Vinjar Fønnebø

Circular instead of hierarchical: methodological principles for the evaluation of complex interventions

BackgroundThe reasoning behind evaluating medical interventions is that a hierarchy of methods exists which successively produce improved and therefore more rigorous evidence based medicine upon which to make clinical decisions. At the foundation of this hierarchy are case studies, retrospective and prospective case series, followed by cohort studies with historical and concomitant non-randomized controls. Open-label randomized controlled studies (RCTs), and finally blinded, placebo-controlled RCTs, which offer most internal validity are considered the most reliable evidence. Rigorous RCTs remove bias. Evidence from RCTs forms the basis of meta-analyses and systematic reviews. This hierarchy, founded on a pharmacological model of therapy, is generalized to other interventions which may be complex and non-pharmacological (healing, acupuncture and surgery).DiscussionThe hierarchical model is valid for limited questions of efficacy, for instance for regulatory purposes and newly devised products and pharmacological preparations. It is inadequate for the evaluation of complex interventions such as physiotherapy, surgery and complementary and alternative medicine (CAM). This has to do with the essential tension between internal validity (rigor and the removal of bias) and external validity (generalizability).SummaryInstead of an Evidence Hierarchy, we propose a Circular Model. This would imply a multiplicity of methods, using different designs, counterbalancing their individual strengths and weaknesses to arrive at pragmatic but equally rigorous evidence which would provide significant assistance in clinical and health systems innovation. Such evidence would better inform national health care technology assessment agencies and promote evidence based health reform.

Use of complementary and alternative medicine in the scandinavian countries

Objective To describe the prevalence of use of complementary and alternative medicine (CAM) in Norway, Denmark and Stockholm County. Design, setting, and subjects In Norway, a national representative sample of 1000 participants completed telephone interviews regarding their CAM use in 1997 (response rate 51). In Denmark, a national representative sample of 16 690 participants completed questionnaires and interviews regarding their health and morbidity in 2000 (response rate 74). In Stockholm County, a randomly selected sample of 1001 participants completed telephone interviews about their CAM use in 2000 (response rate 63). Results Prevalence of ever-use of CAM was 34% in Norway, 45% in Denmark, and 49% in Stockholm. Use of CAM is associated with poor self-reported health in all three studies, and with visits to a medical doctor in Denmark and Norway. More women than men, and more with higher education, reported use of CAM. Most frequently used CAM therapy was homeopathy in Norway, reflexology in Denmark, and massage in Stockholm County. Conclusions Use of CAM is common in the Scandinavian countries, and there are national differences regarding therapy preferences. Many individuals use both CAM and conventional health services.

Chinese red yeast rice (Monascus purpureus) for primary hyperlipidemia: a meta-analysis of randomized controlled trials.

Extracts of Chinese red yeast rice (RYR, a traditional dietary seasoning of Monascus purpureus) contains several active ingredients including lovastatin, and several trials of its possible lipid-lowering effects have been conducted. This meta-analysis assesses the effectiveness and safety of RYR preparations on lipid modification in primary hyperlipidemia. We included randomized controlled trials testing RYR preparation, compared with placebo, no treatment, statins, or other active lipid-lowering agents in people with hyperlipidemia through searching PubMed, CBMdisk, TCMLARS, the Cochrane Library, and AMED up to December 2004. Ninety-three randomized trials (9625 participants) were included and three RYR preparations (Cholestin, Xuezhikang and Zhibituo) were tested. The methodological quality of trial reports was generally low in terms of generation of the allocation sequence, allocation concealment, blinding, and intention-to-treat. The combined results showed significant reduction of serum total cholesterol levels (weighted mean difference -0.91 mmol/L, 95% confidence interval -1.12 to -0.71), triglycerides levels (-0.41 mmol/L, -0.6 to -0.22), and LDL-cholesterol levels (-0.73 mmol/L, -1.02 to -0.043), and increase of HDL-cholesterol levels (0.15 mmol/L, 0.09 to 0.22) by RYR treatment compared with placebo. The lipid modification effects appeared to be similar to pravastatin, simvastatin, lovastatin, atorvastatin, or fluvastatin. Compared with non-statin lipid lowering agents, RYR preparations appeared superior to nicotinate and fish oils, but equal to or less effective than fenofibrate and gemfibrozil. No significant difference in lipid profile was found between Xuezhikang and Zhibituo. RYR preparations were associated with non-serious adverse effects such as dizziness and gastrointestinal discomfort. Current evidence shows short-term beneficial effects of RYR preparations on lipid modification. More rigorous trials are needed, and long-term effects and safety should be investigated if RYR preparations are to be recommended as one of the alternative treatments for primary hyperlipidemia.

Physical activity and predisposition for hip fractures : A review

Studies on the association between physical activity and hip fractures are reviewed. All the studies, which comprise four follow-up studies, one nested case-control study and 17 case-control studies, suggest a protective effect of physical activity with regard to hip fractures. The association is strong and consistent with physical activity in leisure, weaker with respect to physical activity at work. The association is present for physical activity from childhood to adult age, and it is consistent in study populations from the USA, Australia, Asia and Northern and Southern Europe, in spite of very different hip fractures incidences in these populations. The magnitude of the association is difficult to assess because of varying criteria for exposure, but to be among the physically active seems to reduce the risk of later hip fracture by up to 50%. It seems that even daily chores, such as climbing stairs and walking, protect against hip fracture.

The Acupuncture on Hot Flushes Among Menopausal Women (ACUFLASH) study, a randomized controlled trial

Objective: This study compared the effectiveness of individualized acupuncture plus self-care versus self-care alone on hot flashes and health-related quality of life in postmenopausal women. Methods: This study involved a multicenter, pragmatic, randomized, controlled trial with two parallel arms. Participants were postmenopausal women experiencing, on average, seven or more hot flashes per 24 hours during seven consecutive days. The acupuncture group received 10 acupuncture treatment sessions and advice on self-care, and the control group received advice on self-care only. The frequency and severity (0-10 scale) of hot flashes were registered in a diary. Urine excretion of calcitonin gene-related peptide was assessed at baseline and after 12 weeks. The primary endpoint was change in mean hot flash frequency from baseline to 12 weeks. The secondary endpoint was change in health-related quality of life measured by the Womens Health Questionnaire. Results: Hot flash frequency decreased by 5.8 per 24 hours in the acupuncture group (n = 134) and 3.7 per 24 hours in the control group (n = 133), a difference of 2.1 (P < 0.001). Hot flash intensity decreased by 3.2 units in the acupuncture group and 1.8 units in the control group, a difference of 1.4 (P < 0.001). The acupuncture group experienced statistically significant improvements in the vasomotor, sleep, and somatic symptoms dimensions of the Womens Health Questionnaire compared with the control group. Urine calcitonin gene-related peptide excretion remained unchanged from baseline to week 12. Conclusions: Acupuncture plus self-care can contribute to a clinically relevant reduction in hot flashes and increased health-related quality of life in postmenopausal women.

The Tromsø Study: Physical Activity and the Incidence of Fractures in a Middle-Aged Population

We have studied the relation of occupational and recreational physical activity to fractures at different locations. All men born between 1925 and 1959 and all women born between 1930 and 1959 in the city of Tromsø were invited to participate in surveys in 1979–1980 and 1986–1987 (The Tromsø Study). Of 16,676 invited persons, 12,270 (73.6%) attended both surveys. All nonvertebral fractures (n = 1435) sustained from 1988 to 1995 were registered in the only hospital in the area. Average age in the middle of the follow‐up period (December 31, 1991) was 47.3 years among men and 45.1 years among women, ranging from 32 to 66 years. Fracture incidence increased with age at all locations among women, but it decreased with or was independent of age among men. Low‐energetic fractures constituted 74.4% of all fractures among women and 55.2% among men. When stratifying by fracture location, the most physically active persons among those 45 years or older suffered fewer fractures in the weight‐bearing skeleton (relative risk [RR] 0.6, confidence interval [CI] 0.4–0.9, age‐adjusted), but not in the non–weight‐bearing skeleton (RR 1.0, CI 0.7–1.2, age‐adjusted) compared with sedentary persons. The relative risk of a low‐energetic fracture in the weight‐bearing skeleton among the most physically active middle‐aged was 0.3 (CI 0.1–0.7) among men and 0.9 (CI 0.4–1.8) among women compared with the sedentary when adjusted for age, body mass index, body height, tobacco smoking, and alcohol and milk consumption. It seems that the beneficial effect on the skeleton of weight‐bearing activity is reflected also in the incidence of fractures at different sites.

A systematic literature review of complementary and alternative medicine prevalence in EU

Background: Studies suggest that complementary and alternative medicine (CAM) is widely used in the European Union (EU). We systematically reviewed data, reporting research quality and the prevalence of CAM use by citizens in Europe; what it is used for, and why. Methods: We searched for general population surveys of CAM use by using Ovid MEDLINE (1948 to September 2010), Cochrane Library (1989 to September 2010), CINAHL (1989 to September 2010), EMBASE (1980 to September 2010), PsychINFO including PsychARTICLES (1989 to September 2010), Web of Science (1989 to September 2010), AMED (1985 to September 2010), and CISCOM (1989 to September 2010). Additional studies were identified through experts and grey literature. Cross-sectional, population-based or cohort studies reporting CAM use in any EU language were included. Data were extracted and reviewed by 2 authors using a pre-designed extraction protocol with quality assessment instrument. Results: 87 studies were included. Inter-rater reliability was good (kappa = 0.8). Study methodology and quality of reporting were poor. The prevalence of CAM use varied widely within and across EU countries (0.3–86%). Prevalence data demonstrated substantial heterogeneity unrelated to report quality; therefore, we were unable to pool data for meta-analysis; our report is narrative and based on descriptive statistics. Herbal medicine was most commonly reported. CAM users were mainly women. The most common reason for use was dissatisfaction with conventional care; CAM was widely used for musculoskeletal problems. Conclusion: CAM prevalence across the EU is problematic to estimate because studies are generally poor and heterogeneous. A consistent definition of CAM, a core set of CAMs with country-specific variations and a standardised reporting strategy to enhance the accuracy of data pooling would improve reporting quality.

Features of the metabolic syndrome and the risk of non-vertebral fractures : The Tromso Study

Owing to a technical error, a number of non-vertebral fractures had not been included in the database. Owing to changes in the informed consents for some of the participants, at the time of repeated analyses, the study cohort changed from 27,159 to 26,905 participants. A total of 1,882 non-vertebral fractures (not 1,249 as stated in the publication) were registered. After excluding all subjects with missed measurements of any metabolic syndrome criteria (n=152), 750 men and 1108 women (not 438 men and 789 women as stated in the publication) suffered non-vertebral fractures. The risk estimates of the associations between having three or more of the metabolic syndrome criteria and nonvertebral fractures and changed to (RR 0.81, 95% CI 0.64– 1.04) in men and (RR 0.78, 95% CI 0.65–0.93) in women. The trend towards reduced fracture risk by increasing mean BP in men was no longer significant (Fig. 2). We apologize for any inconvenience caused by this unfortunate error. Osteoporos Int (2009) 20:839 DOI 10.1007/s00198-009-0847-8

The Tromsø Study: Body Height, Body Mass Index and Fractures

Abstract: Tall persons suffer more hip fractures than shorter persons, and high body mass index is associated with fewer hip and forearm fractures. We have studied the association between body height, body mass index and all non-vertebral fractures in a large, prospective, population-based study. The middle-aged population of Tromsø, Norway, was invited to surveys in 1979/80, 1986/87 and 1994/95 (The Tromsø Study). Of 16 676 invited to the first two surveys, 12 270 attended both times (74%). Height and weight were measured without shoes at the surveys, and all non-vertebral fractures in the period 1988–1995 were registered (922 persons with fractures) and verified by radiography. The risk of a low-energy fracture was found to be positively associated with increasing body height and with decreasing body mass index. Furthermore, men who had gained weight had a lower risk of hip fractures, and women who had gained weight had a lower risk of fractures in the lower extremities. High body height is thus a risk factor for fractures, and 1 in 4 low-energy fractures among women today might be ascribed to the increase in average stature since the turn of the century. Low body mass index is associated with a higher risk of fractures, but the association is probably too weak to have any clinical relevance in this age category.

Acupuncture adverse effects are more than occasional case reports: Results from questionnaires among 1135 randomly selected doctors, and 197 acupuncturists

Summary The aim of the present paper is to describe what kind of adverse effects of acupuncture Norwegian doctors and acupuncturists have encountered, and to indicate how often these adverse effects occur. The questionnaire was sent to an unweighted, stratified, random sample of 1466 working Norwegian doctors under the age of 71. A similar questionnaire was sent to all 311 acupuncturists found in the Yellow Pages of the telephone directory. A total of 1135 (77%) and 197 acupuncturists (68%) responded. The myth of acupuncture as a therapy without adverse effects has not been substantiated. Pneumothorax, the most common serious adverse effect of acupuncture was reported in 33 patients. Local skin infections (n = 66), perichondritis on the auricle (n = 6), arthritis and osteomyelitis (n = 4), are reported from doctors, but not from the acupuncturists. Fainting during treatment is relatively common among acupuncturists (n = 140), while the doctors report more cases of psychiatric problems (n = 20) and increased pain after acupuncture treatment (n = 56). The study indicates that the acupuncture adverse effects rate is at least 0.21 per year of practice as an acupuncturist. This paper presents a broad panorama of adverse effects of acupuncture. The study should imply more focus on who should practise acupuncture, and when to use the method. Despite the reported adverse effects, acupuncture can still be presented as a relatively safe therapeutic measure.