Left ventricular dyssynchrony predicts response and prognosis after cardiac resynchronization therapy

OBJECTIVES This study was designed to predict the response and prognosis after cardiac resynchronization therapy (CRT) in patients with end-stage heart failure (HF). BACKGROUND Cardiac resynchronization therapy improves HF symptoms, exercise capacity, and left ventricular (LV) function. Because not all patients respond, preimplantation identification of responders is needed. In the present study, response to CRT was predicted by the presence of LV dyssynchrony assessed by tissue Doppler imaging. Moreover, the prognostic value of LV dyssynchrony in patients undergoing CRT was assessed. METHODS Eighty-five patients with end-stage HF, QRS duration >120 ins, and left bundle-branch block were evaluated by tissue Doppler imaging before CRT. At baseline and six months follow-up, New York Heart Association functional class, quality of life and 6-min walking distance, LV volumes, and LV ejection fraction were determined. Events (death, hospitalization for decompensated HF) were obtained during one-year follow-up. RESULTS Responders (74%) and nonresponders (26%) had comparable baseline characteristics, except for a larger dyssynchrony in responders (87 +/- 49 ms vs. 35 +/- 20 ms, p < 0.01). Receiver-operator characteristic curve analysis demonstrated that an optimal cutoff value of 65 ms for LV dyssynchrony yielded a sensitivity and specificity of 80% to predict clinical improvement and of 92% to predict LV reverse remodeling. Patients with dyssynchrony :65 ms had an excellent prognosis (6% event rate) after CRT as compared with a 50% event rate in patients with dyssynchrony <65 ins (p < 0.001). CONCLUSIONS Patients with LV dyssynchrony greater than or equal to65 ms respond to CRT and have an excellent prognosis after CRT. (C) 2004 by the American College of Cardiology Foundation.

Expression profiling correlates with treatment response in women with advanced serous epithelial ovarian cancer

The majority of epithelial ovarian carcinomas are of serous subtype, with most women presenting at an advanced stage. Approximately 70% respond to initial chemotherapy but eventually relapse. We aimed to find markers of treatment response that might be suitable for routine use, using the gene expression profile of tumor tissue. Thirty one women with histologically-confirmed late-stage serous ovarian cancer were classified into 3 groups based on response to treatment (nonresponders, responders with relapse less than 12 months and responders with no relapse within 12 months). Gene expression profiles of these specimens were analyzed with respect to treatment response and survival (minimum 36 months follow-up). Patients' clinical features did not correlate with prognosis, or with specific gene expression patterns of their tumors. However women who did not respond to treatment could be distinguished from those who responded with no relapse within 12 months based on 34 gene transcripts (p < 0.02). Poor prognosis was associated with high expression of inhibitor of differentiation-2 (ID2) (p = 0.001). High expression of decorin (DCN) and ID2 together was strongly associated with reduced survival (p = 0.003), with an estimated 7-fold increased risk of dying (95% CI 1.9-29.6; 14 months survival) compared with low expression (44 months). Immunohistochemical analysis revealed both nuclear and cytoplasmic distribution of ID2 in ovarian tumors. High percentage of nuclear staining vas associated with poor survival, although not statistically significantly. In conclusion, elevated expression of ID2 and DCN was significantly associated with poor prognosis in a homogeneous group of ovarian cancer patients for whom survival could not be predicted from clinical factors. (c) 2006 Wiley-Liss, Inc.

An n-of-1 trial service in clinical practice: Testing the effectiveness of stimulants for attention-deficit/hyperactivity disorder

OBJECTIVE. We sought to describe the clinical use of n-of-1 trials for attention-deficit/hyperactivity disorder in publicly and privately funded family and specialized pediatric practice in Australia. METHODS. We used a within-patient randomized, double-blind, crossover comparison of stimulant (dexamphetamine or methylphenidate) versus placebo or alternative stimulant using 3 pairs of treatment periods. Trials were conducted from a central location using mail and telephone communication, with local supervision by the patients' clinicians. PATIENTS. Our study population included children with clinically diagnosed attention-deficit/ hyperactivity disorder who were aged 5 to 16 years and previously stabilized on an optimal dose of stimulant. They were selected because treatment effectiveness was uncertain. MAIN OUTCOME MEASURES. Our measures included number of patients recruited, number of doctors who used the service, geographic spread, completion rates, response rate, and post-n-of-1 trial decisions. RESULTS. Forty-five doctors across Australia requested 108 n-of-1 trials, of which 86 were completed. In 69 drug-versus-placebo comparisons, 29 children responded better to stimulant than placebo. Immediately posttrial, 19 of 25 drug-versus-placebo responders stayed on the same stimulant, and 13 of 24 nonresponders ceased or switched stimulants. In 40 of 63 for which data were available, posttrial management was consistent with the trial results. For all types of n-of-1 trials, management changed for 28 of 64 children for whom information was available. DISCUSSION. Attention-deficit/hyperactivity disorder n-of-1 trials can be implemented successfully by mail and telephone communication. This type of trial can be valuable in clarifying treatment effect when it is uncertain, and in this series, they had a noticeable impact on short-term management.

The corporatization of community pharmacy:implications for service provision, the public health function, and pharmacy's claims to professional status in the United Kingdom

Background Pharmacy has experienced both incomplete professionalization and deprofessionalization. Since the late 1970s, a concerted attempt has been made to re-professionalize pharmacy in the United Kingdom (UK) through role extension—a key feature of which has been a drive for greater pharmacy involvement in public health. However, the continual corporatization of the UK community pharmacy sector may reduce the professional autonomy of pharmacists and may threaten to constrain attempts at reprofessionalization. Objectives The objectives of the research: to examine the public health activities of community pharmacists in the UK; to explore the attitudes of community pharmacists toward recent relevant UK policy and barriers to the development of their public health function; and, to investigate associations between activity, attitudes, and the type of community pharmacy worked in (eg, supermarket, chain, independent). Methods A self-completion postal questionnaire was sent to a random sample of practicing community pharmacists, stratified for country and sex, within Great Britain (n = 1998), with a follow-up to nonresponders 4 weeks later. Data were analyzed using SPSS (SPSS Inc., Chicago, IL, USA) (v12.0). A final response rate of 51% (n = 1023/1998) was achieved. Results The level of provision of emergency hormonal contraception on a patient group direction, supervised administration of medicines, and needle-exchange schemes was lower in supermarket pharmacies than in the other types of pharmacy. Respondents believed that supermarkets and the major multiple pharmacy chains held an advantageous position in terms of attracting financing for service development despite suggesting that the premises of such pharmacies may not be the most suitable for the provision of such services. Conclusions A mixed market in community pharmacy may be required to maintain a comprehensive range of pharmacy-based public health services and provide maximum benefit to all patients. Longitudinal monitoring is recommended to ensure that service provision is adequate across the pharmacy network.

A Randomized Phase II Crossover Study of Imatinib or Rituximab for Cutaneous Sclerosis after Hematopoietic Cell Transplantation.

PURPOSE: Cutaneous sclerosis occurs in 20% of patients with chronic graft-versus-host disease (GVHD) and can compromise mobility and quality of life. EXPERIMENTAL DESIGN: We conducted a prospective, multicenter, randomized, two-arm phase II crossover trial of imatinib (200 mg daily) or rituximab (375 mg/m(2) i.v. weekly × 4 doses, repeatable after 3 months) for treatment of cutaneous sclerosis diagnosed within 18 months (NCT01309997). The primary endpoint was significant clinical response (SCR) at 6 months, defined as quantitative improvement in skin sclerosis or joint range of motion. Treatment success was defined as SCR at 6 months without crossover, recurrent malignancy or death. Secondary endpoints included changes of B-cell profiles in blood (BAFF levels and cellular subsets), patient-reported outcomes, and histopathology between responders and nonresponders with each therapy. RESULTS: SCR was observed in 9 of 35 [26%; 95% confidence interval (CI); 13%-43%] participants randomized to imatinib and 10 of 37 (27%; 95% CI, 14%-44%) randomized to rituximab. Six (17%; 95% CI, 7%-34%) patients in the imatinib arm and 5 (14%; 95% CI, 5%-29%) in the rituximab arm had treatment success. Higher percentages of activated B cells (CD27(+)) were seen at enrollment in rituximab-treated patients who had treatment success (P = 0.01), but not in imatinib-treated patients. CONCLUSIONS: These results support the need for more effective therapies for cutaneous sclerosis and suggest that activated B cells define a subgroup of patients with cutaneous sclerosis who are more likely to respond to rituximab.

Individual Variation in VO2peak Response Following Sprint Interval Training: The Role of Peripheral Adaptation

There is a large degree of heterogeneity in response to regular physical activity at the individual level, with some exhibiting no or very small improvements in VO2peak following highly controlled exercise training. The purpose of this thesis was to examine individual variation in VO2peak response to sprint interval training (SIT) in relation to individual responses to multiple measures of peripheral physiological adaptation. Specifically, VO2peak, capillary density, fibre-specific SDH content, and type I fibre % were measured in 23 young, healthy, recreationally active males before and after 4 weeks SIT (Tabata protocol 4 x per week). The key findings of this experiment included that, when separated into tertiles of VO2peak response, the high (HI) and low (LO) groups differed significantly in VO2peak change after training. Secondly, there was no difference between HI and LO groups for response in any of capillary density, fibre-specific SDH content, or fibre type %, with no correlation found between individual VO2peak response and changes in any measured peripheral variable. Together, these results confirm that individuals respond heterogeneously to SIT and suggest that this heterogeneity does not result from differences in individual changes in capillary density, fibre-specific SDH content or type I fibre %. It is speculated that some other combination of peripheral physiological adaptation must explain variability in VO2peak response to 4 weeks of SIT.

Arritmias ventriculares en superrespondedores a la terapia de resincronización cardiaca

La terapia de resincronización cardiaca se asocia a mejora de la calidad de vida y reducción de la morbimortalidad de los pacientes con disfunción ventricular grave y QRS ancho. Sobre su papel en la reducción de arritmias ventriculares, hay más discusión. Se comparó la incidencia de arritmias ventriculares en pacientes portadores de desfibrilador automático implantable con función de resincronización cardiaca, según el grado de respuesta ecocardiográfica a la resincronización. Se clasificó a los pacientes en tres subgrupos: superrespondedores, respondedores y no respondedores. Se incluyó a 196 pacientes seguidos durante una mediana de 30,1 [intervalo intercuartílico, 18,0-55,1] meses. Se documentó presencia de arritmias ventriculares en 37 pacientes (18,8%); 3 pacientes (5,9%) del grupo de superrespondedores presentaron arritmias ventriculares, en comparación con 14 (22,2%) del grupo de respondedores y 20 (24,4%) del grupo de no respondedores (p = 0,025). En el análisis multivariable, el implante del dispositivo en prevención secundaria (odds ratio = 4,04; intervalo de confianza del 95%, 1,52-10,75; p = 0,005), la ausencia de superrespuesta ecocardiográfica (odds ratio = 3,81; intervalo de confianza del 95%, 1,04-13,93; p = 0,043), un QRS > 160 ms (odds ratio = 2,39; intervalo de confianza del 95%, 1,00-1,35; p = 0,049) y el tratamiento con amiodarona (odds ratio = 2,47; intervalo de confianza del 95%, 1,03-5,91; p = 0,041) fueron los únicos predictores independientes de aparición de arritmias ventriculares. Los pacientes superrespondedores a la terapia de resincronización cardiaca presentan una disminución significativa en la incidencia de arritmias ventriculares respecto a los demás pacientes. Pese a ello, los episodios arrítmicos no llegan a desaparecer por completo en este subgrupo.