based association methods. Preferential transmission of AVPR1A GATA or complex repeats was not significant for hypersexuality or uninhibited people-seeking, using the transmission disequilibrium test. Similarly, case-control analyses found no significant associations between hypersexuality or uninhibited people-seeking and the number of AVPR1A GATA or complex repeats. For p<0.05, there was about 80% power to detect odds ratios of 5.0 and 4.0 (in the family-based analyses) and 3.5 and 2.6 (in the case-control analyses), for allele frequencies of 0.1 and 0.5, respectively.

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Question 16: Is size-reducing ascending aortoplasty with external reinforcement an option in modern aortic surgery? Enlargement of the ascending aorta is often combined with valvular, coronary, or other cardiac diseases. Reduction aortoplasty can be an optional therapy; however, indications regarding the diameter of aorta, the history of dilatation (poststenosis, bicuspid aortic valve), or the intraoperative management (wall excision, reduction suture, external reinforcement) are not established. In a retrospective study between 1997 and 2005, we investigated 531 patients operated for aneurysm or ectasia of the ascending aorta (diameter: 45-76mm). Of these, in 50 patients, size-reducing ascending aortoplasty was performed. External reinforcement with a non-coated dacron prosthesis was added in order to stabilize the aortic wall. Aortoplasty was associated with aortic valve replacement in 47 cases (35 mechanical vs 12 biological), subvalvular myectomy in 29 cases, and CABG in 13 cases. The procedure was performed with low hospital mortality (2%) and a low postoperative morbidity. Computertomographic and echocardiographic diameters were significantly smaller after reduction (55.8+/-9mm down to 40.51+/-6.2mm (CT), p<0.002; 54.1+/-6.7mm preoperatively down to 38.7+/-7.1mm (echocardiography), p<0.002), with stable performance in long-term follow-up (mean follow-up time: 70 months).

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Question 17: Is motion perception deficit in schizophrenia a consequence of eye-tracking abnormality? Studies have shown that schizophrenia patients have motion perception deficit, which was thought to cause eye-tracking abnormality in schizophrenia. However, eye movement closely interacts with motion perception. The known eye-tracking difficulties in schizophrenia patients may interact with their motion perception. Two speed discrimination experiments were conducted in a within-subject design. In experiment 1, the stimulus duration was 150 msec to minimize the chance of eye-tracking occurrence. In experiment 2, the duration was increased to 300 msec, increasing the possibility of eye movement intrusion. Regular eye-tracking performance was evaluated in a third experiment. At 150 msec, speed discrimination thresholds did not differ between schizophrenia patients (n = 38) and control subjects (n = 33). At 300 msec, patients had significantly higher thresholds than control subjects (p = .03). Furthermore, frequencies of eye tracking during the 300 msec stimulus were significantly correlated with speed discrimination in control subjects (p = .01) but not in patients, suggesting that eye-tracking initiation may benefit control subjects but not patients. The frequency of eye tracking during speed discrimination was not significantly related to regular eye-tracking performance.

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Question 18: Is extended aortic replacement in acute type A dissection justifiable? The aim of this study was to evaluate the effectiveness of our surgical strategy for acute aortic dissection based on the extent of the dissection and the site of the entry, with special emphasis on resection of all dissected aortic segments if technically possible. Between January 1995 and March 2001, 43 consecutive patients underwent operations for acute aortic dissection. In all patients the distal repair was performed under circulatory arrest without the use of an aortic cross-clamp. Fifteen patients underwent aortic arch replacement with additional reconstruction of supra-aortic vessels in 3 patients. Complete replacement of all dissected tissue could be achieved in 21 patients (group 1). Because of the distal extent of the dissection beyond the aortic arch, replacement of all the dissected tissue was not possible in 22 patients (group 2). Early mortality was 4.7% (2 patients), and the incidence of perioperative cerebrovascular events was 7.0% (3 patients). All of these events occurred in group 2 (p<0.025). During the follow-up period of 6 years or less, 5 patients died, all from causes not related to the aorta or the aortic valve. A persisting patent false lumen was observed in 14 of the 36 surviving patients (39%).

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Question 19: Screening History Among Women with Invasive Cervical Cancer in an Academic Medical Center: Will We Miss Cancers Following Updated Guidelines? Updated guidelines for the screening and management of cervical cancer in the United States recommend starting Papanicolaou (Pap) testing at age 21 and screening less frequently with less aggressive management for abnormalities. We sought to examine updated Pap test screening guidelines and how they may affect the detection of invasive cervical cancer, especially among women<30 years of age. Patients diagnosed at Brigham and Women's Hospital with invasive cervical cancer between 2002 and 2012 were retrospectively identified. Prior screening history was obtained and patients were divided into two groups based on age<30 years or age ≥30 years. The two groups were then compared with respect to demographics, pathological findings, and time to diagnosis. A total of 288 patients with invasive cervical carcinoma were identified. Among these patients, 109 had adequate information on prior screening history. Invasive adenocarcinoma (IAC) was diagnosed in 37 (33.94%) patients, whereas 64 (58.72%) patients were diagnosed with invasive squamous cell carcinoma (ISCC). The remaining eight patients were diagnosed with other types of cancers of the cervix. A total of 13 patients were younger than 30 while 96 patients were 30 or older. The mean time from normal Pap to diagnosis of IAC was 15 months in patients younger than 30 years of age compared to 56 months in patients aged 30 and older (p < 0.001). The mean time from normal Pap to diagnosis of ISCC was 38 months in patients younger than 30 years of age and 82 months in patients aged 30 and older (p = 0.018).

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Question 20: High cumulative insulin exposure: a risk factor of atherosclerosis in type 1 diabetes? Since insulin therapy might have an atherogenic effect, we studied the relationship between cumulative insulin dose and atherosclerosis in type 1 diabetes. We have focused on patients with type 1 diabetes instead of type 2 diabetes to minimise the effect of insulin resistance as a potential confounder. An observational study was performed in 215 subjects with type 1 diabetes treated with multiple insulin injection therapy. Atherosclerosis was assessed by measurement of carotid intima-media thickness (CIMT). The cumulative dose of regular insulin showed a positive and significant relation with CIMT: increase of 21 microm in CIMT per S.D. of insulin use (95% CI: 8-35 adjusted for gender and age), which remained unchanged after adjustment for duration of diabetes, HbA1c, BMI, pulse pressure, physical activity and carotid lumen diameter. A similar relation was found for intermediate-acting insulin: 15.5 microm per S.D. (2-29), which was no longer present after further adjustment.

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