Prevalence of insomnia in a general adult population cohort using different diagnostic criteria: The seventh survey of the Tromsø study 2015-2016.

Insomnia disorder is a subjective complaint of sleep dissatisfaction including both night-time and daytime symptoms. Currently there are three commonly used diagnostic manuals each with their own set of criteria, which is often credited for the wide range in insomnia prevalence reported by population-based studies, especially those with self-reported insomnia. However, there are limited studies directly comparing different criteria and little is known about associations with health outcomes. Thus, the aim of this study was to compare the most commonly used diagnostic criteria for insomnia from the literature and to explore the associations with a range of physical and mental health outcomes. We used data from 21,083 women and men from the seventh survey of the population-based Tromsø Study which included adults aged 40-99 years. A revised version of the Bergen Insomnia Scale was used to define insomnia based on the 4th (revised) and 5th edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR and DSM5), the 10th edition of the International Classification of Diseases (ICD-10), and the 3rd edition of the International Classification of Sleep Disorders (ICSD-3). We found the following prevalence of insomnia: DSM-IV-TR 23.6 %, DSM5 8.5 %, ICD-10 9.9 % and ICSD-3 20.0 %. When looking at each symptom, we found over half the participants classified as having insomnia using the DSM-IV-TR and ICSD-3 criteria did not report having impaired daytime functioning at least three days per week. Overall, participants with DSM5 and ICD-10 insomnia appeared to have worse health profiles, based on a higher percentage meeting the cut-off for possible anxiety or depression, reporting a psychological problem or chronic pain, and using antidepressants, painkillers or sleeping pills. However logistic regression models showed largely the same health factors had the same association with the odds for being classified as having insomnia disorder from each set of criteria. Overall, this study suggests that insomnia prevalence may be overestimated if daytime symptoms are not adequately included in accordance with current guidelines.

The association between proportion of night shifts and musculoskeletal pain and headaches in nurses: a cross-sectional study.

BACKGROUND AND PURPOSE: Shift work is associated with musculoskeletal pain and headaches, but little is known about how the intensity of shift work exposure is related to musculoskeletal pain and headaches. This study aimed to investigate whether a higher proportion of night shifts is associated with a higher occurrence of musculoskeletal pain and headaches. Furthermore, to investigate whether sleep duration can mediate this potential association. METHOD: The study included 684 nurses in rotating shift work who responded to a daily questionnaire about working hours, sleep, and pain for 28 consecutive days. The data were treated cross-sectionally. RESULTS: A negative binomial regression analysis adjusted for age and BMI revealed that working a higher proportion of night shifts is not associated with a higher occurrence of musculoskeletal pain and headaches. On the contrary, those working ≥ 50% night shifts had a significantly lower occurrence of pain in the lower extremities than those who worked < 25% night shifts (IRR 0.69 95% CI 0.51, 0.94). There was no indication of a mediation effect with total sleep time (TST). CONCLUSION: The results of this study indicate that working a higher proportion of night shifts is not associated with a higher occurrence of musculoskeletal pain and headaches.

Diagnostic accuracy of the 5.07 monofilament test for diabetes polyneuropathy: influence of age, sex, neuropathic pain and neuropathy severity.

INTRODUCTION: There is a need for simple and cheap diagnostic tools for diabetic polyneuropathy (DPN). We aimed to assess the diagnostic accuracy of the 5.07/10 g monofilament test in patients referred to polyneuropathy assessments, as well as to examine how disease severity, age, sex and neuropathic pain (NP) impact diagnostic accuracy. RESEARCH DESIGN AND METHODS: Five Norwegian university hospitals recruited patients with diabetes aged 18-70 referred to neurological outpatient clinics for polyneuropathy assessments. The 5.07/10 g Semmes-Weinstein monofilament examination (SWME) was validated against the Toronto consensus for diagnosing diabetic neuropathies; the results were stratified by age, sex and NP. Disease severity was graded by a combined nerve conduction study (NCS) Z-score, and logistic regression was applied to assess whether disease severity was a predictor of diagnostic accuracy. RESULTS: In total, 506 patients were included in the study. Global sensitivity was 0.60 (95% CI 0.55, 0.66), specificity 0.82 (95% CI 0.75, 0.87), positive and negative predictive values were 0.86 (95% CI 0.81, 0.90) and 0.52 (95% CI 0.46, 0.58), respectively, positive and negative likelihood ratios were 3.28 (95% CI 2.37, 4.53) and 0.49 (95% CI 0.42, 0.57), respectively. The SWME was less sensitive in females (0.43), had lower specificity in patients with NP (0.56), and performed worse in patients ≥50 years. NCS-based disease severity did not affect diagnostic accuracy (OR 1.15, 95% CI 0.95, 1.40). CONCLUSIONS: This multicenter study demonstrates poor diagnostic performance for the 5.07/10 g SWME in patients with diabetes referred to polyneuropathy assessments; it is particularly unsuited for female patients and those with NP. The diagnostic accuracy of the SWME was not influenced by NCS-based disease severity, demonstrating that it does not perform better in patients with later stages of DPN. We do not recommend the use of the 5.07/10 g monofilament in the evaluation of patients with diabetes referred to polyneuropathy assessments.

Night work, season and alertness as occupational safety hazards in the Arctic: protocol for the Noralert observational crossover study among Norwegian process operators.

INTRODUCTION: The objective of this study is to determine the effects of night work, Arctic seasonal factors and cold working environments on human functions relevant to safety. The study aims to quantify the contribution of (1) several consecutive night shifts, (2) seasonal variation on sleepiness, alertness and circadian rhythm and (3) whether a computational model of sleep, circadian rhythms and cognitive performance can accurately predict the observed sleepiness and alertness. METHODS AND ANALYSIS: In an observational crossover study of outdoor and indoor workers (n=120) on a three-shift schedule from an industrial plant in Norway (70 °N), measurements will be conducted during the summer and winter. Sleep duration and quality will be measured daily by smartphone questionnaire, aided by actigraphy and heart rate measurements. Sleepiness and alertness will be assessed at regular intervals by the Karolinska Sleepiness Scale and the psychomotor vigilance test, respectively. Saliva samples will assess melatonin levels, and a blood sample will measure circadian time. Thermal exposures and responses will be measured by sensors and by thermography. ETHICS AND DISSEMINATION: All participants will give written informed consent to participate in the study, which will be conducted in accordance with the Declaration of Helsinki. The Norwegian Regional Committee for Medical Research Ethics South-East D waivered the need for ethics approval (reference 495816). Dissemination plans include academic and lay publications, and partnerships with national and regional policymakers.

Polyneuropathy in Adolescent Childhood Cancer Survivors: The PACCS Study.

BACKGROUND: Childhood cancer survivors (CCS) are at risk of polyneuropathy due to chemotherapy, but studies in young survivors are scarce and diagnosis is challenging. We aimed to study the presence of polyneuropathy and the possible effect of cumulative doses of chemotherapeutic agents in a representative group of adolescent survivors. METHODS: CCS aged nine to 18 years and age- and sex-matched controls were recruited from the cross-sectional Physical Activity and Fitness among Childhood Cancer Survivors (PACCS) study. CCS with various cancer diagnoses who had ended cancer treatment one year or more before study were included. Polyneuropathy was evaluated clinically and with nerve conduction studies (NCSs) in three motor and five sensory nerves. We used mixed-effects linear regression models to compare CCS and controls, and investigate possible associations between cumulative chemotherapy doses and NCS amplitudes. RESULTS: A total of 127 CCS and 87 controls were included, with 14% CCS having probable or confirmed polyneuropathy. NCS amplitudes were lower in survivors compared with controls in all nerves. The largest mean difference was 3.47 µV (95% confidence interval [CI], 2.18 to 4.75) in the tibial plantar medial sensory and 1.91 mV (95% CI, 0.78 to 3.04) in the tibial motor nerve. The cumulative dose of platinum derivatives was associated with lower tibial motor nerve amplitude (-0.20; 95% CI, -0.35 to -0.04 mV for 100 mg/m2 dose increase) but not in other nerves. We found no significant associations between vinca alkaloids cumulative dose and amplitudes. CONCLUSIONS: CCS without clinical signs or symptoms of polyneuropathy may have subtle nerve affection. The clinical long-term impact of this novel observation should be evaluated in larger, longitudinal studies.

Accuracy of neuropathic pain measurements in patients with symptoms of polyneuropathy: validation of painDETECT, Self-Completed Leeds Assessment of Neuropathic Symptoms and Signs, and Douleur Neuropathique 4.

ABSTRACT: Pain is a common symptom in patients referred to polyneuropathy assessment. Diagnostic evaluation and choice of treatment may depend on whether the pain is likely to be neuropathic or not. This study aimed to investigate the diagnostic accuracy of 3 tools commonly used to differentiate between neuropathic and nonneuropathic pain. To accomplish this, we included patients with bilateral distal lower extremity pain, referred to neurological outpatient clinics at 5 Norwegian University hospitals for polyneuropathy assessment. The patients filled in Norwegian versions of painDETECT, the Self-Completed Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS), and the clinician-rated Douleur Neuropathique 4 (DN4). All patients underwent a clinical examination and nerve conduction measurements and were classified according to the NeuPSIG neuropathic pain criteria (reference standard). In total, 729 patients were included, of which 63% had neuropathic pain by the reference standard. Only DN4 demonstrated high sensitivity (0.87), whereas all 3 tools had low specificity (≤0.65). Importantly, the tools' predictive ability was unsatisfactory; The probability of getting a correct test result was 3 quarters at best, and at worst, no better than two fifths. Consequently, we show that neither DN4, painDETECT, nor S-LANSS can be confidently used to assess neuropathic pain in a neurological outpatient population with symptoms of polyneuropathy.

Review of techniques useful for the assessment of sensory small fiber neuropathies: Report from an IFCN expert group.

Nerve conduction studies (NCS) are an essential aspect of the assessment of patients with peripheral neuropathies. However, conventional NCS do not reflect activation of small afferent fibers, including Aδ and C fibers. A definitive gold standard for laboratory evaluation of these fibers is still needed and therefore, clinical evaluation remains fundamental in patients with small fiber neuropathies (SFN). Several clinical and research techniques have been developed for the assessment of small fiber function, such as (i) microneurography, (ii) laser evoked potentials, (iii) contact heat evoked potentials, (iv) pain-related electrically evoked potentials, (v) quantitative thermal sensory testing, (vi) skin biopsy-intraepidermal nerve fiber density and (vii) corneal confocal microscopy. The first five are physiological techniques, while the last two are morphological. They all have advantages and limitations, but the combined use of an appropriate selection of each of them would lead to gathering invaluable information for the diagnosis of SFN. In this review, we present an update on techniques available for the study of small afferent fibers and their clinical applicability. A summary of the anatomy and important physiological aspects of these pathways, and the clinical manifestations of their dysfunction is also included, in order to have a minimal common background.

Which combined nerve conduction study scores are best suited for polyneuropathy in diabetic patients?

INTRODUCTION/AIMS: Nerve conduction studies (NCS) are widely used in diagnosing diabetic polyneuropathy. Combining the Z scores of several measures (Z-compounds) may improve diagnostics by grading abnormality. We aimed to determine which combination of nerves and measures is best suited for studies of diabetic polyneuropathy. METHODS: Sixty-eight patients with type 1 diabetes and 35 controls were included in this study. NCS measurements were taken from commonly investigated nerves in one arm and both legs. Different Z-compounds were calculated and compared with reference material to assess abnormality. A sensitivity proxy, the accuracy index (AI), and Cohen's d were calculated. RESULTS: Z-compounds with the highest AI consisted of the tibial and peroneal motor, and the sural, superficial peroneal, and tibial medial plantar sensory nerves in one or two legs. All Z-compounds were able to discriminate between diabetic subjects and nondiabetic controls (mean Cohen's d = 1.42 [range, 1.03-1.63]). The association between AI and number of measures was best explained logarithmically (R2  = 0.401), with diminishing returns above approximately 14 or 15 measures. F-wave inclusion may increase the AI of the Z compounds. Although often clinically useful among the non-elderly, the additional inclusion of medial plantar NCS into Z-compounds in general did not improve AI. DISCUSSION: Performing unilateral NCS in several motor and sensory lower extremity nerves is suited for the evaluation of polyneuropathy in diabetic patients. The use of Z-compounds may improve diagnostic accuracy in diabetic polyneuropathy and may be particularly useful for follow-up research studies as single summary measures of NCS abnormality development over time.

Assessing inter-rater reproducibility in MScanFit MUNE in a 6-subject, 12-rater "Round Robin" setup.

OBJECTIVE: To assess the inter-rater reliability of MScanFit MUNE using a "Round Robin" research design. METHODS: Twelve raters from different centres examined six healthy study participants over two days. Median, ulnar and common peroneal nerves were stimulated, and compound muscle action potential (CMAP)-scans were recorded from abductor pollicis brevis (APB), abductor digiti minimi (ADM) and anterior tibial (TA) muscles respectively. From this we calculated the Motor Unit Number Estimation (MUNE) and "A50", a motor unit size parameter. As statistical analysis we used the measures Limits of Agreement (LOA) and Coefficient of Variation (COV). Study participants scored their perception of pain from the examinations on a rating scale from 0 (no pain) to 10 (unbearable pain). RESULTS: Before this study, 41.6% of the raters had performed MScanFit less than five times. The mean MUNE-values were: 99.6 (APB), 131.4 (ADM) and 126.2 (TA), with LOA: 19.5 (APB), 29.8 (ADM) and 20.7 (TA), and COV: 13.4 (APB), 6.3 (ADM) and 5.6 (TA). MUNE-values correlated to CMAP max amplitudes (R2-values were: 0.463 (APB) (p<0.001), 0.421 (ADM) (p<0.001) and 0.645 (TA) (p<0.001)). The average perception of pain was 4. DISCUSSION: MScanFit indicates a high level of inter-rater reliability, even with only limited rater experience and is overall reasonably well tolerated by patients. These results may indicate MScanFit as a reliable MUNE method with potential as a biomarker in drug trials.

Brain monitoring in hospitals needs to be strengthened. / Hjerneovervåking i sykehusene må styrkes.

Careful brain monitoring saves lives and is beneficial to patients' health. Nevertheless, Norway lacks guidelines for brain monitoring in hospitals.

Clinical Utility of the 6-Item CTS, Boston-CTS, and Hand-Diagram for Carpal Tunnel Syndrome.

Background: Self-reported measures are often used in research and clinical practice to diagnose carpal tunnel syndrome (CTS) and guide therapeutic choices. We aimed to assess the clinical utility of the Norwegian versions of two self-reported outcome measures for symptom severity assessment, the 6-item CTS (CTS-6), and Boston-CTS (BCTQ), and of one diagnostic measure, the hand-diagram, by evaluating measurement properties including discriminative ability for severity assessment (CTS-6, BCTQ), and diagnosis of CTS (hand-diagram). Methods: We performed forward and backward translation and cultural adaptation of the Norwegian CTS-6 and BCTQ. Following COSMIN guidelines, we investigated internal consistency, reliability, construct validity, and discriminative ability for distinguishing between severity levels of CTS in patients with confirmed CTS for the CTS-6 and BCTQ and reliability and discriminative ability for diagnosing CTS for the hand-diagram. Results: Two hundred and fifty-one patients referred for diagnostic work-up for CTS with nerve conduction studies (NCS) participated. The CTS-6 and BCTQ had acceptable internal consistency (Crohnbach's α = 0.82 and 0.86, respectively), reliability (ICC = 0.86 and 0.90; SEM = 0.24 and 0.20; SDC95% = 0.68 and 0.55, respectively), construct validity (all eight pre-defined hypotheses confirmed) and discriminative ability to distinguish between severity levels of CTS [Area under the curve (AUC) = 0.75, 95% CI 0.64-0.85]. The hand-diagram had acceptable reliability (Cohen's kappa = 0.69) and discriminative ability to diagnose CTS (sensitivity = 0.72, specificity = 0.90). Conclusion: Our findings support the clinical utility of the CTS-6 and BCTQ for symptom severity assessment and of the hand-diagram for diagnostic screening.

Shift work, low-grade inflammation, and chronic pain: a 7-year prospective study.

OBJECTIVES: We investigated prospective associations of shift work with chronic pain and C-reactive protein (CRP), an indicator of inflammation. Furthermore, we elucidated CRP as a possible mediator and/or moderator of effects of shift work on pain. METHODS: Data from a 7 years follow-up study were analyzed (N = 2323). Shift work and chronic pain of "neck/shoulder", "arm/hand", "upper back", "low back", "hip/leg/feet", and "other regions" were measured by questionnaires. "Chronic widespread pain", "number of chronic pain sites", and "any chronic pain" were computed. CRP was measured in serum samples. Logistic and Poisson regressions were conducted. Mediation was assessed by casual mediation analyses and moderation by the Relative Excess Risk due to Interaction (RERI). RESULTS: Shift work was not associated with any chronic pain variable and no mediation was detected. CRP was associated with low back pain, hip/leg pain, and "number of pain sites", and also with the combination of shift work and CRP of 1-2.99 mg/L (compared to: no shiftwork and CRP < 1). Additionally, shiftwork and CRP 1-2.99 mg/L was associated with risk of "any chronic pain" (OR: 1.76, 95% CI: 1.12, 2.85), which was not associated with CRP alone. Moderation analyses suggested the risks for "any chronic pain" and "number of pain regions" increased when individuals with elevated CRP worked shifts-beyond what the separate effects of CRP and shift would suggest. CONCLUSIONS: We found no evidence of shift work in general affecting CRP or chronic pain. However, shift work and elevated CRP combined may influence chronic pain.

Sleep patterns and insomnia in a large population-based study of middle-aged and older adults: The Tromsø study 2015-2016.

Epidemiological studies assessing adult sleep duration have yielded inconsistent findings and there are still large variations in estimation of insomnia prevalence according to the most recent diagnostic criteria. Our objective was to describe sleep patterns in a large population of middle-aged and older adults, by employing accurate measures of both sleep duration and insomnia. Data stem from the Tromsø Study (2015-2016), an ongoing population-based study in northern Norway comprising citizens aged 40 years and older (n = 21,083, attendance = 64.7%). Sleep parameters were reported separately for weekdays and weekends and included bedtime, rise time, sleep latency and total sleep time. Insomnia was defined according to recent diagnostic criteria (International Classification of Sleep Disorders; ICSD-3). The results show that 20% (95% confidence interval,19.4-20.6) fulfilled the inclusion criteria for insomnia. The prevalence was especially high among women (25%), for whom the prevalence also increased with age. For men, the prevalence was around 15% across all age groups. In all, 42% of the women reported sleeping <7 hr (mean sleep duration of 7:07 hr), whereas the corresponding proportion among males was 52% (mean sleep duration of 6:55 hr). We conclude that the proportion of middle-aged and older adults not getting the recommended amount of sleep is worryingly high, as is also the observed prevalence of insomnia. This warrants attention as a public health problem in this population.

Genome-Wide Association Study of 2,093 Cases With Idiopathic Polyneuropathy and 445,256 Controls Identifies First Susceptibility Loci.

Background: About one third of patients with chronic polyneuropathy have no obvious underlying etiology and are classified as having idiopathic polyneuropathy. The lack of knowledge about pathomechanisms and predisposing factors limits the development of effective prevention and treatment for these patients. We report the first genome-wide association study (GWAS) of idiopathic polyneuropathy. Methods: Cases with idiopathic polyneuropathy and healthy controls were identified by linkage to hospital records. We performed genome-wide association studies using genetic data from two large population-based health studies, the Trøndelag Health Study (HUNT, 1,147 cases and 62,204 controls) and UK Biobank (UKB, 946 cases and 383,052 controls). In a two-stage analysis design, we first treated HUNT as a discovery cohort and UK Biobank as a replication cohort. Secondly, we combined the two studies in a meta-analysis. Downstream analyses included genetic correlation to other traits and diseases. We specifically examined previously reported risk loci, and genes known to cause hereditary polyneuropathy. Results: No replicable risk loci were identified in the discovery-replication stage, in line with the limited predicted power of this approach. When combined in a meta-analysis, two independent loci reached statistical significance (rs7294354 in B4GALNT3, P-value 4.51 × 10-8) and (rs147738081 near NR5A2, P-value 4.75 × 10-8). Idiopathic polyneuropathy genetically correlated with several anthropometric measures, most pronounced for height, and with several pain-related traits. Conclusions: In this first GWAS of idiopathic polyneuropathy we identify two risk-loci that indicate possible pathogenetic mechanisms. Future collaborative efforts are needed to replicate and expand on these findings.

Low Back Pain With Persistent Radiculopathy; the Clinical Role of Genetic Variants in the Genes SOX5, CCDC26/GSDMC and DCC.

In a recently published genome-wide association study (GWAS) chronic back pain was associated with three loci; SOX5, CCDC26/GSDMC and DCC. This GWAS was based on a heterogeneous sample of back pain disorders, and it is unknown whether these loci are of clinical relevance for low back pain (LBP) with persistent radiculopathy. Thus, we examine if LBP with radiculopathy 12 months after an acute episode of LBP with radiculopathy is associated with the selected single nucleotide polymorphisms (SNPs); SOX5 rs34616559, CCDC26/GSDMC rs7833174 and DCC rs4384683. In this prospective cohort study, subjects admitted to a secondary health care institution due to an acute episode of LBP with radiculopathy, reported back pain, leg pain, and Oswestry Disability Index (ODI), were genotyped and followed up at 12 months (n = 338). Kruskal-Wallis H test showed no association between the SNPs and back pain, leg pain or ODI. In conclusion, LBP with radiculopathy 12 months after an acute episode of LBP with radiculopathy, is not associated with the selected SNPs; SOX5 rs34616559, CCDC26/GSDMC rs7833174 and DCC rs4384683. This absent or weak association suggests that the SNPs previously associated with chronic back pain are not useful as prognostic biomarkers for LBP with persistent radiculopathy.

The association between selected genetic variants and individual differences in experimental pain.

OBJECTIVES: The underlying mechanisms for individual differences in experimental pain are not fully understood, but genetic susceptibility is hypothesized to explain some of these differences. In the present study we focus on three genetic variants important for modulating experimental pain related to serotonin (SLC6A4 5-HTTLPR/rs25531 A>G), catecholamine (COMT rs4680 Val158Met) and opioid (OPRM1 rs1799971 A118G) signaling. We aimed to investigate associations between each of the selected genetic variants and individual differences in experimental pain. METHODS: In total 356 subjects (232 low back pain patients and 124 healthy volunteers) were genotyped and assessed with tests of heat pain threshold, pressure pain thresholds, heat pain tolerance, conditioned pain modulation (CPM), offset analgesia, temporal summation and secondary hyperalgesia. Low back pain patients and healthy volunteers did not differ in regards to experimental test results or allelic frequencies, and were therefore analyzed as one group. The associations were tested using analysis of variance and the Kruskal-Wallis test. RESULTS: No significant associations were observed between the genetic variants (SLC6A4 5-HTTLPR/rs25531 A>G, COMT rs4680 Val158Met and OPRM1 rs1799971 A118G) and individual differences in experimental pain (heat pain threshold, pressure pain threshold, heat pain tolerance, CPM, offset analgesia, temporal summation and secondary hyperalgesia). CONCLUSIONS: The selected pain-associated genetic variants were not associated with individual differences in experimental pain. Genetic variants well known for playing central roles in pain perception failed to explain individual differences in experimental pain in 356 subjects. The finding is an important contribution to the literature, which often consists of studies with lower sample size and one or few experimental pain assessments.