Emergent biomarker derived from next-generation sequencing to identify pain patients requiring uncommonly high opioid doses.

Next-generation sequencing (NGS) provides unrestricted access to the genome, but it produces 'big data' exceeding in amount and complexity the classical analytical approaches. We introduce a bioinformatics-based classifying biomarker that uses emergent properties in genetics to separate pain patients requiring extremely high opioid doses from controls. Following precisely calculated selection of the 34 most informative markers in the OPRM1, OPRK1, OPRD1 and SIGMAR1 genes, pattern of genotypes belonging to either patient group could be derived using a k-nearest neighbor (kNN) classifier that provided a diagnostic accuracy of 80.6±4%. This outperformed alternative classifiers such as reportedly functional opioid receptor gene variants or complex biomarkers obtained via multiple regression or decision tree analysis. The accumulation of several genetic variants with only minor functional influences may result in a qualitative consequence affecting complex phenotypes, pointing at emergent properties in genetics.

Network meta-analysis of longitudinal data using fractional polynomials.

Network meta-analysis of randomized controlled trials (RCTs) are often based on one treatment effect measure per study. However, many studies report data at multiple time points. Furthermore, not all studies measure the outcomes at the same time points. As an alternative to a network meta-analysis based on a synthesis of the results at one time point, a network meta-analysis method is presented that allows for the simultaneous analysis of outcomes at multiple time points. The development of outcomes over time of interventions compared in an RCT is modeled with fractional polynomials, and the differences between the parameters of these polynomials within a trial are synthesized across studies with a Bayesian network meta-analysis. The proposed models are illustrated with an analysis of RCTs evaluating interventions for osteoarthritis of the knee. Fixed and random effects second order fractional polynomials were applied to the case study. Network meta-analysis with models that represent the treatment effects in terms of several parameters using fractional polynomials can be considered a useful addition to models for network meta-analysis of repeated measures previously proposed. When RCTs report treatment effects at multiple follow-up times, these models can be used to synthesize the results even if reporting times differ across the studies.

TOXICITY OF SEVERAL FUNGICIDES FOR ORANGE WHEAT BLOSSOM MIDGE, SITODIPLOSIS MOSELLANA (GÉHIN) (DIPTERA: CECIDOMYIIDAE).

The orange wheat blossom midge, Sitadiplosis mosellano (Géhin) (Diptera: Cecidomyiidae), can cause severe losses in wheat grain yield and quality. This pest is known to be susceptible to many insecticides, but various field observations have suggested that some fungicides could also significantly affect S. mosellana. In order to confirm these field observations, the effect on adult midges of several fungicides commonly applied to wheat crops was investigated in the laboratory and in small plots in the field. In each experiment, the fungicides were compared with a positive (insecticide) and a negative control (water). Four fungicides were assessed in the laboratory, each with five doses based on basis of a tenfold dilution starting at the field-recommended dose. The mortality rate was evaluated after 24 hours and the lethal dose 50% (LD50) was determined for each product. In the field, six fungicides were tested at the recommended dose. The effect of each product was compared on the basis of the number of S. mosellana adults caught alive with an insect vacuum sampler (Vortis®) on the morning after the treatments. Both experiments showed a significant effect of several fungicides tested on S. mosellana adults. Chlorothalonil was not toxic for S. mosellana, but tebuconazole, fluxapyroxad and azoxystrobin all induced significant mortality rates.

Pest select database: a new tool to use selective pesticides for IPM.

Crop pests can be naturally controlled by a set of beneficial arthropods, as entomophagous predators or parasites, leading to a global reduction of pest occurrence and insecticide use. The selectivity of plant protection products for these beneficial arthropods is a key factor in the success of IPM strategies. An abundant scientific literature concerning this subject exists, but for the final pesticide users, the information is not always easily accessible or understood. The IOBC working group "Pesticides and Beneficial Organisms" (PBO) has developed a new database to compile all data concerning pesticide selectivity on beneficial arthropods, obtained with methods that followed the IOBC test standard characteristics. These standards have been developed since the 70's by the Working group Pesticide and Beneficial Organisms, in the context of IPM. This database includes a first set of data previously published, coming from the different Joint Pesticide Testing Programs, with the addition of results published later in the IOBC Bulletin. The second set of data has been extracted from the Public verse of the Draft Assessment Report (DAR), established by the different EU member' states in the context of the registration process at the European Level and available online on the EFSA website. As nearly all active ingredients have to be tested on at least 2 to 4 selected beneficial arthropod species with methods that followed the IOBC standard characteristics, these DAR represent an important source of information for pesticide users dealing with beneficial arthropods and selectivity, with about 50% of the actual records. This source was previously only exploited for registration purposes and not accessible to a large public, but a lot of results, mainly from the first tier testing, have been compiled and interpreted for IPM. The new database is available online on the area restricted to the IOBC-members (http:// www.iobc-wprs.org/restricted_member/toolbox.cfm). This database will be updated regularly on basis of the new IOBC publications, EFSA Draft Assessment Report and scientific publication results that followed IOBC standard characteristics.

Aligning text mining and machine learning algorithms with best practices for study selection in systematic literature reviews.

BACKGROUND: Despite existing research on text mining and machine learning for title and abstract screening, the role of machine learning within systematic literature reviews (SLRs) for health technology assessment (HTA) remains unclear given lack of extensive testing and of guidance from HTA agencies. We sought to address two knowledge gaps: to extend ML algorithms to provide a reason for exclusion-to align with current practices-and to determine optimal parameter settings for feature-set generation and ML algorithms. METHODS: We used abstract and full-text selection data from five large SLRs (n = 3089 to 12,769 abstracts) across a variety of disease areas. Each SLR was split into training and test sets. We developed a multi-step algorithm to categorize each citation into the following categories: included; excluded for each PICOS criterion; or unclassified. We used a bag-of-words approach for feature-set generation and compared machine learning algorithms using support vector machines (SVMs), naïve Bayes (NB), and bagged classification and regression trees (CART) for classification. We also compared alternative training set strategies: using full data versus downsampling (i.e., reducing excludes to balance includes/excludes because machine learning algorithms perform better with balanced data), and using inclusion/exclusion decisions from abstract versus full-text screening. Performance comparisons were in terms of specificity, sensitivity, accuracy, and matching the reason for exclusion. RESULTS: The best-fitting model (optimized sensitivity and specificity) was based on the SVM algorithm using training data based on full-text decisions, downsampling, and excluding words occurring fewer than five times. The sensitivity and specificity of this model ranged from 94 to 100%, and 54 to 89%, respectively, across the five SLRs. On average, 75% of excluded citations were excluded with a reason and 83% of these citations matched the reviewers' original reason for exclusion. Sensitivity significantly improved when both downsampling and abstract decisions were used. CONCLUSIONS: ML algorithms can improve the efficiency of the SLR process and the proposed algorithms could reduce the workload of a second reviewer by identifying exclusions with a relevant PICOS reason, thus aligning with HTA guidance. Downsampling can be used to improve study selection, and improvements using full-text exclusions have implications for a learn-as-you-go approach.

Pesticides selectivity list to beneficial arthropods in four field vegetable crops.

Selectivity of pesticides to beneficial arthropods is a key data for the implementation of IPM program. In the context of field vegetables crop, a set of 16 fungicides, 17 herbicides and 14 insecticides commonly used in Belgium were tested on 5 indicator species: the parasitic hymenoptera Aphidius rhopalosiphi (De Stefani-Perez) (Hym., Aphidiidae), the aphid foliage dwelling predators Adalia bipunctata (L.) (Col., Coccinellidae) and Episyrphus balteatus (Dipt., Syrphidae) and the ground-dwelling predators Aleochara bilineata (Col., Staphyllinidae) and Bembidion lampros (Col., Carabidae). Pesticides were tested according a testing scheme including a first assessment on inert substrate (glass plates for adults of A. rhopalosiphi, larvae of A. bipunctata and E. balteatus, sand on adults of A. bilineata and B. lampros) and, for product that were toxic, a second assessment on natural substrate (barley seedlings for A. rhopalosiphi, french bean plants for A. bipunctato and E. balteatus and two type of soil for 8. lampros and A. bilineato). The effects of the product were assessed on basis on mortality, except for A. bilineata (Onion fly pupae parasitism). According to the final results obtained at the end of this testing scheme, the product were listed in toxicity class: green list if effect < or =30%, yellow list 30% < effect < 60% and orange list 60% < effect < or =80%. Products with toxicity higher than 80% on plants or on soils, or that reduce parasitism more than 80% on soil were put in red list and are not recommended for IPM. Results showed that all fungicides and herbicides were included in the green list except tebuconazole and boscalid + pyraclostrobin that were labeled as yellow for A. bipunctata. In opposite, no foliar insecticide was totally selective for all beneficial tested. However some products are in green list for one or several species. Soil insecticides were all are very toxic for ground dwelling arthropods and classed in red list. All results obtained during this study and further upgrade will be available on www.cra.wallonie.be/selectivite. In conclusions, fungicides and herbicides tested are compatible with IPM programs. For foliar insecticides, some treatments can be used carefully according to the selectivity. But for soil insecticide treatments, their toxicity raise the question of their use in IPM programs in vegetables and the need of new compounds or development of alternative pest control programs.

Influence of organic matter on bio-availability of carbosulfan and its toxicity on a carabid beetle.

Study of factors influencing soil insecticide toxicity are needed to reduce negative impacts of these products on beneficial insects. To date, if high toxicity differences between different type of soils have been reported, there is few specific studies on soil parameters influence on selectivity of soil insecticides to beneficial arthropods. To assess the specific impact of organic matter, the relationship between bio-availability of a soil insecticide, carbosulfan [Sheriff 1 Gr], and its toxicity on a small Carabidae, Bembidion lampros (Herbst.) on a sand enriched with increasing quantities of organic matter was studied. In laboratory, adults of B. lampros were put on different substrate, made of sand or sand with addition of organic matter at 3, 6 and 9% w/w, and treated with carbosulfan applied as granule at the rate of 312.5, 625, 1250 and 6250 microg a.i./m corresponding respectively to 0.5, 1, 2 and 10% of the recommended field rate. Mortalities of B. lampros were assessed after 14 day of exposure. In parallel, the total carbosulfan residue (total extraction) and bioavailable fraction (CaCL2 aqueous extraction) were determined 48h after substrate treatments. According to the mortalities and bio-availability obtained, a dose--response relationship was calculated and compared with a reference relation dose--response obtained on sand, where the bio-availability of the product was considered as 100% of the amount of product applied. Carbosulfan was highly toxic on sand for B. lampros, with 100, 57 and 50% mortality at 10, 2 and 1% of the recommended field rate. When organic matter was added to the sand, the toxicity gradually decreased. This reduction in toxicity was more rapidly observed on sand + organic matter than on pure sand. The mortalities were strongly correlated with the bioavailability, indicating first that the organic matter is fixing an important part of the insecticide and secondly reduce its toxicity to beneficial arthropods. The results suggest that it could be possible, with further research, to predict toxicity of products in the field on different kind of soil according previous laboratory toxicity models and soil analysis. In conclusion, the organic matter influences strongly bio-availability of carbosulfan. This bioavailability was strongly correlated to toxicity to B. lampros. With the improvement of bioavailability determination and method validation, the assessment of pesticide bio-availability in the substrate could help to estimate the pesticide toxicity towards carabidae on different type of soils.

Predicting the long term course of low back pain and its consequences for sickness absence and associated work disability.

BACKGROUND: Low back pain is characterised by a dynamic pattern of episodes and recovery but little is known about the long term course of back pain due to lack of cohort studies with sufficiently long follow up periods. METHODS: A cohort of 523 workers in nursing homes and homes for the elderly was followed for two years. Physical load was measured by observations at the workplace. Psychosocial factors at work, individual characteristics, and low back pain were determined by questionnaire once a year. The effect of work load on low back pain and the transition of low back pain into sickness absence was calculated with logistic regression analysis. A Markov model was used to construct a hypothetical cohort of workers with follow up of 40 years (40 cycles of 1 year) with transitional probabilities between no complaints, low back pain, and sickness due to low back pain. Permanent disability was used as end state of health. RESULTS: The transitional probability from no complaints to low back pain varied between p = 0.25 and p = 0.29, from low back pain to sickness absence between p = 0.09 and p = 0.25, and recurrence of sickness absence varied between p = 0.27 and p = 0.50, depending on the level of physical load. During a 40 year career, total sickness absence due to low back pain was approximately 140 weeks (6.6%) among workers with high physical load and about 30 weeks (1.4%) among those with low physical load. CONCLUSION: The Markov approach illustrated the potential impact of physical load on (permanent) disability due to low back pain among workers with exposure to physical load. These consequences may go unnoticed in cohort studies with follow up periods of a few years.

[Thoracic endometriosis with aspecific manifestation]. / Thoracale endometriose met een aspecifieke uiting.

BACKGROUND: Endometriosis is a common disease, especially in subfertile women. The most common location is in the pelvis, but extragenital locations are also possible. This far less common condition has been described in almost all tissues in the body. Symptoms occurring cyclically are characteristic of endometriosis. CASE DESCRIPTION: A 37-year-old woman was discovered by chance to have ascites and pleural effusion. She had no symptoms of this. Thoracoscopy showed an image consistent with thoracic endometriosis. After initial drug therapy was unsuccessful, surgical intervention was performed. CONCLUSION: Thoracic endometriosis is a rare disease, in which the cyclical nature of the symptoms often leads to correct diagnosis. Drug therapy is the preferred treatment for patients.

Economic evaluation of voriconazole in the treatment of invasive aspergillosis in the Netherlands.

OBJECTIVE: To asses the cost-effectiveness of voriconazole in comparison to conventional amphotericin B and itraconazole for the treatment of invasive aspergillosis in the Netherlands. METHODS: The cost-effectiveness of voriconazole in comparison to conventional amphotericin B or itraconazole was evaluated with a decision tree model followed by a life-time Markov model, focusing on long-term survival of patients treated for invasive aspergillosis. Efficacy after 12 weeks of treatment from clinical trials was used to estimate long-term effectiveness by extrapolating these short-term results over time. Information on medical resource consumption, treatment pathways and switch proportions were obtained from both the literature and Experts. Probabilistic analysis was used to compare the cost-effectiveness among the regimens. RESULTS: With voriconazole, the mean cost for treating invasive aspergillosis per patient was E32 651 (2.5th percentile and 97.5th of uncertainty distribution: E30 037; E36 859), compared to E33 616 (E30 920; E39 633) for conventional amphotericin B and E29 115 (E23 537; E61 414) for itraconazole. The mean survival of patients treated with voriconazole was 174.0 life weeks (160.1; 188.8), compared to 116.1 life weeks (104.8; 128.0) for conventional amphotericin B and 150.4 life weeks (109.1; 194.4) for itraconazole. The beneficial effects of voriconazole on both cost and effectiveness compared with conventional amphotericin B resulted in a probability of 69.8% that voriconazole was a dominant treatment (i.e. less costs and longer survival). The incremental cost-effectiveness ratio of voriconazole versus itraconazole was E150 per life week (i.e. 7800 euros per life-year gained). Depending on the willingness to pay (WTP) the probability of being cost-effective vs. itraconazole increased to a maximum probability of 70%. CONCLUSION: In the treatment of invasive aspergillosis, voriconazole is dominant over amphotericin B and cost-effective in comparison to itraconazole.

Aphid parasitoid complex in potato in the context of IPM in Belgium.

Parasitic hymenoptera of potato aphids were collected and identified in 2000 and 2001 in 11 potato fields in Belgium. Nine Aphidiidae species, parasiting seven aphid species, were found: Aphidius ervi, Aphidius matricariae, Aphidius picipes, Binodoxys angelicae, Diaeretiella rapae, Praon abjectum, Praon gallicium, Praon volucre and Toxares deltiger. A. ervi and A. picipes were the dominant and sub-dominant species, with 54% and 28% of the primary parasite collected, respectively. Both species and T. deltiger were found on Aphis nasturti, Aulacorthum solani, Macrosiphum euphorbiae and Myzus persicae, the four most important aphid potato in Belgium. Parasitism rate of A. nasturtii and, to a lesser extent, M. euphorbiae was low compared to A. solani and M. persicae. Parasitism of A. solani was particularly high, with 63.5% in 2000 and 89.2% in 2001, and this species was the preferred host of several Aphidiid species. The abundance of alternative hosts as other crops pest aphids or non-pest aphids on wild plants in agroecosystems could explains the efficacy of these species. The biological control of A. nasturtii and M. euphorbiae by parasitic hymenoptera was poorer, and several studies need to be undertaken to find suitable parasitic hymenoptera species effective on these aphids and agro-environmental measures able to promote them.

Selectivity lists of pesticides to beneficial arthropods for IPM programs in carrot--first results.

In order to improve IPM programs in carrot, 7 fungicides, 12 herbicides and 9 insecticides commonly used in Belgium were tested for their toxicity towards five beneficial arthropods representative of most important natural enemies encountered in carrot: parasitic wasps - Aphidius rhopalosiphi (De Stefani-Perez) (Hym., Aphidiidae), ladybirds - Adalia bipunctata (L.) (Col., Coccinellidae), hoverfly - Episyrphus balteatus (Dipt.. Syrphidae), rove beetle - Aleochara bilineata (Col., Staphylinidae) and carabid beetle - Bembidion lampros (Col., Carabidae). Initialy, all plant protection products were tested on inert substrate glass plates or sand according to the insect. Products with a corrected mortality (CM) or a parasitism reduction (PR) lower than 30% were kept for the constitution of positive list (green list). The other compounds were further tested on plant for A. rhopalosiphi, A. bipunctata, E. balteatus and soil for B. lampros and A. bilineata. With these extended laboratory tests results, products were listed in toxicity class: green category [CM or PR < or = 30%], yellow category [30% < CM or PR < or = 60%] and orange category [60% < CM or PR < or = 80%]. Products with toxicity higher than 80% on plants or that reduce parasitism more than 80% on soil were put in red category and are not recommended to Integrated Pest Management programs in carrot. Results showed that all fungicides tested were harmless to beneficials except Tebuconazole, which was slightly harmful for A. bipunctata. Herbicides were also harmless for soil beneficials, except Chlorpropham. This product was very toxic on sand towards A. bilineata and must be tested on soil. All soil insecticides tested were very toxic for ground beneficials and considered as non-selective. Their use in IPM is subject to questioning in view of negative impacts on beneficials. Among foliar insecticides, Dimethoate and Deltamethrin are not recommended for IPM because their high toxicity for all beneficials. The other foliar insecticides were more selective; any of them were harmless for all species tested.

Postpneumonectomy syndrome in adulthood. Surgical correction using an expandable prosthesis.

The postpneumonectomy syndrome is a rare complication occurring after right pneumonectomy and is seen mainly after pneumonectomy in childhood. The presenting symptoms are dyspnea, stridor, and recurrent pulmonary infections. The syndrome is caused by the shifting and rotation of the heart and mediastinum into the right hemithorax, and anterior herniation of the left lung. This causes tortuosity and stretching of the trachea and compression of the left main bronchus and left lower lobe bronchus, eventually resulting in secondary tracheobronchomalacia. This report reviews two cases of postpneumonectomy syndrome following pneumonectomy in adulthood. After implantation of an expandable prosthesis, an anatomic correction of the shifted mediastinum was achieved, which in both cases resulted in instantaneous and sustained relief.

A multinational investigation of the impact of subcutaneous sumatriptan. II: Health-related quality of life.

The aim of this prospective sequential multinational (5 countries) study was to concurrently evaluate the effects of subcutaneous sumatriptan on clinical parameters, health-related quality-of-life (HRQOL) measures, workplace productivity and patient satisfaction. This report presents the HRQOL results. 582 patients (aged 18 to 65 years) with moderate to severe migraine received their customary antimigraine therapy for 12 weeks and then subcutaneous sumatriptan for 24 weeks. The Short Form-36 Health Survey and the Migraine-Specific Quality of Life Questionnaire were completed at a screening visit (base-line), at the end of the 12-week customary therapy phase, and at 12 and 24 weeks of the sumatriptan phase. Scores for most of the Short Form-36 dimensions improved significantly (p < 0.05) after 12 and 24 weeks of sumatriptan therapy compared with 12 weeks of customary therapy, in each country. Similarly, scores on all Migraine-Specific Quality of Life Questionnaire dimensions were significantly (p < 0.05; paired t-test) improved after 12 weeks (in all countries) and 24 weeks (in 4 of 5 countries) of sumatriptan therapy compared with 12 weeks of customary therapy. This study demonstrates that, in 5 countries, treatment of migraine attacks with subcutaneous sumatriptan compared with customary therapy was associated with improvements in HRQOL, as measured by both general health status and disease-specific instruments.

A multinational investigation of the impact of subcutaneous sumatriptan. III: Workplace productivity and non-workplace activity.

This report presents the workplace productivity and non-workplace activity results of a multinational study of the effects of subcutaneous sumatriptan 6 mg in the acute treatment of migraine compared with patient's customary therapy. Patients diagnosed with migraine treated their symptoms for 24 weeks with subcutaneous sumatriptan after a 12-week period of treating symptoms with their customary (non-sumatriptan) therapy. Patients used diary cards to record information concerning the effects of migraine on workplace productivity and non-workplace activity time. The average workplace productivity time lost was 23.4 hours per patient during 12 weeks of customary therapy, compared with 7.2 and 5.8 hours per patient during the first and second 12-week periods of sumatriptan therapy, respectively. An average of 9.3 hours of non-workplace activity time was lost per patient during the customary therapy phase, compared with 3.2 and 2.8 hours during the first and second 12-week periods of sumatriptan therapy, respectively. Treatment of migraine with subcutaneous sumatriptan compared with customary therapy was associated with an average gain per patient of approximately 16 hours of workplace productivity time and 6 hours of non-workplace activity time, over a 3-month period.

A multinational investigation of the impact of subcutaneous sumatriptan. IV: Patient satisfaction.

This report describes the patient satisfaction results from a prospective, sequential, multinational study. The study was conducted to concurrently evaluate the effects of sumatriptan, compared with customary therapy, on clinical parameters, health-related quality of life, productivity and patient satisfaction in adult patients with moderate to severe migraine. Patients treated migraine attacks for 12 weeks with their customary therapy, followed by 24 weeks' treatment with subcutaneous sumatriptan 6 mg. A questionnaire was conducted at the end of each study phase, or retrospectively at the end of the study, to assess patient satisfaction with customary therapy and sumatriptan. Sumatriptan was considered by most patients (67 to 85%) to be dependable and fast-acting, and to have a long duration of effect, allowing a quick return to normal activities. By comparison, 15 to 32% of patients considered that their customary therapy possessed the same attributes. However, customary therapy was considered to be easy/very easy to use by 82% of patients compared with 62% for subcutaneous sumatriptan. 89% of patients indicated that they would use sumatriptan again in the future. This study demonstrates that treatment of migraine attacks with subcutaneous sumatriptan for 24 weeks is associated with greater patient satisfaction as regards specific drug attributes than customary therapy.

A multinational investigation of the impact of subcutaneous sumatriptan. I: Design, methods and clinical findings.

This report describes the design, methods and clinical results of a prospective sequential multinational (5 countries) study conducted to evaluate the effects of subcutaneous sumatriptan on health-related quality of life, workplace productivity, clinical parameters and patient satisfaction. Adult patients with moderate to severe migraine initially received customary therapy for migraine episodes for 12 weeks, followed by 24 weeks' treatment with self-administered subcutaneous sumatriptan 6 mg. Demographic, baseline, health-related quality of life and patient satisfaction rating data were collected during visits to the clinic. Data relating to migraine symptoms, migraine therapy, work productivity and non-work activity time were collected on diary cards filled out by the patients. 749 patients were recruited to the study and 637 received at least 1 dose of sumatriptan. Overall, 75.5% of migraines were successfully treated within 2 hours with sumatriptan compared with 31.9% with customary therapy; 36% of patients reported complete relief at 2 hours with sumatriptan treatment compared with 1% of patients receiving customary therapy. 69% of patients successfully treated 70% of their migraines with sumatriptan within 2 hours, compared with 12% of patients with customary therapy. No serious adverse events were reported; 50% of patients reported an adverse event during the 12-week customary therapy phase and 89% of patients during the 24-week sumatriptan phase. These clinical results, which are consistent with those reported in randomised blinded studies of subcutaneous sumatriptan, suggest that relief of migraine symptoms occurs more often, and in less time, in patients receiving subcutaneous sumatriptan rather than customary therapy as their primary medication.

Effects of measurement strategy and statistical analysis on dose-response relations between physical workload and low back pain.

BACKGROUND: In epidemiological studies on physical workloads and back complaints, among the important features in modelling dose-response relations are the measurement strategy of the exposure and the nature of the dose-response relation that is assumed. AIM: To evaluate the effect of these two features on the strength of the dose-response relation between physical load and severe low back pain. METHODS: The study population consisted of 769 workers in nursing homes and homes for the elderly. Observations at the workplace were made of 212 subjects. These observations were analysed to determine exposure to physical load according to two measurement strategies: the individual approach and the group approach. The nature of the dose-response relation was evaluated with nested logistic regression models. RESULTS: The group approach resulted in higher odds ratios for the associations between physical load and low back pain than the individual approach. Spline logistic regression models appeared to describe the dose-response relation between physical load and low back pain best. The corresponding curve showed small changes in risk for small changes in exposure, whereas the categorical model only showed sudden large changes in risk at predefined exposure values. CONCLUSION: The choice for a particular measurement strategy of physical load influences the strength of the associations between physical load and severe low back pain. Spline models allow changes in risk over the whole exposure range and are therefore a promising approach to identify quantitative dose-response patterns between physical load and low back pain.

Dose-response relations between occupational exposures to physical and psychosocial factors and the risk of low back pain.

AIMS: To assess dose-response relations between occupational exposures to physical and psychosocial factors and the risk of low back pain. METHODS: A cohort of 523 subjects, working in nursing homes and homes for the elderly, was followed prospectively for one year. Physical load for different occupations was assessed by quantitative observations at the workplace. Information on low back pain and other factors was gathered with questionnaires administered at baseline and at one year. Two outcome measures of low back pain incidence were used: any new episode of pain lasting for at least a few hours during follow up (LBP); and any new episode of disabling pain that interfered with daily activities during follow up (LBP/D). Hierarchical regression analysis with a spline function was used to estimate dose-response relations. RESULTS: The risk of LBP was not associated with physical factors, controlling for confounders; but this outcome was inversely associated with age and weakly, though imprecisely, associated with two psychosocial factors--low decision authority and high work demands. In contrast, the risk of LBP/D was positively associated with age and not associated with the psychosocial factors. Trunk flexion over 45 degrees was monotonically associated with the risk of LBP/D; the estimated relative risk was 3.18 (95% CI 1.13 to 9.00) for 1 hour and 45 minutes of bending per week (90th centile), relative to 30 minutes per week. The hierarchical estimates of effect were more stable than were the maximum likelihood estimates. CONCLUSION: Occupational exposure to trunk flexion over 45 degrees appears to be a risk factor for low back pain with disability among persons employed in nursing homes and homes for the elderly in the Netherlands.