Changing prevalence and treatment outcomes of patients with p16 human papillomavirus related oropharyngeal squamous cell carcinoma in New Zealand.

There has, to our knowledge, been no previous report of changes in the prevalence and outcomes of treatment of HPV-positive (+) oropharyngeal squamous cell carcinoma (SCC) in New Zealand. We identified all affected patients in the greater Wellington region between 1 January 1994 and 30 November 2014 from the New Zealand Cancer Registry. Their personal details, characteristics of their tumours, treatment, complications, and outcomes were collected retrospectively from their casenotes and the New Zealand Death Registry, followed by p16 immunohistochemical staining. Of the 161 patients included, 131 (81%) were men. p16 immunohistochemical staining was done routinely in 13 patients during investigations, and retrospectively for 135 patients. The proportion of p16+ oropharyngeal SCC increased from 24% during 1994-1999, to 76% during 2009-2014 (p<0.001). Oropharyngeal SCC among Europeans was more likely to be p16+ than in non-Europeans (67% compared with 44%, p=0.036). Patients with p16+ disease were younger (mean (SD) 56 (10) compared with 66 (9) years, p<0.01) with fewer coexisting conditions (mean (SD) Charlson Comorbidity Index: 2.45 (0.82) compared with 2.92 (1.16), p=0.01), and less likely to have smoked (57/81(70%) compared with 38/42 (91%) p=0.035), or misused alcohol (12/81 (15%) compared with 14/42 (31%), p=0.042), or both. They were also more likely to have poorly differentiated tumours (30/52 (58%) compared with 9/34 (26%), p=0.019) with nodal metastases (74/85 (87%) compared with 17/30 (57%), p=0.001). Overall 5-year all-cause survival was more favourable for patients with p16+ disease (65/86 (76%) compared with 15/49 (31%), p=0.000). Interestingly, all-cause age at death was younger in p16+ patients (62 (11.1) compared with 71 (11.2) years, p=0.001). The prevalence of p16+ oropharyngeal SCC had tripled in this population between 1994 and 2014, and affected patients have distinct characteristics and outcomes of treatment.

Psychiatric considerations in military aerospace medicine.

Military aerospace medicine requires a psychiatric selection and certification process that determines not only the absence of significant mental disorders, but also the presence of positive qualities in the realms of motivation, ability and stability: not all normal people are fit to fly. Other issues of aerospace psychiatry involve maintenance of mental resilience and hardiness during a flying career, aeromedical decisions about when to remove from flight duties and when to return, criteria for waivers for psychiatric conditions, use of medications for treatment of psychiatric symptoms, questions of substance abuse, and research in such areas as genetics. This report reviews the basis for military aerospace psychiatry, primarily as practiced in the United States Air Force (USAF), and presents some of its underlying principles as they apply to clinical situations.

Aeromedical management of U.S. air force aviators who attempt suicide.

BACKGROUND: Little has been published about the aeromedical management and disposition of aviators who attempt suicide, and almost no such information about military aviators exists in the open literature. The few available data are scattered and frequently anecdotal. METHODS: The authors reviewed all case reports of fliers evaluated at the USAF School of Aerospace Medicine's Aeromedical Consultation Service (ACS) between 1981-96 for possible return to flying duties after a suicide attempt, and prepared a representative case report. RESULTS: Between 1981 and 1996, the ACS evaluated 14 trained aviators (pilots and other aircrew members, excluding flight surgeons) who had attempted suicide. Of these, 11 (79%) ultimately received a recommendation for return to flying duties. CONCLUSIONS: In most instances the underlying stressors included failed intimate interpersonal relationships, administrative or legal problems, psychiatric disorders, death of spouse, or job conflicts. Evidence of abuse of alcoholor other substances was found in 54% of an earlier, larger data set of attempters. Some data on aircrew suicide completion were available and are reported. The top medical priorities after such attempts should be to diagnose what is wrong, and to treat it. In spite of the common assumption that a suicide attempt inevitably ends a military flying career, some attempters can return to safe and effective flying duty after appropriate psychotherapy. If the flier regains physical and mental health and maintains them for at least 6 mo after treatment, then that flier may be evaluated by an outside aeromedical psychiatric consultant such as the ACS (to avoid transference issues between flier and therapist) for possible return to flying duties. Waiver action should be based on the underlying psychiatric diagnosis, not the suicidal attempt itself. Follow-up may be accomplished through periodic mental health evaluations in conjunction with routine physical examination procedures. Issues involving substance abuse and security clearances must be handled through the appropriate channels.

Recent advances in the treatment and outcome of locally advanced rectal cancer.

OBJECTIVE: To compare the outcomes of treatment of locally advanced rectal cancer of the early era (1975-1990) with those of the late era (1991-1997). BACKGROUND: Preoperative therapy has been used in locally advanced rectal cancer to preserve sphincter function, decrease local recurrence, and improve survival. At the University of Florida, preoperative radiation has been used since 1975, and it was combined with chemotherapy beginning in 1991. METHODS: The records of 328 patients who underwent preoperative radiation or chemoradiation followed by complete resection for locally advanced rectal cancer defined as tethered, annular, or fixed tumors were reviewed. The clinicopathologic characteristics, adjuvant treatment administered, surgical procedures performed, and local recurrence-free and overall survival rates were analyzed. RESULTS: There were 219 patients in the early era and 109 in the late era. No significant differences were seen in patients (age, gender, race) or tumor characteristics (mean distance from the anal verge, annularity, fixation). Preoperative radiation regimens were radiobiologically comparable. No patient in the early era received preoperative chemotherapy, compared with 64 in the late era. Of those receiving any pre- or postoperative chemotherapy, three patients received chemotherapy in the early era, compared with 76 in the late era. Sphincter-preserving procedures increased from 13% in the early era to 52% in the late era. Pathologic downstaging for depth of invasion increased from 42% to 58%, but lymph node negativity remained similar. The 1-, 3-, and 5-year local recurrence-free survival rates were comparable. However, in the late era, 1-, 3-, and 5-year overall survival rates improved significantly compared with those of the early era, and also compared with each of the preceding 5-year intervals. CONCLUSION: The addition of a chemotherapy regimen to preoperative radiation therapy improves survival over radiation therapy alone. Likewise, an improvement in downstaging is associated with an increase in sphincter-preserving procedures.

Economic analysis of a randomized placebo-controlled phase III study of granulocyte macrophage colony stimulating factor in adult patients (> 55 to 70 years of age) with acute myelogenous leukemia. Eastern Cooperative Oncology Group (E1490).

PURPOSE: Considerable morbidity and mortality and costs occur during induction therapy for acute myeloid leukemia (AML). Colony-stimulating factors (CSFs) can shorten neutropenia, and may lower costs. We performed a cost-minimization analysis of granulocyte macrophage colony stimulating factor (GM-CSF) for AML patients > 55 to 70 years of age during an Eastern Cooperative Oncology Group Study. PATIENTS AND METHODS: Clinical data were from a randomized double-blind phase III trial of 117 AML patients. Estimates of costs were from financial accounts from seven participating institutions. Costs were reported from the third party payor perspective. Analyses were conducted utilizing a decision analytic model. The primary source of event probabilities was in-hospital care with or without an active infection. Sensitivity analyses were also reported. RESULTS: When compared to AML patients who received placebo. GM-CSF patients had fewer grade 4-5 infections (9.6% versus 36.2%, P = 0.002) and grade 3-5 infections (52% versus 70%. P = 0.07) and $2.310 in savings. Sensitivity analyses indicated that similar cost estimates applied over a range of clinical and economic assumptions. CONCLUSIONS: This analysis can serve as a template for cooperative group cost analyses. Cooperation on study methodologies may allow for results that are relevant to both clinicians and policy makers.

Revised NEO Personality Inventory profiles of male and female U.S. Air Force pilots.

The study of pilot personality characteristics has a long and controversial history. Personality characteristics seem to be fairly poor predictors of training outcome; however, valid personality assessment is essential to clinical psychological evaluations. Therefore, the personality characteristics of pilots must be studied to ensure valid clinical assessment. This paper describes normative personality characteristics of U.S. Air Force pilots based on the Revised NEO Personality Inventory profiles of 1,301 U.S. Air Force student pilots. Compared with male adult norms, male student pilots had higher levels of extraversion and lower levels of agreeableness. Compared with female adult norms, female student pilots had higher levels of extraversion and openness and lower levels of agreeableness. Descriptive statistics and percentile tables for the five domain scores and 30 facet scores are provided for clinical use, and a case vignette is provided as an example of the clinical utility of these U.S. Air Force norms.

A phase II trial of paclitaxel in the treatment of recurrent or metastatic soft tissue sarcomas or bone sarcomas.

The study aimed to determine the activity and toxicity of taxol in the treatment of recurrent or metastatic soft tissue sarcomas or osteosarcomas. The major findings are that five patients had stable disease after two cycles of chemotherapy but two of these patients were subsequently removed from the study at their own request. The other three patients progressed after an additional two cycles of chemotherapy. Seven patients progressed during the first two cycles and were removed from the study. One patient completed only one cycle of therapy and was deemed inevaluable for study response. There were eight episodes of grade 3 or 4 neutropenia and two episodes of grade 3 thrombocytopenia. One patient experienced grade 3 neurological toxicity and one patient grade 3 mucositis. Two patients are currently alive with progressing disease and one patient is alive with no evidence of disease after undergoing surgery and radiotherapy. The principal conclusions are that Paclitaxel is ineffective in treating recurrent or metastatic soft tissue sarcoma and osteosarcoma. Treatment at this dose is quite myelosuppressive, but toxicity is generally manageable. Further study of this agent is not justified in this setting.

Treatment of invasive squamous cell carcinoma complicating anal Buschke-Löwenstein tumor: a case history.

We present here the case of a patient with Buschke-Löwenstein tumor of the anus complicated by invasive squamous cell carcinoma metastatic to the inguinal and periaortic pelvic lymph nodes. Successful local palliation was achieved with 5-fluorouracil and mitomycin-C-based chemotherapy combined with radiation therapy, but systemic progression was unaffected.

Circadian rhythm modulated 5-FUdR infusion with Megace in the treatment of advanced pancreatic cancer.

Thirteen patients with advanced pancreatic carcinoma were treated with circadian rhythm modulated infusion of 5-FUdR and Megace. Treatment was initiated at a dose of 0.15 mg/kg/day for 14 days every 28 days and was increased or decreased by 0.025 mg/kg/day with each subsequent cycle until maximum tolerated dose (MTD) was achieved. Megace (200 mg) was administered daily in divided doses. One-third of the patients were able to complete > or = 6 cycles of treatment, one-half could only complete < or = 2 cycles, and the remainder managed 3-4 cycles. No patients had regression of disease, but a small number, who were able to receive 6-7 months of treatment, achieved stable disease in the short term. In conclusion, treatment was fairly well tolerated. However, increased dose intensity by this method did not significantly increase response rate. In only a few patients was disease stabilized for a brief period. Megace did not materially improve nutritional status. CA-19-9 levels did not correlate well with disease activity.

The prevalence of mental handicap in New Zealand.

The administrative prevalence of mental handicap at the age of 10 years was ascertained for a group of children born 1973 and 1974. There was a birth cohort prevalence of 4.35 per 1000 live births.

Vascularized skull bone grafts in craniofacial surgery.

Vascularized skull bone grafts based on a pedicle of temporalis muscle have been used in 30 zygomatic arch and malar reconstructions, 1 mandible reconstruction, and 1 palate reconstruction. The surgical technique, complications, and postoperative results are reviewed. Technetium bone scans obtained within one week of operation confirm blood supply to the transferred bone. After a mean follow-up of 13 months, there is no evidence of bone graft resorption. We have used a team approach and careful surgical technique, and no serious complications have been encountered.

Effects of clonidine on cerebral blood flow and the response to arterial CO2.

CBF, as measured by the clearance of 133Xe or 85Kr in the pentobarbital-anesthetized cat, displays a monotonic increase as the PaCO2 is elevated over a range of 20-60 mm Hg (slope Xe, 1.65 +/- 0.14 ml/100g/min/mm Hg; slope Kr, 1.40 +/- 0.11 ml/100 g/min/mm Hg). Clonidine (20 micrograms/kg i.v.), a centrally acting, alpha 2-preferring agonist, reduced the slope of the PaCO2-CBF response functions for Xe and Kr by 70 and 64%, respectively. Clonidine reduced normocarbic CBF-Xe by 36%, but had no effect on normocarbic CBF-Kr. ST-91, a polar structural analog of clonidine that does not cross the blood-brain barrier, did not reproduce the effects of clonidine when administered at an equivalent dose. This indicates that the effects of clonidine observed were secondary to its action on central rather than peripheral sites. In addition to the effects on the clearance of CBF markers, clonidine reduced the increased MABP otherwise evoked by elevated PaCO2. Reduction in the MABP response to PaCO2 did not account for the lowering of CBF during hypercarbia. In separate experiments where MABP was elevated to correspond with the PaCO2-MABP response observed in the absence of clonidine, a comparable reduction in the slope of the PaCO2 response was also observed. In addition, the pressure autoregulatory response was unaltered after clonidine treatment. These observations suggest that the central action of alpha 2-receptors on the CBF-CO2 response cannot be attributed to an altered perfusion pressure.

Self-control of psychophysiologic response to motion stress: using biofeedback to treat airsickness.

Investigators of the Neuropsychiatry Branch, Clinical Sciences Division, U.S. Air Force School of Aerospace Medicine (USAFSAM), provided biofeedback-moderated behavioral treatment to 53 fliers grounded for chronic, severe motion sickness, and followed each flier for 2 years after treatment completion. Success was defined as returning to and maintaining satisfactory operational flying status. Of these, 42 fliers (79%) met this criterion; 3 (6%) were partially successful, and 8 (15%) were subsequently grounded for recurrent airsickness. Follow-on studies will investigate psychophysiological mechanisms through which this method of treatment works.

Electromyographic feedback treatment of hemiplegia.

Electromyographic treatment of four elderly hemiplegics was undertaken. Results showed an improvement on what had been obtained by standard physiotherapy. The degree of communication possible seems to be a critical factor in the result.

The significance for intelligence of differences in birth weight and health within monozygotic twin pairs.

This paper presents further evidence to demonstrate the existence of intra-uterine effects within the normal range of intelligence. The argument is then extended further to estimate the effects of organic factors in the environment that are also pathogenic for intelligence. The combination of these and intra-uterine effects is found to be a substantial part of the variance associated with environmental factors. Various implications of these factors are discussed.

The effects of de-caffeinated coffee versus whole coffee on hyperactive children.

The effects of whole coffee and de-caffeinated coffee on hyperactive children were compared, using a double-blind crossover design. Reactions were assessed by tests of concentration, digit recall, visuo-motor co-ordination, and parents' and teachers' rating scales. Whole coffee was associated with a significant improvement on all measures when compared with de-caffeinated coffee. The results suggest that whole coffee as part of the normal diet may be a useful first step in the treatment of hyperactive children.