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Comparative evaluation of diepoxybutane sensitivity and cell cycle blockage in the diagnosis of Fanconi anemia.

Fanconi anemia (FA) is a clinically and genetically heterogenous disease that is usually diagnosed on the basis of chromosomal instability reflecting the hypersensitivity towards the DNA cross-linking agents diepoxybutane (DEB) and/or mitomycin C. A less well-known cellular feature that characterizes FA patients is an intrinsic cell cycle disturbance consisting of prolonged progression through, and arrest within, the G2 phase compartment of the cell cycle. In a collaborative blind study, we have evaluated 72-hour lymphocyte cultures from 66 patients with clinical suspicion of FA both for DEB sensitivity and cell cycle disturbance. A concordant result was obtained in 63 of 66 cases. Each of the 3 discordant, but only 1 of the concordant cases presented with overt leukemia. Seventeen cases were identified as classical FA because of their increased DEB sensitivity and G2 phase blockage. Five cases showed a cell cycle disturbance but only borderline DEB sensitivity. These cases might represent atypical or nonclassical forms of FA. They would have been missed by cell cycle studies without concomitant DEB testing. Used in conjunction, cytogenetic and flow cytometric testing provide for the currently optimal diagnosis of FA in nonleukemic patients.

Cells, Cultured↗

The augmentation of tumor-specific immunity using haptenic muramyl dipeptide (MDP) derivatives. II. Establishment of tumor-specific immunotherapy models utilizing MDP hapten-reactive helper T cell activity.

Preinduction of potent haptenic muramyl dipeptide (MDP)-reactive helper T cell activity and subsequent immunization with MDP hapten-coupled syngeneic tumor cells resulted in enhanced induction of tumor-specific immunity through T-T cell collaboration between anti-MDP hapten helper T cells and tumor-specific effector T cells. The present study establishes two types of tumor-specific immunotherapy protocols utilizing helper T cells against MDP hapten cross-reactive with Bacillus Calmette Guérin (BCG). In the first model, naive normal C3H/He mice or mice in which MDP hapten-reactive helper T cells had been generated by BCG-sensitization were inoculated i.d. with syngeneic X5563 tumor cells. When both groups of mice were allowed to generate MDP hapten-modified tumor cells in the tumor mass in situ by intratumoral injection of MDP hapten, an appreciable number of growing tumors in the BCG-presensitized but not in the unsensitized group were observed to regress. In the second model, a growing X5563 tumor mass was removed by the surgical resection 9 days after the tumor implantation. Approximately 90% of C3H/He mice receiving such treatment died from tumor metastasis by about 30 days after the tumor resection. However, immunization of mice with MDP hapten-coupled X5563 tumor cells subsequent to the tumor resection resulted in an increased survival rate. Such protection from the tumor metastasis was appreciably stronger when compared to the protection obtained by immunization with MDP hapten-uncoupled tumor cells. The mice surviving in both models were also demonstrated to retain X5563 tumor-specific immunity. These results indicate that the presentation of MDP hapten-modified tumor cells to BCG-sensitized recipients results in potent tumor-specific immunity which contributes to the regression of the primary tumor or inhibition of metastatic tumor growth.

Acetylmuramyl-Alanyl-Isoglutamine↗

Reporting sexual function disorders caused by antipsychotic drugs: is there a role for the community pharmacy?

Sexual function disorders are frequent adverse effects of antipsychotic use. These effects can lead to non-compliance to medication, which dramatically worsen the outcome of the psychotic disease. Detecting sexual dysfunction by the carers may be difficult, since feelings of embarrassment may occur in both care-taker as in patient. In order to prevent underreporting, strategies to recognise sexual dysfunction should be developed, based upon collaboration between care providers of the psychotic patient. Community pharmacies in many countries can detect non-compliance to medication in prescription data and report this to psychiatric services of the patient. Exchanging information by cross-sectoral networks may optimise the disease management of the psychotic patient.

Adverse Drug Reaction Reporting Systems↗

A computerized nationwide network for nosocomial infection surveillance in Belgium.

OBJECTIVE: To assess the feasibility of computerized nationwide surveillance of nosocomial infections in Belgium, and to obtain preliminary national and hospital-specific incidence data. DESIGN: Prospective multicenter cohort study of surgical wound infections (SWI). SETTING: All 218 acute care hospitals in Belgium in the period October 14 to December 14, 1991. RESULTS: Eighty-five of 218 acute care hospitals (39%) succeeded in collecting the required information and in completing this pilot study, although 50% of the participating hospitals had no previous experience in nosocomial infection surveillance. Seventy percent of the small-size hospitals (< 200 beds) did not participate, mainly because of shortages of manpower. A lack of collaboration from clinicians was a problem in most participating hospitals. SWI postdischarge surveillance was most successful when based on information collected by the surgeons at the surgical outpatient clinic; by this method, postdischarge information was obtained on 43.9% of all surgical procedures. A total of 201 infections were observed among 10,537 operations, with a crude incidence rate of 1.91 per 100 operations or 1.51 per 1,000 person-days of observation. Infection rates by operation type and risk indicators are congruent with those of the literature. Survival analysis showed that the overall cumulative infection risk at 21 days postprocedure attained 81.6% of the 30-days risk. CONCLUSION: This nationwide network for nosocomial infection surveillance has introduced the practice of computerized surveillance of performance in a large number of hospitals. Still, several aspects of the surveillance demand to be improved: the collaboration of the clinicians, the quality of the data, and the postdischarge surveillance methodology.

Belgium↗

Collaborative research and action to control the geographic placement of outdoor advertising of alcohol and tobacco products in Chicago.

Community activists in Chicago believed their neighborhoods were being targeted by alcohol and tobacco outdoor advertisers, despite the Outdoor Advertising Association of America's voluntary code of principles, which claims to restrict the placement of ads for age-restricted products and prevent billboard saturation of urban neighborhoods. A research and action plan resulted from a 10-year collaborative partnership among Loyola University Chicago, the American Lung Association of Metropolitan Chicago (ALAMC), and community activists from a predominately African American church, St. Sabina Parish. In 1997 Loyola University and ALAMC researchers conducted a cross-sectional prevalence survey of alcohol and tobacco outdoor advertising. Computer mapping was used to locate all 4,247 licensed billboards in Chicago that were within 500- and 1,000-foot radiuses of schools, parks, and playlots. A 50% sample of billboards was visually surveyed and coded for advertising content. The percentage of alcohol and tobacco billboards within the 500- and 1,000-foot zones ranged from 0% to 54%. African American and Hispanic neighborhoods were disproportionately targeted for outdoor advertising of alcohol and tobacco. Data were used to convince the Chicago City Council to pass one of the nation's toughest anti-alcohol and tobacco billboard ordinances, based on zoning rather than advertising content. The ordinance was challenged in court by advertisers. Recent Supreme Court rulings made enactment of local billboard ordinances problematic. Nevertheless, the research, which resulted in specific legislative action, demonstrated the importance of linkages among academic, practice, and grassroots community groups in working together to diminish one of the social causes of health disparities.

Adolescent↗

Prevalence, awareness, treatment, and control of hypertension in china.

The objective of this study was to estimate the prevalence and distribution of hypertension and to determine the status of hypertension awareness, treatment, and control in the general adult population in China. The International Collaborative Study of Cardiovascular Disease in ASIA (InterASIA), conducted in 2000-2001, used a multistage cluster sampling method to select a nationally representative sample. A total of 15 540 adults, age 35 to 74 years, were examined. Three blood pressure measurements were obtained by trained observers by use of a standardized mercury sphygmomanometer after a 5-minute sitting rest. Information on history of hypertension and use of antihypertensive medications was obtained by use of a standard questionnaire. Hypertension was defined as a mean systolic blood pressure > or =140 mm Hg, diastolic blood pressure > or =90 mm Hg, and/or use of antihypertensive medications. Overall, 27.2% of the Chinese adult population age 35 to 74 years, representing 129 824 000 persons, had hypertension. The age-specific prevalence of hypertension was 17.4%, 28.2%, 40.7%, and 47.3% in men and 10.7%, 26.8%, 38.9%, and 50.2% in women age 35 to 44 years, 45 to 54 years, 55 to 64 years, and 65 to 74 years, respectively. Among hypertensive patients, only 44.7% were aware of their high blood pressure, 28.2% were taking antihypertensive medication, and 8.1% achieved blood pressure control (<140/90 mm Hg). Our results indicate that hypertension is highly prevalent in China. The percentages of those with hypertension who are aware, treated, and controlled are unacceptably low. These results underscore the urgent need to develop national strategies to improve prevention, detection, and treatment of hypertension in China.

Adult↗

Patients have treatment preferences: a multicentre, double-blind, crossover study comparing rabeprazole and omeprazole.

It is increasingly common practice to change patients from one medication in a drug class to another, often as part of a general formulary change. The underlying assumption and accepted wisdom is that all compounds within a class are identical. To our knowledge, there has been no published investigation into the patients' views on such changes or on the individual medications. These views may be affected by positive side-effects, not normally sought in clinical trials, as well as negative side-effects, which are always reported. The objectives of this study were to determine whether patients whose primary symptoms were already controlled by a proton pump inhibitor (PPI) could distinguish between rabeprazole and omeprazole; to determine the incidence of positive, as well as negative, side-effects; to elicit patients' opinions on changing medication within a class, and on the importance of certain characteristics of medication. The design was a double-blind, double-dummy, randomised, crossover trial, set in five general practice research centres in the UK and Ireland. 240 eligible patients were randomised to receive daily treatment, first for 4 weeks with omeprazole 20 mg/day, and then for reverse order. Each phase of 4 weeks was separately assessed by patients through questionnaires and by non-directed questioning about positive and negative side-effects. At the end of the 8 weeks, patients compared the two medications in seven treatment characteristics. Patients were further asked their attitude to changing medication within a class. Data were collected by a web-based electronic data capture system. Results showed that the majority of patients could be switched to another PPI therapy, predictably without noticeable difference in maintenance of primary symptom control. About one-quarter to one-half of patients were able to express a preference for one or other of the treatments dependent on the variable assessed. For 'absence of unwanted side-effects' and 'presence of positive side-effects' a statistically significant difference in favour of rabeprazole was detected (p = 0.0467 and p = 0.0188, respectively). In terms of the total treatment preference score, the primary outcome variable, there was no statistically significant difference between the two PPIs (p = 0.0754). This finding is mainly attributable to the two PPIs providing similar relief of primary mask the findings for the other variables assessed. However, there were numerically more patients (10 vs. 3) who reported 'marked' positive side-effects on rabeprazole. On direct questioning, patients indicated that tablets (rabeprazole) were more easily swallowed than capsules (omeprazole) (p < 0.0001), but less easily handled than capsules (p = 0.0003). These analyses may however have been confounded by the fact that the omeprazole medication had to be over-encapsulated to allow blinding for this double-dummy, blinded study. There was no difference in tolerability between rabeprazole and omeprazole, with 52.6% and 51% of patients reporting at least one adverse event, respectively. Of the patients controlled and maintained on omeprazole before the study, 33.9% reported adverse events on omeprazole during the study and seven discontinued the study for that reason. Patients thought the most important drug characteristics for treating this condition were rapid and lasting control of pain. Most (83.6%) would be willing to try an alternative medication within a drug class. In conclusion, most patients already controlled by a PPI would be willing to try another. An individual patient may have a strong preference for one PPI over another, and this difference may be important if treatment is to be long term.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Pegasys (Hoffmann-La Roche).

Hoffmann-La Roche has developed a PEGylated interferon alpha-2a, Pegasys, for the potential treatment of chronic hepatitis C and hepatitis B virus infection. It was first approved in Switzerland in August 2001 [418260] and was expected to be launched in September/October 2001 [419333]. In May 2000, Roche submitted a BLA to the US FDA, for approval to market Pegasys for the treatment of chronic HCV infection in non-cirrhotic and cirrhotic patients with compensated liver disease [329872], [348368], [367781]. Approval was still pending in December 2000 [387363], [392481]. Roche expects the US launch to take place in the second half of 2001 [400857]. In April 2001, Roche received a complete response letter from the FDA for Pegasys and was working with the FDA to address the questions raised in the letter [407595], [418310]. In August 2001, Roche expected approval for HCV in the US in 2002 and for HBV in 2004 [419333]. At this time, Roche planned to file an sNDA for combination with ribavirin [421285]. By March 2001, EU and Canadian filings had been made [401793]. Roche also planned to launch the product for chronic HBV infection and various malignancies in 2004 and 2005, respectively [400857]. Pegasys was filed for registration in Brazil in the first part of 2000 [418310]. As of December 1999, the drug was in phase II for HCV infection in Japan. It is being developed by Nippon Roche, which intended to extrapolate foreign phase III data for use in an NDA application in Japan [351804]. As a result of a meeting of Japan's PMSB in March 2001, Pegasys may be given priority in the review of its NDA, if submitted [403782]. In August 2001, Schering-Plough entered into a licensing agreement with F Hoffman-La Roche Ltd and Hoffmann-La Roche Inc that settles all patent disputes regarding the two companies' PEGinterferon products. Under the terms of the agreement, Schering-Plough and Roche will cross license to each other all patents applicable to Peg-Intron and Pegasys. The settlement agreement also includes a Schering-Plough sublicense of Enzon's branched PEG patents to Roche [418935], [418956]. Roche is collaborating with Maxim Pharmceuticals to develop PEG-IFN alpha-2a in conjunction with Maxim's Maxamine [378609]. In July 1998, Hoffmann-La Roche and Weston Medical signed a global agreement to license INTRAJECT (Weston's single-use, disposable, prefilled, needle-free injector for subcutaneous delivery of injectable liquid pharmaceuticals) for delivery of Pegasys [292119]. In April 1999, ABN Amro predicted annual sales of SFr 25 million in 2000, rising to SFr 75 million in 2002 [328676]. In September 2000, Merrill Lynch predicted sales of SFr 70 million in 2001, rising to SFr 700 million in 2004 [383742]. In March 2001, Deutsche Bank estimated that the product has sales potential of SFr 1600 million [421009].

Animals↗

p53 deficiency accelerates induction and progression of esophageal and forestomach tumors in zinc-deficient mice.

The p53 tumor suppressor protein plays a pivotal role in preventing uncontrolled cellular proliferation. By contrast, zinc deprivation enhances esophageal cell proliferation and the induction of esophageal tumors in rodents by N-nitrosomethylbenzylamine (NMBA). We investigated whether p53 deficiency rendered zinc-deficient (ZD) mice more susceptible to NMBA-induced esophageal/forestomach carcinogenesis. At 6-7 weeks of age, p53 null (-/-), heterozygous (+/-), and wild-type (+/+) mice were placed on ZD or zinc-sufficient (ZS) diets to form six experimental groups: ZD:p53-/-; ZD:p53+/-; ZD:p53+/+; ZS:p53-/-; ZS:p53+/-; and ZS:p53+/+. After 3 weeks, 15-23 mice in each group were treated once with NMBA (2 mg/kg body weight). Control animals were untreated. Zinc deficiency alone induced unrestrained cellular proliferation in the esophagus and forestomach of p53-/- mice. Forestomach tumors were first detected in a ZD:p53-/- mouse at 13 days. By 30 days, 100% (21 of 21) of ZD:p53-/- mice developed forestomach tumors and 38% showed esophageal tumors versus 42 and 0% in ZS:p53-/- mice (P < 0.004, esophagus; P < 0.001, forestomach). ZD:p53-/- mice showed an accelerated progression to malignancy, with 10% of esophageal tumors and 38% of forestomach tumors presenting as carcinomas. Nearly 20% of ZD:p53-/- mice developed esophageal Barrett's metaplasia, a lesion not previously seen in NMBA-induced neoplasia. ZD:p53+/- mice had significantly higher tumor incidence than ZS:p53+/- mice. The order of tumor incidence in forestomach was as follows: naught incidence in ZS:p53+/+ mice; ZD:p53-/- > ZD:p53+/- > ZS:p53-/- > ZD:p53+/+ >/= ZS:p53+/- > ZS:p53+/+. The rapid rate of tumor induction/progression in ZD:p53-/- mice was accompanied by an increase in the rate of cell proliferation and a decrease in apoptosis. cDNA array expression analysis of known genes identified a 5-fold up-regulation of cytokeratin 14 mRNA expression in ZD:p53-/- versus ZS:p53-/- forestomach, a result showing gene-modulating effects of zinc deficiency. Cytokeratin 14 is a biomarker in human esophageal carcinogenesis. Our findings provide in vivo evidence for the collaboration of a deficiency of both p53 and zinc in esophageal carcinogenesis and reveal molecular targets of this collaboration.

Animals↗

Community clinical data exchange for emergency medicine patients.

Little is known about the opportunities for a community clinical data exchange network to influence patient care. Rates of patient "cross-over" among different institutions can provide one estimate of the additional value such systems have over unconnected, independent institutional electronic medical records. The Indiana Network for Patient Care (INPC) represents such a system, involving a collaboration of central Indiana hospitals to improve patient care. During a one year study period, 288,696 patients made 471,640 Emergency Department (ED) visits within the INPC collaboration -- accounting for 92% of all Indianapolis ED visits. Overall 25% of the patients with more than one visit also visited one of the other five hospital systems, accounting for 19% of all visits. Our results help clarify the expected frequency within one large metropolitan area that ED patients could obtain direct benefit from a community clinical data exchange network.

Community Networks↗

Epidemiology of the inherited ataxias.

Current epidemiologic studies of the inherited ataxias are limited by complex and confusing systems of nomenclature and by the lack of minimal diagnostic criteria. Despite the difficulties of comparing one study to another, most descriptive investigations provide a prevalence estimate of less than 6 cases/100,000. In isolated, inbred populations, a prevalence as high as 23 cases/100,000 has been reported. Neuroepidemiologic techniques and current knowledge concerning the epidemiology of the inherited ataxias can be applied to future studies in three broad areas--definition, classification, and etiology. Future etiologic investigations based on a goal-oriented, collaborative effort following a case-control format offer the greatest likelihood of success.

Ataxia↗

Management of acute maxillary sinusitis in Finnish primary care. Results from the nationwide MIKSTRA study.

OBJECTIVES: To study the management of acute maxillary sinusitis (AMS) in Finnish primary care and to compare it both to recommendations in national guidelines and to the management of other upper respiratory tract infections (URTI). DESIGN: A cross-sectional multi-centre epidemiological survey. SETTING: Thirty primary care health centres in Finland. SUBJECTS: 7284 patients with symptoms of possible acute rhinosinusitis during one week in both November 1998 and November 1999. MAIN OUTCOME MEASURE: Symptoms and their duration, use of diagnostic tools, choice of antibiotics, patient outcomes. RESULTS: A total of 1601 patients were diagnosed as having AMS (12% of all patients with infectious disease). In 45% of cases the differentiation between AMS and URTI was based on clinical examination alone. Sinus ultrasound was the most common diagnostic tool used (38%). Sinus radiography or blood tests (CRP or leukocytes) were both studied in 8% of cases. AMS was diagnosed and treated with antibiotics also in the early stages of URTI when viruses are the most likely explanation. In total, 83% of patients with AMS received a prescription for antibiotics; the most common choice was amoxycillin (37%), doxycycline was used in 29% of cases, and macrolides in 15%. CONCLUSIONS: Antibiotics are prescribed for AMS 2 to 5 times more often than true disease incidence would suggest in Finland. The choice of antibiotics follows the guideline recommendations; however, use of macrolides is higher than recommended. Physicians feel strong pressure from patients to prescribe antibiotics for AMS. Primary care physicians need better support in the accurate diagnosis of AMS.

Acute Disease↗

Preparation for cancer care: perceptions of newly qualified health care professionals.

The present paper is derived from a larger survey which examined the perceptions of recently qualified health care professionals' experience on evidence-based practice, team working and cancer care. This study reports solely on the findings relating to cancer care. The perceptions of recently qualified professionals in relation to their initial educational input on issues such as confidence, anxiety, communication skills and practice in cancer care as well as adequacy of support, professional supervision and use of reflection were gathered using a cross-sectional postal survey design. A total of 50 graduates from each professional category in nursing, occupational therapy, physiotherapy, and social work were sampled yielding a total sample of 200. Eighty-five questionnaires were returned yielding a response rate of 43%. Twenty-eight (33%) respondents stated that they were currently involved in working with people with cancer. These were as follows: 5 nurses, 8 physiotherapists, 9 occupational therapists and 6 social workers. Despite the low response rate, the findings suggest that health care professionals' educational input and experiences of working with people with cancer were overall positive; for example, in the respondents' confidence, communication skills, decrease in anxiety and application of knowledge gained in classroom to professional practice. Moreover, most respondents learnt about caring for cancer patients through practice rather than classroom teaching. A high percentage (i.e. 64%;18) across all groups felt supported when caring for people with cancer and reported receiving professional supervision as well as being able to actively reflect on their practice. The implications for education and practice were discussed particularly as there have been few studies conducted in relation to the specific needs and collaborative learning of these health care professional groups.

Attitude of Health Personnel↗

Behaviours and expectations in relation to sexual intercourse among 18-20 year old Asians and non-Asians.

OBJECTIVES: To begin to map the reported behaviours and attitudes of young Britons of south Asian origin that may have implications for sexual health. "South Asian" refers to people able to trace their ancestry from the Indian subcontinent (that is, India, Pakistan, and Bangladesh), henceforth referred to as "Asian". DESIGN: A cross sectional study of sexual behaviour using self report measures in a self complete section of a social survey administered by trained interviewers in 1996. SETTING: Greater Glasgow, Scotland. SUBJECTS: Sample (n = 824) originally recruited aged 14-15 in 1992 in secondary schools in Greater Glasgow and subsequently traced through general practitioner registration for 1996 survey. 492 Asians and non-Asians aged 18-20 years old eventually interviewed in their own homes. MAIN OUTCOME MEASURES: Self reported experience of sexual intercourse, age at first intercourse, and contraceptive practice over year before interview. METHODS: Measures of sexual behaviour and attitudes were elicited through a self complete questionnaire filled out in the presence of, and returned to, a trained social interviewer. RESULTS: Asians, and particularly Asian women, were far less likely to report having had heterosexual intercourse. Those Asian women who had had intercourse were likely to do so for the first time at an older age, and with an older partner, than the non-Asian women. Asian women were less likely to report using the pill than non-Asian women, irrespective of their marital status, and Asian men were less likely than non-Asian men to report using condoms. Asian sexual abstinence was reported to be for religious reasons, which were not important for non-Asians. In contrast with non-Asians, Asians saw themselves as likely to be married with children within the next 5 years. Asian men considered the ideal age to marry for men and women to be younger than the non-Asian men's average estimate. Asian and non-Asian women suggested a similar ideal age for men to marry, but Asian women considered a younger age appropriate for women than did non-Asian women. CONCLUSIONS: The higher level of sexual abstinence among Asians, and particularly women, has implications for the delivery of sexual health services to the minority who are sexually active before marriage. The underreporting of condom use by Asian men compared with their non-Asian counterparts, suggests a failure of the existing sexual health education and health services to reach minority ethnic young men which may be remedied by collaborative work with institutions currently used by the Asian community.

Adolescent↗

Postoperative caffeine for preventing apnea in preterm infants.

BACKGROUND: Growing ex-preterm infants who undergo general anesthesia for surgery at about term-equivalent age may have episodes of apnea, cyanosis and bradycardia during the early postoperative period. Caffeine treatment given at the time of operation might prevent these episodes. OBJECTIVES: In ex-preterm infants who undergo general anesthesia for surgery, does the prophylactic use of caffeine prevent episodes of apnea, cyanosis and bradycardia during the postoperative period without clinically important side effects? SEARCH STRATEGY: The standard strategy of the Neonatal Review Group was used. This included searches of the Oxford Database of Perinatal trials, Medline, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants and journal handsearching mainly in the English language. SELECTION CRITERIA: All trials utilising random or quasi-random patient allocation, in which treatment was compared with placebo or no treatment, were included. DATA COLLECTION AND ANALYSIS: The standard methods of the Cochrane Collaboration and its Neonatal Review Group were used to select trials, evaluate quality and to extract data. The methodological quality of each trial was reviewed by the second author blinded to trial authors and institution(s). Each author extracted data separately, compared and resolved differences. Meta-analysis used relative risk and risk difference. MAIN RESULTS: In each trial apnea/bradycardia occurred in fewer treated than control infants. In two trials (Welborn 1989, LeBard 1989) continuous recordings of oxygen saturation detected hypoxaemic episodes (<90 %) in fewer treatment than control infants. No infant in any trial required intubation and mechanical ventilation. No adverse effects were reported. REVIEWER'S CONCLUSIONS: Implications for practice. Caffeine can be used to prevent postoperative apnea/bradycardia and episodes of oxygen desaturation in growing preterm infants if this is deemed clinically necessary. In view of the small numbers of infants studied in these trials and uncertainty concerning the clinical significance of the episodes, caution is warranted in applying these results to routine clinical practice. Implications for research. There is a need to determine which infants might benefit most by this treatment. Studies confined to those most at risk of apnea (prior history, younger postmenstrual age) and those that might require mechanical ventilation (chronic lung disease) would be of value.

Anesthesia, General↗

Onset of disability in depressed and non-depressed primary care patients.

BACKGROUND: While cross-sectional and longitudinal studies have consistently found depressive illness and disability to be related, understanding whether depression leads to subsequent onset of disability is limited. METHODS: In the context of the multi-centre international WHO Collaborative Study on Psychological Problems in General Health Care, we followed prospectively consulting non-elderly primary care patients who were essentially disability free at baseline but who differed in baseline depression status, comprising 1051 patients free of physical disability at baseline including 14% depression; 914 free of social disability including 9% depression. Depression status was assessed with the CIDI; patient-reported physical disability with the MOS physical functioning scale and social disability with the BDQ role functioning and number of disability days measures; investigator-rated social disability with the Occupational section of Groningen Social Disability schedule; and the treating physicians rated the severity of physical illness. RESULTS: In patients essentially disability free at baseline, depressive illness resulted in a 1.5-fold (at 3 months) and a 1.8-fold (at 12 months) increase in risk of onset of physical disability, after controlling for physical disease severity. Depressive illness also resulted in a 2.2-fold (at 3 months) and a 23-fold (at 12 months) increase in risk of onset of social disability, after controlling for physical disease severity, physical disability and onset of physical disability. CONCLUSIONS: Among non-elderly primary care patients, depressive illness is associated with onset of physical disability and shows an even stronger association with onset of social disability.

Adolescent↗

Utilization of the Ottawa ankle rules by nurses in a pediatric emergency department.

OBJECTIVES: To determine the ability of pediatric emergency department (ED) nurses to accurately apply the Ottawa Ankle Rules (OAR) and to evaluate whether the rate of negative ankle radiographs can be reduced by incorporating the OAR into an existing collaborative practice protocol (CPP). METHODS: The authors' ED currently uses a CPP in which patients with ankle pain, swelling, deformity, or decreased range of motion on primary nursing assessment undergo radiography prior to physician evaluation. A cross-sectional study was conducted between June and November 2000. Patients aged 5-19 years with an ankle injury who met at least one of the CPP criteria were eligible for enrollment. The OAR were applied by the primary nurse after initial assessment. Ankle radiographs were ordered for all enrolled patients. The interobserver variability between nurses was evaluated on a random sample. RESULTS: One hundred ninety subjects were enrolled in the study. The OAR were correctly interpreted by nurses in 98.4% of subjects. Agreement on the interobserver reliability sample was 100%. Of the 185 subjects, 31 (16.8%) had positive radiographs. Positive OAR results were noted in 30 of 31 subjects with positive radiographs. The sensitivity of the OAR was 97% (95% CI = 0.82 to 0.99) with a specificity of 25% (95% CI = 0.18 to 032). Use of the OAR would have reduced the radiography rate by 21%. CONCLUSIONS: Trained nurses can accurately apply and interpret the OAR. The incorporation of the OAR into the nursing assessment of children with acute ankle injuries may reduce the number of radiographs ordered.

Adolescent↗

Silver dressings: their role in wound management.

Dressings have a part to play in the management of wounds; whether they are sutured or open, usually chronic wounds of many aetiologies which are healing by secondary intention. They traditionally provide a moist wound environment, but this property has been extended through simple to complex, active dressings which can handle excessive exudate, aid in debridement, and promote disorganised, stalled healing. The control of infection remains a major challenge. Inappropriate antibiotic use risks allergy, toxicity and most importantly resistance, which is much reduced by the use of topical antiseptics (such as povidone iodine and chlorhexidine). The definition of what is an antimicrobial and the recognition of infection has proven difficult. Although silver has been recognised for centuries to inhibit infection its use in wound care is relatively recent. Evidence of the efficacy of the growing number of silver dressings in clinical trials, judged by the criteria of the Cochrane Collaboration, is lacking, but there are good indications for the use of silver dressings, to remove or reduce an increasing bioburden in burns and open wounds healing by secondary intention, or to act as a barrier against cross contamination of resistant organisms such as MRSA. More laboratory, and clinical data in particular, are needed to prove the value of the many silver dressings which are now available. Some confusion persists over the measurement of toxicity and antibacterial activity but all dressings provide an antibacterial action, involving several methods of delivery. Nanocrystalline technology appears to give the highest, sustained release of silver to a wound without clear risk of toxicity.

Anti-Infective Agents, Local↗