Multimorbidity and mortality in Ontario, Canada: A population-based retrospective cohort study.

OBJECTIVE: To examine the relationship between multimorbidity and mortality, and whether relationship varied by material deprivation/rural location and by age. METHODS: Retrospective population-based cohort study conducted using 2013-14 data from previously created cohort of Ontario, Canada residents classified according to whether or not they had multimorbidity, defined as having 3+ of 17 chronic conditions. Adjusted rate ratios were calculated to compare mortality rates for those with and without multimorbidity, comparing rates by material deprivation/rural location, and by age group. RESULTS: There were 13,581,191 people in the cohort ages 0 to 105 years; 15.2% had multimorbidity. Median length of observation was 365 days. Adjusted mortality rate ratios did not vary by material deprivation/rural location; overall adjusted mortality rate ratio was 2.41 (95% CI 2.37-2.45). Adjusted mortality rate ratios varied by age with ratios decreasing as age increased. Overall rate ratio was 14.7 (95% CI 14.48-14.91). Children (0-17 years) had highest ratio, 40.06 (95% CI 26.21-61.22). Youngest adult age group (18-24 years) had rate ratio of 9.96 (95% CI 7.18-13.84); oldest age group (80+ years) had rate ratio of 1.97 (95% CI 1.94-2.04). CONCLUSION: Compared to people without multimorbidity, multimorbidity conferred higher risk of death in this study at all age groups. Risk was greater in early and middle adulthood than in older ages. Results reinforce the fact multimorbidity is not just a problem of aging, and multimorbidity leads not only to poorer health and higher health care utilization, but also to a higher risk of death at a younger age.

Enzyme catalysis of 1,2-amino shifts: the cooperative action of B6, B12, and aminomutases.

Ab initio molecular orbital theory is used to investigate 1,2-amino shifts catalyzed by aminomutases, coenzyme B12, and vitamin B6 (in the form of pyridoxal 5'-phosphate or PLP). Our calculations suggest essential catalytic roles for each of B12, B6, and the enzyme in aminomutase-catalyzed reactions. In the first place, coenzyme B12 provides a source of abstracting radicals, allowing the rearrangement reaction to take place on the radical surface. The involvement of radicals is supported by comparison of experimental and theoretical electron paramagnetic resonance parameters. Next, B6 allows the enzyme to lower the barrier height by introducing a double bond (allowing a low-energy intramolecular rearrangement pathway) and by providing a suitable site for partial protonation (preventing overstabilization of the reaction intermediate which could lead to enzyme inactivation). The PLP hydroxyl group is also identified as an important participant in these reactions. Finally, the enzyme holds the various reaction components in place and is the source of acidic functional groups that can provide partial protonation.

Interconversion of (S)-glutamate and (2S,3S)-3-methylaspartate: a distinctive B(12)-dependent carbon-skeleton rearrangement.

The interconversion of (S)-glutamate and (2S,3S)-3-methylaspartate catalyzed by B(12)-dependent glutamate mutase is discussed using results from high-level ab initio molecular orbital calculations. Evidence is presented regarding the possible role of coenzyme-B(12) in substrate activation and product formation via radical generation. Calculated electron paramagnetic resonance parameters support experimental evidence for the involvement of substrate-derived radicals and will hopefully aid the future detection of other important radical intermediates. The height of the rearrangement barrier for a fragmentation-recombination pathway, calculated with a model that includes neutral amino and carboxylic acid substituents in the migrating glycyl group, supports recent experimental evidence for the interconversion of (S)-glutamate and (2S,3S)-3-methylaspartate through such a pathway. Our calculations suggest that the enzyme may facilitate the rearrangement of (S)-glutamate through (partial) proton-transfer processes that control the protonation state of substituents in the migrating group.

Clostridium difficile colitis following antibiotic prophylaxis for dental procedures.

Clostridium difficile-induced diarrhea and colitis are common complications of therapeutic courses of antibiotics in the hospital setting. We report a case of Clostridium difficile colitis following antibiotic prophylaxis for endocarditis prior to dental procedures in the community setting. The infection necessitated hospital admission and a prolonged hospital stay. Dental practitioners must be aware of the significance of the disease and the risk associated with antibiotics, whether they are used for prophylaxis or treatment.

HDL-cholesterol-raising effect of orange juice in subjects with hypercholesterolemia.

BACKGROUND: Orange juice-a rich source of vitamin C, folate, and flavonoids such as hesperidin-induces hypocholesterolemic responses in animals. OBJECTIVE: We determined whether orange juice beneficially altered blood lipids in subjects with moderate hypercholesterolemia. DESIGN: The sample consisted of 16 healthy men and 9 healthy women with elevated plasma total and LDL-cholesterol and normal plasma triacylglycerol concentrations. Participants incorporated 1, 2, or 3 cups (250 mL each) of orange juice sequentially into their diets, each dose over a period of 4 wk. This was followed by a 5-wk washout period. Plasma lipid, folate, homocyst(e)ine, and vitamin C (a compliance marker) concentrations were measured at baseline, after each treatment, and after the washout period. RESULTS: Consumption of 750 mL but not of 250 or 500 mL orange juice daily increased HDL-cholesterol concentrations by 21% (P: < 0.001), triacylglycerol concentrations by 30% (from 1.56 +/- 0.72 to 2.03 +/- 0.91 mmol/L; P: < 0.02), and folate concentrations by 18% (P: < 0.01); decreased the LDL-HDL cholesterol ratio by 16% (P: < 0.005); and did not affect homocyst(e)ine concentrations. Plasma vitamin C concentrations increased significantly during each dietary period (2.1, 3.1, and 3.8 times, respectively). CONCLUSIONS: Orange juice (750 mL/d) improved blood lipid profiles in hypercholesterolemic subjects, confirming recommendations to consume >/=5-10 servings of fruit and vegetables daily.

Is respite care available for chronically ill seniors?

OBJECTIVE: To determine family physicians' perceptions of how available respite care is and how easy it is to refer chronically ill older people to it, and to examine their opinions of respite care. DESIGN: Mailed survey to family physicians on the Thames Valley Family Practice Research Unit's mailing list. SETTING: London, Ont, and surrounding area. PARTICIPANTS: Of the 448 surveys mailed to eligible physicians, 288 were completed and returned for a response rate of 64.3%. MAIN OUTCOME MEASURES: Respondents' perceptions of how available respite care is and how easy it is to refer chronically ill older people to it and their opinions on the effectiveness of respite care. RESULTS: More than half the respondents reported that outpatient respite care is always available, but how available depended on practice location. Inpatient respite care was reported as less available. More than half the respondents found referral to respite care difficult. Respondents were very positive about the role of respite services in long-term care and in lowering caregiver stress. Respondents' perceptions varied according to where they had attended medical school. Their perceptions of respite care's role in long-term care and in helping patients remain at home were influenced by whether they thought respite care was available. CONCLUSION: Family physicians need education in the value of respite services for their chronically ill older patients and their families. Physicians also need information on the respite services available and strategies for accessing them. Our findings suggest a need for greater attention to regional discrepancies in availability of services.

Biological denitrification in a closed seawater system.

Build-up of high nitrate concentrations in closed seawater systems where primary productivity is undesirable and water changes are impractical presents unique problems. Nitrate concentration in Ocean Tank at the New Jersey State Aquarium reached 9500 microM after 6 years of operation. A biological denitrification system was installed in 1998 and nitrate concentration in the aquarium decreased to 7000 microM within the first 100 days of operation. The system offers additional benefits by increasing the pH and alkalinity of seawater and providing a reducing environment to balance the oxidizing disinfection environment in the aquarium. The initial performance of the denitrification system was monitored and two semi-empirical models were developed: one based on the actual methanol additions, and another based on the daily amounts of nitrogen gas removed. The first model predicts a net nitrate decrease of 39 microM/day in the aquarium. The second model predicts a net decrease of 25 microM/day, in good agreement with the empirical value of 23 microM/day. This indicates that nitrogen gas removal is the controlling factor during denitrification in this facility, and the second model can be used to predict and optimize the operation of the system.

Interactive effects of the middle ear pathology and the associated hearing loss on transient-evoked otoacoustic emission measures.

Sixty-three children aged 4 to 17 years were examined by tympanometry, pure-tone audiometry, transient-evoked otoacoustic emissions (TEOAEs), and otoscopy to evaluate the effects of middle ear pathologies and the associated hearing loss on TEOAEs. TEOAE measures were highly specific (93.8%) in identifying normal ears that passed both audiometric and tympanometric criteria. The sensitivity for identifying abnormal ears was also reasonable (83. 3%). The effects of the middle ear abnormality were most significant, regardless of the degree of hearing loss, when the tympanogram was type B with normal volume measures, which is associated with reduced eardrum mobility and middle ear fluid. The middle ear conditions producing the greater negative pressure, which in turn led to more conductive hearing loss, also produced more TEOAE failures. The mere presence of an open ventilation tube was not a determining factor for absent TEOAEs because 60% of the open ventilation tubes had normal TEOAEs. Provided that the clinician understands the effects of middle ear pathologies on otoacoustic emissions, TEOAEs can be a great asset for diagnosis of both otologic and audiologic disorders.

Cryosurgery for common skin lesions. Treatment in family physicians' offices.

OBJECTIVE: To review the principles of use, common techniques, and effectiveness of cryosurgery for common skin lesions that can be treated by family physicians in their offices. QUALITY OF EVIDENCE: MEDLINE and the Cochrane Database controlled trials register (1998 version) were searched. Much of the evidence for the effectiveness of cryosurgery or cryotherapy is based on of cryosurgery for treating common warts, external genital warts, lentigines, and basal cell carcinomas. Many of the trials reviewed were conducted in specialty clinics and, therefore, the results might not apply accurately to family practice. MAIN MESSAGE: Evidence from case report and series suggests that cryosurgery is effective for actinic keratoses, seborrheic keratoses, dermatofibroma, keloids, molluscum contagiosum, and benign nevi. Randomized comparative trials show that, for external genital warts, cryosurgery is more effective than podophyllin treatment, better than or equal to trichloroacetic acid, but less effective than electrodesiccation or surgical removal. Prospective randomized trials of cryosurgery for common warts showed that weekly cryotherapy produced more rapid cures, but the overall cure rate depended on number of treatments. Two freeze-thaw cycles and paring before freezing improved the cure rate for plantar warts.

Immunologic and histologic observations in reovirus-induced otitis media in the mouse.

The goals of this study were to develop a mouse model for virally induced otitis media, and to study the immune response to infection. Intranasal inoculation of mice by reovirus was used to induce otitis media. Immunohistochemical evidence for the presence of reovirus in the nasopharynx, eustachian tubes, and middle ears and the amount of infiltrating B-cells and T-cells in those sites were serially evaluated by painlessly sacrificing animals over a 21 -day period. Reovirus antigen was detected in the middle ear mucosa by day 4 in 75% of infected animals, and histologic evidence for otitis media was found in 54% of all infected animals. A significant increase in B-cells in the nasopharynx and eustachian tubes was noted 7 to 10 days following infection. The number of infiltrating T-cells did not vary significantly from that in the control animals at any of the sites. These results provide a basis for further investigations of the immune response in otitis media.

Procedures in ambulatory care. Which family physicians do what in southwestern Ontario?

OBJECTIVE: To determine how often family physicians perform 12 ambulatory care procedures and factors associated with procedure performance. DESIGN: Mailed, self-administered survey. The survey was conducted according to the Dillman Total Design method. SETTING: Family physicians' offices in London, Ont, and in surrounding communities. PARTICIPANTS: A total of 395 family physicians practising within the London area were mailed surveys, 237 in London and 158 outside London. Response rates were 80.6% and 75.9%, respectively. Nonresponders did not differ significantly from responders in sex but included more solo practitioners. MAIN OUTCOME MEASURES: Performance of ambulatory care procedures, sex, and practice characteristics of participant family physicians. RESULTS: For all responders, activities significantly associated with procedure performance were delivering babies, managing psychological problems, working emergency, and teaching. Mean total procedure scores ranged from 6.55 for managing psychological problems to 7.68 for working emergency. Sex-specific analysis showed that practice location and years in practice were significant factors for female but not for male family physicians. Mean total procedure scores for female physicians were 7.06 (outside London) and 4.74 (in London). CONCLUSIONS: Factors associated with procedure performance for family physicians in and around London included delivering babies, working in emergency, managing psychological problems, and teaching. Practice location was a significant factor for only female family physicians; those practising outside London performed procedures more than their urban counterparts and at similar rates to male physicians.

Adenovirus and respiratory syncytial virus in chronic sinusitis using polymerase chain reaction.

The aim of this study is to investigate the role of adenovirus and respiratory syncytial virus (RSV) in chronic sinusitis using the polymerase chain reaction (PCR) to assay for the viruses. PCR has proved to be more sensitive and specific than viral cultures and immunoassays in the detection of viruses. Adenovirus and RSV are among the most common viruses to cause upper respiratory tract infections. Sinus mucosa biopsies from 20 patients undergoing endoscopic sinus surgery were sterilely collected. Four specimens (20%) tested positive for RSV by PCR and none tested positive for adenovirus. Only one specimen tested positive for RSV and one for adenovirus by viral culture and immunofluorescence. Bacterial cultures tested positive in 40% of the 20 specimens. PCR can be used to detect RSV in patients with chronic sinusitis and PCR is more sensitive than viral culture and immunofluorescence techniques on sinus polyps and mucosa.

Effects of substituting dietary soybean protein and oil for milk protein and fat in subjects with hypercholesterolemia.

OBJECTIVES: To determine whether, in individuals with hypercholesterolemia, substituting dietary soybean products for cows' milk products improves the plasma lipid profile and whether any change in the profile is due partially to soy oil. DESIGN: Randomized 3-treatment crossover trial. SETTING: Family practice clinics and an outpatient clinic in London, Ont. PARTICIPANTS: Seventeen healthy men and 17 healthy women with elevated plasma levels of total and low-density-lipoprotein (LDL) cholesterol and with normal plasma levels of triglycerides. INTERVENTIONS: Participants incorporated into their normal diet either 2% cows' milk products, soybean products or a combination of skim milk products and soy oil, each over period of 4 weeks, with 22-week wash-out periods. Plasma lipid profile, blood pressure and body weight were assessed after each dietary and wash-out period. OUTCOME MEASURES: Plasma levels of total and lipoprotein cholesterol, plasma levels of triglycerides, apolipoprotein B and A1 levels, blood pressure and plasma lipid peroxidation. RESULTS: The change in diet had no effect on body mass index, levels of apolipoproteins B and A1 and most plasma lipids. During the soybean period, the subjects' mean level of high-density-lipoprotein (HDL) cholesterol increased 9% (p < 0.04) and their mean LDL/HDL cholesterol ratio decreased 14% (p < 0.007). These effects were less pronounced during the skim milk/soy oil period. In the 24 subjects with the highest initial LDL cholesterol level and LDL/HDL cholesterol ratio, the mean LDL cholesterol level decreased 11% after the soybean period. In all subjects, changes in the LDL/HDL cholesterol ratio induced by a soybean diet were negatively correlated with the initial LDL/HDL cholesterol ratio and positively correlated with the initial HDL cholesterol level. CONCLUSIONS: In people with hypercholesterolemia, the plasma lipid profile improved after treatment with a soybean-product diet, and this improvement was partially due to soy oil. The degree of responsiveness was associated with initial risk factors for coronary artery disease.

Contemporary management of cerebrospinal fluid rhinorrhea.

Management of patients with cerebrospinal fluid rhinorrhea (CSF) remains controversial. Most studies recommend either an endoscopic or an external extracranial approach, depending on the surgeon's preference. Eighteen patients with CSF rhinorrhea have been managed at our institution since 1990. The causes of the CSF rhinorrhea consisted of functional endoscopic sinus surgery (7), lateral rhinotomy with excision of a benign nasal tumor (3), spontaneous rhinorrhea (7), and secondary repair after intranasal ethmoidectomy (1). In 11 patients the CSF leak was recognized at the time of surgery; in 10 of these patients it was repaired during the primary surgery, whereas one patient underwent secondary repair after failure of conservative management of his CSF fistula. Seven patients underwent exploration for spontaneous CSF rhinorrhea. Four patients had computer tomography scans that showed the leak, and two patients had cisternography to localize the leak. One patient underwent magnetic resonance cisternography. Both of these leaks were identified with cisternography and were then confirmed intraoperatively. Repair methods included a pedicled septal mucosal flap (4), a free mucosal graft from the septum (7), and a middle turbinate (5). Two patients had obliteration of the sinus with muscle/fascia and fibrin glue. Eight patients were repaired endoscopically. The remainder underwent repair through external approaches. Seventeen patients (at a minimum 1 year follow-up) remain free from leakage. One patient required a second repair 8 months after surgery. Iatrogenic trauma remains the most common cause of CSF rhinorrhea. Management at the initial setting is the least morbid approach and is successful in 95% of cases. Whether an endoscopic or external approach is used depends on surgical expertise and experience.

Incidence of adenovirus and respiratory syncytial virus in chronic otitis media with effusion using the polymerase chain reaction.

The aim of this study is to investigate the role of adenovirus and respiratory syncytial virus in the cause of chronic otitis media with effusion by use of the polymerase chain reaction for detection. The polymerase chain reaction has proved to be more sensitive and specific than viral cultures and immunoassays in the detection of viruses in other specimens. Adenovirus and respiratory syncytial virus were chosen because these viruses have been the most commonly isolated viruses in middle ear effusions in studies using other techniques. The effusions (132 total) were sterilely collected from 88 children undergoing myringotomy and ventilation tube placement for chronic otitis media with effusion. Nine (6.8%) specimens were positive for adenovirus by the polymerase chain reaction, and 13 (9.9%) were positive for respiratory syncytial virus by the polymerase chain reaction. Only one specimen was positive for adenovirus and respiratory syncytial virus by viral culture and immunofluorescence, respectively. Our results show that the polymerase chain reaction can be used to detect adenovirus and respiratory syncytial virus in chronic middle ear effusions and that PCR is more sensitive than viral culture and immunofluorescence techniques.

Adenocarcinoma of the ethmoid sinus.

BACKGROUND: Carcinoma of the paranasal sinuses is rare. The majority of these originate in the maxillary sinus with primary ethmoid carcinomas occurring in up to 20% of cases. Adenocarcinomas comprise up to 50% of the ethmoid malignancy. The relative rarity of tumors originating in this area has led to their inclusion in series that consist mainly of maxillary antral tumors. METHODS: A retrospective chart review of all patients presenting with primary ethmoid adenocarcinoma at West Virginia University Hospitals between 1988 and 1993 was undertaken. Only patients whose epicenter was believed to be in the ethmoids were included in this analysis. CT scans, MRIs, operative notes, pathology, and final outcome were all analyzed. RESULTS: Eight patients with primary ethmoid adenocarcinoma were treated during this time span. The male to female ratio was 1:1 with a mean age of 50 years. Symptoms had been present from 3 to 18 months (mean 8 months). All patients underwent craniofacial resection with 5 patients receiving postoperative radiotherapy. Pathologically 4 patients had cribriform plate erosion, 2 had dural involvement, and 1 had extension into the sphenoid sinus. With a mean follow-up of 45 months (9-71 months) 7 patients are disease free and 1 patient has died of disease. CONCLUSIONS: Obtaining clear margins by craniofacial resection is essential to the management of adenocarcinoma of the ethmoid sinuses. Radiotherapy is reserved for positive margins, cribriform plate penetration, dural invasion, and high-grade lesions that are close to the cribriform plate. Local control was obtained in 87% of our patients.