The development and validation of the impact of multiple sclerosis scale and the symptoms of multiple sclerosis scale

Objective

To develop and validate the Impact of Multiple Sclerosis Scale (IMSS) and the Symptoms of Multiple Sclerosis Scale (SMSS) using the Extended Disability Status Scale (EDSS) for construct validity.
Design

Panel design involving test-retest over 4 months.
Setting

A mailed survey.
Participants

Volunteers with a diagnosis of multiple sclerosis (MS) recruited from an MS support service in Australia: 193 people (mean age, 39y) and 150 people participated at time 1 and time 2, respectively.
Interventions

Not applicable.
Main Outcome Measures

Principal components analyses, the Cronbach α, and descriptive statistics for the 2 scales; correlations for construct validity with the EDSS and retest; and confirmatory factor analysis to test the stability of IMSS and SMSS components over time.
Results

The IMSS yielded 5 independent and reliable components; the SMSS yielded 3 components; both component structures were stable over time. These scales showed convergent validity with the EDSS.
Conclusions

The IMSS and SMSS are psychometrically sound scales suitable for clinical and research purposes to assess the symptoms and impact of MS.

Asymptomatic hypoechoic regions on patellar tendon ultrasound : a 4-year clinical and ultrasound followup of 46 tendons

Patellar tendon ultrasound appearance is commonly used in clinical practice to diagnose patellar tendinopathy and guide management. Using a longitudinal study design we examined whether or not the presence of a hypoechoic ultrasonographic lesion in an asymptomatic patellar tendon conferred a risk for developing jumper's knee compared with a tendon that was ultrasonographically normal. Ultrasonographic, symptomatic and anthropometric assessment was completed at baseline and followup. Magnetic resonance imaging was performed on four tendons that resolved ultrasonographically in the study period. Forty-six patellar tendons were followed over 47±11.8 months. Eighteen tendons were hypoechoic at baseline and 28 were ultrasonographically normal. Five tendons resolved ultrasonographically in the study period. Magnetic resonance imaging in four of these tendons was normal. Seven normal patellar tendons at baseline developed a hypoechoic area but only two became symptomatic. Analysis of ultrasonography at baseline and clinical outcome with Fisher's exact test shows there is no association between baseline ultrasound changes and symptoms at followup. In this study there is no statistically significant relationship between ultrasonographic patellar tendon abnormalities and clinical outcome in elite male athletes. Management of jumper's knee should not be solely based on ultrasonographic appearance; clinical assessment remains the cornerstone of appropriate management.

Clinical features of patellar tendinopathy and their implications for rehabilitation

This study investigated the clinical features of patellar tendinopathy (PT), with focus on individuals with unilateral and bilateral PT. A cross-sectional study design was employed to compare individuals with unilateral (n = 14) or bilateral (n = 13) PT and those without PT (control, n = 31). Features assessed included thigh strength (normalized peak knee extensor torque) and flexibility (sit-and-reach and active knee extension), calf endurance (heel-rise test), ankle flexibility (dorsiflexion), alignment measures (arch height and leg length difference), and functional measures (hop for distance and 6 m hop test). Groups were matched for age and height; however, unilateral and bilateral PT had greater mass with a higher body mass index (BMI) than control. Also, bilateral PT performed more sport hours per week than both unilateral PT and control. Unilateral PT had less thigh strength than control and bilateral PT, whereas bilateral PT had more thigh flexibility than control and unilateral PT. Both unilateral and bilateral PT had altered alignment measures compared to control. Features that predicted symptoms in PT were lower thigh flexibility and strength, whereas those that predicted function were higher thigh strength and lower ankle flexibility.  These findings indicate that unilateral and bilateral PT represent distinct entities, and that thigh strength appears particularly important in PT as it predicted both symptoms and function in PT.

Psychoeducational approaches to managing behavioural symptoms of dementia

Behavioural symptoms of dementia, such as wandering, aggression, and restlessness, are commonly manifested by residents of long-term residential facilities, and are associated with a range of negative outcomes. This paper reviews the literature on the efficacy of psychoeducation programs to improve the skills of residential care staff in managing these symptoms. The benefits and limitations of this approach are illustrated through presentation of case studies from clinical practice, with a focus on organisational and motivational factors. Preliminary data from a psychoeducation program delivered by an Aged Persons Mental Health Team are presented. Recommendations are made for future research and practice.

Novel and effective treatment modality for medically unexplained symptoms

Medically unexplained symptoms (MUS) confound physicians, and the incidence and prevalence of these conditions is poorly documented.  This is not least due to the complex nature of MUS and mimicry of morbidity with conditions that have common clinical assessment and treatment modalities, e.g. migraine headaches which stress headaches commonly are misdiagnosed as.  Effective treatment modalities for MUS have been more or less non-existent.  In the following we present a modality for the assessment, diagnosis and treatment of MUS that in our experience leads to cure, at least in better than half of these cases measured in terms of allowing the individual back to work.  These results are at least twice as high as those described hitherto (see below), and yet, our treatment modality is beset with many obstacles, not the least of which is the intrasigence of a system that will not and/or can not understand why this modality is so much better than what they are able to offer.  The most importance obstacle is financing, as this modality requires long term and committed financing to work.  The economic implications of not dealing with these issues are described.

The association between physical activity and depressive symptoms in young women : a review

Objective : This review synthesises results of studies examining the association between physical activity (PA) and depressive symptoms and the effects of PA intervention studies on depression among young women.
Methods : A search of electronic databases and bibliographic searches of observational and intervention studies was conducted that included women between the ages of 18 and 35.
Results : A total of eight observational and five intervention studies were identified. Evidence from observational studies indicated that physical activity was inversely associated with depressive symptoms in young women. Even a small amount of physical activity was found to be associated with reduced depressive symptoms. No clear dose–response relationship was shown. Evidence from intervention studies indicated that physical activity reduced depressive symptoms. Direct study comparisons were difficult due to variations in study methods and measures. The studies provided little or no information on understanding dose–response effects or on the mechanisms involved.
Conclusion : The limited number of studies examining physical activity and depressive symptoms in young women and the methodological problems identified in a number of these studies, make it difficult to draw firm conclusions. However, this review suggests that engaging in even low levels of physical activity may be protective against depressive symptoms in young women. There is a need for objective measures of physical activity in future studies, particularly with a focus on those with clinical depression in non-student populations.

Diagnosing borderline personality disorder : examination of how clinical indicators are used by professionals in the health setting

This paper reviews the history of the recognition of borderline personality disorder as a clinical disorder, followed by a review of the contemporary practice of diagnosing borderline personality disorder in psychiatric settings. Many researchers have cautioned against the conflation of difficult patients with the diagnostic category of borderline personality disorder. The current study examines how clinical indicators used to screen for this complex disorder differ across service settings, professions, specialised training and years of clinical experience. A purpose-designed survey was administered to 108 mental and emergency medicine health practitioners across an Australian health service and a New Zealand health service to record the level of significance placed on different clinical indicators in the application of the diagnosis of borderline personality disorder. A heavy reliance was placed on observable behavioural symptoms, such as self-mutilation and impulsive behaviours that are self-damaging, in the screening of borderline personality disorder as a psychiatric diagnosis. Statistically significant differences were found between emergency medical staff and mental health clinicians in their use of diagnostic indicators of borderline personality disorder, χ²(4) = 17.248, p = .002. Implications of these findings for the screening, assessment and diagnosis of patients with borderline personality disorder are discussed.

Effects of laterally wedged insoles on symptoms and disease progression in medial knee osteoarthritis: a protocol for a randomised, double-blind, placebo controlled trial

Background: Whilst laterally wedged insoles, worn inside the shoes, are advocated as a simple, inexpensive, non-toxic self-administered intervention for knee osteoarthritis (OA), there is currently limited evidence to support their use. The aim of this randomised, double-blind controlled trial is to determine whether laterally wedges insoles lead to greater improvements in knee pain, physical function and health-related quality of life, and slower structural disease progression as well as being more cost-effective, than control flat insoles in people with medial knee OA.

Methods/Design: Two hundred participants with painful radiographic medial knee OA and varus malalignment will be recruited from the community and randomly allocated to lateral wedge or control insole groups using concealed allocation. Participants will be blinded as to which insole is considered therapeutic. Blinded follow up assessment will be conducted at 12 months after randomisation. The outcome measures are valid and reliable measures recommended for OA clinical trials. Questionnaires will assess changes in pain, physical function and health-related quality-of-life. Magnetic resonance imaging will measure changes in tibial cartilage volume. To evaluate cost-effectiveness, participants will record the use of all health-related treatments in a log-book returned to the assessor on a monthly basis. To test the effect of the intervention using an intention-to-treat analysis, linear regression modelling will be applied adjusting for baseline outcome values and other demographic characteristics.

Discussion: Results from this trial will contribute to the evidence regarding the effectiveness of laterally wedged insoles for the management of medial knee OA.

Trial registration: ACTR12605000503628; NCT00415259.

Basic symptoms in young people at ultra high-risk of psychosis

Basic Symptoms are cognitive and emotional disturbances characteristic of the early stage of psychosis. This study established the utility of an instrument to identify Basic Symptoms amongst young people at high-risk for developing psychosis, thereby facilitating the pathway to treatment for these individuals. The portfolio focuses on how having an unwell parent contributes to and influences the development of psychopathology in offspring. The four clinical case studies are presented in detail, and the intervention strategies for each individual are evaluated.

N-acetyl cysteine for depressive symptoms in bipolar disorder - a double blind, randomized, placebo-controlled trial

Background: Treatment-resistant subthreshold depression is a major problem in bipolar disorder. Both depression and bipolar disorderare complicated by glutathione depletion. We hypothesized that treatment with N-acetyl cysteine (NAC), a safe, orally bioavailable precursor of glutathione, may improve the depressive component of bipolar disorder.

Methods: A randomized, double-blind, multicenter, placebo-controlled study of individuals (n 75) with bipolar disorder in the maintenance phase treated with NAC (1 g twice daily) adjunctive to usual medication over 24 weeks, with a 4-week washout. The two primary outcomes were the Montgomery Asberg Depression Rating Scale (MADRS) and time to a mood episode. Secondary outcomes included the Bipolar Depression Rating Scale and 11 other ratings of clinical status, quality of life, and functioning.

Results: NAC treatment caused a significant improvement on the MADRS (least squares mean difference [95% confidence interval]: 8.05 [13.16, 2.95], p .002) a n d most secondary scales at end point. Benefit was evident by 8 weeks on the Global Assessment of Functioning Scale and Social and Occupational Functioning Assessment Scale and at 20 weeks on the MADRS. Improvements were lost after washout. There was no effect of NAC on time to a mood episode (log-rank test: p .968) and no significant between-group differences inadverse events. Effect sizes at end point were medium to high for improvements in MADRS and 9 of the 12 secondary readouts.

Conclusions: NAC appears a safe and effective augmentation strategy for depressive symptoms in bipolar  disorder.

A role for glutathione in the pathophysiology of bipolar disorder and schizophrenia? Animal models and relevance to clinical practice.

The tripeptide, glutathione (glutamylcysteinylglycine) is the primary endogenous free radical scavenger in the human body. When glutathione (GSH) levels are reduced there is an increased potential for cellular oxidative stress, characterised by an increase and accruement of reactive oxygen species (ROS). Oxidative stress has been implicated in the pathology of schizophrenia and bipolar disorder. This could partly be caused by alterations in dopaminergic and glutamatergic activity that are implicated in these illnesses. Glutamate and dopamine are highly redox reactive molecules and produce ROS during normal neurotransmission. Alterations to these neurotransmitter pathways may therefore increase the oxidative burden in the brain. Furthermore, mitochondrial dysfunction, as a source of oxidative stress, has been documented in both schizophrenia and bipolar disorder. The combination of altered neurotransmission and this mitochondrial dysfunction leading to oxidative damage may ultimately contribute to illness symptoms. Animal models have been established to investigate the involvement of glutathione depletion in aspects of schizophrenia and bipolar disorder to further characterise the role of oxidative stress in psychopathology. Stemming from preclinical evidence, clinical studies have recently shown antioxidant precursor treatment to be effective in schizophrenia and bipolar disorder, providing a novel clinical angle to augment often suboptimal conventional treatments.

Bipolar missed states : the diagnosis and clinical salience of bipolar mixed states

Objective: To explore diagnostic and treatment issues concerning bipolar mixed states.

Method: Bipolar mixed states are described and concerns about diagnostic and treatment difficulties are summarized and discussed.

Result: Mixed states can present with equal admixtures of depressive or manic symptoms, or more commonly one component predominates. There is fair consensus, although little data, regarding the management of manic mixed states. However depressive mixed states are far more complex both in terms of recognition and management. People suffering from mixed states characteristically present with complaints of depression.

Conclusions: The boundaries between depressive mixed states and agitated depression are vague, yet carry substantial therapeutic implications. Bipolar mixed states are often difficult to treat, and tend to take much longer to settle than either pure mania or depression.  Furthermore there is data that treatment with antidepressants can worsen the course of mixed states. Hence missed diagnoses can potentially have negative clinical implications.  Therefore in this paper the clinical presentation, diagnosis and therapy of mixed states is reviewed with a view to improving management.

Do we need to flick the switch? The need for a broader conceptualization of iatrogenic course aggravation in clinical trials of bipolar disorder?

The term ‘switching’ is often used in bipolar disorder when describing polarity changes in bipolar disorder, but this term is ambiguous and imprecise, and is sometimes used interchangeably with the term ‘cycling’. Furthermore, polarity changes in bipolar disorder can be understood in different ways, because their clinical manifestations range from the emergence of subthreshold symptoms to a full episode of the opposite pole. Besides the need to tighten the meaning of the term ‘switching’, this paper also argues that switching does not adequately describe the complex phenomena that occur with course aggravation of bipolar disorder, such as alteration in episode frequency or amplitude. A more-fine grained approach to course aggravation in bipolar disorder is proposed, which incorporates trans-polar switching, index polarity aggravation, as well as alterations in episodic amplitude, episodic duration, and interepisode length. This approach has the potential to capture a broader, more fine-grained and clinically relevant picture of the process of aggravation of the bipolar cycle.

A prospective study of the impact of subthreshold mixed states on the 24-month clinical outcomes of bipolar I disorder or schizoaffective disorder

Objectives: Subthreshold mixed states are common, yet their clinical significance is unclear. This study investigated the clinical outcomes of subthreshold mixed states in participants with bipolarI disorder or schizoaffective disorder, using the Cassidy and Benazzi criteria for manic and depressive mixed states, respectively.

Methods: The Bipolar Comprehensive Outcomes Study (BCOS) is a prospective observational study of treatment and outcomes for patients with bipolar I or schizoaffective disorder, bipolar type. Participants (N=239) were grouped based on study entry clinical presentation as having pure depression (n=63) if they satisfied DSM-IV-TR criteria for a Major Depressive Episode (MDE), depressive mixed state (DMX) if they also had at least three concurrent hypomanic symptoms (n=33), or not depressed (n=143) if they did not satisfy the criteria for MDE. Participants were similarly grouped as having pure mania (n=3) if they satisfied DSM-IV criteria for a Manic Episode, manic mixed state (MMX) if they also had at least two concurrent depressive symptoms (n=33), or not manic (n=203). Clinical data were collected by interview every 3-months over a 24-month period.

Results: Measures of quality of life, mental and physical health over the 24-month period were significantly worse for participants who were classified as having mixed states at study entry on most outcome measures compared to participants who were not in an illness episode at study entry. DMX was predictive of greater manic symptomatology over the 24 months compared to participants with pure depression.

Conclusion: In participants with a current episode of mood disorder, the presence of subthreshold symptoms of opposite polarity was associated with poorer clinical outcomes over a 24-month period.

Quality of life in restless legs syndrome: A systematic review of clinical trials and a critical review of instruments

Restless legs syndrome (RLS) is a neurological movement disorder characterized by sensory symptoms and motor disturbances. While the underlying cause remains unknown, it is suggested that 20–25% of people with RLS are affected seriously enough to require pharmacological treatment. Dopamine agonists (DAs) are the most common treatment and act by increasing the low levels of dopamine to which RLS is often attributed. A growing literature highlights the debilitating and distressing nature of this condition from the patient's perspective. While sleep problems are most commonly reported, the impact of RLS on quality of life (QOL) is wide ranging, affecting relationships with partners, sex life, family life, social life, leisure activities, friendships, everyday activities, concentration, travel, career/work, sleep, and health.

We conducted a systematic review of clinical trials in which DAs have been evaluated in terms of RLS-specific QOL, i.e. their impact on the QOL of people with RLS, and critically reviewed the development history and measurement properties of RLS-specific QOL instruments.

A systematic search using terms synonymous with RLS, DAs and QOL was conducted using Scopus software, which includes MEDLINE, PsycINFO, EMBASE, and CINAHL. Our search covered publications from 2000 (prior to which RLS-specific QOL measures did not exist) to August 2009. Trials were included in our review if they evaluated DAs for the treatment of adults with RLS and reported evaluation using an RLS-specific QOL measure. We also ran citation searches to identify papers reporting the development history and measurement properties of the identified RLS-specific QOL instruments.

Three measures of RLS-specific QOL have been developed in recent years and are reviewed here: the Restless Legs Syndrome Quality of Life (RLSQOL) questionnaire, the Restless Legs Syndrome Quality of Life Instrument (RLS-QLI), and the Quality of Life Restless Legs Syndrome (QOL-RLS) measure. Critical review indicates that each has limitations (particularly in terms of published developmental history and content validity). Eleven trials of DAs were identified that included assessment of RLS-specific QOL (nine using the RLSQOL and two using the QOL-RLS). In all studies, significant improvements in RLS-specific QOL were observed, although these were mostly short term (12 weeks) and large placebo effects were also noted.

In people with RLS, the use of DAs has been shown to improve RLS-specific QOL. Longer-term, large-scale studies may be needed to confirm these findings and demonstrate statistically significant improvements in RLS-specific QOL at lower doses. Further development of the RLS-specific QOL measures is needed to ensure that the full impact of RLS (and the full benefit of new treatments) on aspects of life identified as important to individuals is captured in future studies.