Development and internal validation of a model for postoperative morbidity in adults undergoing major elective colorectal surgery: the peri-operative quality improvement programme (PQIP) colorectal risk model.

Over 1.5 million major surgical procedures take place in the UK NHS each year and approximately 25% of patients develop at least one complication. The most widely used risk-adjustment model for postoperative morbidity in the UK is the physiological and operative severity score for the enumeration of mortality and morbidity. However, this model was derived more than 30 years ago and now overestimates the risk of morbidity. In addition, contemporary definitions of some model predictors are markedly different compared with when the tool was developed. A second model used in clinical practice is the American College of Surgeons National Surgical Quality Improvement Programme risk model; this provides a risk estimate for a range of postoperative complications. This model, widely used in North America, is not open source and therefore cannot be applied to patient populations in other settings. Data from a prospective multicentre clinical dataset of 118 NHS hospitals (the peri-operative quality improvement programme) were used to develop a bespoke risk-adjustment model for postoperative morbidity. Patients aged ≥ 18 years who underwent colorectal surgery were eligible for inclusion. Postoperative morbidity was defined using the postoperative morbidity survey at postoperative day 7. Thirty-one candidate variables were considered for inclusion in the model. Death or morbidity occurred by postoperative day 7 in 3098 out of 11,646 patients (26.6%). Twelve variables were incorporated into the final model, including (among others): Rockwood clinical frailty scale; body mass index; and index of multiple deprivation quintile. The C-statistic was 0.672 (95%CI 0.660-0.684), with a bootstrap optimism corrected C-statistic of 0.666 at internal validation. The model demonstrated good calibration across the range of morbidity estimates with a mean slope gradient of predicted risk of 0.959 (95%CI 0.894-1.024) with an index-corrected intercept of -0.038 (95%CI -0.112-0.036) at internal validation. Our model provides parsimonious case-mix adjustment to quantify risk of morbidity on postoperative day 7 for a UK population of patients undergoing major colorectal surgery. Despite the C-statistic of < 0.7, our model outperformed existing risk-models in widespread use. We therefore recommend application in case-mix adjustment, where incorporation into a continuous monitoring tool such as the variable life adjusted display or exponentially-weighted moving average-chart could support high-level monitoring and quality improvement of risk-adjusted outcome at the population level.

Transmission of two Australian strains of murine cytomegalovirus (MCMV) in enclosure populations of house mice (Mus domesticus).

To control plagues of free-living mice (Mus domesticus) in Australia, a recombinant murine cytomegalovirus (MCMV) expressing fertility proteins is being developed as an immunocontraceptive agent. Real-time quantitative PCR was used to monitor the transmission of two genetically variable field strains of MCMV through mouse populations after 25% of founding mice were infected with the N1 strain, followed by the G4 strain 6 weeks later. Pathogen-free wild-derived mice were released into outdoor enclosures located in northwestern Victoria (Australia). Of those mice not originally inoculated with virus, N1 DNA was detected in more than 80% of founder mice and a third of their offspring and similarly, G4 DNA was detected in 13% of founder mice and in 3% of their offspring. Thus, prior immunity to N1 did not prevent transmission of G4. This result is promising for successful transmission of an immunocontraceptive vaccine through Australian mouse populations where MCMV infection is endemic.

Ecological basis for fertility control in the house mouse (Mus domesticus) using immunocontraceptive vaccines.

Laboratory studies confirm the potential for fertility control in the house mouse Mus domesticus using mouse cytomegalovirus (MCMV) as a vector for an immunocontraceptive vaccine. This article presents an overview of key results from research in Australia on enclosed and field populations of mice and the associated epidemiology of MCMV. The virus is geographically widespread in Australia. It also persists in low population densities of mice, although if population densities are low for at least a year, transmission of the virus is sporadic until a population threshold of approximately 40 mice ha(-1) is reached. The serological prevalence of MCMV was high early in the breeding season of four field populations. Enclosure studies confirm that MCMV has minimal impact on the survival and breeding performance of mice and that it can be transmitted to most adults within 10-12 weeks. Other enclosure studies indicate that about two-thirds of females would need to be sterilized to provide effective control of the rate of growth of mouse populations. If this level is not maintained for 20-25 weeks after the commencement of breeding, the mouse population can compensate through increased recruitment per breeding female. The findings from this series of descriptive and manipulative population studies of mice support the contention that MCMV would be a good carrier for an immunocontraceptive vaccine required to sustain female sterility levels at or above 65%.

Treatment of paragangliomas with radiation therapy.

Paragangliomas of the head and neck may be treated successfully with surgery, radiation therapy, or stereotactic radiosurgery. The choice of treatment depends on the location and extent of the tumor, the presence of multiple tumors, the age and health of the patient, and the preference of the patient and attending physician. This article reviews the role of radiation therapy in the treatment of patients with paragangliomas of the head and neck.

Reproductive changes in fluctuating house mouse populations in southeastern Australia.

House mice (Mus domesticus) in the Victorian mallee region of southeastern Australia show irregular outbreaks. Changes in reproductive output that could potentially drive changes in mouse numbers were assessed from 1982 to 2000. Litter size in females is positively correlated with body size. When standardized to an average size female, litter size changes seasonally from highest in spring to lowest in autumn and winter. Litter size is depressed throughout breeding seasons that begin when the abundance of mice is high, but is similar in breeding seasons over which the abundance of mice increases rapidly or remains low. Breeding begins early and is extended on average by about five weeks during seasons when mouse abundance increases rapidly. The size at which females begin to reproduce is larger during breeding seasons that begin when mouse abundance is high. An extended breeding season that begins early in spring is necessary for the generation of a house mouse plague, but it is not in itself sufficient. Reproductive changes in outbreaks of house mice in Australia are similar but not identical to reproductive changes that accompany rodent population increases in the Northern Hemisphere. We conclude that food quality, particularly protein, is a probable mechanism driving these reproductive changes, but experimental evidence for field populations is conflicting.

The prevalence of viral antibodies during a large population fluctuation of house mice in Australia.

We studied the seroprevalence of three viruses (mouse cytomegalovirus (MCMV), minute virus of mice (MVM), and mouse parvovirus (MPV)) in house mice (Mus domesticus) in 1995 7. In the first year average mouse density was less than 1 mouse/ha. From November 1995 to May 1996 the population increased at an average rate of 7% per week, a doubling time of about 10 weeks. From August 1996 to May 1997 the population increased at an average rate of 10% per week, a doubling time of about 7.5 weeks. From a peak around 250 mice/ha in May 1997, the mouse population fell 19% per week to 5 mice/ha in October 1997. The seroprevalence for all three viruses varied dramatically over time. MCMV had the highest seroprevalence (61.7%), followed by MVM (8.5%) and MPV (18.4%). Time series data indicated that MCMV spread rapidly through the population of mice once trap success was greater than 14% (40-100 mice/ha). By contrast MVM and MPV seroprevalence occurred with a 2-3 month and 3-4 month time lag, respectively. The current study supports the contention that MCMV would be a good carrier for an immunocontraceptive vaccine for controlling field populations of mice.

The Cryptosporidium "mouse" genotype is conserved across geographic areas.

A 298-bp region of the Cryptosporidium parvum 18S rRNA gene and a 390-bp region of the acetyl coenzyme A synthetase gene were sequenced for a range of Cryptosporidium isolates from wild house mice (Mus domesticus), a bat (Myotus adversus), and cattle from different geographical areas. Previous research has identified a distinct genotype, referred to as the "mouse"-derived Cryptosporidium genotype, common to isolates from Australian mice. Comparison of a wider range of Australian mouse isolates with United Kingdom and Spanish isolates from mice and cattle and also an Australian bat-derived Cryptosporidium isolate revealed that the "mouse" genotype is conserved across geographic areas. Mice are also susceptible to infection with the "cattle" Cryptosporidium genotype, which has important implications for their role as reservoirs of infection for humans and domestic animals.

Canalplasty for chronic tympanic membrane atelectasis.

PURPOSE: Canalplasty to prevent accumulation of squamous debris has been proposed as an alternative to tympanoplasty for the treatment of tympanic membrane atelectasis and early cholesteatoma. The goal of this article is to report our experience with canalplasty for the treatment of advanced middle ear atelectasis. MATERIALS AND METHODS: A retrospective review was performed on all patients that underwent tympanoplasty or canalplasty at the University of Florida since 1992. Eight ears (seven patients) with severe atelectasis were found to have been treated with canalplasty (without middle ear reconstruction) to marsupialize the retraction pockets. RESULTS: Follow-up was conducted at an average of 22 months. Four ears required repeat surgical intervention after an average of 12 months: three required canal wall down mastoidectomies for cholesteatoma, and a tympanoplasty was necessary in one case for persistent perforation. Four ears not requiring revision were without cholesteatoma or perforation at an average follow-up time of 26 months. Mean audiometric thresholds were stable or improved, irrespective of the need for revision surgery. CONCLUSIONS: Canalplasty may be an alternative for the treatment of atelectasis in selected patients; however, close follow-up after surgery is necessary because of the potential for progression to cholesteatoma.

Intratympanic gentamicin treatment for Meniere's disease.

OBJECTIVES: The purpose of this study was to evaluate the safety and efficacy of a modified intratympanic gentamicin technique in patients with intractable unilateral or bilateral Meniere's disease. METHODS: A retrospective review of 25 consecutive patients who underwent gentamicin treatment for Meniere's disease was conducted between 1992 and 1996. Two separate delivery systems were used during this study, with the last 13 subjects undergoing placement of the new system (flanged polyethylene tubing). RESULTS: Follow-up averaged 23 months. Absence of vertigo spells was reported in 88%, and substantial control was achieved in 12%. Four of five patients with bilateral disease achieved complete control. Results for the two delivery systems were not significantly different. Absence of ice-water caloric response was seen in 75% (15 of 20) patients. Clinically significant sensorineural hearing loss occurred in 5 (20%) of 25 ears. Nonserviceable hearing developed in only two (8%) patients. CONCLUSIONS: Our results support the previously reported efficacy and relative safety of gentamicin infusion therapy for intractable Meniere's disease. Polyethylene tubing may be more advantageous than T-tube delivery because of anatomic concerns in certain patients.

Bioglass middle ear prosthesis: long-term results.

The purpose of this study was to review the University of Florida's long-term results with Bioglass middle ear prostheses. Between April 1984 and November 1987, 37 patients were implanted with Bioglass prostheses (25 total and 12 partial ossicular replacements). Twenty-one patients had postoperative data of at least 24 months (range, 24 to 126 months; mean, 86 months; median, 100 months), and five patients had > 10 years' follow-up. In three cases, portions of fractured prostheses extruded, leaving an intact tympanic membrane. One patient with a total ossicular prosthesis was reexplored at 38 months for conductive hearing loss and found to have a prosthesis fracture (n = 1). There were no extrusions of intact prostheses, even in patients in whom the prosthesis was placed directly under the tympanic membrane or graft (n = 12). After 24 months, the mean pure-tone average air-bone gap was 24 dB (24% had ABG < or = 10 dB; 53% had ABG < or = 20 dB). Air-bone gap closures were stable over time. Our results demonstrated that Bioglass middle ear prostheses have excellent long-term tissue compatibility. The four failures are attributed to fractures in early experimental prototypes.

A manipulative field experiment to examine the effect of Capillaria hepatica (Nematoda) on wild mouse populations in southern Australia.

A 12-month manipulative field study of the effect of a liver parasite, Capillaria hepatica, on mouse populations (Mus domesticus) was conducted in the Mallee wheatlands of northwestern Victoria. There were 2 untreated and 4 treated sites each consisting of a 16 km2 sampling zone. The parasite was released in September (spring) 1993 into an increasing mouse population which had a medium density (100-250 mice per ha). A third untreated site was monitored from January 1994. A simple but effective baiting method was developed and with the assistance of local farmers about 40,000 mice were dosed on the 4 sites; an estimated 5-7% of the population. During a second release, a month later, a further 20,000 mice were infected, boosting the level of infection to around 10%. Two months after the release approximately 30% of the population was infected. Thereafter, although there was effective transmission of the parasite, this was associated with a significant reduction in prevalence with time. The parasite reduced host survival by 5-10%, although this difference was not statistically significant, and had a minimal effect on the breeding and the rate of growth of mouse populations. Densities of 500-800 mice per ha were attained at each site in autumn 1994. Thus a spring release of the parasite into a rapidly increasing mouse population in the Victorian Mallee wheatlands did not prevent the population from increasing. The occurrence of very dry conditions following its release and the low but sustained transmission of the parasite indicate that we need to know more about factors that influence the survival and transmission of the parasite under field conditions.

A survey of the reasons for culling pregnant cows.

This survey analysed the history of cows which were pregnant when they were slaughtered at an abattoir in south west England by sending a questionnaire to their farm of origin to determine the reason(s) for culling them and their recent reproductive history. Of the slaughtered cows, 23.5 per cent were pregnant and 26.9 per cent of these were in the third trimester. The three main reasons for culling were infertility (28.2 per cent), mastitis (21.8 per cent) and old age (15.8 per cent). In 50.9 per cent of cases the farmer thought that the cow was not pregnant. In 66 per cent of the returns the cow had run with a bull. The average age of the slaughtered cows was 7.9 years. The records were categorised as 'OK' when they were consistent with the stage of pregnancy found post mortem, as 'error' when there were slight inconsistencies and 'gross error' when there were more serious discrepancies. Thirty-six per cent of the returns were classed as 'OK', 56.6 per cent as 'error' and 27.2 per cent as 'gross error'. It is estimated that these errors represent an annual loss of 30.78 million pounds to the cattle industry of the United Kingdom.

Adjuvant drug strategies in the treatment of recurrent respiratory papillomatosis.

The purpose of this study was to evaluate adjuvant drug therapies combined with standard laser excision in the treatment of recurrent respiratory papillomatosis. Previous studies have presented conflicting data on the efficacy of various treatments, including interferon and isotretinoin. A retrospective study of 34 patients with moderate to severe papillomatosis who underwent both laser surgery and adjuvant therapy was therefore performed. All patients were treated with interferon. Five interferon failures received isotretinoin, and three with recalcitrant disease received methotrexate. Interferon produced a complete response in 16 patients and partial response in 12 patients. Juvenile-onset disease had a slightly higher response to interferon than adult-onset disease. isotretinoin produced no response in all five patients. Methotrexate demonstrated a marked improvement in both severity of disease and treatment interval in all three patients. Serious side effects were limited to one interferon patient with febrile seizures, which resolved with discontinuation of therapy. We conclude that adjuvant therapy including interferon and methotrexate is clearly of benefit in the treatment of patients with respiratory papillomatosis. A detailed approach to surgery combined with an interferon dosing regimen is presented. Further study of methotrexate appears warranted.

Radiotherapy in the management of temporal bone chemodectoma.

Forty patients with 42 temporal bone chemodectomas were treated with radiotherapy alone (37 tumors) or subtotal resection and irradiation (5 tumors) at the University of Florida between 1968 and 1992. Thirty-three lesions were previously untreated, whereas 9 had undergone prior treatment (surgery, 6 lesions; radiotherapy, 1 lesion; or both, 2 lesions) and were treated for locally recurrent disease. All 3 patients who received prior radiotherapy had been treated at other institutions. Patients had minimum follow-up times as follows: 2 years, 40 patients (100%); 5 years, 31 patients (78%); 10 years, 21 patients (53%); 15 years, 16 patients (40%); 20 years, 9 patients (23%); and 25 years, 2 patients (5%). The local control rate at 20 years, calculated by the Kaplan-Meier product-limit method for the overall group of 42 lesions, was 89%. The likelihood of cause-specific survival at 20 years was 94%. The incidence of treatment-related complications was acceptable. We conclude that irradiation offers a high probability of tumor control with relatively minimal risks for patients with chemodectomas of the temporal bone.