Jan Reimer

Resource Use and Costs in a Swedish Cohort of Patients with Parkinson's Disease

We estimated resource use and costs in patients with Parkinsons disease (PD), thereby providing baseline data for future economic evaluations of therapeutic interventions. Data were collected from medical records of a South Swedish cohort of 127 PD patients during 1 year (1996) and a mailed questionnaire inquiring about cost‐related consequences and resource use in 1996 and in 2000. Annual costs were calculated based on prevalence and expressed in SEK (monetary value of the year 2000). Direct health care costs averaged approximately SEK 29,000 (≈USD 2,900; EUR 3,200) per patient per year, of which drugs were the most costly component. Nonmedical direct costs were higher than direct health care costs, averaging approximately SEK 43,000 (≈USD 4,300; EUR 4,800) per patient per year, and costs due to lost production were approximately SEK 52,000 (≈USD 5,200; EUR 5,800) per patient per year. The mean total annual cost for PD in our sample approximated SEK 124,000 (≈USD 12,400; EUR 13,800) per patient. These findings are roughly within the same range as estimates from other countries and show that PD causes a considerable societal burden. In addition to other outcomes, evaluations of the economic implications of new therapeutic interventions are highly warranted. In this perspective, the present study provides valuable baseline data.

A Swedish family with de novo α-synuclein A53T mutation: Evidence for early cortical dysfunction

A de novo alpha-synuclein A53T (p.Ala53 Th; c.209G > A) mutation has been identified in a Swedish family with autosomal dominant Parkinsons disease (PD). Two affected individuals had early-onset (before 31 and 40 years), severe levodopa-responsive PD with prominent dysphasia, dysarthria, and cognitive decline. Longitudinal clinical follow-up, EEG, SPECT and CSF biomarker examinations suggested an underlying encephalopathy with cortical involvement. The mutated allele (c.209A) was present within a haplotype different from that shared among mutation carriers in the Italian (Contursi) and the Greek-American Family H kindreds. One unaffected family member carried the mutation haplotype without the c.209A mutation, strongly suggesting its de novo occurrence within this family. Furthermore, a novel mutation c.488G > A (p.Arg163His; R163H) in the presenilin-2 (PSEN2) gene was detected, but was not associated with disease state.

Use and interpretation of on/off diaries in Parkinson’s disease

Objective: To explore the use and interpretation of self reported on/off diary data for assessment of daily motor fluctuations in Parkinson’s disease. Methods: 26 consecutive non-demented patients with fluctuating Parkinson’s disease received standardised training on how to fill out the four category CAPSIT-PD on/off diary, followed by four hours of clinical observation and four weeks of daytime on/off diaries every 30 minutes at home. Results: Overall patient–clinician agreement in diary entries was good (κ = 0.62; weighted κ = 0.84). Agreement for individual diary categories was good for “off” and “on with dyskinesias” (κ = ⩾0.72), but moderate for “partial off” and “on” (κ = 0.49). The overall validity of patient kept diaries was supported by expected symptom severity variability across diary categories, as assessed in the clinic. One day’s home diary data failed to predict outcomes from the full four weeks for all diary categories, and data from three days failed to yield good prediction (predefined as R2 = ⩾~0.7) for the time spent in “off” and “partial off”. Data from one week yielded good prediction (R2 = ⩾0.74) in all instances except “partial off”, which could not be well predicted even when two weeks’ home diary data were considered (R2 = 0.52). Conclusions: The data provide support for the overall accuracy and validity of the four category CAPSIT-PD on/off diary, but suggest that a three category diary format may improve accuracy and validity. Interpretation of diary data beyond the assessed time frame should be made with caution unless diaries have been kept for sufficiently long periods.

Interpretation of response categories in patient-reported rating scales: a controlled study among people with Parkinson's disease

BackgroundUnambiguous interpretation of ordered rating scale response categories requires distinct meanings of category labels. Also, summation of item responses into total scores assumes equal intervals between categories. While studies have identified problems with rating scale response category functioning there is a paucity of empirical studies regarding how respondents interpret response categories. We investigated the interpretation of commonly used rating scale response categories and attempted to identify distinct and roughly equally spaced response categories for patient-reported rating scales in Parkinsons disease (PD) and age-matched control subjects.MethodsTwenty-one rating scale response categories representing frequency, intensity and level of agreement were presented in random order to 51 people with PD (36 men; mean age, 66 years) and 36 age-matched controls (14 men; mean age, 66). Respondents indicated their interpretation of each category on 100-mm visual analog scales (VAS) anchored by Never - Always, Not at all - Extremely, and Totally disagree - Completely agree. VAS values were compared between groups, and response categories with mean values and non-overlapping 95% CIs corresponding to equally spaced locations on the VAS line were sought to identify the best options for three-, four-, five-, and six-category scales.ResultsVAS values did not differ between the PD and control samples (P = 0.286) or according to educational level (P = 0.220), age (P = 0.220), self-reported physical functioning (P = 0.501) and mental health (P = 0.238), or (for the PD sample) PD duration (P = 0.213) or presence of dyskinesias (P = 0.212). Attempts to identify roughly equally spaced response categories for three-, four-, five-, and six-category scales were unsuccessful, as the 95% CIs of one or several of the identified response categories failed to include the criterion values for equal distances.ConclusionsThis study offers an evidence base for selecting more interpretable patient-reported rating scale response categories. However, problems associated with raw rating scale data, primarily related to their ordinal structure also became apparent. This argues for the application of methodologies such as Rasch measurement. Rating scale response categories need to be treated with rigour in the construction and analysis of rating scales.

Initial Validation of a Self-Administered Version of the Freezing of Gait Questionnaire (FOGQsa)

Degeneration of the nigrostriatal dopaminergic system has traditionally been considered the pathological hallmark of Parkinson’s disease (PD). Recent neuropathological work, however, revealed that PD specific brain pathology extends far beyond the nigrostriatal dopaminergic system and affects widespread brain areas, including the olfactory system, autonomic and gain setting brainstem nuclei, and the cerebral cortex. In parallel, there has been a revival of interest in the non-motor features of PD. PD is now considered as a multisystem disorder, manifesting itself by a combination of the classical motor deficits and a wide range of non-motor disturbances, including autonomic dysregulation, hyposmia, sleep disturbances, depression, cognitive dysfunction, and psychosis. Evidence is accumulating that certain non-motor features of PD can develop at least several years before the onset of the motor symptoms. This has most convincingly been demonstrated for impaired olfaction and REM sleep behaviour disorder (RBD). Retrospective studies suggest that other symptoms, such as depression, autonomic dysfunction, and excessive daytime sleepiness may also antedate the motor symptoms. These so-called pre-motor symptoms most likely reflect early pathological changes in the olfactory bulb and tract, the lower brainstem, and possibly the peripheral autonomic nervous system, prior to the involvement of the substantia nigra. As such, pre-motor symptoms are an interesting target for the development of clinical screening tests to detect PD in the pre-motor phase. One of the most promising clinical pre-motor markers of PD is an impairment of the sense of smell, because of its high prevalence (8090% in the motor phase) and the non-invasiveness and low cost of olfactory testing. Prospective studies in first-degree relatives of PD patients and in a population-based cohort have established hyposmia as a risk factor for the development of PD, although the positive predictive value is low and the lead time appears to be relatively short. Idiopathic RBD has a higher positive predictive value than hyposmia and a longer lead time, but lacks sensitivity as only up to one third of PD patients suffer from this disorder. Although at this point no single pre-motor symptom is able to predict PD with high sensitivity and specificity, it is clear that clinical pre-motor markers of PD will be crucial to the development of neuroprotective treatment strategies.

Perceived relevance of generic and disease-specific patient-reported outcome measures in Parkinson’s disease

Background and purposes: The World Health Organization Quality of Life questionnaire (WHOQOL) is widely used to assess quality of life in the world. Although the WHOQOLTaiwan version has also been developed well in Taiwan, the QOL of some people cannot be assessed using the WHOQOL-Taiwan version, because about 70% of the residents of Taiwan use the local dialect, Taiwanese Southern Min, as their everyday language. In particular, more than half of the elderly cannot read or understand Chinese characters. Therefore, developing a WHOQOL for Minnanspeaking people living in Taiwan (WHOQOL-MV) is warranted.This journal issue entitled: Abstracts of the 11th Annual Conference of the International Society for Quality of Life Research ... 2004