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BACKGROUND: Digital assistive technology (DAT) may support time management in people with dementia or mild cognitive impairment (MCI), but research on DAT for time management is limited. We aimed to explore how everyday could be supported by DAT for time management in persons with dementia or MCI from informal carers' perspectives. This study focused on a DAT device for time management called MEMOplanner (MMP). METHOD: Using a mixed-methods design, we utilized the Time-Proxy© questionnaire and a study-specific interview guide to investigate the perspectives of informal carers (n = 8) regarding the use of MMP by individuals with dementia or MCI. RESULT: The MMP was helpful in keeping track of time and activity. It helped to maintain an active lifestyle and facilitated communication. However, the MMP did not reduce the need for assistance from the informal carers, and it took time to learn the different functions of the device. Further research into employing a more extensive array of DAT for time management or other areas to assist individuals with dementia will yield valuable insights into enhancing and sustaining a higher quality of life despite cognitive decline.

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OBJECTIVE: Depression is associated with accelerated aging and age-related diseases. However, mechanisms underlying this relationship remain unclear. The aim of this study was to longitudinally assess the link between depressive symptoms, brain atrophy, and cortisol levels. METHOD: Participants from the Betula prospective cohort study (mean age = 59 years, SD = 13.4 years) underwent clinical, neuropsychological and brain 3T MRI assessments at baseline and a 4-year follow-up. Cortisol levels were measured at baseline in four saliva samples. Cortical and hippocampal atrophy rates were estimated and compared between participants with and without depressive symptoms (n = 81) and correlated with cortisol levels (n = 49). RESULTS: Atrophy in the left superior frontal gyrus and right lingual gyrus developed in parallel with depressive symptoms, and in the left temporal pole, superior temporal cortex, and supramarginal cortex after the onset of depressive symptom. Depression-related atrophy was significantly associated with elevated cortisol levels. Elevated cortisol levels were also associated with widespread prefrontal, parietal, lateral, and medial temporal atrophy. CONCLUSION: Depressive symptoms and elevated cortisol levels are associated with atrophy of the prefrontal and limbic areas of the brain.

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BACKGROUND: Family history of venous thromboembolism (VTE) has been suggested to be more useful in risk assessment than thrombophilia testing. OBJECTIVES: We investigated established genetic susceptibility variants for association with VTE and evaluated a genetic risk score in isolation and combined with known trigger factors, including family history of VTE. PATIENTS/METHOD: A total of 18 single nucleotide polymorphisms (SNPs) selected from the literature were genotyped in 2835 women participating in a Swedish nationwide case-control study (the ThromboEmbolism Hormone Study [TEHS]). Association with VTE was assessed by odds ratios (ORs) with 95% confidence interval (CI) using logistic regression. Clinical and genetic predictors that contributed significantly to the fit of the logistic regression model were included in the prediction models. SNP-SNP interactions were investigated and incorporated into the models if found significant. Risk scores were evaluated by calculating the area under the receiver-operating characteristics curve (AUC). RESULTS: Seven SNPs (F5 rs6025, F2 rs1799963, ABO rs514659, FGG rs2066865, F11 rs2289252, PROC rs1799810 and KNG1 rs710446) with four SNP-SNP interactions contributed to the genetic risk score for VTE, with an AUC of 0.66 (95% CI, 0.64-0.68). After adding clinical risk factors, which included family history of VTE, the AUC reached 0.84 (95% CI, 0.82-0.85). The goodness of fit of the genetic and combined scores improved when significant SNP-SNP interaction terms were included. CONCLUSION: Prediction of VTE in high-risk individuals was more accurate when a combination of clinical and genetic predictors with SNP-SNP interactions was included in a risk score.

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BACKGROUND: Following the establishment of the National Quality Registry for systemic psoriasis treatment (PsoReg), the two psoriasis outcome measurements, Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI), are now integrated in clinical practice in Sweden. According to current guidelines, the initiation of a biological treatment should depend on a combination of the physician's (PASI) and the patients' assessment of the disease impact on a health-related quality of life measure (DLQI). OBJECTIVE: To evaluate if either of the two measures, PASI or DLQI, is more strongly associated with initiation of biological therapy. METHODS: The study is based on 2216 patients suffering from moderate to severe psoriasis who were biological naïve at enrolment to PsoReg. The relationship between the two measures PASI and DLQI and initiation of biological treatment (as outcome) were estimated by a logistic regression and a Cox proportional hazard's model with combinations of PASI and DLQI as independent variables. RESULTS: The adjusted regression models showed that patients with high PASI score and low DLQI score had a higher chance to receive biological treatment compared to patients with low PASI score and high DLQI score. CONCLUSION: The decision to initiate biological treatment is more strongly associated with PASI than with DLQI. However, since the DLQI reflects both socio-economic costs and patient suffering better than PASI, the relevance of the DLQI may be underestimated in clinical practice.

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Three potentially protective responses to hypoxia have been reported to be enhanced in divers: (1) the diving response, (2) the blood-boosting spleen contraction, and (3) a long-term enhancement of hemoglobin concentration (Hb). Longitudinal studies, however, have been lacking except concerning the diving response. Ten untrained subjects followed a 2-week training program with 10 maximal effort apneas per day, with pre- and posttraining measurements during three maximal duration apneas, and an additional post-training series when the apneic duration was kept identical to that before training. Cardiorespiratory parameters and venous blood samples were collected across tests, and spleen diameters were measured via ultrasound imaging. Maximal apneic duration increased by 44 s (P < 0.05). Diving bradycardia developed 3 s earlier and was more pronounced after training (P < 0.05). Spleen contraction during apneas was similar during all tests. The arterial hemoglobin desaturation (SaO2) nadir after apnea was 84% pretraining and 89% after the duration-mimicked apneas post-training (P < 0.05), while it was 72% (P < 0.05) after maximal apneas post-training. Baseline Hb remained unchanged after training, but reticulocyte count increased by 15% (P < 0.05). We concluded that the attenuated SaO2 decrease during mimic apneas was due mainly to the earlier and more pronounced diving bradycardia, as no enhancement of spleen contraction or Hb had occurred. Increased reticulocyte count suggests augmented erythropoiesis.

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OBJECTIVE: To measure small-area variations in sales per capita of tumour necrosis factor (TNF) inhibitors. METHODS: For 2000-2009, sales data on etanercept, infliximab, and adalimumab were retrieved from the Swedish National Corporation of Pharmacies, which keeps data on drugs dispensed in ambulatory care and hospitals. As points of reference, data were retrieved on all drugs, non-biologic treatments for chronic inflammatory disorders (sulfasalazine, methotrexate, azathioprine), and for a biologic used in a different therapeutic area (trastuzumab). As a corollary measure to sales per capita, penetration of biologics in the rheumatoid arthritis (RA) population was calculated using nationwide registers. Small areas were defined as the 21 counties of Sweden. RESULTS: From 2000 to 2009, annual TNF inhibitor sales increased 9-fold from 195 to 1779 million SEK (0.7-5.0% of total drug expenditure). The county variation in sales per capita, initially 6.2-fold (coefficient of variation 42%), decreased to 2.3-fold in 2009 (24%). During the same period, total drug expenditure per capita remained at a 1.2-fold county variation (4-6%). Sales per capita variations of non-biologic treatments against chronic inflammatory diseases ranged from 1.5 to 1.8 (12-16%). For trastuzumab, a 3.2-fold variation (30%) was observed in 2009. At the patient level, there was a 2-fold county variation (from 10% to 21%) in biologic penetration in RA. County-specific sales per capita were associated with mean RA duration (r = -0.52, p = 0.015) and C-reactive protein at treatment initiation (r = -0.49, p = 0.025), while pain was borderline significant (r = -0.43, p = 0.055). CONCLUSIONS: Despite universal access to treatment, substantial but decreasing small-area variations were observed. Although geographic variations are anticipated initially, their persistence calls for investigation of patient equity and treatment appropriateness as counties seem to have different initiation thresholds.

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OBJECTIVE: To determine coverage and generalisability of data in the Swedish Biologics Register ARTIS. METHODS: Patients with adult onset rheumatoid arthritis (RA) were identified in the National Patient Register and the Swedish Rheumatology Quality Register, including the ARTIS cohort of patients exposed to biological agents. Exposure to etanercept and adalimumab between 2006 and 2008 was determined by register linkage to the Prescribed Drug Register which contains patient-level data on >99% of all etanercept and adalimumab use in Sweden. RESULTS: Of 62 897 patients with RA, 6510 had received treatment with etanercept or adalimumab according to the Prescribed Drug Register. Of these, 5673 were also registered in ARTIS, resulting in a national coverage of 87%. The regional variation was small with >85% coverage in 18 of 21 counties. In multivariable analysis, ARTIS-registered and non-registered patients did not differ by age (p=0.62), sex (p=0.84) or education level (p=0.24). CONCLUSION: Nationwide drug dispensing and demographic data may function as quality metrics for coverage and generalisability assessments. Using such data, the coverage of ARTIS was estimated at 87% with no indications of compromised external generalisability regarding demography.

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The efficacy of antihypertensive drug therapy is undisputed, but observational studies show that few patients reach a target blood pressure <140/90 mm Hg. However, there is limited data on the drug prescribing patterns and their effectiveness in real practice. This retrospective observational survey of electronic patient records extracted data from 24 Swedish primary health-care centres, with a combined registered population of 330 000 subjects. We included all patients > 30 years with a recorded diagnosis of hypertension who consulted the centres in 2005 or 2006 (n=21 167). Main outcome measures were systolic and diastolic blood pressures, and prescribed antihypertensive drug classes. Only 27% had a blood pressure <140/90 mm Hg. The number of prescribed drugs increased with age, except among the oldest (> 90 years). Only 29% of patients given monotherapy had a blood pressure <140/90 mm Hg. Women more often received diuretics (52 vs 42%), and less often angiotensin-converting enzyme inhibitors (22 vs 33%) and calcium channel blockers (26 vs 31%) than men. ß-Blockers and diuretics were the most common drug classes prescribed, independent of comorbidity. In conclusion, one out of four primary care patients with hypertension reach target blood pressure. More frequent use of drug combinations may improve blood pressure control.

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Self-reported cognitive symptoms are frequent in persons with amalgam-related complaints, but few studies have focused on their cognitive function. The aim was to examine a symptom profile and whether participants with amalgam-related complaints have cognitive deficits in comparison with control individuals. We drew 342 participants with amalgam-related complaints and 342 one-to-one matched control individuals from a longitudinal population-based study. For 81 of the participants with amalgam-related complaints and controls, data were available approximately five years before the onset of complaints, making a longitudinal analysis possible. All participants were assessed by a self-reported health questionnaire and a comprehensive cognitive test battery. The participants with amalgam-related complaints reported more symptoms, mainly musculoskeletal and neuropsychological, compared with control individuals (p < 0.001). The results revealed no significant difference between the amalgam and control group, either cross-sectionally or longitudinally, for any of the cognitive tests. These results suggest that cognitive decline is not associated with amalgam-related complaints.

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OBJECTIVE: To assess whether use of tranexamic acid is associated with an increased risk of venous thromboembolism (VTE). DESIGN: Nested case-control study. SETTING: Database study using the General Practice Research Database for the years 1992-1998. POPULATION: Women aged 15-49 years with a diagnosis of menorrhagia. METHODS: Multivariate conditional logistic regression was used to estimate the risk for VTE associated with different drug treatments for menorrhagia, adjusting for confounders. MAIN OUTCOME MEASURES: Adjusted odds ratios with 95% CI. RESULTS: A total of 134 cases of VTE and 552 matched controls were identified. Recent use of tranexamic acid was scarce, yielding an adjusted odds ratio for VTE of 3.20 (95% CI 0.65-15.78). The use of mefenamic acid (ORadj 5.54 [95% CI 2.13-14.40]) or norethisterone (ORadj 2.41 [95% CI 1.00-5.78]) was associated with an increased risk of VTE, as was a recent--in relation to menorrhagia--diagnosis of anaemia or a haemoglobin value <11.5 g/dl (ORadj 2.23 [95% CI 1.02-4.86]). CONCLUSIONS: We found that tranexamic acid was associated with an increased risk of VTE, although the risk estimate did not reach statistical significance. Increased risks of VTE associated with other treatments for menorrhagia were observed. The increased risk of VTE observed with a diagnosis of anaemia--a proxy for more severe menorrhagia--suggests that menorrhagia could be a prothrombotic condition. The observed association between VTE, tranexamic acid and other treatments for menorrhagia may thus partly be explained by confounding by indication. The possibility that menorrhagia is itself a risk factor for VTE merits further investigation.

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PRIMARY OBJECTIVE: To assess the incidence of fatigue for persons following a mild traumatic brain injury (MTBI) and to evaluate the relationship between fatigue and APOE genotype. As fatigue is often found to be influenced by anxiety, depression and sleep disturbance, these factors were also measured. METHODS AND PROCEDURES: Thirty-one persons who sustained a MTBI were drawn from a population-based longitudinal study. Each person who sustained a MTBI was matched by age, gender, education and APOE genotype with two non-head injury controls. Self-reported pre- and post-injury incidence of fatigue, anxiety, depression and sleep disturbance was compared within-group and between groups. RESULTS: For the MTBI group, incidence of fatigue was almost twice as common post- than pre-injury, whereas there was no corresponding change in a non-injured control group. Within the MTBI-group, post-injury fatigue was particularly common for carriers of the APOE epsilon4 allele. CONCLUSIONS: Fatigue is common sequela after a MTBI and especially pronounced for carriers of the APOE epsilon4 allele.

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BACKGROUND: The epsilon4 allele of apolipoprotein E (APOE) and head injury are risk factors for dementia diseases, and may act synergistically to further increase the risk. The aim of this study was to examine the association between mild head injury, APOE and dementia. METHODS: Data were obtained from the Betula prospective population-based study of aging, memory, and health. The study included 543 participants in the age range 40-85 years, free of dementia at baseline, who were followed up within a 5-year interval. Dementia was classified using DSM-IV criteria. Information on previous head injury was obtained through screening of the participants' answers to health questionnaires at baseline and at follow-up. RESULTS: Subjects with head injury but without APOE epsilon4 had no increased risk of dementia. Subjects with APOE epsilon4 had an increased risk and those with both APOE epsilon4 and head injury had the highest risk of dementia (odds ratio = 5.2). CONCLUSIONS: APOE epsilon4 constitutes a risk factor for dementia, mild injury in isolation does not increase the risk, but head injury in combination with the APOE epsilon4 leads to increased risk of dementia.

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BACKGROUND: In a large Swedish multicenter randomized controlled trial (RCT) on intra partum fetal monitoring with automatic analysis of fetal ECG waveform (STAN) in combination with cardiotocography (CTG) (4966 parturients, 300 obstetricians and midwives managing the patients), interim analysis revealed protocol violations. By a post hoc analysis of the results over time, factors affecting the acceptance of the new technique were analyzed. METHODS: The rates of primary and secondary outcome measures (fetal outcome, operative deliveries) were compared in the two study groups (CTG + ST and CTG only). Changes over time were statistically evaluated using a test for homogeneity between the two periods. RESULTS: After retraining, the CTG + ST group showed the lowest rates of operative delivery for fetal distress, fetal blood sampling and admissions to neonatal intensive care unit. Operative deliveries (p = 0.02) and the number of fetal blood sampling decreased significantly over time (p = 0.001). CONCLUSIONS: Training and education probably predisposed the clinicians to a change and reinforced it when it occurred as a result of increased personal experience. The audit and feedback together with the influence of opinion leaders and inter-collegial interactions seem to have been of importance for the successively increasing acceptance of the new method during the RCT.

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OBJECTIVE: To examine the relationship between neuropsychological outcome following mild head injury (MHI) and APOE genotype. METHODS: Data from a population-based longitudinal study (n = 3,500) were used to identify 34 adults who experienced MHI during the course of the study. Their pre- and postinjury performances on a battery of nine neuropsychological tests were compared within person, and the postinjury performance was compared with that of age- and gender-matched control subjects. RESULTS: The within-person comparisons showed that participants with at least one APOE epsilon4 allele (n = 11) had a significantly decreased postinjury performance on three of the tests, whereas the postinjury performance for APOE epsilon4-negative participants (n = 23) was unchanged. There was no significant difference in postinjury performance between participants with/without the epsilon4 allele, and neither group was impaired relative to controls. CONCLUSIONS: APOE genotype may influence the outcome following an MHI. Pre/postinjury within-person comparisons seem more sensitive than control group comparisons for detecting injury-related effects.

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BACKGROUND: Previous studies indicate that analysis of the ST waveform of the fetal electrocardiogram provides information on the fetal response to hypoxia. We did a multicentre randomised controlled trial to test the hypothesis that intrapartum monitoring with cardiotocography combined with automatic ST-waveform analysis results in an improved perinatal outcome compared with cardiotocography alone. METHODS: At three Swedish labour wards, 4966 women with term fetuses in the cephalic presentation entered the trial during labour after a clinical decision had been made to apply a fetal scalp electrode for internal cardiotocography. They were randomly assigned monitoring with cardiotocography plus ST analysis (CTG+ST group) or cardiotocography only (CTG group). The main outcome measure was rate of umbilical-artery metabolic acidosis (pH <7.05 and base deficit >12 mmol/L). Secondary outcomes included operative delivery for fetal distress. Results were first analysed according to intention to treat, and secondly after exclusion of cases with severe malformations or with inadequate monitoring. FINDINGS: The CTG+ST group showed significantly lower rates of umbilical-artery metabolic acidosis than the cardiotocography group (15 of 2159 [0.7%] vs 31 of 2079 [2%], relative risk 0.47 [95% CI 0.25-0.86], p=0.02) and of operative delivery for fetal distress (193 of 2519 [8%] vs 227 of 2447 [9%], 0.83 [0.69-0.99], p=0.047) when all cases were included according to intention to treat. The differences were more pronounced after exclusion of 291 in the CTG+ST group and 283 in the CTG group with malformations or inadequate recording. INTERPRETATION: Intrapartum monitoring with cardiotocography combined with automatic ST-waveform analysis increases the ability of obstetricians to identify fetal hypoxia and to intervene more appropriately, resulting in an improved perinatal outcome.

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OBJECTIVE: Minocycline is an antibacterial drug used in the treatment of acne. Concern has been expressed over the possibility of severe adverse reactions to minocycline, including hepatitis. This study set out to identify and characterise reported cases of hepatotoxicity associated with the use of minocycline. METHODS: A systematic review of the literature including a search of computerised databases and analysis of data from the Uppsala Monitoring Centre (WHO Collaborating Centre for International Drug Monitoring) was conducted. The review involved a search for original case reports involving liver damage in people using minocycline. Patients taking minocycline for reasons other than acne or those given intravenous minocycline were excluded. The search strategy involved an enquiry of computerised databases and a search for secondary references. Cases were then classified appropriately. RESULTS: 65 reported cases of hepatitis or liver damage in association with minocycline from either case reports or case series were identified from the literature review. 58% of cases occurred in females and 94% were aged under 40 years. For 20 case reports there was insufficient information to classify the type of event, but for the remaining 45, 2 types of hepatic reaction were recognised: autoimmune hepatitis associated with lupus-like symptoms occurring after a median duration of exposure to minocycline of 365 days in females (n = 20) and 730 days in males (n = 9), hypersensitivity reaction associated with eosinophilia and exfoliative dermatitis occurring within 35 days of therapy (n = 16). Reports to the WHO of hepatic adverse drug reactions associated with minocycline accounted for 6% (493) of all minocycline-related adverse drug reactions (8025). The pattern of distribution in relation to exposure demonstrated 2 groups, similar to that described by the case reports. CONCLUSIONS: Severe cases of minocycline-associated hepatotoxicity appear to be a hypersensitivity reaction and occur within a few weeks of commencing therapy. An autoimmune hepatitis usually presents after exposure to minocycline of a year or more, is more common in women and is sometimes associated with lupus-like symptoms.

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