Arja Virtanen

Long-term exercise improves functional impairment but not quality of life in multiple sclerosis.

AbstractRegular exercise is important for patients with multiple sclerosis (MS) to maintain their functional ability and general health. The aim of this study was to determine whether a long–term exercise program has any effect on functional impairment or healthrelated quality of life (HRQOL) in subjects with mild to moderate MS. In a randomised controlled trial, subjects in the intervention group (n = 47) exercised according to a progressive exercise program, mainly consisting of resistance training, for six months. Subjects in the control group (n = 48) received no intervention. The subjects were assessed at baseline and at six months using the Multiple Sclerosis Functional Composite (MSFC), the Expanded Disability Status Scale (EDSS), the Functional Independence Measure (FIM), the MS Quality of Life–54 (MSQOL–54) questionnaire and the Centre for Epidemiologic Studies Depression Scale (CES–D). The drop–out rate was low (4%) with 91 subjects completing the study. At six months, the exercising subjects showed improvement on the MSFC (mean score change 0.114, 95% confidence interval [CI] 0.010 to 0.218), whereas the control subjects showed deterioration (mean score change –0.128, 95 % CI –0.232 to –0.025). The change between groups was statistically significant (interaction, p = 0.001). Consistent with the physical nature of the intervention, the change predominantly occurred in leg function/ambulation. The effect seen in the EDSS, FIM, MSQOL–54 or CES–D was nil. These findings indicate that MSFC is more sensitive than EDSS in the detection of improvement in functional impairment as a result of regular exercise. The unfavourable results from HRQOL do not rule out the possibility that other types of exercise programs may improve it in MS.

Effects of aerobic and strength exercise on motor fatigue in men and women with multiple sclerosis: a randomized controlled trial

Objective: To investigate the effects of aerobic and strength exercise on motor fatigue of knee flexor and extensor muscles in subjects with multiple sclerosis (MS). Design: A randomized controlled trial. Setting: At Masku Neurological Rehabilitation Centre, Masku, and the Social Insurance Institution, Research Department, Turku, Finland. Subjects: Ninety-five MS patients with mild to moderate disability were randomized into exercise group (n = 47) and a control group (n = 48). Intervention: Participants in the exercise group attended in a supervised exercise period of three weeks, which was followed by a home exercise programme lasting for 23 weeks. Patients in the control group continued with their normal living. Outcome measures: Motor fatigue of knee flexor and extensor muscles was measured during a static 30-s maximal sustained muscle contraction. The decline in force (Nm) during the 30 s was recorded, and a fatigue index (FI) was calculated. Subjective fatigue was measured by using the Fatigue Severity Scale (FSS). The Ambulatory Fatigue Index (AFI) was calculated on the basis of a 500-m walking test. Assessment took place at baseline, at the third week (not for the control group) and at the 26th week. All outcome variables were analysed, men and women together, and some interesting contrasts were analysed by gender. Results: Associations were observed with changes in extension FI and Expanded Disability Status Scale (EDSS) score and mean extension torque (Nm), but not with changes in FI and aerobic or strength exercise activity, mean AFI, mean FSS or in mean knee flexion torque. AFI was decreased in all subject groups (p = 0.007). Motor fatigue was reduced in knee flexion (p = 0.0014) and extension (ns) among female but not in male exercisers after six months of exercise. The exercise activity of women was 25% higher than that of the men. Conclusions: Six months of exercise reduced motor fatigue in women, but not in men.

Does simvastatin affect mood and steroid hormone levels in hypercholesterolemic men? A randomized double-blind trial

Epidemiological and clinical studies have suggested that powerful cholesterol lowering may have adverse effects on mood and psychological well-being. Inhibition of cholesterol biosynthesis by simvastatin (a hydroxymethyl glutaryl coenzyme A reductase inhibitor) may also reduce steroid hormone biosynthesis. To explore if mood changes are related with steroid hormone levels, we designed a randomized double-blind placebo-controlled crossover trial. The separate and combined effects of a Mediterranean-type diet intervention and treatment with simvastatin 20 mg/day PO for 12 weeks were studied in 120 hypercholesterolemic but otherwise healthy middle-aged men. Psychological functioning was assessed with questionnaires, and steroid hormone levels in blood were assayed radioimmunologically before and after the treatments. Simvastatin resulted in a statistically significant increase of depression and somatization without changes in the anxiety, hostility or aggression scores. Mood changes seemed to be unrelated with the statistically significant but clinically insignificant decline in serum testosterone levels and unrelated with the increase in serum dehydroepiandrosterone levels.

Effects of Diet and Simvastatin on Fatty Acid Composition in Hypercholesterolemic Men A Randomized Controlled Trial

Objective—To explore the separate and combined effects of simvastatin and a low-saturated diet rich in &agr;-linolenic acid on serum fatty acids. Methods and Results—120 hypercholesterolemic men were randomly allocated to a habitual diet or dietary treatment group and to receive, in random order, simvastatin 20 mg/d or placebo, each for 12 weeks, in a double-blind manner. Dietary treatment decreased proportions from total fatty acids of palmitic acid (C16:0) by 3.3% (P<0.05), stearic acid (C18:0) by 3.7% (P<0.05) and increased proportions of oleic acid (C18:1n-9) by 4.2% (P<0.01), and &agr;-linolenic acid (C18:3n-3) by 29.8% (P<0.001). Simvastatin decreased proportions from total fatty acids of palmitic acid by 2.0% (P<0.01), linoleic acid (C18:2n-6) by 5.3% (P<0.001), and &agr;-linolenic acid by 6.8% (P<0.05), and increased proportions of &ggr;-linolenic acid (C18:3n-6) by 11.1% (P<0.001), dihomo-&ggr;-linolenic acid (C20:3n-6) by 4.2% (P<0.01), arachidonic acid (C20:4n-6) by 14.2% (P<0.001), and the sum of long-chain polyunsaturated fatty acids (C20-22) by 9.0% (P<0.001). Simvastatin increased ratios of stearic to palmitic, &ggr;-linolenic to linoleic, and arachidonic to dihomo-&ggr;-linolenic acid by 7.6%, 17.0%, and 10.0% (P<0.001 for all), respectively, suggesting increased fatty acid elongase and &Dgr;6- and &Dgr;5-desaturase enzyme activities. Conclusions—Increased formation of long-chain polyunsaturated fatty acids and their metabolites may contribute a substantial part of the pleiotropic effects of simvastatin.

Assessment of muscle strength and motor fatigue with a knee dynamometer in subjects with multiple sclerosis: a new fatigue index

Objective: To measure muscle strength and motor fatigue with a knee dynamometer and to assess the intra-rater reliability of measurements for maximal isometric extensor and flexor torques and the reliability of a new fatigue index (FI) in patients with mild to moderate multiple sclerosis (MS). Design: Repeated assessments with one-week intervals. Setting: The Masku Neurological Rehabilitation Centre, Masku, and the Social Insurance Institution, Research Department, Turku, Finland. Subjects: Twenty-eight MS patients. Outcome measures: Maximal isometric torque during 5 s and fatigue of knee flexors and extensors during isometric contractions of 30 s were assessed. A new FI was established and compared with the two previously used indices (FI1 and FI2). All three indices are based on the calculated area under the force versus time curve (AUFC), with FI1 using the 30-s recording time in its entirety and F2 omitting the initial 5 s in the calculation. In the new fatigue index (FI3), the time point of maximum (TPM) torque achieved by the subject is used as the starting point in the calculation. The patients subjective fatigue was measured by Fatigue Severity Scale (FSS). Results: The intraclass correlation coefficient (ICC) was 0.97 in maximal isometric torque measurements. FI3 showed good intra-rater reliability (ICC 0.68-0.86). None of the fatigue indices correlated with FSS. Conclusions: Maximal isometric torque and motor fatigue of knee flexor and extensor muscles can be reliably measured using a knee dynamometer in MS patients. The new FI proved to be a reliable model for MS patients.

Maternal midtrimester serum AFP and free β-hCG levels in in vitro fertilization twin pregnancies

We aimed to compare the levels of alpha‐fetoprotein (AFP) and free β‐human chorionic gonadotrophin (β‐hCG) levels as multiples of the median (MoM) values between spontaneous and in vitro fertilized (IVF) twin pregnancies. The control group of spontaneous singleton pregnancies was used for calculating the gestational age specific median levels of the values. Within a cohort of 19 310 pregnancies, 145 twin pregnancies were identified. The data were collected from Down syndrome (DS) screening programmes in four University catchment areas in Finland between 1994–98. Maternal midtrimester serum marker levels were measured across gestational weeks 14–18. There were no fetal chromosome anomalies in either of the twin groups or the singleton group. Serum AFP of 145 and β‐hCG values of 39 spontaneous twin pregnancies were compared to the values of 6548 singleton pregnancies. In IVF twins 30 AFP and 29 β‐hCG values were compared to the levels of the control group. Both AFP and β‐hCG values were twice as high in the spontaneous twin pregnancies (medians 2.18 and 1.83 MoM respectively) as in the singleton group (medians 1.00 and 1.00 MoM respectively). In IVF twin pregnancies β‐hCG levels were higher (median 2.20 MoM) than in spontaneous twins (p=0.08), whereas no significant difference was found in AFP levels (2.30 MoM). In conclusion, the higher levels of β‐hCG levels in IVF twin pregnancies should be considered in DS screening to avoid high false positive rates. Copyright

Biological Day-to-Day Variation and Daytime Changes of Testosterone, Follitropin, Lutropin and Oestradiol-17β in Healthy Men

Abstract Information on biological day-to-day variation is needed for detecting within-subject changes over time. In this study the daytime changes and the biological day-to-day variation of serum testosterone, follitropin, lutropin and oestradiol-17β concentrations were investigated in 31 healthy males. To analyse daytime changes, blood specimens were taken at 0800 h, 1200 h, 1600 h and 2000 h during one day (n=31) and two days (n=8). The day-to-day variation was analysed from blood specimens collected at 0800 h on days 1 and 2 (n=31) and additionally on days 3, 4, 6 and 9 (n=8). The evaluation of the day-to-day variation was based on calculations of the within-subject (CVA+I) and between-subject (CVG) coefficients of variation. When the within-subject day-to-day variances were not too heterogeneous, they were used for the calculation of 95 % reference change limits. Serum testosterone and oestradiol-17βconcentrations showed a significant daytime variation; testosterone had higher serum concentrations at 0800 and 1200 h. A peak in the serum concentration of oestradiol-17β occurred at 1200 h with a decrease towards the evening. There were no clear daytime changes in the serum concentrations of follitropin or lutropin. For different analytes the reference change limits were: serum testosterone ± 32.0 %, serum follitropin ± 24.1 % and serum oestradiol-17β ± 38.3 %. The reference change limit was not calculated for serum lutropin, as a high degree of heterogeneity and individuality was found. The interpretation of the results of hormone measurements requires recognition of the biological daytime and day-to-day changes of hormones. The reference change limits determine what changes are significant when monitoring the patient.

Frequent prescribing of drugs with potential gastrointestinal toxicity among continuous users of non-steroidal anti-inflammatory drugs

ObjectiveA number of drugs used concurrently with non-steroidal anti-inflammatory drugs (NSAIDs) increase the risk of gastrointestinal (GI) haemorrhage. We studied the prescribing of NSAIDs with corticosteroids, oral anticoagulants or selective serotonin re-uptake inhibitors (SSRIs), as well as the use of gastroprotection among continuous and non-continuous users of NSAIDs in Finland.MethodsConcurrent use of various drugs was analysed in a nested case-control study in a population-based cohort of NSAID users in 2000 using data in the National Prescription Database.ResultsPrescribing of any other drug with the potential to increase the risk of GI bleeding with NSAIDs was five times [5.2; 95% confidence interval (CI) 4.7–5.9] more common among continuous than non-continuous NSAID users, and the odds ratio for oral corticosteroids was 8.0 (95% CI 6.6–9.6). Of patients using continuous NSAIDs with oral corticosteroids, 73.3% had rheumatoid arthritis (RA). After excluding RA patients, the odds ratio remained high (4.5; 95% CI 3.3–6.1) and at the same level as for SSRIs (3.7; 3.1–4.4). Gastroprotective drugs were prescribed for 6.8% of the continuous users of NSAIDs alone, and for 20.4% of patients taking any of the studied drug combinations with NSAIDs. The continuous users of NSAIDs alone had gastroprotection 2.9 (2.5–3.3) times more often than other users of NSAIDs. With drug combinations (NSAID+corticosteroid, NSAID+SSRI, NSAID+anticoagulants), the use of gastroprotection did not differ from patients using lower amounts of NSAIDs.ConclusionsWhen prescribing NSAIDs, situations leading to habitual use should be avoided, potential complications due to clustering of risk factors recognised, and gastroprotection prescribed for patients with increased risk of GI haemorrhage.

The effects of heat stress on physical functioning in persons with multiple sclerosis

Heat sensitivity is a well-recognised feature in multiple sclerosis (MS). However, little is known about how heat affects physical performance in persons with MS. The objective of the study was to evaluate the effects of short-term heat stress on physical functioning in persons with MS. Twenty-three heat-sensitive MS subjects and 19 healthy controls participated. Moderate heat exposure took place in a dry Finnish sauna. Measures of upper and lower extremity function, static and dynamic balance, and walking capacity were applied. Core body temperature was measured by a telemetric physiological monitoring system. Assessments were conducted before, immediately, 1 hour, and 1 day after the heat exposure. Subjects with MS showed a significantly (P=0.002) higher core body temperature than the controls following the heat stress. Performances in walking (P<0.001), chair rise (P=0.005) and functional reach (P=0.04) were poorer in MS subjects than in controls immediately after the heat. No prolonged heat effects were observed. An increase in ambient temperature causes a higher core body temperature rise in MS subjects than in healthy controls. This rise in temperature is associated with acute, but not prolonged detrimental effects on physical functioning.

Adoption of celecoxib and rofecoxib: a nationwide database study

Background and objective:  Cyclooxygenase 2‐selective non‐steroidal anti‐inflammatory drugs (NSAIDs, coxibs) are recommended primarily for patients at high risk of gastrointestinal bleeding, most of them being elderly. Our objective was to describe and analyse patient‐ and physician‐related factors affecting the adoption of celecoxib and rofecoxib 2 years after their launch in Finland.