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PubMed2001

Measuring complete diagnostic evaluation in colorectal cancer screening.

Complete diagnostic evaluation, or CDE (i.e., a colonoscopy or combined barium enema X-ray and flexible sigmoidoscopy) is recommended for individuals who have an abnormal screening fecal occult blood test result. Accurate measures of CDE use are needed in colorectal cancer (CRC) screening programs. This study compares the sensitivity and specificity of different methods for measuring CDE recommendation and performance. We identified 17 primary-care practices with 120 patients who had a positive fecal occult blood test result in a CRC screening program operated by a managed-care organization. Approaches used to measure CDE recommendation and performance included external chart audit (ECA) only; internal chart audit (ICA) only; administrative data review (ADR) of electronic claims data; ICA plus ADR; and ECA plus ADR (the "gold standard"). Sensitivity and specificity of each method were assessed relative to CDE recommendation and performance as measured by ECA plus ADR. For CDE recommendation, sensitivity measures were ECA only, 0.926; ICA only, 0.790; ADR only, 0.617; and ICA plus ADR, 0.901. The specificity of each method for CDE recommendation was no less than 0.95. In terms of CDE performance, sensitivity measures were ECA only, 0.877; ICA only, 0.790; ADR only, 0.877; and ICA plus ADR, 0.965. The specificity of each method for CDE performance was 1.0. The ICA-plus-ADR method was a highly sensitive and specific measure of CDE use. This method should be considered in situations that involve primary-care physician follow-up of patients with abnormal CRC screening test results.

Barium Sulfate↗

PubMedDate not supplied

Narrowing the organ donation gap: hospital development methods that maximize hospital donation potential.

The purpose of this article is to identify and describe this organ procurement organization's hospital development methods that have markedly increased the quantity and quality of organ donor referrals. Procedures used include the establishment of organ donor programs (hospital donor programs) within each donor hospital. The goal for these hospital donor programs is to monitor and maximize organ procurement within each institution. Routine quality assurance or death audits along with referral data from the organ procurement organization's database provide both the organ procurement organization and the hospital donor program with the necessary information to evaluate organ procurement strengths and weaknesses. This data is used in concert with ongoing development activities, which include, but are not limited to, physician and staff education and frequent marketing visits. Early referral to the organ procurement organization of all nonsurvivable head injuries for evaluation as potential organ donors, and a timely request for donation by the organ procurement organization coordinator are emphasized. The results of these efforts have been gratifying. In 1989, 138 referrals and 41 organ donations occurred. In 1990, 174 referrals and 66 organ donations occurred. In 1991, 213 referrals and 71 organ donations occurred. In 1992, 228 referrals and 70 organ donations occurred. In the first 6 months of 1993, 146 referrals and 40 organ donations occurred, for a prorated figure of 292 referrals and 80 organ donations annually. In conclusion, these results appear to validate the benefits of this approach and its significant contribution to narrowing the donation supply and demand gap.

Brain Death↗

PubMed2006

Carotid endarterectomy under regional anaesthesia at Dunedin Hospital, New Zealand: 1994-2003.

AIM: Carotid endarterectomy (CEA) under local or regional anaesthesia is being considered more often by vascular surgeons to improve cerebral monitoring and to reduce general anaesthetic complications. The purpose of this study was to audit the results of CEA under regional anaesthesia in a New Zealand hospital (Dunedin Hospital, Otago Province). METHODS: All carotid endarterectomies performed consecutively by one surgeon under regional anaesthesia over a 9-year period from November 1994 were reviewed. The cases and early complications were identified from a computerised audit database with prospective data input and all case notes were retrospectively reviewed for demographic data, comorbidity, the primary endpoints of stroke or death, and other complications of CEA. General practitioners and neurologists were contacted where follow-up information was incomplete. RESULTS: During the review period, 135 CEAs were performed in 132 patients. The need for shunting was accurately predicted in all but one patient. The stroke rate was 0.7% and 30-day mortality rate 0.7% thus giving a combined risk of stroke or mortality of 1.4%. No patient had a myocardial infarction in the perioperative period despite 46% of the patients having ischaemic heart disease. There were 10 late deaths over the 9-year period of review. CONCLUSION: CEA under regional anaesthesia is a safe operation even in patients with coronary disease and in a low volume setting. Moreover, it allows monitoring of cerebral ischaemia and the safe use of selective shunting. The results are comparable to other recently published series and provide a baseline for comparison with newer treatment modalities.

Aged↗

PubMed1997

Hernia surgery in a defined population: a prospective three year audit.

OBJECTIVE: To establish a register of inguinal hernia surgery that allows audit and analyses of data from several centres. DESIGN: Prospective recording of data on a common protocol. SETTING: Eight Swedish hospitals. SUBJECTS: All groin hernia operations done for patients over 15 years old from January 1992 to December 1994. MAIN OUTCOME MEASURES: Methods of repair, postoperative complications including mortality, day surgery rate, and reoperations for recurrence. RESULTS: During the three years studied 4879 hernia operations were undertaken in 4474 patients. Postoperative mortality within 30 days of operation for emergency and elective hernia repairs was 3.5% and 0.07%, respectively. Of all herniorrhaphies 798 (16%) were done for recurrences, 142 of these after operations between 1992 and 1994. At 24 months 4% of all operations had been redone because of recurrences with highly significant variations among hospitals ranging from 1.5% to 6.7%. Postoperative complications within 30 days after operation, direct hernia, recurrent hernia, and the use of absorbable sutures were associated with an increased risk of reoperation. CONCLUSIONS: A quality register recorded voluntarily can identify significant interhospital differences in outcome as well as variables associated with an increased risk of reoperation, thereby raising quality awareness and facilitating the process of improvement.

Adolescent↗

PubMed1987

Computerized discharge summaries: a new window for patient care monitoring.

Automated fact extraction from discharge summaries of the hospital chart yielded a useful set of facts for characterizing the clinical history and care of a hospitalized patient. The extracted facts depict the clinical events of a single patient, whereas the aggregate of the facts reflects the hospital's pattern of health care. Automated analysis of the discharge summaries provides good data for monitoring quality of care: Appropriateness and timeliness of hospitalization, effectiveness of diagnostic hypothesis generation, judicious use of resources, iatrogenic problems (surgical complications, other therapeutic mishaps), and inconsistencies (such as an abnormal finding without follow-up) are some of the issues recognizable when studying the care rendered. Fiscal studies are facilitated by the 50 to 100 facts on each patient considered pertinent and significant by the physician. These facts on each patient provide a much better definition of the illness and the resources used than the currently used discharge abstract data for DRG grouping. Medical audit: Ongoing clinical self-audit and cost study should stimulate a hospital's medical staff to constantly improve the quality of patient care management, and to be aware of the cost of the various resources. Alternative treatment patterns can be compared in the institutional audit reports, based on outcome, patient satisfaction, and/or cost. Clinical medicine could use a multi-institutional fact data-base as a retrievable source of yesterday's clinical experience, to guide clinical decisions of today.

Electronic Data Processing↗

PubMed2001

[Users' experiences with modern hearing aids. An audit].

INTRODUCTION: The aim of the study was to evaluate satisfaction with use and manipulation of hearing aids (HA), and to compare these parameters for analogue (A-HA), programmable (P-HA), and digital signal processing aids (DSP-HA). METHOD: An audit was made of data on users' experiences, as indicated in a questionnaire posted 3-4 months after the HA fitting. MATERIAL: Questionnaires were posted to 18,702 persons, who, during the period 1997-1999, had been provided with a HA at a median age of 77 years (range 18-98), 41.8% of whom were men, and 58.2% women. Responses were returned by 12,866 (68.8%), and, as there were no differences between the respondents and non-respondents with respect to age, gender, and distribution of HA type, the responses were considered representative. RESULTS: According to the replies, 71.5% were very satisfied/satisfied with their HA; 89% used the instrument daily/weekly, and 75% were able to manipulate the HA without problems. However, 10.7-12.7% said they never used the fitted HA. A significantly higher proportion were satisfied with A-HAs as compared to P-HAs and DSP-HAs, whereas there was no significant difference in use as a function of type. A significantly higher number of the users fitted with a DSP-HA could manipulate them, but 36.5% of these needed follow-up in contrast to 25.5% fitted with a P-HA, and 21.6% fitted with an A-HA. A significantly smaller proportion of the elderly were able to manipulate the HA. CONCLUSION: The users of modern HAs are satisfied with them, use them, and most are able to manipulate the HA without problems. The new technology has raised unrealistic expectations in the users, and the DSP-HAs account for larger costs to the national health services, because they are more expensive and the need for staff resources is greater.

Adolescent↗

PubMed1986

NTP Toxicology and Carcinogenesis Studies of Chlorpheniramine Maleate (CAS No. 113-92-8) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

Toxicology and carcinogenesis studies of chlorpheniramine maleate (99% pure), a widely used antihistaminic drug in human and veterinary medicine, were conducted by administering this chemical in deionized water by gavage to groups of 50 male and 50 female F344/N rats and B6C3F1 mice, 5 days per week for 103 weeks. The doses used were: male rats-- 0, 15, or 30 mg/kg; female rats-- 0, 30, or 60 mg/kg; male mice-- 0, 25, or 50 mg/kg; female mice-- 0, 100, or 200 mg/kg. The selection of these doses was based largely on data from 14-day or 16-day studies and 13-week studies in which reduced body weight gain and reduced survival occurred at higher doses. Doses used in the 2-week studies ranged from 40 to 640 mg/kg in rats and 25 to 800 mg/kg in mice; in the 13-week studies, doses ranged from 3.75 to 60 mg/kg in rats and 12.5 to 200 mg/kg in mice. The recommended human adult daily oral dose of chlorpheniramine maleate is up to 0.32 mg/kg. Doses originally selected for male mice in the 2-year study were 0, 100, or 200 mg/kg; however, because of poor survival, that study was stopped and a new study was started at doses of 0, 25, or 50 mg/kg. At the termination of the study (week 104), survival of high dose female rats (6/50) and high dose male mice (15/50) was lower than that of the vehicle controls (29/50 and 39/50, respectively). Survival of all other dosed groups was comparable to that of respective vehicle control groups. Mean body weights of dosed rats were about 10%-15% (male) or about 10%-25% (female) lower than those of vehicle controls; mean body weights of female mice were generally 20%-35% lower than those of vehicle controls. No compound-related gross or microscopic pathologic effects were observed in either species in the 16-day or 13-week studies. Hyperactivity and hyperexcitability associated with dosing were frequently noted in the 13-week and 2-year studies. There were no significant positive trends or increases in the incidences of neoplasms in either male or female rats dosed with chlorpheniramine maleate for 103 weeks. Marginal increases in the incidences of adrenal gland capsule adenomas in male mice (vehicle control, 2/50; low dose, 7/49; high dose, 4/49) were not considered to be compound related, since there was not a corresponding increase in the incidence of adrenal gland capsule hyperplasia (46/50; 33/49; 22/49). A positive trend was seen for subcutaneous tissue tumors in male mice (4/50; 5/49; 8/50); this marginal effect was not considered to be compound related. The incidences of thyroid gland follicular cell cysts (2/48; 10/49; 13/47), thyroid gland follicular cell hyperplasia (3/48; 29/49; 36/47), and thyroid gland follicular cell adenomas (0/48; 4/49; 2/47) were greater in dosed female mice than in vehicle controls. This finding is toxicologically important,since thyroid gland neoplasms are uncommon in mice and are often preceded by hyperplasia of the follicular epithelium. The major route of excretion of chlorpheniramine or its metabolites is in the urine. In male F344 rats orally administered 14C-chlorpheniramine maleate at doses of 2 or 20 mg/kg, there was essentially no difference in the percentage of urinary or fecal excretion of radioactivity between these dose levels. Chlorpheniramine maleate was not mutagenic to Salmonella strains TA98, TA100, TA1535, or T1537 in the presence or absence of S9 metabolic activation systems prepared from the liver of Aroclor 1254-treated male Sprague-Dawley rats or male Syrian hamsters. Chlorpheniramine maleate did not induce forward mutations at the TK locus of L5178Y mouse lymphoma cells with or without metabolic activation. In Chinese hamster ovary cells in culture, chlorpheniramine maleate induced a weak but reproducible increase in sister-chromatid exchanges in the absence of exogenous metabolic activation. Chromosomal aberrations were induced at the highest dose tested but only in the presence of S9 from Aroclor 1254-induced Sprague-Dawley male rat liver. An audit of the experimental data was conducted for these 2-year carcinogenesis studies on chlorpher these 2-year carcinogenesis studies on chlorpheniramine maleate. No data discrepancies were found that influenced the final interpretations. Under the conditions of these 2-year gavage studies, there was no evidence of carcinogenicity for F344/N rats or B6C3F1 mice of either sex administered chlorpheniramine maleate in deionized water, 5 days per week for 2 years. Due to high mortality in high dose female rats and high dose male mice, the sensitivity of these groups to detect a carcinogenic response was reduced. Chlorpheniramine maleate had a proliferative effect in the thyroid gland of female mice, as shown by the increased incidences of follicular cell cysts and hyperplasia in both low dose and high dose groups. Synonyms: 2-p-chloro-a-(2-dimethylaminoethyl) benzyl]pyridine maleate; 2-Pyridinepropanamine; gamma-[4-chlorophenyl]-N,N-dimethyl-[z]-2-butenedioate Trade Names: Allerclor; Allergisan; Antagonate; Chlormene; Chlorprophenpyridamine maleate; Chlor-Trimeton; Chlor-Tripolon; Chloropiril; C-Meton; Histadur; Histaspan; Lorphen; M.P. Chlorcaps T.D.; Piriton; Pyridamal-100; Teldrin

Journal Article↗

PubMed2002

Validation of undergraduate clinical data by electronic capture (barcode).

Assessment of clinical activity is common in dental schools. An audit project to confirm that dental undergraduate clinical activity recorded by electronic data capture is an accurate representation of the clinical case entry is reported. A printout of clinical activity for a period of a week was generated retrospectively and used to identify case notes. Activity recorded in the case notes was compared with the computer printout. All discrepancies were noted. A total of 125 patient files with 270 barcoded items of treatment were retrieved; 29 of 78 (37.1%) paediatric and 23 of 47 (48.9%) orthodontic cases had discrepancies between the case notes and the computer entry. However, some items recorded in the notes do not require barcoding and vice versa. When these were accounted for, only 19 items of treatment appeared in the notes that should have been barcoded, a 7% shortfall in recording of clinical activity. The barcode system is an accurate and reliable way of recording undergraduate clinical activity.

Data Collection↗

PubMed2004

[The role of clinical audit in the quality improvement of health care].

The aim of clinical audit is continuous improvement of the quality of care through systematic and critical review of current practice against explicit criteria and the implementation of change if necessary. The audit is a regular multidisciplinary activity by which all participants of care including doctors, nurses and other health professionals carry out a systematic review of their own practice. Data collected during the process of audit should be handled with care, and individual data concerning care-givers, patients or health professionals must be treated confidentially. Clinical audit needs realistic timeframe and necessary resources as well as tolerant culture of learning organisations. Furthermore the success of clinical audit depends on the commitment and support of the management of the organisations. Clinical audit could relatively easily be embodied into the current practice of peer-review processes and other quality improvement initiatives in Hungary. Widespread and systemic application of clinical audit may improve the quality of patient care and maintain the trust of the population. However, clinical audit should be effective and cost-effective. The recently published methodological guideline by the Ministry intends to promote good practice in clinical audit.

Humans↗

PubMed1986

NTP Toxicology and Carcinogenesis Studies of Benzene (CAS No. 71-43-2) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

Benzene ranks 16th in production volume for chemicals produced in the United States, with approximately 9.9 billion pounds being produced in 1984, 9.1 billion pounds in 1983, and 7.8 billion pounds in 1982. This simplest aromatic chemical in used in the synthesis of styrene (polystyrene plastics and synthetic rubber), phenol (phenolic resins), cyclohexane (nylon), aniline, maleic anhydride (polyester resins), alkylbenzenes (detergents), chlorobenzenes, and other products used in the production of drugs, dyes, insecticides, and plastics. Benzene, along with other light, high-octane aromatic hydrocarbons, such as toluene and xylenes, is a component of motor gasoline. Benzene is also used as a solvent, but for most applications, it has been replaced by less hazardous solvents. During the 17-week studies, groups of 10 or 15 male and female F344/N rats and B6C3F1 mice were gavaged 5 days per week with benzene in corn oil (5 ml/kg) at doses of 0 to 600 mg/kg. No benzene-related deaths occurred; in rats that received benzene, final mean body weights were 14%-22% lower compared with vehicle controls and in mice, slight dose-related reductions were observed (less than 10% differences). Doses for the 2-year studies were selected based on clinical observations (tremors in higher dosed mice), on clinical pathologic findings (lymphoid depletion in rats and leukopenia in mice), and on body weight effects. Two-year toxicology and carcinogenesis studies of benzene (greater than 99.7% pure) were conducted in groups of 50 F344/N rats and 50 B6C3F1 mice of each sex and for each dose. Doses of 0, 50, 100, or 200 mg/kg body weight benzene in corn oil (5 ml/kg) were administered by gavage to male rats, 5 days per week, for 103 weeks. Doses of 0, 25, 50, or 100 mg/kg benzene in corn oil were administered by gavage to female rats and to male and female mice for 103 weeks. Ten additional animals in each of the 16 groups were killed at 12 months and necropsies were performed. Hematologic profiles were performed at 3-month intervals. These studies were designed and conducted because of large production volume and potential human exposure, because of the epidemiologic association with leukemia, and because previous experiments were considered inadequate or inconclusive for determining potential carcinogenicity in laboratory animals. In the 2-year studies, mean body weights of the 200 mg/kg male rats (-23%) and the 100 mg/kg mice (-14% to -19%) were lower than those of the vehicle controls, and survival of dosed groups decreased with increasing dose (rats--male: vehicle control, 32/50; low dose, 29/50; mid dose, 25/50; high dose, 16/50; female: 46/50; 38/50; 34/50; 25/50; mice--male: 28/50; 23/50; 18/50; 7/50; female: 30/50; 26/50; 24/50; 18/50). At week 92 for rats and week 91 for mice, survival was greater than 60% in all groups; most of the dosed animals that died before week 103 had neoplasia. Compound-related nonneoplastic or neoplastic effects on the hematopoietic system, Zymbal gland, forestomach, and adrenal gland were found both for rats and mice. Further, the oral cavity was affected in rats, and the lung, liver, harderian gland, preputial gland, ovary, and mammary gland were affected in mice. Significantly increased (P<0.05) incidences of neoplasms were observed at multiple sites for male and female rats and for male and female mice. Primary neoplasms observed in rats and mice are summarized in Table 1 (see page 12 of the Technical Report). Hematologic data from vehicle control and dosed rats and mice were obtained at 3-month intervals from 0 to 24 months. Reliably identifiable hematologic effects were limited to lymphocytopenia and associated leukocytopenia in benzene-dosed rats and mice. These effects were seen from 3 to 18 months in dosed male rats and in dosed male mice; a similar but less pronounced response was observed in dosed female rats during this same time period. The effect in female mice was limited to 12-18 months. The technical quality of certain of these data was questionable; thus, more detailed analyses (e.g., investig questionable; thus, more detailed analyses (e.g., investigation of the association between hematologic and pathologic changes) are deemed inappropriate for these data. Benzene increased the frequency of micronucleated normchromatic peripheral erythrocytes in male and female mice (rats were not examined); males were more sensitive than females. The hematopoietic system of rats and mice of each sex was affected by benzene in the 2-year studies. The incidences of malignant lymphomas in all dosed groups of mice were greater than those in the vehicle controls (male: 4/49; 9/48; 9/50; 15/49; female: 15/49; 24/45; 24/50; 20/49). Lymphoid depletion of the splenic follicles (rats) and thymus (male rats) was observed at increased incidences. Bone marrow hematopoietic hyperplasia was observed at increased incidences in dosed mice of each sex (male: 0/49; 11/48; 10/50; 25/49; female: 3/49; 14/45; 8/50; 13/49). The incidences of Zymbal gland carcinomas in mid and high dose male rats and in dosed female rats were greater than those in the vehicle controls (male: 2/32; 6/46; 10/42; 17/42; female: 0/45; 5/40; 5/44; 14/46). The incidences of Zymbal gland carcinomas in mid and high dose male mice and in high dose female mice were greater than those in the vehicle controls (male: 0/43; 1/34; 4/40; 21/39; female: 0/43; 0/32; 1/37; 3/31). In mid and high dose male mice and in high dose female mice, the incidences of epithelial hyperplasia of the Zymbal gland were also increased (male: 0/43; 3/34; 12/40; 10/39; female: 1/43; 1/32; 2/37; 6/31). Hyperplasia of the adrenal capsule was observed at increased incidences in dosed mice of each sex (male: 2/47; 32/48; 14/49; 4/46; female: 5/49; 19/44; 34/50; 30/48). The incidence of pheochromocytomas in mid dose male mice was greater than that in the vehicle controls (male: 1/47; 1/48; 7/49; 1/46), whereas the incidences in dosed female mice were lower than that in the vehicle controls (female: 6/49; 1/44; 1/50; 1/48). Hyperplasia of the zona fasciculata of the adrenal cortex was observed at increased incidences in low dose rats of each sex (male: 0/50; 13/49; 0/48; 2/49; female: 0/50; 17/50; 0/47; 0/49). Benzene was associated with increased incidences of neoplasms of the skin and oral cavity of rats. The incidences of squamous cell papillomas and squamous cell carcinomas of the skin in high dose male rats were greater than those in the vehicle controls (squamous cell papilloma: 0/50; 2/50; 1/50; 5/50; squamous cell carcinoma: 0/50; 5/50; 3/50; 8/50). Increased incidences of uncommon squamous cell papillomas or squamous cell carcinomas (combined) of the oral cavity were observed in dosed male and female rats (male: 1/50; 9/50; 16/50; 19/50; female: 1/50; 5/50; 12/50; 9/50). Incidences of squamous cell papillomas or carcinomas (combined) (male: 2/45; 2/42; 3/44; 5/38; female: 1/42; 3/40; 6/45; 5/42), hyperkeratosis, and epithelial hyperplasia of the forestomach were increased in some dosed groups of male and female mice; incidences of hyperkeratosis and acanthosis were increased in high dose male rats. Compound-related effects in the lung, harderian gland, preputial gland, ovary, mammary gland, and liver were seen in mice but not in rats. Administration of benzene was associated with increased incidences of alveolar epithelial hyperplasia in mid and high dose mice (male: 2/49; 3/48; 7/50; 10/49; female: 1/49; 1/42; 9/50; 6/49). Increased incidences of alveolar/bronchiolar carcinomas and alveolar/bronchiolar adenomas or carcinomas (combined) were observed in high dose male mice (carcinomas: 5/49; 11/48; 12/50; 14/49; adenomas or carcinomas: 10/49; 16/48; 19/50; 21/49). Alveolar/bronchiolar adenomas were seen at increased incidences in high dose female mice (4/49; 2/42; 5/50; 9/49), as were alveolar/bronchiolar carcinomas (0/49; 3/42; 6/50; 6/49) and alveolar/bronchiolar adenomas or carcinomas combined (4/49; 5/42; 10/50; 13/49) in mid and high dose female mice. The incidences of focal or diffuse hyperplasia of the harderian gland were increased in dosed mice of each sex (male: 0/49; 5/46; 11/49; 7/48; female: 6/48; 10/44; 11/50; 10/47). The incidences of harderian gland adenomas (0/49; 9/46; 13/49; 11/48) in dosed male mice were greater than that in the vehicle controls. A marginal increase in the incidence of adenomas or carcinomas (combined) of the harderian gland was seen in high dose female mice (5/48; 6/44; 10/50; 10/47). The administration of benzene to male mice was associated with increased incidences of hyperplasia (1/21; 18/28; 9/29; 1/35) and squamous cell carcinomas (0/21; 3/28; 18/29; 28/35) of the preputial gland. Increased incidences of mammary gland carcinomas were found in mid dose and high dose female mice (0/49; 2/45; 5/50; 10/49) and carcinosarcomas in high dose female mice (0/49; 0/45; 1/50; 4/49). Increased incidences of various uncommon neoplastic and nonneoplastic lesions of the ovary (papillary cystadenoma, luteoma, granulosa cell tumor, tubular adenoma, benign mixed tumor, epithelial hyperplasia, and senile atrophy) were associated with the administration of benzene to female mice. In mid and high dose female mice, the incidences of granulosa cell tumors (1/47; 1/44; 6/49; 7/48) and benign mixed tumors (0/47; 1/44; 12/49; 7/48) were greater than those in the vehicle controls. Increased incidences of hepatocellular adenomas were observed in low dose female mice (1/49; 8/44; 5/50; 4/49) and hepatocellular adenomas or carcinomas (combined) in low dose and mid dose female mice (4/49; 12/44; 13/50; 7/49). An audit of the experimental data was conducted for these 2-year carcinogenesis studies on benzene. No data discrepancies were found that influenced the final interpretations. Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenicity of benzene for male F344/N rats, for female F344/N rats, for male B6C3F1 mice, and for female B6C3F1 mice. For male rats, benzene caused increased incidences of Zymbal gland carcinomas, squamous cell papillomas and squamous cell carcinomas of the oral cavity, and squamous cell papillomas and squamous cell carcinomas of the skin. For female rats, benzene caused increased incidences of Zymbal gland carcinomas and squamous cell papillomas and squamous cell carcinomas of the oral cavity. For male mice, benzene caused increased incidences of Zymbal gland squamous cell carcinomas, malignant lymphomas, alveolar/bronchiolar carcinomas and alveolar/bronchiolar adenomas or carcinomas (combined), harderian gland adenomas, and squamous cell carcinomas of the preputial gland. For female mice, benzene caused increased incidences of malignant lymphomas, ovarian granulosa cell tumors, ovarian benign mixed tumors, carcinomas and carcinosarcomas of the mammary gland, alveolar/bronchiolar adenomas, alveolar/bronchiolar carcinomas, and Zymbal gland squamous cell carcinomas. Dose-related lymphocytopenia was observed for male and female F344/N rats and male and female B6C3F1 mice. Synonyms: benzol, cyclohexatriene, pyrobenzol

Journal Article↗

PubMed1987

NTP Toxicology and Carcinogenesis Studies of 1,4-Dichlorobenzene (CAS No. 106-46-7) in F344/N Rats and B6C3F1 Mice (Gavage Studies).

1,4-Dichlorobenzene is commonly used as a space deodorant in toilets and for moth control. Because of its extensive production and use and the absence of carcinogenicity data, carcinogenesis studies were conducted by administering 1,4-dichlorobenzene (greater than 99% pure) in corn oil by gavage (5 days per week) to male F344/N rats at doses of 0, 150, or 300 mg/kg and to female F344/N rats and male and female B6C3F1 mice at doses of 0, 300, or 600 mg/kg per day for 2 years (50 animals per group). Fourteen-day and 13-week studies were performed to characterize the toxicity, identify affected sites, and set doses for the 2-year studies. Clinical chemistry and hematologic studies were performed during the 13-week studies to assess the effects of 1,4-dichlorobenzene on the liver, kidney, and hematopoietic system and to assess whether the compound produced hepatic porphyria. Two 13-week studies were performed in rats. In the first study, rats were dosed with 300-1,500 mg/kg 1,4-dichlorobenzene. Because histologic changes were observed in the kidney of male rats at all doses, a second 13-week study was performed at doses of 38-600 mg/kg. In the 13-week studies, survival was decreased in groups of male rats given 1,200 or 1,500 mg/kg and in female rats given 1,500 mg/kg. Weight gain was decreased in male rats receiving doses of 300 mg/kg or more and in female rats given doses of 1,200 or 1,500 mg/kg. Doses of 1,200 or 1,500 mg/kg produced degeneration and necrosis of hepatocytes, hypoplasia of the bone marrow, lymphoid depletion of the spleen and thymus, and epithelial necrosis of the nasal turbinates in male and female rats. Renal tubular cell degeneration was observed in male rats receiving 300 mg/kg or more in the first study, but only slight changes were seen at 300 mg/kg in the second study. Liver weight to brain weight ratios were increased at 900 mg/kg or more for both male and female rats. The kidney weight to brain weight ratio was increased in male rats receiving doses of 600 mg/kg or more. Administration of 1,4-dichlorobenzene to rats for 13 weeks produced slight but statistically significant decreases in the hematocrit, red blood cell count, and hemoglobin level in all males receiving doses of 300-1,200 mg/kg. No clear hematologic changes were observed in female rats. 1,4-Dichlorobenzene produced minimal changes in clinical chemistry parameters in the 13-week studies. Serum cholesterol levels were increased by doses of 600 mg/kg or more in male rats and 900 mg/kg or more in female rats. Serum triglycerides were reduced by doses of 300 mg/kg or more in male rats. The blood urea nitrogen level was increased slightly in male rats dosed with 900 mg/kg or more. Urinary porphyrins were increased slightly in male rats administered 1,200 or 1,500 mg/kg and female rats receiving 1,200 mg/kg. However, these increases were modest and indicative of a mild porphyrinuria rather than hepatic porphyria. Liver porphyrins were not increased at any dose. Two 13-week studies were performed in mice. The doses selected for the first study were 600-1,800 mg/kg. Survival was decreased in male and female mice receiving doses of 1,500 mg/kg or more, and body weight gain was decreased at all doses. Hepatocellular degeneration was observed in both sexes at all doses, and the liver weight to brain weight ratio was increased at doses of 900 mg/kg or more. Serum cholesterol levels were increased in male mice at doses of 900 mg/kg or more, whereas serum protein and triglycerides were increased at doses of 1,500 mg/kg or more. These relatively modest clinical chemistry changes probably reflect the hepatic effects of this compound. The white blood cell count was reduced significantly in male mice receiving doses of 600 mg/kg or more and female mice receiving 1,000 mg/kg or more, but this effect was not dramatic. Hepatic porphyria was not found in mice at any dose in the 13-week study. Because hepatic effects were seen in all dose groups in the first study, a second 13-week study was performed at doses of 85-900 mg/kg. In this study, hepatocellularellular cytomegaly was observed im male and female mice at doses of 675 mg/kg or more but not at 338 mg/kg. Renal damage was not observed in mice in either 13-week study. Based on the histopathologic findings in the kidney of male rats and in the liver of both sexes of rats and mice in the 13-week studies, the doses selected for the 2-year studies were 150 and 300 mg/kg for male rats and 300 and 600 mg/kg for female rats and male and female mice. In the 2-year studies, survival of female rats and of both sexes of mice was comparable to that of the vehicle controls; survival of high dose male rats was significantly lower than that of the vehicle controls (vehicle control, 32/50; low dose, 31/50; high dose, 20/50). Mean body weights of high dose male rats were 5&percnt;-8&percnt; lower than those of vehicle controls after week 38, and those of high dose female rats were 5&percnt;-7&percnt; lower than those of vehicle controls after week 55. Mean body weights of mice dosed with 1,4-dichlorobenzene were comparable to those of vehicle controls throughout the studies. Administration of 1,4-dichlorobenzene to male rats increased the average seveity of nephropathy and caused epithelial hyperplasia of the renal pelvis (1/50; 30/50; 31/50), mineralization of the collecting tubules in the renal medulla (4/50; 46/50; 47/50), and focal hyperplasia of renal tubular epithelium (0/50; 1/50; 9/50). There were increased incidences of nephropathy in both low and high dose female rats compared with vehicle controls (21/49; 32/50; 41/49). 1,4-Dichlorobenzene produced a dose-related increase in the incidence of tubular cell adenocarcinomas of the kidney in male rats (1/50; 3/50; 7/50); one tubular cell adenoma was observed in a high dose male rat. These malignant tumors are uncommon in male F344/N rats. They have been diagnosed in only 4/1,098 (0.4&percnt;) corn oil gavage controls in previous NTP studies. There were no tubular cell tumors in dosed or vehicle control female rats. There was a marginal increase in the incidence of mononuclear cell leukemia in dosed male rats compared with that in vehicle controls (5/50; 7/50; 11/50). 1,4-Dichlorobenzene increased the incidences of nonneoplastic liver lesions in male and female mice, including alteration in cell size (cytomegaly and karyomegaly), hepatocellular degeneration, and individual cell necrosis. 1,4-Dichlorobenzene also increased the incidences of nephropathy in male mice and renal tubular regeneration in female mice. 1,4-Dichlorobenzene increased the incidences of hepatocellular carcinomas in high dose male (14/50; 11/49; 32/50) and female (5/50; 5/48; 19/50) mice and hepatocellular adenomas in dosed male (5/50; 13/49; 16/50) and high dose female (10/50; 6/48; 21/50) mice. Hepatoblastomas were observed in four high dose male mice but not in vehicle controls. This rare tumor has not occurred in 1,091 male vehicle control mice in NTP studies. An increase in thyroid gland follicular cell hyperplasia was observed in dosed male mice (1/47; 4/48; 10/47), and there was a marginal positive trend in the incidence of follicular cell adenomas of the thyroid gland in female mice (0/48; 0/45; 3/46). Pheochromocytomas (benign or malignant, combined) of the adrenal gland occurred with a positive trend in dosed male mice, and the incidence in the high dose group was significantly greater than in vehicle controls (0/47; 2/48; 4/49). The incidence of adrenal gland medullary hyperplasia in male mice was 2/47; 4/48; and 4/49. Focal hyperplasia of the adrenal gland capsule was also observed in dosed male mice (11/47;21/48; 28/49). 1,4-Dichlorobenzene was not mutagenic in Salmonella typhimurium strains TA98, TA100, TA1535, or TA1537 with or without activation by Aroclor 1254-induced male Sprague-Dawley rat or male Syrian hamster liver S9 when tested according to a preincubational protocol at concentrations up to 100 ug/plate. 1,4-Dichlorobenzene did not induce forward mutations in the mouse lymphoma L5178Y/TK± assay in the absence of exogenous metabolic activation; however, the results were equivocal in this system in the presence of metabolic activation. 1,4-Dichlorobenzene did not produce an increase in sister-chromatid exchanges or chromosomal aberrations in Chinese hamster ovary cells in culture with or without exogenous metabolic activation. No increase in micronucleated cells was seen in erythrocytes of mice from the first 13-week studies. An audit of the experimental data was conducted for the 2-year studies of 1,4-dichlorobenzene. No data discrepancies were found that influenced the final interpretations. Under the conditions of these 2-year gavage studies, 1,4-dichlorobenzene produced clear evidence of carcinogenicity for male F344/N rats, as shown by an increased incidence of renal tubular cell adenocarcinomas. There was no evidence of carcinogenicity for female F344/N rats receiving doses of 300 or 600 mg/kg. There was clear evidence of carcinogenicity for both male and female B6C3F1 mice, as shown by increased incidences of hepatocellular carcinomas and hepatocellular adenomas. Marginal increases were observed in the incidences of pheochromocytomas of the adrenal gland in male mice. Nonneoplastic effects in the kidney of male and female rats, in the liver of male and female mice, and in the thyroid gland and adrenal gland of male mice were also associated with the administration of 1,4-dichlorobenzene. Synonyms: p-dichlorobenzene; para-dichlorobenzene; para-chlorophenyl chloride

Journal Article↗

PubMed2001

Continuing medical education: the paradigm is changing.

With the realization that lifelong learning is more than attending conferences, the potential for greatly expanding effective continuing medical education (CME) has never been more encouraging. Databases from groups and individual managed care practices and advances in information technology are providing major opportunities toward this goal by identifying specific information deficits and promoting practice-linked education. The National Committee for Quality Assurance (NCQA) standards, requiring audited Health Plan Employer Data and Information Set (HEDIS) reports, are a step forward in the development of CME linked closely to practice. The optimal educational use of practice data to improve clinical outcomes will require research to determine the best methods. HEDIS standards will probably continue to deal with common problems of omission rather than with those caused by physicians' lack of knowledge, which will require other approaches. Development of these methods will provide rich opportunities for demonstration studies. The spectacular advances in information technology, especially the almost limitless capabilities of the Internet and electronic mail, offer boundless possibilities of information sources and enhanced communication among physicians about puzzling patients. The further implementation of the electronic medical record with computerized reminders and other clinical information delivered at the point of need will trigger major advances. An appealing user-friendly, practice-linked, and self-directed CME is on the horizon, promising to help the practicing physician optimize patient care.

Curriculum↗

PubMedDate not supplied

The Red Cross classification of war wounds: the E.X.C.F.V.M. scoring system.

The Red Cross classification of war wounds is based upon features of the wound, not upon weaponry. It is proposed as a new means of understanding, communicating, and gathering information about war wounds and their management. The wound score is based on the skin wounds and the presence of a cavity, fracture, vital injury, or metallic bodies in the wound. All wounds so scored can be graded according to severity and typed according to structures injured; consequently, wounds are identified by their clinical significance. A study of 247 wounds shows the feasibility of scoring wounds in the field and yields surgically relevant information about bullet and fragment wounds. The applications of the classification are to wound assessment, establishing a scientific basis to war surgery, surgical audit, and collecting wound data from the field.

Humans↗

PubMed1999

Admission patterns and outcomes in a paediatric intensive care unit in South Africa over a 25-year period (1971-1995).

OBJECTIVE: To describe admission and outcome patterns of diseases managed at a paediatric intensive care unit (PICU) in a developing country between 1971 and 1995, in order to provide data which will assist in improving the management of diseases and the rational allocation of health resources. METHOD: This study is based on data collated from annual audits conducted by the head of the PICU, King Edward VIII Hospital, Durban, South Africa. This unit serves a childhood population of about 3-4 million aged from 0-12 years. RESULTS: The proportion of children admitted to the ICU as a percentage of the general paediatric admission has increased from 1.5% in 1971 to 7% in 1995. During this period, 7580 children were admitted to the unit, an average of 303 cases per annum. The overall mortality rate was 35.44% (range 29.9 to 45.4%); over 90% of the children admitted were intubated and 80% required intermittent positive pressure ventilation. Common childhood vaccine preventable infections have declined substantially and have been replaced by HIV related syndromes, lower respiratory tract infections, metabolic disorders, septicaemia and hyaline membrane disease. The mean duration of ICU stay per survivor over the study period 1991-1995 was 13.891 days. Tetanus, septicaemia and HIV related diseases required the longest ICU stay per survivor (>20 days), while accidental injuries, neonatal apnoea and asthma required the shortest duration of ICU stay per survivor (<6 days); 23.9% of all deaths occurred in the first 24 h. CONCLUSION: The profile of diseases in children admitted to this PICU has changed considerably over 25 years. Some of these changes can be attributed to the shift in emphasis to primary health care, especially higher vaccination coverage rates. Profitable utilisation of limited ICU facilities would probably be enhanced by the use of outcome measures such as mortality and mean number of ICU days of stay per survivor.

Child↗

PubMed2007

Molecular diagnosis of neurofibromatosis type 1: 2 years experience.

Our experience of providing an NF1 gene diagnostic mutation detection service as part of the U.K. Genetic Testing Network (UKGTN) is presented. A total of 169 unrelated individuals suspected of having neurofibromatosis type I (NF1) were referred for NF1 diagnostic testing over a 2 year period. Mutation analysis of the entire NF1 coding region and the flanking splice sites was carried out, and included the use of a combination of FISH, dHPLC and MLPA. Possible disease causing mutations were identified in 109 (64%) cases. These comprised 88 different sequence alterations, of which 57 were novel. Out of the 169 cases referred, there were 102 patients with reliable clinical data, of whom 78 satisfied the NIH diagnostic criteria for NF1. Within this better defined cohort of NF1 patients, NF1 mutations were identified in 61 individuals (78%), showing the importance of clinical selection on overall test sensitivity, and highlighting the problem of full clinical data collection in the audit of routine services. As mutation detection technologies advance, facilitating direct sequencing of all coding and flanking non-coding regions of the NF1 gene, the development of an even more cost-effective, quick and sensitive diagnostic test for future testing of NF1 is discussed.

Alternative Splicing↗

PubMed1998

How frequently do endobronchial secondaries occur in an unselected series?

Isolated endobronchial secondaries are reported usually as single cases or in series from either specialist surgical or cancer units. The latter two are selected populations and are not a good guide to the true frequency of occurrence of such isolated endobronchial secondaries. The incidence of such endobronchial secondaries in a 15 yr prospective series is reported. Results of all fibre-optic bronchoscopies carried out in the Blackburn, Hyndburn and Ribble Valley districts from 1981 to 1995 together with histology were recorded prospectively throughout the period. These had been audited yearly throughout, the data were collated, and the individual records of cases of endobronchial secondaries examined. A total of 3353 bronchoscopies were carried out in the years 1981-1995 inclusive. Of these, 1391 had visible endobronchial abnormalities, from which 1059 had positive endobronchial histology. Sixteen of the 1059 (1.5%) were with endobronchial secondaries. Over the same period eight bronchial carcinoids (none biopsied, but later surgically resected) were encountered. Isolated endobronchial secondaries made up a higher proportion of endobronchial histology than expected at 1.5% and were twice as frequently found as bronchial carcinoids. The possibility of endobronchial secondaries should always be considered in those with a history of previous carcinomas at other sites.

Adult↗

PubMed2005

An analysis of urinary tract trauma in Scotland: imnpact on management and resource needs.

OBJECTIVE: We report the incidence, distribution, aetiology and outcome of urological trauma in a unique national database to provide an insight into its contemporary management. PATIENTS AND METHODS: The Scottish Trauma Audit Group prospectively collected data from severe trauma presenting to all major Scottish hospitals. We examined data from 24,666 trauma admissions from 1999 to 2002. Patients who sustained urological injuries were identified and studied in detail. RESULTS: 362 patients had urological injuries, comprising 1.5% of the trauma population, and an incidence of 1 per 45,000 head of adult population per year. Blunt injury (n = 285, 79%) was the main cause of urological trauma. Road traffic accidents were most frequent (197 patients, 54%), followed by assaults (76, 21%) and high falls (45, 12%). Renal injuries were the most common (n = 241, 67%), followed by injuries to the external genitalia (71, 20%), bladder (65, 18%), urethra (16, 4%) and ureter (3, 1%). Only 52 patients (14%) had isolated urological trauma. One hundred and fifty nine out of 310 (51%) urological patients with associated injuries were physiologically compromised on arrival in A&E, compared with only 4/52 (8%) patients with isolated urological trauma. All patients with isolated urological trauma survived, whereas 110/310 (35%) of those with associated injuries died. CONCLUSION: Urological injuries in Scotland mostly result from blunt trauma due to high-energy impacts. Isolated urological injuries are uncommon and all such patients survived. The majority of patients with urological trauma have multiple injuries and require a multi-disciplinary approach. Current urological services appear adequately distributed to cope with contemporary demands of urological trauma.

Adult↗

PubMed2001

Retinal detachment in Chinese, Malay and Indian residents in Singapore: a comparative study on risk factors, clinical presentation and surgical outcomes.

PURPOSE: To evaluate the risk factors, clinical presentation and surgical outcomes of retinal detachment (RD) among Chinese, Malay and Indian residents in Singapore. METHODS: A retrospective descriptive study from January 1995 to December 1998. All RD operations performed at a tertiary ophthalmic center in Singapore were initially identified from a computerized audit database. Case records data of all Malay and Indian patients as well as a 10% randomized sample of Chinese patients were retrieved and analyzed. Tractional and exudative RD's were excluded. RESULTS: Of the Singapore residents who had a RD operation over the 4-year period, 597 (89.6%) were Chinese, 47 (7.1%) were Malays and 22 (3.3%) were Indians. The age (mean: 46.1 +/- 15.5 years), gender distribution (70.5% males) and presenting visual acuities were similar in the 3 races. The most common site of the retinal break(s) was the superotemporal retina (44.9%), followed by the inferotemporal retina (15.3%). Chinese patients were more likely to have multiple or indeterminate breaks (p = 0.09) and macula-on RD (p = 0.04), compared to Malays and Indians. The distribution of known risk factors (myopia, lattice degeneration, prior cataract surgery and prior ocular trauma) was similar between the three races. The majority of patients required a scleral buckling operation either in isolation (71.3%), or in combination with vitrectomy (19.4%), and only 10 (7.8%) had vitrectomies without buckles. At 6 months postoperatively, anatomical success (defined as an attached retina on ocular examination) and functional success (defined as visual acuities of 6/60 or better) were achieved in 108 (94.7%) and 62 patients (54.4%), respectively, with no significant racial variation seen. The overall rate of redetachment after the initial operation was low (9.3%). CONCLUSION: Variation in risk factors, clinical presentations and postoperative outcomes of retinal detachment appears to be minimal among Chinese, Malays and Indians in Singapore.

Adult↗