Trends in hypnotic drug use in depression 2007-2017: A Swedish population-based study.

Insomnia is a common feature of depression; however, depression treatment guidelines provide limited recommendations regarding hypnotic drugs. Few studies have thoroughly investigated the use of hypnotic drugs in depression. In this cohort study using national Swedish registers, we included all patients ≥18 years with incident unipolar depression during 2007-2017. Patients were followed for 3 years, noting the annual and quarterly prevalence of hypnotic drug use from prescription fills. Prevalence ratios (PR) comparing 2017 to 2007 were calculated with 95% confidence intervals (CI). A total of 222,077 patients with depression were included (mean age 41 years, 59% women). In the year following diagnosis, 44.1% used any hypnotic drug in 2017, compared with 46.7% in 2007 (PR 0.94, 95% CI 0.92-0.97). The most commonly used drugs were Z-drugs (zopiclone, zolpidem, and zaleplon) with a prevalence of 27.6% in 2017 and 35.6% in 2007 (PR 0.78, 95% CI 0.75-0.80). Melatonin use increased sharply to 12.0% in 2017 from 0.4% in 2007 (PR 28.9, 95% CI 23.5-35.7). Hypnotic drug use was most prevalent in the first two quarters after diagnosis; however, after 3 years, the quarterly prevalence was still 19.2%. Hypnotics were more common among women, older patients, those with somatic comorbidities, more severe depression, or a history of suicide attempt. Evidence from this large register-based study demonstrates that hypnotics were used to a large extent in depression in Sweden 2007-2017. Z-drugs use declined and melatonin use increased dramatically. Hypnotic drug use remained high even 3 years after diagnosis.

Atmospheric deposition and soil water chemistry in Swedish forests since 1985 - Effects of reduced emissions of sulphur and nitrogen.

Trends for the atmospheric deposition of sulphur (S) and inorganic nitrogen (inorg-N) to forests and changes in the forest soil water chemistry in Sweden have been assessed since 1985, with special focus on the last 25 years, based on measurements within the Swedish Throughfall Monitoring Network (SWETHRO). The reductions in the deposition of S and inorg-N in the southern part of Sweden corresponded relatively well with the pollutant emission reductions for S and inorg-N from both EU27 + UK and Sweden during 1996/97-2021/22. For northern Sweden the deposition of S and inorg-N decreased to a lesser extent than both European and Swedish emissions. The bulk deposition of NO3-N has decreased more than the deposition of NH4-N over the last 25-year period, which is consistent with the much larger emission reductions for NOx compared to NH3 from EU27 + UK and Sweden. The S concentrations in the soil water, at 50 cm below soil surface, have decreased during the last 25 years, however somewhat less than the S deposition. At sites with low ANC and pH in the beginning of the period, the increase in ANC was generally greater and the increase in pH was smaller, but at sites with high pH and ANC above zero, the increase in pH was dominant, in line with the nonlinear relationship between pH and ANC in the soil water. The incidence of elevated concentrations of NO3-N in the soil water was highest in southwest Sweden, ranging between 4 and 19 % of all measuring occasions since 1985/86. The reduced deposition of N over the 35-year period was not reflected in the incidence of elevated concentrations of NO3-N in the soil water over time.

Genomic characterisation of hormone receptor-positive breast cancer arising in very young women.

BACKGROUND: Very young premenopausal women diagnosed with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+HER2-) early breast cancer (EBC) have higher rates of recurrence and death for reasons that remain largely unexplained. PATIENTS AND METHODS: Genomic sequencing was applied to HR+HER2- tumours from patients enrolled in the Suppression of Ovarian Function Trial (SOFT) to determine genomic drivers that are enriched in young premenopausal women. Genomic alterations were characterised using next-generation sequencing from a subset of 1276 patients (deep targeted sequencing, n = 1258; whole-exome sequencing in a young-age, case-control subsample, n = 82). We defined copy number (CN) subgroups and assessed for features suggestive of homologous recombination deficiency (HRD). Genomic alteration frequencies were compared between young premenopausal women (<40 years) and older premenopausal women (≥40 years), and assessed for associations with distant recurrence-free interval (DRFI) and overall survival (OS). RESULTS: Younger women (<40 years, n = 359) compared with older women (≥40 years, n = 917) had significantly higher frequencies of mutations in GATA3 (19% versus 16%) and CN amplifications (CNAs) (47% versus 26%), but significantly lower frequencies of mutations in PIK3CA (32% versus 47%), CDH1 (3% versus 9%), and MAP3K1 (7% versus 12%). Additionally, they had significantly higher frequencies of features suggestive of HRD (27% versus 21%) and a higher proportion of PIK3CA mutations with concurrent CNAs (23% versus 11%). Genomic features suggestive of HRD, PIK3CA mutations with CNAs, and CNAs were associated with significantly worse DRFI and OS compared with those without these features. These poor prognostic features were enriched in younger patients: present in 72% of patients aged <35 years, 54% aged 35-39 years, and 40% aged ≥40 years. Poor prognostic features [n = 584 (46%)] versus none [n = 692 (54%)] had an 8-year DRFI of 84% versus 94% and OS of 88% versus 96%. Younger women (<40 years) had the poorest outcomes: 8-year DRFI 74% versus 85% and OS 80% versus 93%, respectively. CONCLUSION: These results provide insights into genomic alterations that are enriched in young women with HR+HER2- EBC, provide rationale for genomic subgrouping, and highlight priority molecular targets for future clinical trials.

Twenty years of nitrogen deposition to Norway spruce forests in Sweden.

The yearly, total (dry+wet) deposition of inorganic nitrogen (inorg-N) to Norway spruce forests was estimated with a full spatial coverage over Sweden for a twenty-year period, 2001-2020, based on combined measurements with Teflon string samplers, throughfall deposition and bulk deposition to the open field. The results were based on a novel method to apply estimates of the dry deposition based on measurements at a limited number of sites, to a larger number of sites with only bulk deposition measurements, in turn based on the existence of a strong geographical gradient in the dry deposition of inorg-N from southwest to northeast Sweden. The method should be applicable for other geographical regions where gaseous NH3, NO2 and HNO3 are not main drivers of N dry deposition and where geographical gradients in dry deposition could be defined. It was shown that Norway spruce forests in south Sweden receive more N from deposition than has been previously estimated, based on modelling. Clear time trends were demonstrated for decreased deposition of inorg-N to Norway spruce forests in all parts of Sweden. The decreases were somewhat larger than what could be expected from the decrease in the reported emissions of inorg-N from Europe. The results emphasize that estimates of the total deposition are necessary in order to map levels and follow the development of N deposition in forests.

Continuous versus intermittent extended adjuvant letrozole for breast cancer: final results of randomized phase III SOLE (Study of Letrozole Extension) and SOLE Estrogen Substudy.

BACKGROUND: Late recurrences in postmenopausal women with hormone receptor-positive breast cancers remain an important challenge. Avoidance or delayed development of resistance represents the main objective in extended endocrine therapy (ET). In animal models, resistance was reversed with restoration of circulating estrogen levels during interruption of letrozole treatment. This phase III, randomized, open-label Study of Letrozole Extension (SOLE) studied the effect of extended intermittent letrozole treatment in comparison with continuous letrozole. In parallel, the SOLE estrogen substudy (SOLE-EST) analyzed the levels of estrogen during the interruption of treatment. PATIENTS AND METHODS: SOLE enrolled 4884 postmenopausal women with hormone receptor-positive, lymph node-positive, operable breast cancer between December 2007 and October 2012 and among them, 104 patients were enrolled in SOLE-EST. They must have undergone local treatment and have completed 4-6 years of adjuvant ET. Patients were randomized between continuous letrozole (2.5 mg/day orally for 5 years) and intermittent letrozole treatment (2.5 mg/day for 9 months followed by a 3-month interruption in years 1-4 and then 2.5 mg/day during all of year 5). RESULTS: Intention-to-treat population included 4851 women in SOLE (n = 2425 in the intermittent and n = 2426 in the continuous letrozole groups) and 103 women in SOLE-EST (n = 78 in the intermittent and n = 25 in the continuous letrozole groups). After a median follow-up of 84 months, 7-year disease-free survival (DFS) was 81.4% in the intermittent group and 81.5% in the continuous group (hazard ratio: 1.03, 95% confidence interval: 0.91-1.17). Reported adverse events were similar in both groups. Circulating estrogen recovery was demonstrated within 6 weeks after the stop of letrozole treatment. CONCLUSIONS: Extended adjuvant ET by intermittent administration of letrozole did not improve DFS compared with continuous use, despite the recovery of circulating estrogen levels. The similar DFS coupled with previously reported quality-of-life advantages suggest intermittent extended treatment is a valid option for patients who require or prefer a treatment interruption.

Survival patterns of invasive lobular and invasive ductal breast cancer in a large population-based cohort with two decades of follow up.

BACKGROUND: Invasive lobular carcinoma (ILC) comprises 8-15 % of all invasive breast cancers and large population-based studies with >10 years of follow-up are rare. Whether ILC has a long-time prognosis different from that of invasive ductal carcinoma, (IDC) remains controversial. PURPOSE: To investigate the excess mortality rate ratio (EMRR) of patients with ILC and IDC and to correlate survival with clinical parameters in a large population-based cohort. MATERIAL AND METHODS: From 1989 through 2006, we identified 17,481 patients diagnosed with IDC (n = 14,583) or ILC (n = 2898), younger than 76 years from two Swedish Regional Cancer Registries. Relative survival (RS) during 20 years of follow up was analysed. RESULTS: ILC was significantly associated with older age, larger tumours, ER positivity and well differentiated tumours. We noticed an improved survival for patients with ILC during the first five years, excess mortality rate ratio (EMRR) 0.64 (CI 95 % 0.53-0.77). This was shifted to a significant decreased survival 10-15 years after diagnosis (EMRR 1.49, CI 95 % 1.16-1.93). After 20 years the relative survival rates were similar, 0.72 for ILC and 0.73 for IDC. CONCLUSIONS: During the first five years after surgery, the EMRR was lower for patients with ILC as compared to patients with IDC, but during the years 10-15 after surgery, we observed an increased EMRR for patients with ILC as compared to IDC. These EMRR between ILC and IDC were statistically significant but the absolute difference in excess mortality between the two groups was small.

Myopathic changes in patients with long-term fatigue after COVID-19.

OBJECTIVE: To investigate the peripheral nerve and muscle function electrophysiologically in patients with persistent neuromuscular symptoms following Coronavirus disease 2019 (COVID-19). METHODS: Twenty consecutive patients from a Long-term COVID-19 Clinic referred to electrophysiological examination with the suspicion of mono- or polyneuropathy were included. Examinations were performed from 77 to 255 (median: 216) days after acute COVID-19. None of the patients had received treatment at the intensive care unit. Of these, 10 patients were not even hospitalized. Conventional nerve conduction studies (NCS) and quantitative electromyography (qEMG) findings from three muscles were compared with 20 age- and sex-matched healthy controls. RESULTS: qEMG showed myopathic changes in one or more muscles in 11 patients (55%). Motor unit potential duration was shorter in patients compared to healthy controls in biceps brachii (10.02 ± 0.28 vs 11.75 ± 0.21), vastus medialis (10.86 ± 0.37 vs 12.52 ± 0.19) and anterior tibial (11.76 ± 0.31 vs 13.26 ± 0.21) muscles. All patients with myopathic qEMG reported about physical fatigue and 8 patients about myalgia while 3 patients without myopathic changes complained about physical fatigue. CONCLUSIONS: Long-term COVID-19 does not cause large fibre neuropathy, but myopathic changes are seen. SIGNIFICANCE: Myopathy may be an important cause of physical fatigue in long-term COVID-19 even in non-hospitalized patients.

Diagnosis and prevalence of diabetic polyneuropathy: a cross-sectional study of Danish patients with type 2 diabetes.

BACKGROUND AND PURPOSE: Diabetic polyneuropathy (DPN) is a common complication of diabetes. Using the Toronto criteria for diabetic polyneuropathy and the grading system for neuropathic pain, the performance of neuropathy scales and questionnaires were assessed by comparing them to a clinical gold standard diagnosis of DPN and painful DPN in a cohort of patients with recently diagnosed type 2 diabetes. METHODS: A questionnaire on neuropathy and pain was sent to a cohort of 5514 Danish type 2 diabetes patients. A sample of 389 patients underwent a detailed clinical examination and completed neuropathy questionnaires and scales. RESULTS: Of the 389 patients with a median diabetes duration of 5.9 years, 126 had definite DPN (including 53 with painful DPN), 88 had probable DPN and 53 had possible DPN. There were 49 patients with other causes of polyneuropathy, neuropathy symptoms or pain, 10 with subclinical DPN and 63 without DPN. The sensitivity of the Michigan Neuropathy Screening Instrument questionnaire to detect DPN was 25.7% and the specificity 84.6%. The sensitivity of the Toronto Clinical Neuropathy Scoring System, including questionnaire and clinical examination, was 62.9% and the specificity was 74.6%. CONCLUSIONS: Diabetic polyneuropathy affects approximately one in five Danish patients with recently diagnosed type 2 diabetes but neuropathic pain is not as common as previously reported. Neuropathy scales with clinical examination perform better compared with questionnaires alone, but better scales are needed for future epidemiological studies.

Trigeminal nociceptive function and oral somatosensory functional and structural assessment in patients with diabetic peripheral neuropathy.

This case-control study primarily compared the trigeminal nociceptive function, the intraoral somatosensory profile and possible structural nerve changes between diabetic peripheral neuropathy (DPN, n = 12) patients and healthy participants (n = 12). The nociceptive blink reflex (nBR) was recorded applying an electrical stimulation over the entry zone of the right supraorbital (V1R), infraorbital (V2R) and mental (V3R) and left infraorbital (V2L) nerves. The outcomes were: individual electrical sensory (I0) and pain thresholds (IP); root mean square (RMS), area-under-the-curve (AUC) and onset latencies of R2 component of the nBR. Furthermore, a standardized full battery of quantitative sensory testing (QST) and intraepidermal nerve fibre density (IENFD) or  nerve fibre length density (NFLD) assessment were performed, respectively, on the distal leg and oral mucosa. As expected, all patients had altered somatosensory sensitivity and lower IENFD in the lower limb. DPN patients presented higher I0, IP, RMS and AUC values (p < 0.050), lower warm detection thresholds (WDT) (p = 0.004), higher occurrence of paradoxical heat sensation (PHS) (p = 0.040), and a lower intraoral NFLD (p = 0.048) than the healthy participants. In addition, the presence of any abnormal intraoral somatosensory finding was more frequent in the DPN patients when compared to the reference group (p = 0.013). Early signs of trigeminal nociceptive facilitation, intraoral somatosensory abnormalities and loss of intraoral neuronal tissue can be detected in DPN patients.

Ethyl carbamate in Swedish and American smokeless tobacco products and some factors affecting its concentration.

BACKGROUND: We are interested in comparing the levels of harmful or potentially harmful constituents in Swedish and American smokeless tobacco products (STPs). We report here the concentrations of the IARC Group 2 A (probable human) carcinogen ethyl carbamate (EC) in seventy commercial STPs from the US and Sweden, representing 80-90% of the market share of the major STP categories in these countries. We also examine the effects of various additives, processing and storage conditions on EC concentrations in experimental snus samples. RESULTS: EC was determined from aqueous extracts of the STPs using ultra performance liquid chromatography tandem mass spectrometry (UPLC/MS/MS). EC was undetectable (< 20 ng/g wet weight basis WWB) in 60% of the commercial STPs, including all the chewing tobacco (CT), dry snuff (DS), hard pellet (HP), soft pellet (SP), and plug products. Measurable levels of EC were found in 11/16 (69%) of the moist snuff (MS) samples (average 154 ng/g in those samples containing EC) and 19/32 (59%) of the Swedish snus samples (average 35 ng/g). For the experimental snus samples, EC was only observed in ethanol treated samples. EC concentrations increased significantly with ethanol concentrations (0-4%) and with storage time (up to 24 weeks) and temperature (8 °C vs 20 °C). EC concentrations were lower at lower pHs but were unaffected by adding nitrogenous precursors identified from food studies (citrulline and urea), increasing water content or by pasteurisation. Added EC was stable in the STP matrix, but evaporative losses were significant when samples were stored for several weeks in open containers at 8 °C. CONCLUSIONS: EC was found in measurable amounts only in some moist STPs i.e. pasteurised Swedish snus and unpasteurised US MS; it is not a ubiquitous contaminant of STPs. The presence of ethanol contributed significantly to the presence of EC in experimental snus samples, more significantly at higher pH levels. Sample age also was a key determinant of EC content. In contrast, pasteurisation and fermentation do not appear to directly influence EC levels. Using published consumption rates and mouth level exposures, on average STP consumers are exposed to lower EC levels from STP use than from food consumption.

A pain in the skin. Regenerating nerve sprouts are distinctly associated with ongoing burning pain in patients with diabetes.

BACKGROUNDS: Patients with diabetic polyneuropathy commonly suffer from ongoing burning pain and dynamic mechanical allodynia. In this clinical and skin biopsy study, we aimed at assessing how intraepidermal regenerating nerve sprouts are associated with these two types of pain. METHODS: We consecutively enrolled 85 patients with diabetic polyneuropathy. All patients underwent skin biopsy at the distal leg. Intraepidermal nerve fibres were immunostained with the anti-protein gene product 9.5 (PGP9.5) to quantify all intraepidermal nerve fibres, and the growth-associated protein 43 (GAP43) to quantify regenerating nerve sprouts. RESULTS: We found that the GAP43-stained intraepidermal nerve fibre density and the ratio GAP43/PGP9.5 were significantly higher in patients with ongoing burning pain than in those without. The area of receiver operating characteristic (ROC) curve for the ratio GAP43/PGP9.5 was 0.74 and yielded a sensitivity and specificity for identifying ongoing burning pain of 72% and 71%, respectively. Conversely, although the density of PGP9.5 and GAP43 intraepidermal nerve fibre was higher in patients with dynamic mechanical allodynia than in those without, this difference was statistically weak and the ROC curve analysis of skin biopsy variables for this type of pain failed to reach the statistical significance. CONCLUSION: Our clinical and skin biopsy study showed that ongoing burning pain was strongly associated with regenerating sprouts, as assessed with GAP43 immunostaining. This finding improves our understanding on the mechanisms underlying neuropathic pain in patients with diabetic polyneuropathy and suggests that the GAP43/PGP 9.5 ratio might be used as an objective marker for ongoing burning pain due to regenerating sprouts. SIGNIFICANCE: Our skin biopsy study showing that regenerating sprouts, as assessed with GAP43-staining, were strongly associated with ongoing burning pain, improves our knowledge on the mechanisms underlying neuropathic pain in patients with diabetes.

De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017.

The 15th St. Gallen International Breast Cancer Conference 2017 in Vienna, Austria reviewed substantial new evidence on loco-regional and systemic therapies for early breast cancer. Treatments were assessed in light of their intensity, duration and side-effects, seeking where appropriate to escalate or de-escalate therapies based on likely benefits as predicted by tumor stage and tumor biology. The Panel favored several interventions that may reduce surgical morbidity, including acceptance of 2 mm margins for DCIS, the resection of residual cancer (but not baseline extent of cancer) in women undergoing neoadjuvant therapy, acceptance of sentinel node biopsy following neoadjuvant treatment of many patients, and the preference for neoadjuvant therapy in HER2 positive and triple-negative, stage II and III breast cancer. The Panel favored escalating radiation therapy with regional nodal irradiation in high-risk patients, while encouraging omission of boost in low-risk patients. The Panel endorsed gene expression signatures that permit avoidance of chemotherapy in many patients with ER positive breast cancer. For women with higher risk tumors, the Panel escalated recommendations for adjuvant endocrine treatment to include ovarian suppression in premenopausal women, and extended therapy for postmenopausal women. However, low-risk patients can avoid these treatments. Finally, the Panel recommended bisphosphonate use in postmenopausal women to prevent breast cancer recurrence. The Panel recognized that recommendations are not intended for all patients, but rather to address the clinical needs of the majority of common presentations. Individualization of adjuvant therapy means adjusting to the tumor characteristics, patient comorbidities and preferences, and managing constraints of treatment cost and access that may affect care in both the developed and developing world.

Improved sampling and analysis of images in corneal confocal microscopy.

INTRODUCTION: Corneal confocal microscopy (CCM) is a noninvasive clinical method to analyse and quantify corneal nerve fibres in vivo. Although the CCM technique is in constant progress, there are methodological limitations in terms of sampling of images and objectivity of the nerve quantification. The aim of this study was to present a randomized sampling method of the CCM images and to develop an adjusted area-dependent image analysis. Furthermore, a manual nerve fibre analysis method was compared to a fully automated method. METHODS: 23 idiopathic small-fibre neuropathy patients were investigated using CCM. Corneal nerve fibre length density (CNFL) and corneal nerve fibre branch density (CNBD) were determined in both a manual and automatic manner. Differences in CNFL and CNBD between (1) the randomized and the most common sampling method, (2) the adjusted and the unadjusted area and (3) the manual and automated quantification method were investigated. RESULTS: The CNFL values were significantly lower when using the randomized sampling method compared to the most common method (p = 0.01). There was not a statistical significant difference in the CNBD values between the randomized and the most common sampling method (p = 0.85). CNFL and CNBD values were increased when using the adjusted area compared to the standard area. Additionally, the study found a significant increase in the CNFL and CNBD values when using the manual method compared to the automatic method (p ≤ 0.001). CONCLUSION: The study demonstrated a significant difference in the CNFL values between the randomized and common sampling method indicating the importance of clear guidelines for the image sampling. The increase in CNFL and CNBD values when using the adjusted cornea area is not surprising. The observed increases in both CNFL and CNBD values when using the manual method of nerve quantification compared to the automatic method are consistent with earlier findings. This study underlines the importance of improving the analysis of the CCM images in order to obtain more objective corneal nerve fibre measurements.

Stakeholders' views of the introduction of assistive technology in the classroom: How family-centred is Australian practice for students with cerebral palsy?

BACKGROUND: With family-centred care widely recognized as a cornerstone for effective assistive technology service provision, the current study was undertaken to investigate to what extent such approaches were used by schools when assistive technology assessments and implementation occurred in the classroom. METHOD: In this cross-sectional study, we compare survey results from parents (n = 76), school staff (n = 33) and allied health professionals (n = 65) with experience in the use of high-tech assistive technology. Demographic characteristics and the stakeholders' perceived helpfulness and frequency attending assessment and set-up sessions were captured. To evaluate how family-centred the assistive technology services were perceived to be, the parents filled out the Measure of Processes of Care for Caregivers, and the professionals completed the Measure of Processes of Care for Service Providers. Descriptive statistics and one-way analysis of variance were used to conduct the data analysis. RESULTS: Findings show that parents are more involved during the assessment stage than during the implementation and that classroom teachers are often not involved in the initial stage. Speech pathologists in particular are seen to be to a great extent helpful when implementing assistive technology in the classroom. This study found that family-centred service is not yet fully achieved in schools despite being endorsed in early intervention and disability services for over 20 years. No statistically significant differences were found with respect to school staff and allied health professionals' roles, their years of experience working with students with cerebral palsy and the scales in the Measure of Processes of Care for Service Providers. CONCLUSION: To enhance the way technology is matched to the student and successfully implemented, classroom teachers need to be fully involved in the whole assistive technology process. The findings also point to the significance of parents' involvement, with the support of allied health professionals, in the process of selecting and implementing assistive technology in the classroom.

Challenges of evaluating a computer-based educational programme for women diagnosed with early-stage breast cancer: a randomised controlled trial.

In a two-group, multi-centre, randomised controlled 9 months trial, we (1) evaluated the impact of a computer-based educational programme compared to standard care and (2) examined whether different patterns of programme usage could be explained by demographic, medical and psychosocial factors. We involved 226 Swedish-speaking women diagnosed with early-stage breast cancer and scheduled for surgery. Primary outcomes were health self-efficacy and health care participation measured by the Comprehensive Health Enhancement Supportive System instrument. Secondary outcomes were anxiety and depression levels measured by the Hospital Anxiety and Depression scale. The Functional Assessment of Cancer Therapy-Breast and Sense of Coherence scales measured psychosocial factors for the study's secondary aim. Multi-level modelling revealed no statistically significant impact of the computer-based educational programme over time on the outcomes. Subsequent exploratory regression analysis revealed that older women with axillary dissection and increased physical well-being were more likely to use the programme. Furthermore, receiving post-operative chemotherapy and increased meaningfulness decreased the likelihood of use. Providing reliable and evidence-based medical and rehabilitation information via a computer-based programme might not be enough to influence multi-dimensional outcomes in women diagnosed with breast cancer. The use of these programmes should be further explored to promote adherence to e-Health supportive interventions.

Functional and structural assessment of patients with and without persistent pain after thoracotomy.

BACKGROUND: Persistent pain is frequent after thoracotomy, with a reported prevalence of up to 60%. It remains unclear why some patients develop pain, whereas others do not. We therefore examined patients with and without pain after thoracotomy to identify pathophysiological contributors to persistent pain. METHODS: Twenty patients with persistent pain, 12 patients without pain and 20 healthy controls underwent detailed functional and structural assessment including psychometric and neuropathic pain questionnaires, bedside examination for pinprick hyperalgesia and brush allodynia, quantitative sensory testing according to the protocol of the German Research Network on Neuropathic Pain, measurement of capsaicin-evoked flare response, intradermal nerve density as determined by skin biopsies and laser- and heat-evoked potentials. RESULTS: Bedside testing revealed evoked pain in 16 of 20 patients with pain, but only in 2 of 12 patients without pain (p < 0.001). Quantitative sensory testing showed increased mechanical pain sensitivity (p = 0.018) on the operated side in patients with pain, but there were no differences between the two patient groups with regard to intradermal nerve fibre density, area and flux following capsaicin application and laser- and heat-evoked potentials. CONCLUSION: Different and individual pathophysiological mechanisms of pain may obscure the clinical picture and thus preclude identification of a specific pain profile in patients with persistent post-thoracotomy pain. SIGNIFICANCE: Evoked pain is more frequent in patients with pain. Assessment of intradermal nerve density, capsaicin-induced flare response and contact and laser heat-evoked potentials revealed no differences between pain patients and pain-free patients.

No breast cancer subgroup can be spared postoperative radiotherapy after breast-conserving surgery. Fifteen-year results from the Swedish Breast Cancer Group randomised trial, SweBCG 91 RT.

BACKGROUND: Breast-conserving surgery (BCS) followed by radiotherapy (RT) is an established treatment for women with T1-2N0 breast cancers. Since subgroups of patients have low ipsilateral breast tumour recurrence (IBTR) rates, it is important to study whether RT is necessary for all patients. PATIENTS AND METHODS: A total of 1187 women with primary T1-2N0M0 breast cancer were randomised, after standardised sector resection, to postoperative whole breast RT or no local treatment. Adjuvant systemic therapy was offered to patients with stage II cancers. Patients were followed with clinical examinations and annual mammography for 10 years and thereafter referred to the Swedish mammography screening program. RESULTS: After 15 years of follow-up, a higher cumulative incidence of IBTR was observed in control patients, 23.9%, versus irradiated patients, 11.5%, P<0.001. Recurrence-free survival was inferior, 51.7% versus 60.4%, P=0.0013. The main effect of RT was seen during the first 5 years. However, overall survival was not significantly lower 68.4% versus 71.1%, P=0.68, nor was breast cancer-specific mortality significantly higher. CONCLUSIONS: RT after BCS significantly reduced the incidence of IBTR at 15 years of follow-up. We were unable to identify subgroups which could be spared RT. Breast cancer mortality was not significantly reduced after RT. Good predictive markers for radiation sensitivity and improved adjuvant systemic therapy are needed to omit RT after BCS.