Establishment and cryptic transmission of Zika virus in Brazil and the Americas.

Transmission of Zika virus (ZIKV) in the Americas was first confirmed in May 2015 in northeast Brazil. Brazil has had the highest number of reported ZIKV cases worldwide (more than 200,000 by 24 December 2016) and the most cases associated with microcephaly and other birth defects (2,366 confirmed by 31 December 2016). Since the initial detection of ZIKV in Brazil, more than 45 countries in the Americas have reported local ZIKV transmission, with 24 of these reporting severe ZIKV-associated disease. However, the origin and epidemic history of ZIKV in Brazil and the Americas remain poorly understood, despite the value of this information for interpreting observed trends in reported microcephaly. Here we address this issue by generating 54 complete or partial ZIKV genomes, mostly from Brazil, and reporting data generated by a mobile genomics laboratory that travelled across northeast Brazil in 2016. One sequence represents the earliest confirmed ZIKV infection in Brazil. Analyses of viral genomes with ecological and epidemiological data yield an estimate that ZIKV was present in northeast Brazil by February 2014 and is likely to have disseminated from there, nationally and internationally, before the first detection of ZIKV in the Americas. Estimated dates for the international spread of ZIKV from Brazil indicate the duration of pre-detection cryptic transmission in recipient regions. The role of northeast Brazil in the establishment of ZIKV in the Americas is further supported by geographic analysis of ZIKV transmission potential and by estimates of the basic reproduction number of the virus.

No difference in antidepressant prescription in rheumatoid arthritis and controls. Results from a population-based, matched inception cohort.

OBJECTIVE: Depression occurs at least two times more often in rheumatoid arthritis (RA) patients than in controls, but little is known about the treatment of depression in RA. The primary objective of this study was to compare the 1 year period prevalence of antidepressant prescription in patients with RA versus controls. METHOD: We included a retrospective inception cohort of 509 patients with incident RA and 2545 frequency-matched population controls ascertained from 1995 to 2002. The cohort was followed until 31 December 2017 and linked with nationwide Danish registers. From the Danish National Prescription Register, we obtained information on redeemed prescriptions of antidepressants (Anatomical Therapeutic Chemical code N06A). RESULTS: We did not demonstrate significant differences in the 1 year period prevalence ratios and the incidence rate ratios for either antidepressant prescription or the frequency of hospital admissions with depressive episode. The most frequent indication for antidepressant prescription in patients with RA was depression. Cox regression analyses showed no association between RA and antidepressant prescription. CONCLUSION: We found no significant differences in the occurrence of antidepressant prescription in patients with RA versus matched controls. The main indication for antidepressant prescription in RA was depression.

Early indicators of primary brain tumours: a population-based study with 10 years' follow-up.

BACKGROUND AND PURPOSE: To improve diagnoses of primary brain tumours, knowledge about early indicators is needed. Nationwide Danish health registries were used to conduct a population-based case-control study including all persons diagnosed with a primary brain tumour between 2005 and 2014 in Denmark. METHODS: All 5135 adults diagnosed with a primary brain tumour in the Danish Cancer Registry were matched to 19 572 general population comparisons from the Danish Civil Registration System. Conditional logistic regression analyses were applied to estimate age- and multivariable-adjusted odds ratios (ORs) for the occurrence of a primary brain tumour up to 10 years after hospital diagnoses or prescription of medications related to nervous system diseases and mental and behavioural disorders. RESULTS: Increased odds for primary brain tumour after nervous system diseases and mental and behavioural disorders manifested up to 10 years before tumour diagnosis were found. Increased odds were seen especially for hospital contacts for inflammatory nervous system diseases [OR 11.3; 95% confidence interval (CI) 6.5-19.7], epilepsy (OR 9.0; 95% CI 7.6-10.7) and antiepileptic medications (OR 3.6; 95% CI 3.2-4.0), whilst antidementia medications provided a strong, protective association for primary brain tumours (OR 0.5; 95% CI 0.3-0.8). CONCLUSIONS: Sub-groups of patients diagnosed with or being prescribed certain medications targeting nervous system diseases and mental and behavioural disorders may be at increased risk of being diagnosed with a primary brain tumour. Further studies should disentangle the potential underlying common pathogenetic pathways. The results are important for the development of systematic clinical approaches to ensure early diagnosis of primary brain tumours.

Benefit from extended surveillance interval on colorectal cancer risk in Lynch syndrome.

AIM: Although patients with Lynch syndrome have an increased risk of developing colorectal cancer, surveillance can reduce morbidity and mortality. Whether or not affected individuals benefit from lifetime surveillance depends on individual factors and patient adherence, and these may vary, complicating risk modelling. The aim of this study was to identify individual factors which influence patient adherence to surveillance programmes and whether extended surveillance interval influenced their risk of developing colorectal cancer. METHOD: Demographics and survival data were obtained from patients (n = 1223) with Lynch syndrome, identified by interrogating the Danish Hereditary Non-Polyposis Colorectal Cancer Register. These data were linked to patient surveillance interval data which had been divided into three subsets (< 27 months, adherent to the recommended biennial programme; > 27 months, extended surveillance interval; and no surveillance) to estimate the cumulative risks and hazard ratios (HRs) for colorectal cancer. RESULTS: In all, 147 colorectal cancers (99 first; 48 metachronous) were identified in 1223 patients. Factors associated with adherence to surveillance were female sex, a previous history of cancer and age < 75 years. The cumulative incidence for colorectal cancer was 38% (95% CI 27%-50%) for surveillance intervals < 27 months, 48% (95% CI 29%-67%) for intervals > 27 months and 72% (95% CI 61%-83%) with no surveillance. Adjusted HRs were 0.22 for surveillance intervals < 27 months and 0.32 for surveillance intervals > 27 months. Extended surveillance intervals > 27 months had a non-significant benefit with an HR of 1.51 (95% CI 0.83-2.75) compared to surveillance intervals < 27 months. CONCLUSION: This study demonstrates that adherence to colonoscopic surveillance in Lynch syndrome varies with age, sex and cancer history and demonstrates a consistent benefit from colorectal cancer surveillance, though it might be lower for individuals with extended intervals.

Effective Altruism as an Ethical Lens on Research Priorities.

Effective altruism is an ethical framework for identifying the greatest potential benefits from investments. Here, we apply effective altruism concepts to maximize research benefits through identification of priority stakeholders, pathosystems, and research questions and technologies. Priority stakeholders for research benefits may include smallholder farmers who have not yet attained the minimal standards set out by the United Nations Sustainable Development Goals; these farmers would often have the most to gain from better crop disease management, if their management problems are tractable. In wildlands, prioritization has been based on the risk of extirpating keystone species, protecting ecosystem services, and preserving wild resources of importance to vulnerable people. Pathosystems may be prioritized based on yield and quality loss, and also factors such as whether other researchers would be unlikely to replace the research efforts if efforts were withdrawn, such as in the case of orphan crops and orphan pathosystems. Research products that help build sustainable and resilient systems can be particularly beneficial. The "value of information" from research can be evaluated in epidemic networks and landscapes, to identify priority locations for both benefits to individuals and to constrain regional epidemics. As decision-making becomes more consolidated and more networked in digital agricultural systems, the range of ethical considerations expands. Low-likelihood but high-damage scenarios such as generalist doomsday pathogens may be research priorities because of the extreme potential cost. Regional microbiomes constitute a commons, and avoiding the "tragedy of the microbiome commons" may depend on shifting research products from "common pool goods" to "public goods" or other categories. We provide suggestions for how individual researchers and funders may make altruism-driven research more effective.[Formula: see text] Copyright © 2020 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

The epidemic of methylisothiazolinone contact allergy in Europe: follow-up on changing exposures.

BACKGROUND: Methylisothiazolinone (MI) has caused an unprecedented epidemic of contact allergy in Europe and elsewhere. Subsequently, regulatory action has been taken, at least in Europe, aiming at reducing risk of MI sensitization. OBJECTIVE: To follow-up on the prevalence of contact allergy to MI in consecutively patch tested patients and assess the spectrum of products containing MI or methylchloroisothiazolinone (MCI)/MI in patients positive to MI which elicited current allergic contact dermatitis. METHODS: A cross-sectional survey was performed in 2016 and 2017, including all adult patients patch tested with the baseline series (including MI 0.2% aq.) between 1 May and 31 October at 14 centres in 11 European countries. Patients with positive reactions (+ to +++) to MI were further examined regarding history, clinical characteristics and eliciting products, which were categorized into 34 types and 4 classes (leave-on, rinse-off, household, occupational). The results were compared with the reference year 2015. RESULTS: A total of 317 patients, n = 202 of 4278 tested in 2016 (4.72%) and n = 115 of 3879 tested in 2017 (2.96%), had positive reactions to MI; the previous result from 2015 was 5.97% (P < 0.0001). The share of currently relevant contact allergy among all positive reactions declined significantly as well (P = 0.0032). Concerning product classes, a relative decline of leave-on and a relative increase of rinse-off and household products was noted. CONCLUSION: The prevalence of MI contact allergy decreased by 50% from 2015 to 2017. As a consequence of regulation, the share of cosmetics products (leave-on in particular) eliciting allergic contact dermatitis is decreasing. The chosen method of analysing causative products in sensitized patients has proven useful to monitor effects of intervention.

Use of topical antipsoriatic drugs in Denmark: a nationwide drug utilization study.

BACKGROUND: The reported real-life use of prescribed topical antipsoriatic drugs is conflicting and based on heterogeneous data sources. OBJECTIVES: To describe the utilization of topical antipsoriatic drugs among patients with psoriasis in Denmark. METHODS: A drug utilization study was performed based on nationwide Danish health registry data. We identified patients who received a first-time hospital diagnosis of psoriasis and redeemed at least one topical drug prescription in the period 2005-2015 (n = 7743). Patients were followed for 3 years from the time of diagnosis. Use of topical and systemic antipsoriatic drugs was described, specified by the type of treatment. RESULTS: The total use of topical drugs was divided between corticosteroids with calcipotriol (31%), calcipotriol (6·5%), very potent corticosteroids (24%), potent corticosteroids (30%), moderate corticosteroids (7·2%) and corticosteroids with antimicrobials (1·6%). There was a 19% reduction in the overall use of topical drugs during the study period. Use increased around the time of diagnosis and the majority of patients redeemed more than two packages of topical drugs during the first year after being diagnosed. Regional differences in patients' use of topical drugs varied considerably. The distribution of use of topical drugs was uneven, with a minority of all patients (25%) using 70% of the total amount of topical treatment. There was a 70% increase in the use of methotrexate over the study period. Biologics were used by up to 6%. CONCLUSIONS: The study provides further evidence that the use of topical antipsoriatic drugs shows considerable heterogeneity over time and regional practices, and differences between patients.

Modeling Epidemics in Seed Systems and Landscapes To Guide Management Strategies: The Case of Sweet Potato in Northern Uganda.

Seed systems are critical for deployment of improved varieties but also can serve as major conduits for the spread of seedborne pathogens. As in many other epidemic systems, epidemic risk in seed systems often depends on the structure of networks of trade, social interactions, and landscape connectivity. In a case study, we evaluated the structure of an informal sweet potato seed system in the Gulu region of northern Uganda for its vulnerability to the spread of emerging epidemics and its utility for disseminating improved varieties. Seed transaction data were collected by surveying vine sellers weekly during the 2014 growing season. We combined data from these observed seed transactions with estimated dispersal risk based on village-to-village proximity to create a multilayer network or "supranetwork." Both the inverse power law function and negative exponential function, common models for dispersal kernels, were evaluated in a sensitivity analysis/uncertainty quantification across a range of parameters chosen to represent spread based on proximity in the landscape. In a set of simulation experiments, we modeled the introduction of a novel pathogen and evaluated the influence of spread parameters on the selection of villages for surveillance and management. We found that the starting position in the network was critical for epidemic progress and final epidemic outcomes, largely driven by node out-degree. The efficacy of node centrality measures was evaluated for utility in identifying villages in the network to manage and limit disease spread. Node degree often performed as well as other, more complicated centrality measures for the networks where village-to-village spread was modeled by the inverse power law, whereas betweenness centrality was often more effective for negative exponential dispersal. This analysis framework can be applied to provide recommendations for a wide variety of seed systems.[Formula: see text] Copyright © 2019 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Body size and risk of atrial fibrillation: a cohort study of 1.1 million young men.

BACKGROUND: Whilst tall stature has been related to lower risk of vascular disease, it has been proposed as a risk factor for atrial fibrillation. Little is known about other anthropometric measures and their joint effects on risk of atrial fibrillation. OBJECTIVES: We aim to investigate associations and potential joint effects of height, weight, body surface area (BSA) and body mass index (BMI) with risk of atrial fibrillation. METHODS: In a cohort covering 1 153 151 18-year-old men participating in the Swedish military conscription (1972-1995), Cox regression was used to investigate associations of height, weight, BSA and BMI with risk of atrial fibrillation. RESULTS: During a median of 26.3 years of follow-up, higher height was associated with higher risk of atrial fibrillation (hazard ratio [HR] 2.80; 95% CI 2.63-2.98; for 5th vs. 1st quintile) and so was larger BSA (HR 3.05; 95% CI 2.82-3.28; for 5th vs. 1st quintile). Higher weight and BMI were to a lesser extent associated with risk of atrial fibrillation (BMI: 1.42; 95% CI 1.33-1.52, for 5th vs. 1st quintile). We found a multiplicative joint effect of height and weight. Adjusting for muscle strength, exercise capacity and diseases related to atrial fibrillation attenuated these measures. CONCLUSIONS: Higher height and weight are strongly associated with higher risk of atrial fibrillation. These associations are multiplicative and independent of each other and are summarized in a strong association of body surface area with risk of atrial fibrillation. The mechanisms remain unknown but may involve increased atrial volume load with larger body size.

A smartphone application supporting patients with psoriasis improves adherence to topical treatment: a randomized controlled trial.

BACKGROUND: Adherence to topical psoriasis treatments is low, which leads to unsatisfactory treatment results. Smartphone applications (apps) for patient support exist but their potential to improve adherence has not been systematically evaluated. OBJECTIVES: To evaluate whether a study-specific app improves adherence and reduces psoriasis symptoms compared with standard treatment. METHODS: We conducted a randomized controlled trial (RCT, clinicaltrials.gov registration: NCT02858713). Patients received once-daily medication [calcipotriol/betamethasone dipropionate (Cal/BD) cutaneous foam] and were randomized to no app (n = 66) or app intervention (n = 68) groups. In total, 122 patients (91%) completed the 22-week follow-up. The primary outcome was adherence, which was defined as medication applied ≥ 80% of days during the treatment period and assessed by a chip integrated into the medication dispenser. Secondary outcomes were psoriasis severity measured by the Lattice System Physician's Global Assessment (LS-PGA) and quality of life, measured using the Dermatology Life Quality Index (DLQI) at all visits. RESULTS: Intention-to-treat analyses using regression was performed. More patients in the intervention group were adherent to Cal/BD cutaneous foam than those in the nonintervention group at week 4 (65% vs. 38%, P = 0·004). The intervention group showed a greater LS-PGA reduction than the nonintervention group at week 4 (mean 1·86 vs. 1·46, P = 0·047). A similar effect was seen at weeks 8 and 26, although it did not reach statistical significance. CONCLUSIONS: This RCT demonstrates that the app improved short-term adherence to Cal/BD cutaneous foam treatment and psoriasis severity.

Monitoring and Modeling the Rapid Evolution of Earth's Newest Volcanic Island: Hunga Tonga Hunga Ha'apai (Tonga) Using High Spatial Resolution Satellite Observations.

We have monitored a newly erupted volcanic island in the Kingdom of Tonga, unofficially known as Hunga Tonga Hunga Ha'apai, by means of relatively frequent high spatial resolution (~50 cm) satellite observations. The new ~1.8 km2 island formed as a tuff cone over the course of a month-long hydromagmatic eruption in early 2015 in the Tonga-Kermadec volcanic arc. Such ash-dominated eruptions usually produce fragile subaerial landscapes that wash away rapidly due to marine erosion, as occurred nearby in 2009. Our measured rates of erosion are ~0.00256 km3/year from derived digital topographic models. Preliminary measurements of the topographic expression of the primary tuff cone over ~30 months suggest a lifetime of ~19 years (and potentially up to 42 years). The ability to measure details of a young island's landscape evolution using satellite remote sensing has not previously been possible at these spatial and temporal resolutions.

Stroke case-fatality and marital status.

OBJECTIVES: Most studies show that marriage conveys a survival advantage. Whether this is valid also for stroke patients is unclear. Results of studies have been inconsistent and conflicting. MATERIAL & METHODS: We studied 1-week and 1-month stroke case-fatality in relation to marital status (married, unmarried, divorced, and widowed) in all patients admitted to hospital for incident stroke in Denmark during 2003-2012. We used information from Danish registries on stroke merged to information on age, sex, marital status, stroke severity, stroke subtype, socioeconomic status, cardiovascular risk profile, and causes of death. We studied deaths due to the index stroke within the first week and month after stroke. Multivariate Cox regression models were applied to estimate cause-specific hazards and relative risks. RESULTS: We included 60507 patients with an incident stroke of which 51.19% were married, 9.47% were unmarried, 13.29% were divorced, and 26.05% were widowers. Death within the first week and first month was caused by stroke in 2110 (3.5%) and 3423 (5.7%) patients, respectively. Compared to married stroke patients, 1-week/1-month case-fatality (by stroke) was lower for the unmarried (HR (hazard ratio):0.69/0.74), divorced (HR:0.69/0.72), and widowed (HR:0.80/0.74) men and the unmarried (HR:0.84/0.86), divorced (HR:0.82/0.80), and widowed (HR:0.87/0.88) women with stroke. CONCLUSIONS: One-week and one-month case-fatality by stroke was lower among the unmarried, divorced, and widowed than among the married stroke patients. Selection by so-called mortality displacement linked to shorter life expectancy among divorced, widowed, and singles may explain our findings.

Married, unmarried, divorced, and widowed and the risk of stroke.

OBJECTIVES: Most studies report that marriage carries a lower risk of stroke than single living. Whether the marriage advantage is applicable with respect to all other marital status categories (unmarried, divorced, widow) remains unclear. We studied marital status and its association with incident stroke. MATERIAL AND METHODS: We included all patients > 40 years of age admitted to hospital for stroke in Denmark during 2003-2012 and compared marital status to the general Danish population (5.5 millions). Relative risks (RR) for stroke were estimated in log-linear Poisson regression models adjusting for age, sex, calendar year, income, and length of education. RESULTS: A total of 58 847 patients with incident stroke were included. Crude incidence rates of stroke (per 1000 per year) among the four marital status categories were as follows: 1.96 (married), 1.52 (unmarried), 2.36 (divorced), and 5.43 (widowed). Compared to married persons, adjusted risk of stroke was significantly increased for divorced (RR 1.23; CI 1.19-1.27) and unmarried men (RR 1.07; CI 1.03-1.11) but not for widowed men (RR 1.02; CI 0.98-1.06); risk was slightly increased for divorced women (RR 1.10; CI 1.06-1.15) while not for widowed (RR 1.0; CI 0.97-1.03) and unmarried women (RR 0.97; CI 0.97-1.03). CONCLUSIONS: Divorce was associated with higher risk of stroke, especially in men. Living in marriage or as unmarried or widower had only little or no impact on the risk of stroke.

Resistance Genes in Global Crop Breeding Networks.

Resistance genes are a major tool for managing crop diseases. The networks of crop breeders who exchange resistance genes and deploy them in varieties help to determine the global landscape of resistance and epidemics, an important system for maintaining food security. These networks function as a complex adaptive system, with associated strengths and vulnerabilities, and implications for policies to support resistance gene deployment strategies. Extensions of epidemic network analysis can be used to evaluate the multilayer agricultural networks that support and influence crop breeding networks. Here, we evaluate the general structure of crop breeding networks for cassava, potato, rice, and wheat. All four are clustered due to phytosanitary and intellectual property regulations, and linked through CGIAR hubs. Cassava networks primarily include public breeding groups, whereas others are more mixed. These systems must adapt to global change in climate and land use, the emergence of new diseases, and disruptive breeding technologies. Research priorities to support policy include how best to maintain both diversity and redundancy in the roles played by individual crop breeding groups (public versus private and global versus local), and how best to manage connectivity to optimize resistance gene deployment while avoiding risks to the useful life of resistance genes. [Formula: see text] Copyright © 2017 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .

Epidemic Network Analysis for Mitigation of Invasive Pathogens in Seed Systems: Potato in Ecuador.

Seed systems have an important role in the distribution of high-quality seed and improved varieties. The structure of seed networks also helps to determine the epidemiological risk for seedborne disease. We present a new approach for evaluating the epidemiological role of nodes in seed networks, and apply it to a regional potato farmer consortium (Consorcio de Productores de Papa [CONPAPA]) in Ecuador. We surveyed farmers to estimate the structure of networks of farmer seed tuber and ware potato transactions, and farmer information sources about pest and disease management. Then, we simulated pathogen spread through seed transaction networks to identify priority nodes for disease detection. The likelihood of pathogen establishment was weighted based on the quality or quantity of information sources about disease management. CONPAPA staff and facilities, a market, and certain farms are priorities for disease management interventions such as training, monitoring, and variety dissemination. Advice from agrochemical store staff was common but assessed as significantly less reliable. Farmer access to information (reported number and quality of sources) was similar for both genders. However, women had a smaller amount of the market share for seed tubers and ware potato. Understanding seed system networks provides input for scenario analyses to evaluate potential system improvements. [Formula: see text] Copyright © 2017 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .

Factors associated with combined hand and foot eczema.

BACKGROUND: As for hand eczema, the aetiology of foot eczema is multifactorial and not very well understood. The aim of the present study was to identify factors associated with foot eczema in a cohort of hand eczema patients being classified into different subgroups. METHODS: Associations between foot and hand eczema were studied in a cross-sectional design in a cohort of hand eczema patients. Consecutive patients were recruited from nine different European Centres during the period October 2011-September 2012. Data on demographic factors, presence of foot eczema, hand eczema duration and severity, and whether the hand eczema was work-related or not were available, as well as patch-test results. RESULTS: Of a total of 427 hand eczema patients identified, information on foot eczema was available in 419 patients who were included in the present study. A total of 125 patients (29.8%) had concomitant foot and hand eczema. It was found more often in association with hyperkeratotic hand eczema (P = 0.007) and was less often associated with irritant hand eczema (P < 0.001). However, foot eczema was nevertheless found in 18% of patient with irritant hand eczema and in 25% of patients with occupational hand eczema. Combined foot and hand eczema was associated with more severe and long-standing hand eczema (P < 0.001 and P = 0.004, respectively). Contact allergy was found in 51.8% with no difference between patients with combined foot and hand eczema and patients with hand eczema only. CONCLUSION: Occurrence of combined foot and hand eczema is a common finding and not restricted to endogenous hand eczema.

Prediction of treatment response to adalimumab: a double-blind placebo-controlled study of circulating microRNA in patients with early rheumatoid arthritis.

At least 30% of patients with rheumatoid arthritis (RA) do not respond to biologic agents, which emphasizes the need of predictive biomarkers. We aimed to identify microRNAs (miRNAs) predictive of response to adalimumab in 180 treatment-naïve RA patients enrolled in the OPtimized treatment algorithm for patients with early RA (OPERA) Study, an investigator-initiated, prospective, double-blind placebo-controlled study. Patients were randomized to adalimumab 40 mg (n=89) or placebo-adalimumab (n=91) subcutaneously in combination with methotrexate. Expressions of 377 miRNAs were determined using TaqMan Human MicroRNA LDA, A Card v2.0 (Applied Biosystems). Associations between miRNAs and treatment response were tested using interaction analyses. MiRNAs with a P-value <0.05 using three different normalizations were included in a multivariate model. After backwards elimination, the combination of low expression of miR-22 and high expression of miR-886.3p was associated with EULAR good response. Future studies to assess the utility of these miRNAs as predictive biomarkers are needed.

Cumulative dosages of antipsychotic drugs are associated with increased mortality rate in patients with Alzheimer's dementia.

OBJECTIVE: We wished to investigate the effects of cumulative dosages of antipsychotic drug in Alzheimer's dementia, when controlling for known risk factors, including current antipsychotic exposure, on all-cause mortality. METHOD: We utilized a nationwide, population-based, retrospective cohort study design with mortality as outcome in individual patients diagnosed with Alzheimer's dementia. RESULTS: We included a total of 45 894 patients and followed them for 3 803 996 person-years in total, presenting 27 894 deaths in the study population. Cumulative antipsychotic exposure increased mortality: more than 0 Daily Defined Dosage (DDDs) but less than 90: HR 2.20, 95% CI (2.14-2.27), P < 0.001; more than or equal to 90 DDDs but less than 365: HR 1.81, 95% CI (1.74-1.89), P < 0.001; more than or equal to 365 DDDs but less than 730: HR 1.38, 95% CI (1.428-1.49), P < 0.001; and more than or equal to 730 DDDs: HR 1.06, 95% CI (0.95-1.18), P = 0.322, when controlling for proxy markers of severity, somatic and mental comorbid disorders. CONCLUSION: In this nationwide cohort study of 45 894 patients diagnosed with Alzheimer's dementia, we found that cumulative dosages of antipsychotic drugs were associated with increased mortality rates.

Association between sensory dysfunction and pain 1 week after breast cancer surgery: a psychophysical study.

BACKGROUND: Breast cancer patients treated with axillary lymph node dissection (ALND) have a higher risk of both acute and persistent pain than those treated with sentinel lymph node biopsy (SLNB). This could be attributed to a higher risk of nerve injury with ALND. We hypothesized that (1) pain patients have more pronounced sensory dysfunction than pain-free patients, (2) ALND have more sensory dysfunction and pain than SLNB patients and (3) patients with preserved intercostobrachial nerve (ICBN) preservation have less sensory dysfunction compared to a sectioned ICBN. METHODS: Twenty-seven patients treated with ALND and 27 with SLNB examined with a standardized Quantitative Sensory Testing (QST) protocol, including sensory mapping, mechanical and thermal thresholds, as well as recording intraoperative ICBN handling and pain status 1 week post-operative. RESULTS: The area of cold hypoaesthesia was significantly associated with movement-related pain (P = 0.004), with a similar tendency for warmth (P = 0.018) and brush (P = 0.030) hypoaesthesia areas. 14 (26%) of the patients had moderate/severe pain at rest and 13 (24%) during movement without differences between ALND and SLNB, but ALND was associated with more sensory dysfunction than SLNB. Patients with sectioned ICBN reported lower pain intensity than those with preserved ICBN (P = 0.005), but without differences in sensory dysfunction. CONCLUSION: Pain was increased in patients having larger areas of hypoaesthesia and reduced in patients where ICBN-section was done. Sensory dysfunction was related to extent of axillary surgery, but not with ICBN handling. Our data suggest that acute pain after breast cancer surgery may be related to nerve injury.