A Comparative Trial of Single Dose Chemotherapy in Paucibacillary Leprosy Patients with Two to Three Skin Lesions.

A multicentric double-blind, controlled, clinical trial was carried out to compare the efficacy of a combination of rifampicin 600 mg plus ofloxacin 400 mg plus minocycline 100 mg (ROM) administered as single dose with that of standard WHO/MDT/PB six months regimen. The study subjects were 236 previously untreated, smear-negative patients, without nerve trunk involvement and having only two or three skin lesions. Randomization was done on individual patient basis. Results were analyzed for mean clincal score for improvement, marked clinical improvement and complete clinical cure at the time of release from treatment and at 12 months and 18 months of follow-up. Clinical improvement was seen in most patients in both regimens. Marked improvement (i.e., more than 90% reduction in clinical score) at 18 months was seen in 46.2% and 53.4% of the patients treated with ROM and standard regimens, respectively. But, significant difference in favour of standard PB regimen was seen in patients with three skin lesions and in patients in whom more than one body part was affected. Reversal reaction and adverse drug reactions were minimal in both groups

Cancer and thrombosis: Managing the risks and approaches to thromboprophylaxis

Patients with cancer are at increased risk of venous thromboembolism (VTE) compared with patients without cancer. This results from both the prothrombotic effects of the cancer itself and iatrogenic factors, such as chemotherapy, radiotherapy, indwelling central venous devices and surgery, that further increase the risk of VTE. Although cancer-associated thrombosis remains an important cause of morbidity and mortality, it is often underdiagnosed and undertreated. However, evidence is accumulating to support the use of low-molecular-weight heparins (LMWHs) in the secondary prevention of VTE in patients with cancer. Not only have LMWHs been shown to be at least as effective as coumarin derivatives in this setting, but they have a lower incidence of complications, including bleeding, and are not associated with the practical problems of warfarin therapy. Furthermore, a growing number of studies indicate that LMWHs may improve survival among patients with cancer due to a possible antitumor effect. Current evidence suggests that LMWHs should increasingly be considered for the long-term management of VTE in patients with cancer

Does Preexisting Antiplatelet Treatment Influence Postthrombolysis Intracranial Hemorrhage in Community‐treated Ischemic Stroke Patients? An Observational Study

Objectives Intracranial hemorrhage ( ICH ) after acute stroke thrombolysis is associated with poor outcomes. Previous investigations of the relationship between preexisting antiplatelet use and the safety of intravenous ( IV ) thrombolysis have been limited by low event rates. The objective of this study was to determine whether preexisting antiplatelet therapy increased the risk of ICH following acute stroke thrombolysis. The primary hypothesis was that antiplatelet use would not be associated with radiographic evidence of ICH after controlling for relevant confounders. Methods Consecutive cases of thrombolysis patients treated in the emergency department (ED) were identified using multiple methods. Retrospective data were collected from four hospitals from 1996 to 2004 and 24 other hospitals from 2007 to 2010 as part of a cluster‐randomized trial. The same chart abstraction tool was used during both time periods, and data were subjected to numerous quality control checks. Hemorrhages were classified using a prespecified methodology: ICH was defined as presence of hemorrhage in radiographic interpretations of follow‐up imaging (primary outcome). Symptomatic ICH ( sICH ) was defined as radiographic ICH with associated clinical worsening. A multivariable logistic regression model was constructed to adjust for clinical factors previously identified to be related to postthrombolysis ICH. Sensitivity analyses were conducted where the unadjusted and adjusted results from this study were combined with those of previously published external studies on this topic via meta‐analytic techniques. Results There were 830 patients included, with 47% having documented preexisting antiplatelet treatment. The mean (± standard deviation [SD]) age was 69 (±15) years, and the cohort was 53% male. The unadjusted proportion of patients with any ICH was 15.1% without antiplatelet use and 19.3% with antiplatelet use (absolute risk difference = 4.2%, 95% confidence interval [CI] = −1.2% to 9.6%); for sICH this was 6.1% without antiplatelet use and 9% with antiplatelet use (absolute risk difference = 3.1%, 95% CI = −1% to 6.7%). After adjusting for confounders, antiplatelet use was not significantly associated with radiographic ICH (odds ratio [OR] = 1.1, 95% CI = 0.8 to 1.7) or sICH (OR = 1.3, 95% CI = 0.7 to 2.2). In patients 81 years and older, there was a higher risk of radiographic ICH (absolute risk difference = 11.9%, 95% CI = 0.1% to 23.6%). The meta‐analyses combined the findings of this investigation with previous similar work and found increased unadjusted risks of radiographic ICH (absolute risk difference = 4.9%, 95% CI = 0.7% to 9%) and sICH (absolute risk difference = 4%, 95% CI = 2.3% to 5.6%). The meta‐analytic adjusted OR of sICH for antiplatelet use was 1.6 (95% CI = 1.1 to 2.4). Conclusions The authors did not find that preexisting antiplatelet use was associated with postthrombolysis ICH or sICH in this cohort of community treated patients. Preexisting tobacco use, younger age, and lower severity were associated with lower odds of sICH . The meta‐analyses demonstrated small, but statistically significant increases in the absolute risk of radiographic ICH and sICH , along with increased odds of sICH in patients with preexisting antiplatelet use. Resumen ¿Influye el Tratamiento Antiagregante Previo en la Hemorragia Intracraneal tras la Trombolisis en los Pacientes con Ictus Isquémicos Tratados en la Comunidad? Un Estudio Observacional Objetivos La hemorragia intracraneal ( HIC ) tras la trombolisis de un ictus agudo se asocia con malos resultados. Los estudios previos de la relación entre el uso de antiagregantes y la seguridad de la trombolisis intravenosa ( IV ) han estado limitados por los porcentajes bajos de sucesos. El objetivo de este estudio fue determinar si el tratamiento antiagregante previo está asociado con la evidencia radiológica de HIC tras el control por los factores de confusión relevantes. Metodología Se identificaron los casos consecutivos de pacientes tratados con trombolisis en el SU de múltiples formas. Se recogieron los datos de forma retrospectiva de cuatro hospitales de 1996 a 2004 y de 24 hospitales distintos de 2007 a 2010 como parte de un ensayo clínico aleatorizado en racimos. Se utilizó la misma tabla resumen de historia clínica durante ambos periodos de tiempo y los datos fueron sometidos a numerosos controles de calidad. Las hemorragias se clasificaron siguiendo una metodología preestablecida: la HIC se definió como la presencia de hemorragia en las interpretaciones radiológicas de las imágenes de seguimiento (resultado primario); y la HIC sintomática ( HIC s) se definió como la HIC radiológica asociada con un empeoramiento clínico. Se construyó un modelo multivariable de regresión logística para ajustar los factores clínicos previamente identificados como relacionados con un la HIC tras la trombolisis. Los análisis de sensibilidad se realizaron mediante técnicas de metanálisis y se combinaron los resultados ajustados y no ajustados de esta investigación con los estudios externos previamente publicados en este tema. Resultados Se incluyeron 830 pacientes, de los cuales el 47% tenía documentado tratamiento antiagregante previo. La media de edad fue de 69 años, y el 53% eran varones. La proporción no ajustada de pacientes con cualquier tipo de HIC fue del 15,1% sin toma de antiagregante y del 19,3% con la toma de antiagregante (diferencia del riesgo absoluto 4,2%, IC 95% = −1,2% a 9,6%); y para las HIC s fue del 6,1% sin toma de antiagregantes y del 9% con la toma de antiagregantes (diferencia absoluta del riesgo 3,1%, IC 95% = −1% a 6,7%). Tras ajustar por los factores de confusión, la toma de antiagregantes no se asoció de forma significativa con la HIC radiológica ( OR 1,1, IC 95% = 0,8 a 1,7]) o HIC s ( OR 1,3, IC 95% = 0,7 a 2,2). En los pacientes de 81 años o más, hubo mayor riesgo de HIC radiológica (diferencia de riesgo absoluta 11,9%, IC 95% = 0,1% a 23,6%). El metanálisis que combinó los hallazgos de esta investigación con los trabajos similares previos encontró un riesgo no ajustado incrementado para la HIC radiológica (diferencia absoluta del riesgo 4,9%, IC 95% = 0,7% a 9%) y de HIC s (diferencia absoluta del riesgo 4%, IC 95% = 2,3% a 5,6%). La odds ratio ajustada del metanálisis de HIC s para los pacientes con tratamiento de antigregantes fue de 1,6 ( IC 95% = 1,1 a 2,4). Conclusiones Los autores no encontraron que la toma previa de antigregantes se asocie con la HIC o la HIC s tras la trombolisis en esta cohorte de pacientes tratados en la comunidad. El consumo previo de tabaco, la edad más joven y la menor gravedad se asociaron con odds ratio menores de HIC s. El metanálisis demostró un incremento bajo, aunque estadísticamente significativo, de riesgo absoluto de HIC radiológica o de HIC s, con una odds ratio aumentada de HIC s en los pacientes con toma previa de antiagregantes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/96759/1/acem12077.pd

Geography, private costs and uptake of screening for abdominal aortic aneurysm in a remote rural area

BACKGROUND: The relationship between geographical location, private costs, health provider costs and uptake of health screening is unclear. This paper examines these relationships in a screening programme for abdominal aortic aneurysm in the Highlands and Western Isles of Scotland, a rural and remote area of over 10,000 square miles. METHODS: Men aged 65–74 (n = 9323) were invited to attend screening at 51 locations in 50 settlements. Effects of geography, deprivation and age on uptake were examined. Among 8,355 attendees, 8,292 completed a questionnaire detailing mode of travel and costs incurred, time travelled, whether accompanied, whether dependants were cared for, and what they would have been doing if not attending screening, thus allowing private costs to be calculated. Health provider (NHS) costs were also determined. Data were analysed by deprivation categories, using the Scottish Indices of Deprivation (2003), and by settlement type ranging from urban to very remote rural. RESULTS: Uptake of screening was high in all settlement types (mean 89.6%, range 87.4 – 92.6%). Non-attendees were more deprived in terms of income, employment, education and health but there was no significant difference between non-attendees and attendees in terms of geographical access to services. Age was similar in both groups. The highest private costs (median £7.29 per man) and NHS screening costs (£18.27 per man invited) were observed in very remote rural areas. Corresponding values for all subjects were: private cost £4.34 and NHS cost £15.72 per man invited. CONCLUSION: Uptake of screening for abdominal aortic aneurysm in this remote and rural setting was high in comparison with previous studies, and this applied across all settlement types. Geographical location did not affect uptake, most likely due to the outreach approach adopted. Private and NHS costs were highest in very remote settings but still compared favourably with other published studies

Drug Treatment of Rheumatoid Arthritis

Inflammation is the central and essential component of rheumatoid arthritis, and control of inflammation by various drugs is paramount to the success of treatment of the disease. No specific cure is available for rheumatoid arthritis, but judicious and individualised treatment regimes can relieve symptoms, if not modify the disease process. A number of different types of drugs are available and will be discussed

The utility and predictive value of combinations of low penetrance genes for screening and risk prediction of colorectal cancer

Despite the fact that colorectal cancer (CRC) is a highly treatable form of cancer if detected early, a very low proportion of the eligible population undergoes screening for this form of cancer. Integrating a genomic screening profile as a component of existing screening programs for CRC could potentially improve the effectiveness of population screening by allowing the assignment of individuals to different types and intensities of screening and also by potentially increasing the uptake of existing screening programs. We evaluated the utility and predictive value of genomic profiling as applied to CRC, and as a potential component of a population-based cancer screening program. We generated simulated data representing a typical North American population including a variety of genetic profiles, with a range of relative risks and prevalences for individual risk genes. We then used these data to estimate parameters characterizing the predictive value of a logistic regression model built on genetic markers for CRC. Meta-analyses of genetic associations with CRC were used in building science to inform the simulation work, and to select genetic variants to include in logistic regression model-building using data from the ARCTIC study in Ontario, which included 1,200 CRC cases and a similar number of cancer-free population-based controls. Our simulations demonstrate that for reasonable assumptions involving modest relative risks for individual genetic variants, that substantial predictive power can be achieved when risk variants are common (e.g., prevalence > 20%) and data for enough risk variants are available (e.g., ~140–160). Pilot work in population data shows modest, but statistically significant predictive utility for a small collection of risk variants, smaller in effect than age and gender alone in predicting an individual’s CRC risk. Further genotyping and many more samples will be required, and indeed the discovery of many more risk loci associated with CRC before the question of the potential utility of germline genomic profiling can be definitively answered

An individual patient data meta-analysis of adjuvant therapy with uracil–tegafur (UFT) in patients with curatively resected rectal cancer

Uracil–Tegafur (UFT), an oral fluorinated pyrimidine chemotherapeutic agent, has been used for adjuvant chemotherapy in curatively resected colorectal cancer patients. Past trials and meta-analyses indicate that it is somewhat effective in extending survival of patients with rectal cancer. The objective of this study was to perform a reappraisal of randomised clinical trials conducted in this field. We designed an individual patient-based meta-analysis of relevant clinical trials to examine the benefit of UFT for curatively resected rectal cancer in terms of overall survival (OS), disease-free survival (DFS), and local relapse-free survival (LRFS). We analysed individual patient data of five adjuvant therapy randomised clinical trials for rectal cancer, which met the predetermined inclusion criteria. These five trials had a combined total of 2091 patients, UFT as adjuvant chemotherapy compared to surgery-alone, 5-year follow-up, intention-to-treat-based analytic strategy, and similar endpoints (OS and DFS). In a pooled analysis, UFT had significant advantage over surgery-alone in terms of both OS (hazard ratio, 0.82; 95% confidence interval (CI), 0.70–0.97; P=0.02) and DFS (hazard ratio, 0.73; 95%CI, 0.63–0.84; P<0.0001). This individual patient-based meta-analysis demonstrated that oral UFT significantly improves both OS and DFS in patients with curatively resected rectal cancer

Guidelines for the management of pregnancy in women with cystic fibrosis

Women with cystic fibrosis (CF) now regularly survive into their reproductive years in good health and wish to have a baby. Many pregnancies have been reported in the literature and it is clear that whilst the outcome for the baby is generally good and some mothers do very well, others find either their CF complicates the pregnancy or is adversely affected by the pregnancy. For some, pregnancy may only become possible after transplantation. Optimal treatment of all aspects of CF needs to be maintained from the preconceptual period until after the baby is born. Clinicians must be prepared to modify their treatment to accommodate the changing physiology during pregnancy and to be aware of changing prescribing before conception, during pregnancy, after birth and during breast feeding. This supplement offers consensus guidelines based on review of the literature and experience of paediatricians, adult and transplant physicians, and nurses, physiotherapists, dietitians, pharmacists and psychologists experienced in CF and anaesthetist and obstetricians with experience of CF pregnancy. It is hoped they will provide practical guidelines helpful to the multidisciplinary CF teams caring for pregnant women with CF

The third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke

<p>Abstract</p> <p>Background</p> <p>Intravenous recombinant tissue plasminogen activator (rt-PA) is approved for use in selected patients with ischaemic stroke within 3 hours of symptom onset. IST-3 seeks to determine whether a wider range of patients may benefit.</p> <p>Design</p> <p>International, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rt-PA in acute ischaemic stroke. Suitable patients must be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracerebral haemorrhage. With 1000 patients, the trial can detect a 7% absolute difference in the primary outcome. With3500 patients, it can detect a 4.0% absolute benefit & with 6000, (mostly treated between 3 & 6 hours), it can detect a 3% benefit.</p> <p>Trial procedures</p> <p>Patients are entered into the trial by telephoning a fast, secure computerised central randomisation system or via a secure web interface. Repeat brain imaging must be performed at 24–48 hours. The scans are reviewed 'blind' by expert readers. The primary measure of outcome is the proportion of patients alive and independent (Modified Rankin 0–2) at six months (assessed via a postal questionnaire mailed directly to the patient). Secondary outcomes include: events within 7 days (death, recurrent stroke, symptomatic intracranial haemorrhage), outcome at six months (death, functional status, EuroQol).</p> <p>Trial registration</p> <p>ISRCTN25765518</p