A quantitative assessment of the number of disease foci in papillary thyroid cancer.

AIM: Multifocality is a frequent feature of papillary thyroid carcinoma (PTC). Its prognostic value is controversial although national guidelines recommend treatment intensification if present. However, multifocality is not a binary but discrete variable. This study aimed to examine the association between increasing number of foci and risk of recurrence following treatment. METHODS: 577 patients with PTC were identified with median follow-up of 61 months. Number of foci were taken from pathology reports. Log-rank test was used to assess significance. Multivariate analysis was performed and Hazard Ratios were calculated. RESULTS: Of 577 patients, 206(35%) had multifocal disease and 36(6%) recurred. 133(23%), 89(15%) and 61(11%) had 3+, 4+ or 5+ foci respectively. The 5-year RFS stratified by number of foci was 95%v93% for 2+foci (p = 0.616), 95%v96% for 3+foci (p = 0.198) and 89%v96% for 4+foci (p = 0.022). The presence of 4 foci was associated with an over 2-fold risk of recurrence (HR 2.296, 95% CI 1.106-4.765, p = 0.026) although this was not independent of TNM staging. Of the 206 multifocal patients, 31(5%) had 4+foci as their sole risk factor for treatment intensification. CONCLUSION: Although multifocality per se does not confer worse outcome in PTC, finding 4+foci is associated with worse outcome and could therefore be appropriate as a cut-off for treatment intensification. In our cohort, 5% of patients had 4+foci as a sole indication for treatment intensification, suggesting that such a cut off could impact clinical management.

Access to Burn Care in Low- and Middle-Income Countries: An Assessment of Timeliness, Surgical Capacity, and Affordability in a Regional Referral Hospital in Tanzania.

This study investigates patients' access to surgical care for burns in a low- and middle-income setting by studying timeliness, surgical capacity, and affordability. A survey was conducted in a regional referral hospital in Manyara, Tanzania. In total, 67 patients were included. To obtain information on burn victims in need of surgical care, irrespective of time lapsed from the burn injury, both patients with burn wounds and patients with contractures were included. Information provided by patients and/or caregivers was supplemented with data from patient files and interviews with hospital administration and physicians. In the burn wound group, 50% reached a facility within 24 hours after the injury. Referrals from other health facilities to the regional referral hospital were made within 3 weeks for 74% in this group. Of contracture patients, 74% had sought healthcare after the acute burn injury. Of the same group, only 4% had been treated with skin grafts beforehand, and 70% never received surgical care or a referral. Together, both groups indicated that lack of trust, surgical capacity, and referral timeliness were important factors negatively affecting patient access to surgical care. Accounting for hospital fees indicated patients routinely exceeded the catastrophic expenditure threshold. It was determined that healthcare for burn victims is without financial risk protection. We recommend strengthening burn care and reconstructive surgical programs in similar settings, using a more comprehensive health systems approach to identify and address both medical and socioeconomic factors that determine patient mortality and disability.

The economic impact of the transition from branded to generic oncology drugs.

Background: Economic evaluations are an integral component of many clinical trials. Costs used in those analyses are based on the prices of branded drugs when they first enter the market. The effect of genericization on the cost-effectiveness (ce) or cost-utility (cu) of an intervention is unknown because economic analyses are rarely updated using the costs of generic drugs. Methods: We re-examined the ce or cu of regimens previously evaluated in Canadian Cancer Trials Group (cctg) studies that included prospective economic evaluations and where genericization has occurred or is anticipated in Canada. We incorporated the new costs of generic drugs to characterize changes in ce or cu. We also determined acceptable cost levels of generic drugs that would make regimens reimbursable in a publicly funded health care system. Results: The four randomized controlled trials included (representing 1979 patients) were cctg br.10 (early lung cancer, adjuvant vinorelbine-cisplatin vs. observation, n = 172), cctg br.21 (metastatic lung cancer, erlotinib vs. placebo, n = 731), cctg co.17 (metastatic colon cancer, cetuximab vs. best supportive care, n = 557), and cctg ly.12 (relapsed or refractory lymphoma, gemcitabine-dexamethasone-cisplatin vs. cytarabine-dexamethasone-cisplatin, n = 619). Since the initial publication of those trials, the genericization of vinorelbine, erlotinib, cetuximab, and cisplatin has taken place or is expected in Canada. Costs of generics improved the ces and cus of treatment significantly. For example, genericization of erlotinib ($1460.25 per 30 days) resulted in an incremental cost-effectiveness ratio (icer) of $45,746 per life-year gained compared with $94,638 for branded erlotinib. Likewise, genericization of cetuximab ($275.80 per 100 mg) produced an icer of $261,126 per quality-adjusted life-year (qaly) gained compared with $299,613 for branded cetuximab. Decreases in the cost of generic cetuximab to $129.39 and $63.51 would further improve the icer to $150,000 and $100,000 per QALY respectively. Conclusions: Genericization of a costly oncology drug can modify the ce and cu of a regimen significantly. Failure to revisit economic analyses with the costs of generics could be a missed opportunity for funding bodies to optimize value-based allocation of health care resources. At current levels, the costs of generics might not be sufficiently low to sustain publicly funded health care systems.

Estimation of drug cost avoidance and pathology cost avoidance through participation in NCIC Clinical Trials Group phase III clinical trials in Canada.

BACKGROUND: Cost avoidance occurs when, because of provision of a drug therapy [drug cost avoidance (dca)] or a pathology test [pathology cost avoidance (pca)] during trial participation, health care payers need not pay for standard treatments or testing. The aim of our study was to estimate the total dca and pca for Canadian patients enrolled in relevant phase iii trials conducted by the ncic Clinical Trials Group. METHODS: Phase iii trials that had completed accrual and resulted in dca or pca were identified. The pca was calculated based on the number of patients screened and the test cost. The dca was estimated based on patients randomized, the protocol dosing regimen, drug cost, median dose intensity, and median duration of therapy. Costs are presented in Canadian dollars. No adjustment was made for inflation. RESULTS: From 1999 to 2011, 4 trials (1479 patients) resulted in pca and 17 trials (3195 patients) resulted in dca. The total pca was estimated at $4,194,849, which included testing for KRAS ($141,058), microsatellite instability ($18,600), and 21-gene recurrence score ($4,035,191). The total dca was estimated at $27,952,512, of which targeted therapy constituted 43% (five trials). The combined pca and dca was $32,147,361. CONCLUSIONS: Over the study period, trials conducted by the ncic Clinical Trials Group resulted in total cost avoidance (pca and dca) of approximately $7,518 per patient. Although not all trials lead to cost avoidance, such savings should be taken account when the financial impact of conducting clinical research is being considered.

A cost-effective protocol for screening patients for methicillin-resistant Staphylococcus aureus.

The incidence of hospital-acquired infection with methicillin-resistant Staphylococcus aureus (MRSA) is rising worldwide. Rapid identification of MRSA carriers is an important step in reducing the risk of transmission to other patients. Molecular methods are increasingly popular but are technically demanding and expensive. This study assesses the modification of one of the commercially available latex agglutination tests (Mastalex-MRSA) for the identification of penicillin-binding protein 2' on known strains of MRSA as well as other organisms identified from chromogenic agar plates. A total of 3050 patients with unknown MRSA status were processed through the routine laboratory during the investigation period and 73 of these were presumptive positive following overnight incubation. Of 70 patients who could be evaluated, 32 (43.8%) specimens would be suitable for use with the kit directly from overnight incubation on chromogenic agar, and the other 38 (52.1%) would be suitable following four hours' incubation on blood agar. The cost of one positive MRSA test with the inclusion of this test is Euro 15.15 compared with published reports of Euro 35.00 for a commercial polymerase chain reaction (PCR) test. This protocol would allow the reporting of presumptive positive MRSA results approximately 24 hours earlier than currently achieved.

Paracetamol and ibuprofen for the treatment of fever in children: the PITCH randomised controlled trial.

OBJECTIVES: To establish the relative clinical effectiveness and cost-effectiveness of paracetamol plus ibuprofen compared with paracetamol and ibuprofen separately for time without fever, and the relief of fever-associated discomfort in young children who can be managed at home. DESIGN: The trial design was a single-centre (multisite), individually randomised, blinded, three-arm trial comparing paracetamol and ibuprofen together with paracetamol or ibuprofen separately. SETTING: There were three recruitment settings, as follows: 'local' where research nurses were recruited from NHS primary care sites; 'remote' where NHS sites notified the study of potentially eligible children; and 'community' where parents contacted the study in response to local media advertisements. PARTICIPANTS: Children aged between 6 months and 6 years with fever > or = 37.8 degrees C and < or = 41 degrees C due to an illness that could be managed at home. INTERVENTIONS: The intervention was the provision of, and advice to give, the medicines for up to 48 hours: paracetamol every 4-6 hours (maximum of four doses in 24 hours) and ibuprofen every 6-8 hours (maximum of three doses in 24 hours). Every parent received two bottles, with at least one containing an active medicine. Parents, research nurses and investigators were blinded to treatment allocation by the use of identically matched placebo medicines. The dose of medicine was determined by the child's weight: paracetamol 15 mg/kg and ibuprofen 10 mg/kg per dose. RESULTS: For additional time without fever in the first 4 hours, use of both medicines was superior to use of paracetamol alone [adjusted difference 55 minutes, 95% confidence interval (CI) 33 to 77 minutes; p < 0.001] and may have been as good as ibuprofen (adjusted difference 16 minutes, 95% CI -6 to 39 minutes; p = 0.2). Both medicines together cleared the fever 23 minutes (95% CI 2-45 minutes; p = 0.015) faster than paracetamol alone, but no faster than ibuprofen alone (adjusted difference -3 minutes, 95% CI 24-18 minutes; p = 0.8). For additional time without fever in the first 24 hours, both medicines were superior to paracetamol (adjusted difference 4.4 hours, 95% CI 2.4-6.3 hours; p < 0.001) or ibuprofen (adjusted difference 2.5 hours, 95% CI 0.6-4.5 hours; p = 0.008) alone. No reduction in discomfort or other fever-associated symptoms was found, although power was low for these outcomes. An exploratory analysis showed that children with higher discomfort levels had higher mean temperatures. No difference in adverse effects was observed between treatment groups. The recommended maximum number of doses of paracetamol and ibuprofen in 24 hours was exceeded in 8% and 11% of children respectively. Over the 5-day study period, paracetamol and ibuprofen together was the cheapest option for the NHS due to the lower use of health-care services:14 pounds [standard deviation (SD) 23 pounds] versus 20 pounds (SD 38 pounds) for paracetamol and 18 pounds (SD 40 pounds) for ibuprofen. Both medicines were also cheapest for parents because the lower use of health care services resulted in personal saving on travel costs and less time off work: 24 pounds (SD 46 pounds) versus 26 pounds (SD 63 pounds) for paracetamol and 30 pounds (SD 91 pounds) for ibuprofen. This more than compensated for the extra cost of medication. However, statistical evidence for these differences was weak due to lack of power. Overall, a quarter of children were 'back to normal' by 48 hours and one-third by day 5. Five (3%) children were admitted to hospital, two with pneumonia, two with bronchiolitis and one with a severe, but unidentified 'viral illness'. CONCLUSIONS: Young children who are unwell with fever should be treated with ibuprofen first, but the relative risks (inadvertently exceeding the maximum recommended dose) and benefits (extra 2.5 hours without fever) of using paracetamol plus ibuprofen over 24 hours should be considered. However, if two medicines are used, it is recommended that all dose times are carefully recorded to avoid accidentally exceeding the maximum recommended dose. Manufacturers should consider supplying blank charts for this purpose. Use of both medicines should not be discouraged on the basis of cost to either parents or the NHS. Parents and clinicians should be aware that fever is a relatively short-lived symptom, but may have more serious prognostic implications than the other common symptom presentations of childhood.

Therapeutic hypothermia in comatose patients after out-of-hospital cardiac arrest.

Our intensive care unit has been treating comatose patients, following an out-of-hospital cardiac arrest, with therapeutic hypothermia since 2002. In all, 139 out-of-hospital cardiac arrest patients were admitted in the 4-year period 2002-5. Of these, 27% had a favourable outcome (discharged home or to rehabilitation). Forty-one per cent of patients presenting with ventricular fibrillation (VF) and 7% of non-VF patients had a favourable outcome. No patient with an estimated time from collapse to first attempt at cardiopulmonary resuscitation over 12 min survived to hospital discharge. Twenty-two per cent of patients over 70 years were discharged home, suggesting age was not a barrier to surviving out-of-hospital cardiac arrest. The introduction of a therapeutic hypothermia clinical pathway, at the end of 2003 improved the efficiency of cooling. The percentage of patients cooled to below 34 degrees C within 4 h increased from 15 to 51% and those cooled for more than 12 h increased from 30 to 83%.

[Dyslipidemia associated with food]. / La dislipidemia asociada con los alimentos.

The increase of the morbi-mortality due to CHD in México, particularly among the Social Security Institute (IMSS) workers led us to do research on the relative risk and the protection provided by foodstuffs usually consumed by these workers. We found significant evidence of low levels of cholesterol associated with dry alcoholic drinks, skimmed milk and yogurt as well as fresh cheeses. C-LDL was low among people that usually consume sweet alcoholic drinks and fresh cheese. High levels of TG were associated with those people consuming food products containing saturated fat (bacon, pork crackling, fatty red meat, fowl with skin) and viscera, more than three standard cups of alcoholic drinks three times a week, soft drinks and salt. Skimmed milk and yogurt and all vegetables were related to low levels of TG. Products related to high levels of C-HDL were all kinds of vegetables and beans. This study of IMSS worker eating habits could be useful to do research on the food intake of other worker populations, and could help us to design Health Education programs based on scientific knowledge.

Follow up of an immunocompromised contact group of a case of open pulmonary tuberculosis on a renal unit.

BACKGROUND: The organisation, management, outcome and cost of follow up of a large group of mainly immunocompromised patients and healthcare workers who were exposed to a staff member of a London renal unit with smear positive pulmonary tuberculosis are described. METHODS: Following British Thoracic Society (BTS) guidelines, 576 close contacts were identified and divided into three groups: (1) 303 renal patients including 61 with renal transplants; (2) 90 surgical patients; and (3) 183 staff members. Screened contacts were interviewed, completed a symptoms questionnaire, and were offered a chest radiograph and Heaf or Mantoux test if appropriate with referral to a chest physician if required. RESULTS: Overall, 524 (85%) living contacts have been screened: 243 (97%) renal (first screening), 63 (70%) surgical, and 135 (74%) staff contacts. Thirty one transplant patients were prescribed isoniazid chemoprophylaxis. Fifty two renal patients had died before screening and 11 deaths occurred after first interview. One case of tuberculosis epidemiologically related to the index case was diagnosed on clinical criteria. A review of the case records and/or death certificates and entries on to tuberculosis registers indicated no further cases. The cost of the investigation was estimated to be approximately franc25 000, or franc44 per contact screened, with staff costs comprising 79% of the total. CONCLUSIONS: Undiagnosed tuberculosis in healthcare workers working with immunosuppressed patients can lead to large and expensive follow up studies. The applicability of the 1990 and 1994 BTS guidelines to the investigation of tuberculosis in an immunocompromised nosocomial group, and the role of the infection control doctor and the consultant in Communicable Disease Control in overlapping nosocomial and community incidents, are discussed.

Inflammatory bowel disease: costs-of-illness.

We have evaluated the economic costs to society for the two major types of inflammatory bowel disease, Crohn's disease and ulcerative colitis, using a medical decision algorithm costing methodology augmented by examination of 1988-89 claims data from a major U.S. commercial insurer. The average annual medical cost per patient with Crohn's disease was estimated at $6,561 (1990 U.S. dollars). The total annual medical costs for U.S. Crohn's disease patients in 1990 was estimated at $1.0-1.2 billion. The average annual medical cost per patient with ulcerative colitis was estimated at $1,488. The total annual medical costs for U.S. patients with ulcerative colitis in 1990 was estimated at $0.4-0.6 billion. Adjusting for productivity losses, we estimated the annual economic cost for both diseases at $1.8 billion to $2.6 billion. Analysis of insurance claims data for inflammatory bowel disease patients showed that the distribution of annual medical expenses charged and paid is highly uneven by patient. The top 2% of Crohn's disease patients accounted for 28.9% of total charges and 34.3% of the total amount paid. The top 2% of ulcerative colitis patients accounted for 36.2% of total charges and 39.0% of the total amount paid. We used a multivariate regression model to examine potential cost-effectiveness tradeoffs between different types of medical services in treatment of inflammatory bowel disease.

Inflammatory bowel disease: medical cost algorithms.

In this study we describe medical cost estimates for the two major types of inflammatory bowel disease, Crohn's disease and ulcerative colitis, using a literature-based medical decision algorithm costing methodology. Surgery and inpatient costs were estimated to account for roughly half of inflammatory bowel disease medical costs. Outpatient medical care represented only 3.0-7.1% of average cost of medical care for inflammatory bowel disease; initial diagnostic workups were only 1.5-7.8% of medical costs. Long-term complications were estimated to average $439 for ulcerative colitis, nearly twice the average for Crohn's disease. Medications averaged about 10% of total costs. The average annual medical cost per patient with Crohn's disease was estimated at $6,561 (1990 U.S. dollars). The total annual medical costs for U.S. Crohn's disease patients in 1990 was estimated at $1.0-1.2 billion. The average annual medical cost per patient with ulcerative colitis was estimated at $1,488. The total annual medical costs for U.S. patients with ulcerative colitis in 1990 was estimated at $0.4-0.6 billion.

A recent assessment of cocoa and pesticides in Brazil: an unhealthy blend for plantation workers.

Cocoa is the major source of income for the Brazilian state of Bahia and some 2.3 million people rely on the crop for their livelihood. Most cocoa is grown on large plantations where working conditions are often extremely poor. Few workers using pesticides on plantations, or on small-holdings, have had instruction about safe working practices. Protective clothing is rarely available. The result is frequent complaints about health. None of this likely to improve in the short term given Brazil's perilous economic situation.