Single patient (n-of-1) trials with binary treatment preference

The use of a fully parametric Bayesian method for analysing single patient trials based on the notion of treatment 'preference' is described. This Bayesian hierarchical modelling approach allows for full parameter uncertainty, use of prior information and the modelling of individual and patient sub-group structures. It provides updated probabilistic results for individual patients, and groups of patients with the same medical condition, as they are sequentially enrolled into individualized trials using the same medication alternatives. Two clinically interpretable criteria for determining a patient's response are detailed and illustrated using data from a previously published paper under two different prior information scenarios. Copyright (C) 2005 John Wiley & Sons, Ltd.

E-Government, targeting and data profiling: Policy and ethical issues of differential treatment

Networked information and communication technologies are rapidly advancing the capacities of governments to target and separately manage specific sub-populations, groups and individuals. Targeting uses data profiling to calculate the differential probabilities of outcomes associated with various personal characteristics. This knowledge is used to classify and sort people for differentiated levels of treatment. Targeting is often used to efficiently and effectively target government resources to the most disadvantaged. Although having many benefits, targeting raises several policy and ethical issues. This paper discusses these issues and the policy responses governments may take to maximise the benefits of targeting while ameliorating the negative aspects.

Evidence-based medicine is affordable: The cost-effectiveness of current compared with optimal treatment in rheumatoid and osteoarthritis

Objective. To determine the cost-effectiveness of averting the burden of disease. We used secondary population data and metaanalyses of various government-funded services and interventions to investigate the costs and benefits of various levels of treatment for rheumatoid arthritis (RA) and osteoarthritis (OA) in adults using a burden of disease framework. Method. Population burden was calculated for both diseases in the absence of any treatment as years lived with disability (YLD), ignoring the years of life lost. We then estimated the proportion of burden averted with current interventions, the proportion that could be averted with optimally implemented cut-rent evidence-based guidelines, and the direct treatment cost-effectiveness ratio in dollars per YLD averted for both treatment levels. Results. The majority of people with arthritis sought medical treatment. Current treatment for RA averted 26% of the burden, with a cost-effectiveness ratio of $19,000 per YLD averted. Optimal, evidence-based treatment would avert 48% of the burden. with a cost-effectiveness ratio of $12,000 per YLD averted. Current treatment of OA in Australia averted 27% of the burden, with a cost-effectiveness ratio of $25,000 per YLD averted. Optimal, evidence-based treatment would avert 39% of the burden, with an unchanged cost-effectiveness ratio of $25,000 per YLD averted. Conclusion. While the precise dollar costs in each country will differ, the relativities at this level of coverage should remain the same. There is no evidence that closing the gap between evidence and practice would result in a drop in efficiency.

Re-treatment of chronic hepatitis C patients after relapse: efficacy of peginterferon-alpha-2a (40 kDa) and ribavirin

SUMMARY. We conducted a randomized multinational study to determine whether 48 weeks of re-treatment with peginterferon- alpha-2a (40 kDa) plus ribavirin would induce a sustained virological response (SVR) in relapsed chronic hepatitis C patients. Patients who had previously relapsed during 24 weeks of untreated follow-up, after having achieved an end-of-treatment virological response with 24 weeks of peginterferon-alpha-2a (40 kDa)/ribavirin combination therapy, within a phase III trial, were studied. Although the recommended dosage was the same as that used at the end of the initial trial, adjustments were permitted. Data on serious adverse events, or adverse events that resulted in dose reductions or discontinuations, were collected. Following re-treatment, the overall SVR rate in the 64 patients was 55%. The SVR rates in patients infected with hepatitis C virus (HCV) genotype 1 and non-1 genotypes were 51% and 63%, respectively. Early (week 12) virological responses were seen in 39 patients (61%) and were predictive of an SVR. Re-treatment was well tolerated. The most frequent adverse events recorded were fatigue (5%) and abdominal pain (3%). Dosages of peginterferon-alpha-2a (40 kDa) and/or ribavirin were modified because of adverse events in 3% and 13% of patients, and because of laboratory abnormalities in 23% and 5% of patients, respectively. Thus, a 48-week course of peginterferon-alpha-2a (40 kDa) plus ribavirin induces an SVR in 55% of patients who relapsed during follow-up after 24 weeks of combination therapy. Physicians should not hesitate to offer re-treatment to patients who relapse after an initial, 24-week course of combination therapy, or who have prematurely stopped treatment because, for example, of laboratory abnormalities.

Successful treatment of post-influenza pseudomembranous necrotising bronchial aspergillosis with liposomal amphotericin, inhaled amphotericin B, gamma interferon and GM-CSF

A case of aspergillus tracheobronchitis following influenza A infection in an immunocompetent 35 year old woman is described that required prolonged mechanical ventilation for airways obstruction. Treatment included liposomal amphotericin, inhaled amphotericin, gamma interferon and GM-CSF. Liposomal amphotericin therapy was associated with reversible hepatosplenomegaly. Inhaled corticosteroids with continued antifungal therapy were used for the management of severe recurrent airway obstruction. After a prolonged course of treatment she survived with fixed airways obstruction unresponsive to corticosteroids.

Costs and Benefits of Stem Cell Research and Treatment: Media Presentation and Audience Understanding in Hungary

This study examined the press coverage and audience understanding of the costs and benefits of stem cell research/treatment in Hungary. A content analysis of five newspapers and a focus group study was conducted. The way participants talked about the costs and benefits in many aspects echoed the dominant framing of the issue in the press (medical benefits = main benefit, high expense of treatment = dominant negative aspect). Even though participants applied analogical reasoning to formulate some risks that were missing from the reporting on stem cells, many gaps of the media coverage were echoed in gaps in lay discussions.

Commitment language as a predictor of alcohol and marijuana use outcomes among adolescents in school -based group treatment

Despite widespread recognition of the problem of adolescent alcohol and other drug (AOD) abuse, research on its most common treatment modality, group work, is lacking. This research gap is alarming given that outcomes range from positive to potentially iatrogenic. This study sought to identify change mechanisms and/or treatment factors that are observable within group treatment sessions and that may predict AOD use outcomes. This NIH (F31 DA 020233-01A1) study evaluated 108, 10-19 year olds and the 19 school-based treatment groups to which they were previously assigned (R01 AA10246; PI: Wagner). Associations between motivational interviewing (MI) based change talk variables, group leader MI skills, and alcohol and marijuana use outcomes up to 12-months following treatment were evaluated. Treatment session audio recordings and transcripts (1R21AA015679-01; PI: Macgowan) were coded using a new discourse analysis coding scheme for measuring group member change talk (Amrhein, 2003). Therapist MI skills were similarly measured using the Motivational Interviewing Treatment Integrity instrument. Group member responses to commitment predicted group marijuana use at the 1-month follow up. Also, group leader empathy was significantly associated with group commitment for marijuana use at the middle and ending stages of treatment. Both of the above process measures were applied in a group setting for the first time. Building upon MI and social learning theory principles, group commitment and group member responses to commitment are new observable, in-session, process constructs that may predict positive and negative adolescent group treatment outcomes. These constructs, as well as the discourse analysis method and instruments used to measure them, raise many possibilities for future group work process research and practice.

Treatment attrition among racial /ethnic minority adolescents participating in a brief motivational intervention for substance use problems: The influence of individual, social, cultural, and treatment factors

The present study has the primary aim of examining the predictors of treatment attrition among racial/ethnic minority adolescents with substance use problems. This study explores the potential differential influence of specific individual, social, cultural, and treatment factors on treatment attrition within three racial/ethnic subgroups of adolescents. Participants: A unique feature of the study is the use of a racial/ethnic minority sample (N=453), [U.S.-born Hispanics (n = 262), Foreign-born Hispanics (n = 117), and African-Americans (n = 74)]. Multivariate logit analyses were used to examine the influence of specific factors on treatment attrition among the full sample of adolescents, as well as within each racial/ethnic subgroup. Consistent with expectations, multivariate logit analyses reveal that, the specific factors associated with attrition varied across the three racial/ethnic subgroups. Having parents with problem substance use, being on the waitlist, and being court mandated to treatment emerged as predictors of attrition among the US-born Hispanics, while only Conduct Disorder was significantly associated with greater attrition among foreign-born Hispanics. Finally, among African-Americans, parental crack/cocaine use, parental abstinence from alcohol, and being on the waitlist were predictive of attrition. Multiple factors were associated with treatment attrition among racial/ethnic minority adolescents with specific factors differentially predicting attrition within each racial/ethnic subgroup. African-American youth were more than twice as likely as their Hispanic counterparts to leave treatment prematurely. It is critically important to understand the predictors of attrition among racial/ethnic minority youth in order to better meet the needs of youth most at risk of dropping out. ^

Identity as a moderator of guided -self change treatment outcomes with adolescents

Despite recent calls to examine the possible moderating effects of developmental variables on treatment outcomes with adolescents, most research has continued to focus on age as a main developmental variable. Building upon the theoretical notion that identity development is a central task of adolescence, this study investigated whether adolescents' response to an alcohol and other drug (AOD) use reduction intervention, Guided-Self Change (GSC), was influenced by their approach to self-defining questions and situations. While past research has established associations between maladaptive identity development and alcohol and other drug use, very little research attention has been given to the potential relationship that may exist between identity variables and AOD treatment response. Given GCS's promotion of self-reflective, self-exploring, and problem-focused coping skills as a way of addressing AOD problems, it was hypothesized that adolescents with positive identity development (i.e., greater identity coherence and adaptive identity processing styles) would respond more positively to GCS's change producing therapeutic techniques than their counterparts. This hypothesis was tested with an ethnically diverse sample of 134 adolescents between the ages of 14-18 years who were randomly assigned to either a GSC intervention or a comparison control group. Results revealed that identity development was significantly associated with AOD use, such that adolescents with diffused/avoidant styles and high levels of distress over identity-related issues used more alcohol at the baseline assessment than those with more positive identity development. Results also indicated that while identity distress or identity coherence did not moderate GSC treatment outcomes, high scores for a diffused/avoidant style did moderate treatment outcomes and thus proved to be a significant predictor of treatment response. These results indicate that identity development influences adolescents' alcohol use and that while use of certain approaches to self-defining questions does not predict treatment outcomes, high use for negative approaches does moderate intervention-related change. ^

Treatment attrition among racial/ethnic minority adolescents participating in a brief motivational intervention for substance use problems : the influence of individual, social, cultural, and treatment factors

The present study has the primary aim of examining the predictors of treatment attrition among racial/ethnic minority adolescents with substance use problems. This study explores the potential differential influence of specific individual, social, cultural, and treatment factors on treatment attrition within three racial/ethnic subgroups of adolescents. Participants: A unique feature of the study is the use of a racial/ethnic minority sample (N=453), [U.S.-born Hispanics (n = 262), Foreign-born Hispanics (n = 117), and African- Americans (n = 74)]. Multivariate logit analyses were used to examine the influence of specific factors on treatment attrition among the full sample of adolescents, as well as within each racial/ethnic subgroup. Consistent with expectations, multivariate logit analyses reveal that, the specific factors associated with attrition varied across the three racial/ethnic subgroups. Having parents with problem substance use, being on the waitlist, and being court mandated to treatment emerged as predictors of attrition among the US-born Hispanics, while only Conduct Disorder was significantly associated with greater attrition among foreign-born Hispanics. Finally, among African-Americans, parental crack/cocaine use, parental abstinence from alcohol, and being on the waitlist were predictive of attrition. Multiple factors were associated with treatment attrition among racial/ethnic minority adolescents with specific factors differentially predicting attrition within each racial/ethnic subgroup. African-American youth were more than twice as likely as their Hispanic counterparts to leave treatment prematurely. It is critically important to understand the predictors of attrition among racial/ethnic minority youth in order to better meet the needs of youth most at risk of dropping out.

An examination of the role of the sports and exercise medicine specialist in Ireland- from epidemiology to treatment

The expansion of the specialty of sports and exercise medicine (SEM) is a relatively recent development in the medical community and the role of the SEM specialist continues to evolve and develop. The SEM specialist is ideally placed to care for all aspects of physical activity not only in athletes but also in the general population. As an advocate for physical activity the SEM specialist plays a broad role in advising safe effective sports and recreation participation; screening for disease related to sports participation; examining and contributing to the evidence behind treatment strategies and evaluating any potential negative impact of sports injury prevention measures. In this thesis I will demonstrate the breadth of the role the Sports and Exercise Medicine Specialist from epidemiology to in-depth examination of treatment strategies. In Chapter 2, I examined the epidemiology of sports and recreation related injury (SRI) in Ireland, an area that has previously been poorly studied. We report on 3,172 SRI (14% of total presentations) presentations to the ED over 6 months. Paediatric patients (4-16 yrs) were over represented comprising 39.9% of all SRI presentation compared to 16% of total ED presentations and 18% of the general population. These injuries were serious (32% fractures) and though 49% of injuries occurred during organised competition/practice, 41.5% occurred during recreation-most often at home. In Chapter 3, I examined risk factors associated with hand injury in hurling. The previous chapter highlighted the importance of a firm evidence base underpinning treatment strategies. When measures to improve welfare are introduced not only must potential benefits be measured, so too must potential unwanted adverse outcomes. In this study I examined a cohort of adult hurlers who had presented to the ED with a hurling related injury in order to highlight the variables associated with hand injury in this population. I found the athletes who wore a helmet were far more likely (OR 3.15 95% CI (1.51-6.56) p= 0.002) to suffer a hand injury than athletes who did not. Very few of those interviewed (4.9%) used hand protection compared to 65% who used helmet and faceguard. The introduction of the helmet and faceguard in hurling has undeniably decreased the incidence of head and face injury in hurling. However in tandem with this intervention several observational studies have demonstrated an increase in the occurrence of hurling related hand injuries. This study highlights the importance of being cognisant of unanticipated or unintended consequences when implementing a new treatment or intervention. In Chapter 4, I examined the role of population screening as applied to sport and exercise. This is a controversial area –cardiac screening in the exercising population has been the subject of much debate. Specifically I define the prevalence of exercise induced bronchoconstriction (EIB) using a specifically designed sports specific field-testing protocol. In this study I found almost a third (29%) of a full international professional rugby squad had confirmed asthma or EIB, as compared with 12-15% of the general population. Despite regular medical screening, 5 ‘new’ untreated cases (12%) were elicited by the challenge test and in the group already on treatment for asthma/EIB; over 50% still displayed EIB. In Chapter 5, I examined the evidence supporting current treatment options for iliotibial band friction syndrome (ITBFS). The practice of sports medicine has traditionally been ‘eminence based’ rather than ‘evidence based’. This may be problematic as some of these practices are based upon flawed principles- for example the treatment of iliotibial band friction syndrome (ITBFS). In this chapter, using cadaveric and biomechanical studies I expand upon the growing base of evidence clarifying the anatomy and biomechanics of the area-thereby re-examining the principles on which current treatments are based. The role of the SEM specialist is broad; we chose to examine specific examples of some of the roles that they execute. An understanding of the epidemiology of SRI presenting to the ED has implications for individual patients, sports governing bodies and health resource utilisation. Population screening is an important tool in health promotion and disease prevention in the general population. Screening in SEM may have similar less well-recognised benefits. The SEM specialist needs to be conversant in screening for medical conditions concerning physical activity. A comprehensive understanding of the pathophysiology of a disease is required for its diagnosis and treatment. Due to the ongoing evolution of SEM many treatments are eminence-based rather than evidence‐based practice. Continued re-examination of the fundamentals of current practice is essential. An awareness of potential unwanted side effects is essential prior to the introduction of any new treatment or intervention. The SEM specialist is ideally placed to advise sports governing bodies on these issues prior to and during their implementation.

Three-dimensional outcomes of twin-block appliance treatment and the influence of the postured wax bite

Aims 1 To identify the 3D soft tissue volumetric and linear landmark changes following treatment with the Twin-Block Appliance TBA. 2 To estimate the TBA treatment outcome on the soft tissue facial profile volumetric and linear landmark changes from the Postured Wax Bite (PWB). 3 To identify if there is any association between certain soft tissue landmark variables and successful treatment outcome of the TBA as measured by the reduction in overjet. 4 To assess the effects of TBA treatment on facial expressions. Materials and Methods Forty-seven Caucasian subjects with Class II division 1 were recruited. 3D images captured of each subject, pre-treatment (T1), with the PWB (T2) and at the end of treatment (T3). Soft tissue volumetric and linear changes as well as the correlation between facial parameters and successful treatment were calculated. Results The mean soft tissue volumetric change from T1 to T3 was 22.24 ± 16.73 cm³. Soft tissue profile linear changes from T1-T3 for lower facial landmarks were 4-5 mm. From T1-T3, the mean soft tissue volumetric change of the total sample was 60% of the change produced by the PWB (T1 to T2). Correlations were weak for all 3D facial parameters and successful overjet reduction. Facial expression changes were only significant for the lower landmarks. Conclusions 1 TBA treatment, in growing subjects, increased the lower facial soft tissue volume and caused forward movement of the lower soft tissue facial profile landmarks.2 The PWB can be used to estimate the treatment outcome of the TBA on soft tissue profile changes.3 No association was found between soft tissue landmark variables and successful overjet reduction.4 TBA treatment had no effect on the upper facial landmarks for each facial expression but it changed the lower facial expressions significantly except for maximal smile in males.

Knowledge of the patients regarding leprosy and adherence to treatment

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. It is known for its great disfiguring capacity and is considered an extremely serious disease to public health worldwide. The state of Ceará ranks 13th in number of cases of leprosy in Brazil, and fourth in Northeastern region, with an average of 2,149 new cases diagnosed every year. This study aimed to evaluate the knowledge of leprosy patients regarding treatment, and to assess the level of treatment adherence and its possible barriers. The study was conducted in the reference center for dermatology, from September 2010 to October 2010, in Fortaleza, Ceará. The study data were collected by means of a structured interview, along with the Morisky-Green test, in order to assess treatment adherence and barriers to adherence. A total of 70 patients were interviewed, out of whom 66 were new cases. The majority of patients were between 42 and 50 years old, and 37 (52.9%) were male. Most patients were clinically classified as presentingmultibacillary leprosy (80%), and 78.6% of them were from Fortaleza, Brazil. The Morisky-Green test indicated that 62.9% of patients presented a low level of adherence (p < 0.005), despite claiming to aware of the disease risks. However, it was observed that 57.1% of the patients had no difficulty adhering to treatment, while 38.6% reported little difficulty. This study shows that despite the patients claiming to be familiar with leprosy and its treatment, the Morisky-Green test clearly demonstrated that they actually were not aware of the principles of therapy, which is evidenced by the low degree of treatment adherence

Surgical treatment of thymoma. Personal experience

Introduction. Thymomas (THs) are rare epithelial tumors of the thymus gland. In this study we report our personal experience in the management and surgical treatment of THs. Case reports. We report two clinical cases treated with combined therapy (surgery followed by adjuvant therapy). Results. Total transternal thymectomy was performed in both patients. The post-operative course was uneventful. The patients received adjuvant radiotherapy and chemotherapy. No relapse has been observed during follow-up. Discussion. THs are usually slowly growing tumors with similar incidence in both sexes. They occur through a wide age range, with a peak in the fifth and sixth decades. Distinctive features reminiscent of the normal thymus make the pathologic diagnosis of THs easy in most cases. Malignant behaviour is indicated by microscopic or macroscopic invasion of the tumor capsule or surrounding organs or by the presence of metastases. Although there is no standardized staging system for thymoma, the one proposed by Masaoka is commonly employed. Total thymectomy is the procedure of choice, even for encapsulated tumors, with carefully exploration of the mediastinum for evidence of ectopic thymic tissue or local invasion. Conclusions. Despite an indolent course and a cytologically bland appearance, all thymic tumors can manifest a malignant behavior. Surgery continues to be the mainstay of treatment, and the ability to achieve complete resection seems to be the most important prognostic factor. Multimodality treatment involving postoperative chemotherapy and radiotherapy appears to increase the rate of complete resection and improves survival in advanced THs.

Knowledge of the patients regarding leprosy and adherence to treatment

Leprosy is a chronic infectious disease caused by Mycobacterium leprae. It is known for its great disfiguring capacity and is considered an extremely serious disease to public health worldwide. The state of Ceará ranks 13th in number of cases of leprosy in Brazil, and fourth in Northeastern region, with an average of 2,149 new cases diagnosed every year. This study aimed to evaluate the knowledge of leprosy patients regarding treatment, and to assess the level of treatment adherence and its possible barriers. The study was conducted in the reference center for dermatology, from September 2010 to October 2010, in Fortaleza, Ceará. The study data were collected by means of a structured interview, along with the Morisky-Green test, in order to assess treatment adherence and barriers to adherence. A total of 70 patients were interviewed, out of whom 66 were new cases. The majority of patients were between 42 and 50 years old, and 37 (52.9%) were male. Most patients were clinically classified as presentingmultibacillary leprosy (80%), and 78.6% of them were from Fortaleza, Brazil. The Morisky-Green test indicated that 62.9% of patients presented a low level of adherence (p < 0.005), despite claiming to aware of the disease risks. However, it was observed that 57.1% of the patients had no difficulty adhering to treatment, while 38.6% reported little difficulty. This study shows that despite the patients claiming to be familiar with leprosy and its treatment, the Morisky-Green test clearly demonstrated that they actually were not aware of the principles of therapy, which is evidenced by the low degree of treatment adherence