Minimal clinically important difference in days at home up to 30 days after surgery.

Patient-centred outcomes are increasingly recognised as crucial measures of healthcare quality. Days alive and at home up to 30 days after surgery (DAH30 ) is a validated and readily obtainable patient-centred outcome measure that integrates much of the peri-operative patient journey. However, the minimal difference in DAH30 that is clinically important to patients is unknown. We designed and administered a 28-item survey to evaluate the minimal clinically important difference in DAH30 among adult patients undergoing inpatient surgery. Patients were approached pre-operatively or within 2 days postoperatively. We did not study patients undergoing day surgery or nursing home residents. Patients ranked their opinions on the importance of discharge home using a Likert scale (from 1, not important at all to 6, extremely important) and the minimum number of extra days at home that would be meaningful using this scale. We recruited 104 patients; the survey was administered pre-operatively to 45 patients and postoperatively to 59 patients. The mean (SD) age was 53.5 (16.5) years, and 51 (49%) patients were male. Patients underwent a broad range of surgery of mainly intermediate (55%) to major (33%) severity. The median minimal clinically important difference for DAH30 was 3 days; this was consistent across a broad range of scenarios, including earlier discharge home, complications delaying hospital discharge and the requirement for admission to a rehabilitation unit. Discharge home earlier than anticipated and discharge home rather than to a rehabilitation facility were both rated as important (median score = 5). Empirical data on the minimal clinically important difference for DAH30 may be useful to determine sample size and to guide the non-inferiority margin for future clinical trials.

Defining peri-operative anaemia in pregnant women - challenging the status quo.

Peri-operative anaemia is a significant risk factor for morbidity and mortality. Anaemia during pregnancy is associated with adverse maternal and neonatal outcomes, and postpartum haemorrhage remains a leading cause of maternal mortality worldwide. Caesarean section is an operation incurring moderate risk of bleeding, and rates are rising globally. Recent international consensus guidelines recommend targeting a pre-operative haemoglobin > 130 g.l-1 for all patients having surgery with moderate-to-high risk of bleeding, regardless of sex. It is unclear how this recommendation translates to pregnant women, where anaemia is defined at a much lower haemoglobin level of < 110 g.l-1 . Long-standing definitions of anaemia during pregnancy are likely to be the result of flawed sampling of a so-called 'normal' but anaemic female population, given the high prevalence of iron deficiency and anaemia in healthy menstruating women. Contemporary data suggest that haemoglobin values in iron-replete pregnant women are higher than previously thought. The definition of anaemia has significant clinical implications, particularly for peri-operative management of women undergoing caesarean section. In addition, we should differentiate between lower reference values and optimal haemoglobin targets. The haemoglobin level associated with optimal obstetric and neonatal outcomes requires further investigation in pregnant women.

A pilot study of cardiopulmonary exercise testing and cardiac stress positron emission tomography before major non-cardiac surgery.

Cardiac events are a common cause of peri-operative morbidity. Cardiopulmonary exercise testing can objectively assess risk, but it does not quantify myocardial ischaemia. With appropriate dietary preparation to suppress basal myocardial glucose uptake, positron emission tomography with 18 F-fluorodeoxyglucose can identify post-ischaemic myocardium, providing an attractive complement to exercise testing. We aimed to investigate the feasibility of this diagnostic algorithm. Patients referred for cardiopulmonary exercise testing before major cancer surgery were prospectively recruited. Exercise testing and positron emission tomography imaging were performed after a high fat-low carbohydrate meal. Protocol feasibility (primary end-point) included compliance with pre-test diet instructions and the completion of tests. Stress myocardial perfusion imaging was performed if either exercise testing or positron emission tomography was equivocal or positive for ischaemia. We recorded cardiac complications for 30 postoperative days. We enrolled 26 participants, 20 of whom completed protocol. Twenty-one participants proceeded to surgery: myocardial injury or infarction was diagnosed in three participants, two of whom had positive or equivocal positron emission tomography but negative myocardial perfusion imaging. We have shown that pre-operative cardiac positron emission tomography after cardiopulmonary exercise testing is feasible; protocol deviations were minor and did not affect image quality. Our findings warrant further investigation to compare the diagnostic utility of cardiac positron emission tomography imaging with standard pre-operative stress tests.

Isoform-specific effects of apolipoprotein E on cognitive performance in targeted-replacement mice overexpressing human APP.

The epsilon 4 allele of apolipoprotein E (apoE4) is the predominant genetic risk factor for late-onset Alzheimer's disease (AD) and is also implicated in cognitive deficits associated with normal aging. The biological mechanisms by which APOE genotype affects cognitive processes or AD pathogenesis remain unclear, but interactions of apoE with amyloid beta peptide (A beta) are thought to play an important role in mediating apoE's isoform-specific effects on brain function. Here, we investigated the potential isoform-dependent effects of apoE on behavioral and cognitive performance in human apoE3 and apoE4 targeted-replacement (TR) mice that also overexpress the human amyloid precursor protein (APP). Beginning at 6-7 months of age, female APP-Yac/apoE3-TR ('poE3') and APP-Yac/apoE4-TR ('poE4') mice were tested on a battery of tests to evaluate basic sensorimotor functioning, spatial working memory, spatial recognition, episodic-like memory and attentional processing. Compared with apoE3 mice, a generalized reduction in locomotor activity was observed in apoE4 mice. Moderate, but significant, cognitive impairments were also detected in apoE4 mice in the novel object-location preference task, the contextual fear conditioning test, and a two-choice visual discrimination/detection test, however spontaneous alternation performance in the Y-maze was spared. These results offer additional support for the negative impact of apoE4 on both memory and attention and further suggest that APP-Yac/apoE-TR mice provide a novel and useful model for investigating the role of apoE in mediating susceptibility to cognitive decline.

The utility of anoscopy and colposcopy in the evaluation of male sexual assault victims.

STUDY OBJECTIVE: We sought to compare the use of anoscopy and colposcopy in examinations of male sexual assault victims and to characterize the demographics of male sexual assault victims. METHODS: This is a case series of 67 male sexual assault victims evaluated over an 8-year period by the Sexual Assault Forensic Examination team. The setting is a university-based emergency department serving as the primary site for examination of sexual assault victims by trained nurse practitioners and physician's assistants. Police and victims' advocates are available at the time of the examination. Anoscopy was done routinely over the entire study period in all patients with any anal penetration or involvement. Colposcopy use started in 1994 to magnify and take pictures. Patients were categorized into 2 groups. Group 1 consisted of subjects receiving only anoscopy, and group 2 consisted of subjects receiving initial colposcopy. Anoscopy in group 1 and colposcopy in group 2 were compared for positive results. A positive result was defined as an additional finding to those obtained by means of gross examination by using the test being evaluated (anoscopy versus colposcopy). Colposcopy and anoscopy were also compared among the subjects receiving both tests. Groups were compared by using a Pearson chi(2) test. RESULTS: Sixty-seven male sexual assault victims were evaluated between 1991 and 1998. The average age was 26+/-8 years, and the distribution of races was 30% black, 62% white, and 8% Hispanic. Results of gross examination were positive in 42 (63%) subjects. Four patients did not receive either anoscopy or colposcopy. Of the remaining 63, 25 patients had anoscopy only (group 1), and 38 patients had initial colposcopy (group 2). There were no significant differences in age, race, or rate of positive gross examination results between groups. Findings in addition to those obtained by means of gross examination were revealed by means of anoscopy in 8 (32%) of 25 subjects in group 1 and colposcopy in 3 (8%) of 38 subjects in group 2 (P =.03, difference 24%, 95% confidence interval 4% to 44%). In the 36 subjects who had both examinations, the gross examination revealed at least one finding in 22 (61%). The combination of anoscopy and colposcopy yielded positive findings in 17 subjects, including 4 subjects who had no findings on gross examination (increasing the positive rate to 26/36 [72%]). CONCLUSION: In male sexual assault victims with anal penetration, anoscopy is significantly better for gathering evidence than is colposcopy. The addition of colposcopy and anoscopy increased the rate of cases with positive findings from 61% to 72%. These 2 methods together may be a valuable adjunct in gathering evidence of damage.

Cervicomedullary compression: an unrecognized cause of vocal cord paralysis in rheumatoid arthritis.

Cervicomedullary compression (CMC) from traumatic, infectious, or congenital processes of the atlanto-axial joint is a known cause of vocal cord immobility. Cervicomedullary compression can also occur from destructive arthritic changes and inflammatory pannus formation at the occipito-atlanto-axial joint in patients with rheumatoid arthritis (RA). We present findings suggesting that CMC in patients with RA is an unrecognized cause of vocal cord immobility. Previously, vocal cord immobility in patients with RA has been assumed to be cricoarytenoid arthritis with joint fixation. We report 3 patients with RA and radiographically demonstrated CMC with vocal cord immobility. One patient had bilateral vocal cord immobility and airway obstruction; 2 patients had unilateral cord paralysis and contralateral paresis without airway compromise. All patients had myelopathy and neck pain in addition to brain stem symptoms. All patients underwent transoral-transpharyngeal decompression of the anterior craniocervical junction with subsequent posterior fusion. These patients demonstrated full return of vocal cord function within 3 months of decompression. We propose that CMC is a cause of vocal cord paralysis in patients with RA that may go unrecognized without appropriate imaging studies of the skull base and physician awareness of symptoms of occipito-atlanto-axial subluxation and/or basilar invagination with brain stem compression. Our results demonstrate that CMC in RA is a potentially reversible cause of vocal cord paralysis.

Verrucous carcinoma of the larynx.

Verrucous carcinoma is a well-differentiated squamous cell carcinoma with minimal cytologic atypia. Characteristically, the surface shows papillary fronds with prominent hyperkeratosis. Its benign appearance makes diagnosis difficult and often delays treatment. This is a review of 52 histologically confirmed cases of verrucous carcinoma of the larynx treated at the Mayo Clinic between 1960 and 1987. The follow-up ranged from 2 to 304 months. The most common primary treatment modality was surgery. Two patients died of laryngeal cancer. In both cases, the recurrence was a high-grade carcinoma histologically distinct from the original verrucous carcinoma. The T stage, clinical stage, and type of surgical excision failed to predict survival. The presence of extensive leukoplakia surrounding the exophytic tumor approached statistical significance (p = .08) in predicting recurrence. Four patients were treated with radiotherapy--in each, to control residual disease. One of these patients developed a local recurrence. None of the irradiated tumors in this series showed anaplastic dedifferentiation, and none of the irradiated patients died of uncontrolled local or regional disease. We conclude that verrucous carcinoma of the larynx should be treated by conservative surgical resection when possible. Radiotherapy can be effectively used for disease that cannot be resected with preservation of laryngeal function. Total laryngectomy should be reserved for recurrent disease or the rare case of anaplastic transformation.