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Sofia Eriksson,1 Maaike Giezeman,2,3 Mikael Hasselgren,2,3 Christer Janson,4 Marta A Kisiel,5 Scott Montgomery,2,6,7 Anna Nager,8 Hanna Sandelowsky,7,9 Björn Ställberg,10 Josefin Sundh,11 Karin Lisspers10 1Region Dalarna, Falun, Sweden; 2School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 3Centre for Clinical Research and Education, Region Värmland, Karlstad, Sweden; 4Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden; 5Department of Medical Sciences, Occupational and Environment Medicine, Uppsala University, Uppsala, Sweden; 6Clinical Epidemiology Division, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; 7Department of Epidemiology and Public Health, University College, London, UK; 8NVS, Section for Family Medicine and Primary Care, Karolinska Institutet, Stockholm, Sweden; 9Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institutet, Stockholm, Sweden; 10Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 11Department of Respiratory Medicine, Faculty of Medicine and Health, Örebro University, Örebro, SwedenCorrespondence: Karin Lisspers, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Box 564, Uppsala, SE-75122, Sweden, Tel +46703524721, Email Karin.lisspers@regiondalarna.se; Karin.lisspers@uu.sePurpose: To study risk factors for uncontrolled asthma and insufficient quality of life (QoL) in patients with mild asthma, ie those without preventer treatment.Patients and Methods: Patients aged 18– 75 years with a doctor’s diagnosis of asthma randomly selected from primary and secondary care in Sweden. Mild asthma was defined as self-reported current asthma and no preventer treatment. Data were collected from self-completed questionnaires in 2012 and 2015. Well-controlled asthma was defined as Asthma Control Test (ACT) ≥ 20 points and no exacerbation and uncontrolled asthma as ACT< 20 points and/or at least one exacerbation in the previous six months. QoL was measured by the Mini Asthma Quality of Life Questionnaire (Mini-AQLQ), where a total mean score of ≥ 6 indicated sufficient and < 6 insufficient QoL. Multivariate logistic regression analyses were performed using asthma control and Mini-AQLQ as dependent variables. Asthma control was dichotomized as controlled and uncontrolled asthma and the Mini-AQLQ as sufficient QoL (mean score ≥ 6) and insufficient QoL (mean score < 6).Results: Among 298 patients, 26% had uncontrolled asthma, 40% insufficient QoL and 20% both uncontrolled asthma and insufficient QoL. Age ≥ 60 years, obesity, daily smoking, rhinitis and inadequate knowledge of asthma self-management were independently associated with poor asthma control. Factors independently associated with insufficient QoL were age ≥ 60 years, overweight, obesity, rhinitis, sinusitis and inadequate knowledge of asthma self-management. Age ≥ 60 years, obesity, rhinitis and inadequate knowledge of asthma self-management were independently associated with both uncontrolled asthma and insufficient QoL.Conclusion: Among asthma patients without preventer medication, 26% had uncontrolled asthma and 40% had insufficient asthma-related QoL. Older age, obesity, and rhinitis were risk factors for both poor asthma control and a reduced QoL, but having good knowledge of asthma self-management reduced this risk. Our findings suggest that this group of patients requires further attention and follow-up.Plain Language Summary: Many patients with little symptoms of asthma do not take asthma-preventer medication as their asthma is recognized as mild. Still, it is well-known that in this group there are patients with frequent and severe symptoms and acute attacks of asthma, defined as uncontrolled asthma. Quality of life (QoL) is less studied in these patients. Our aim was to study patient characteristics and factors with a higher risk for uncontrolled asthma and insufficient QoL in patients with mild asthma.We studied patients with asthma diagnosis 18– 75 of age in Sweden who reported asthma and no asthma preventer medication. They answered questionnaires about characteristics, knowledge of asthma, asthma symptoms, acute asthma attacks and QoL. A test for asthma symptom control, the Asthma Control Test (ACT), was answered, where 20 points or more meant good asthma symptom control. Patients were regarded as having uncontrolled asthma if they had less than 20 points and/or at least one acute asthma attack the last six months. QoL was measured by the Mini Asthma Quality of Life Questionnaire. A mean score of 6 or more meant sufficient and less than 6 insufficient QoL.Of the 298 patients, 26% had uncontrolled asthma, 40% had insufficient QoL and 20% had both. Patients with risk for both uncontrolled asthma and insufficient QoL were 60 years and over, with obesity, rhinitis and those who reported insufficient knowledge of how to handle asthma. Our results suggest that patients with mild asthma need more attention, better management and follow-ups.Keywords: asthma, management, risk factors, asthma outcomes

Carolina Smith,1,2 Ayako Hiyoshi,1,3 Mikael Hasselgren,2,4 Hanna Sandelowsky,5– 7 Björn Ställberg,8 Scott Montgomery1,5,9 1Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 2Centre for Clinical Research and Education, Region Värmland, Karlstad, Sweden; 3Department of Public Health Sciences, Stockholm University, Stockholm, Sweden; 4School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; 5Clinical Epidemiology Division, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden; 6Department of Neurobiology, Care Sciences and Society, Division of Family Medicine and Primary Care, Karolinska Institutet, Stockholm, Sweden; 7Academic Primary Health Care Center, Region Stockholm, Stockholm, Sweden; 8Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 9Department of Epidemiology and Public Health, University College, London, UKCorrespondence: Carolina Smith, School of Medical Sciences, Faculty of Medicine and HealthÖrebro University, Örebro, 701 82, Sweden, Email Carolina.smith@oru.sePurpose: Patients with a diagnosis of chronic obstructive pulmonary disease (COPD) often have other chronic disorders. This study aims to describe the life-course pattern of morbidity in patients with COPD.Patients and Methods: Among all residents aged 50– 90 years in Sweden in 1997, people with a hospital COPD diagnosis were identified using Swedish national registers (1997– 2018). Each patient with COPD was matched by sex, birthyear and county of residency with up to five COPD-free controls. Other chronic disease diagnoses were identified during 1987– 2018. Conditional logistic regression calculated risk of diseases diagnosed prior to first COPD diagnosis, producing odds ratios (OR) and 95% confidence intervals (95% CI). Cox regression estimated risk of diagnoses after first COPD diagnosis, producing hazard ratios (HR) and 95% CI.Results: Among 2,706,814 individuals, 225,159 (8.3%) had COPD. The nested case–control sample included 223,945 COPD-cases with 1,062,731 controls. Prior to first COPD diagnosis, future COPD patients had higher risks than controls for most examined conditions. Highest risks were seen for chronic heart failure (OR = 3.25, 3.20– 3.30), peripheral arterial disease (OR = 3.12, 3.06– 3.18) and lung cancer (OR = 12.73, 12.12– 13.37). Following the COPD diagnosis, individuals with COPD had higher risks of most conditions than individuals without COPD. Chronic heart failure (HR = 3.50, 3.46– 3.53), osteoporosis (HR = 3.35, 3.30– 3.42), depression (HR = 2.58, 2.53– 2.64) and lung cancer (HR = 6.04, 5.90– 6.18) predominated. The risk of vascular dementia was increased after COPD diagnosis (HR = 1.53, 1.48– 1.58) but not Alzheimer’s disease.Conclusion: Accumulation of chronic morbidity may precede COPD. Following the diagnosis, an increased burden of cardiovascular disease and cancer is to be expected, but subsequent depression, osteoporosis, and vascular dementia should also be noted. Management strategies for patients with COPD should consider the higher-than-average risk of multimorbidity.Keywords: COPD, multimorbidity, register-study

Lisa Roberts,1 Solomon Renati,2 Shreeletha Solomon,3 Susanne Montgomery4 1School of Nursing, Loma Linda University, Loma Linda, CA 92350, USA; 2Department of Psychology, Veer Wajekar A. S. & C. College, Navi Mumbai 400702, India; 3Veer Wajekar A. S. & C. College, Navi Mumbai 400702, India; 4School of Behavioral Health, Behavioral Health Institute, Loma Linda University, Loma Linda, CA 92350, USACorrespondence: Lisa RobertsSchool of Nursing, Loma Linda University, 11262 Campus Street, Loma Linda, CA 92350, USATel +1 (909) 558-1000Fax +1 (909) 558-0719Email lroberts@llu.eduBackground: Infertility is a global problem, with high prevalence in India. As a pronatalist society, infertility is particularly problematic in India, causing stigma, shame, and blame especially for women. Infertility consequences for women include discrimination, social exclusion, and abandonment, putting them at high risk for mental health distress. Furthermore, mental health is highly stigmatized and specialized care is largely unavailable. Despite the cultural importance of childbearing, research on infertility distress and resulting mental health sequelae is lacking, particularly among low-income women. The purpose of this study is to assess mental health, using validated scales, among Mumbai slum-dwelling women with a history of infertility.Methods: We conducted a mixed-method, cross-sectional study. A focus group discussion with community health workers (n = 7) informed the development of a comprehensive survey. The survey consisted of validated scales whenever possible, in addition to questions pertaining to women’s sociodemographic and reproductive history. After rigorous forward and back translation, the surveys were conducted as face-to-face structured interviews due to low literacy levels and the research naiveté of our respondents. Interviews were conducted by culturally, linguistically, gender-matched, trained research assistants.Results: Mumbai slum-dwelling women of reproductive age suffering from infertility (N = 74) participated. Most (85%) women and their husbands (66%) reported previous infertility testing. Participants had elevated mental health distress (anxiety and depression symptomology) largely explained by general health, length of marriage, and coping strategy employed.Conclusion: Women facing the double stigma of mental health and infertility need innovative programs to address their challenges.Keywords: infertility, mental health, stigma, low-income women, Mumbai, India

Stroke is a leading cause of serious long-term disability in adults and is the second leading cause of death worldwide. Early reperfusion and neuroprotection techniques have been the focus of much effort with the aim of very acute treatment of the stroke. Targeting different mechanisms, pharmacological therapies have the potential to reduce disability in a large fraction of patients who survive the acute stroke. The brain's capacity to reorganize after stroke through plasticity mechanisms can be modulated by pharmacological agents. A number of therapeutic interventions are under study, including small molecules, growth factors, and monoclonal antibodies. Recently it has been shown that the SSRI fluoxetine improved motor deficit in patients with ischaemic stroke and hemiplegia which appeared to be independent of the presence of depression. In this context, it is of major importance to support innovative research in order to promote the emergence of new pharmacological treatments targeting neurological recovery after stroke, as opposed to acute de-occlusion and neuroprotection. This paper is the work of a group of 14 scientists with aim of (1) addressing key areas of the basic and clinical aspects of human brain plasticity after stroke and potential pharmacological targets for recovery, (2) asking questions about the most appropriate characteristics of clinical trials testing drugs in post stroke recovery and (3) proposing recommendations for future clinical trials.

Joakim Åberg,1 Mikael Hasselgren,1 Scott Montgomery,2–4 Karin Lisspers,5 Björn Ställberg,5 Christer Janson,6 Josefin Sundh71School of Medical Sciences, Örebro University, Örebro 70185, Sweden; 2Clinical Epidemiology and Biostatistics, Örebro University, Örebro 70182, Sweden; 3Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; 4Department of Epidemiology and Public Health, University College, London, UK; 5Department of Public Health and Caring Sciences, Family Medicine and Preventive medicine, Uppsala University, Uppsala 75122, Sweden; 6Department of Medical Sciences, Respiratory, Allergy & Sleep Research, Uppsala University, Uppsala 75105, Sweden; 7Department of Respiratory Medicine, School of Medical Sciences, Örebro University, Örebro 70185, SwedenPurpose: Women with chronic obstructive pulmonary disease (COPD) have more symptoms, more exacerbations, lower health status scores, and more comorbidity. However, it is unclear whether management of COPD differs by sex. The aim of the study was to investigate differences by sex in the care of patients with COPD.Patients and methods: The population included 1329 primary and secondary care patients with a doctor´s diagnosis of COPD in central Sweden. Data were obtained from patient questionnaires and included patient characteristics and data on achieved COPD care. Analyses included cross-tabulations, chi-squared test and multiple logistic regression using several measures in COPD management as dependent variables, female sex as independent variable, and with adjustment for age groups, previous exacerbations, COPD Assessment Test, level of dyspnea assessed by the modified Medical Research Council scale, comorbid conditions, self-rated moderate/severe disease, level of education and body mass index.Results: Women were more likely to receive triple therapy (OR 1.86 (95% CI 1.38–2.51)), to have any maintenance treatment (OR 1.82 (95% CI 1.31–2.55)), to be on sick leave (OR 2.16 (95% CI 1.19–3.93)), to have received smoking cessation support (OR 1.80 (95% CI 1.18–2.75)) and to have had pneumococcal vaccination (OR 1.82 (95% CI 1.37–2.43)), all independently of age, severity of disease or other potential confounders.Conclusion: Management of COPD differs by sex, with women being more actively managed than men. It is unclear whether this is due to patient- or care-related factors.Keywords: gender, triple inhaled therapy, maintenance treatment, sick leave, smoking support, pneumococcal vaccination

Since an initial case in 2006, we noted multiple patients undergoing heart transplantation (HTx) for Chagas cardiomyopathy (CC) at our transplant program. The clinical characteristics, laboratory results and outcomes of patients with CC undergoing HTx in the United States have not been reported previously. In 2010, we implemented a systematic screening and management program for patients undergoing HTx for CC. Before HTx, all patients with idiopathic dilated cardiomyopathy who were born in a Chagas disease endemic country were screened for Trypanosoma cruzi (TC) infection with serology. After HTx, monitoring for TC reactivation was performed using clinical visits, echocardiography, endomyocardial biopsy and serial whole blood polymerase chain reaction (PCR) testing. Between June 2006 and January 2012, 11 patients underwent HTx for CC. One patient was empirically treated due to the presence of TC amastigotes in explanted cardiac tissue. Two patients experienced allograft dysfunction due to TC reactivation and three patients experienced subclinical reactivation (positive PCR results), which were treated. Chagas disease is a common cause of dilated cardiomyopathy in patients from endemic countries undergoing HTx at a transplant program in the United States. Reactivation is common after transplantation and can cause adverse outcomes.

Maaike Giezeman,1,2 Mikael Hasselgren,1 Karin Lisspers,3 Björn Ställberg,3 Scott Montgomery,4–6 Christer Janson,7 Josefin Sundh8 1School of Medical Sciences, Örebro University, Örebro, Sweden; 2Centre for Clinical Research, County Council of Värmland, Karlstad, Sweden; 3Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden; 4Clinical Epidemiology and Biostatistics, Örebro University, Örebro, Sweden; 5Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; 6Department of Epidemiology and Public Health, University College, London, UK; 7Department of Medical Sciences, Respiratory, Allergy and Sleep Research, Uppsala University, Uppsala, Sweden; 8Department of Respiratory Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden Purpose: The aim of this study was to examine the changing influence over time of comorbid heart disease on symptoms and health status in patients with COPD. Patients and methods: This is a prospective cohort study of 495 COPD patients with a baseline in 2005 and follow-up in 2012. The study population was divided into three groups: patients without heart disease (no-HD), those diagnosed with heart disease during the study period (new-HD) and those with heart disease at baseline (HD). Symptoms were measured using the mMRC. Health status was measured using the Clinical COPD Questionnaire (CCQ) and the COPD Assessment Test (CAT; only available in 2012). Logistic regression with mMRC ≥2 and linear regression with CCQ and CAT scores in 2012 as dependent variables were performed unadjusted, adjusted for potential confounders, and additionally adjusted for baseline mMRC, respectively, CCQ scores. Results: Mean mMRC worsened from 2005 to 2012 as follows: for the no-HD group from 1.8 (±1.3) to 2.0 (±1.4), (P=0.003), for new-HD from 2.2 (±1.3) to 2.4 (±1.4), (P=0.16), and for HD from 2.2 (±1.3) to 2.5 (±1.4), (P=0.03). In logistic regression adjusted for potential confounding factors, HD (OR 1.71; 95% CI: 1.03–2.86) was associated with mMRC ≥2. Health status worsened from mean CCQ as follows: for no-HD from 1.9 (±1.2) to 2.1 (±1.3) with (P=0.01), for new-HD from 2.3 (±1.5) to 2.6 (±1.6) with (P=0.07), and for HD from 2.4 (±1.1) to 2.5 (±1.2) with (P=0.57). In linear regression adjusted for potential confounders, HD (regression coefficient 0.12; 95% CI: 0.04–5.91) and new-HD (0.15; 0.89–5.92) were associated with higher CAT scores. In CCQ functional state domain, new-HD (0.14; 0.18–1.16) and HD (0.12; 0.04–0.92) were associated with higher scores. After additional correction for baseline mMRC and CCQ, no statistically significant associations were found. Conclusion: Heart disease contributes to lower health status and higher symptom burden in COPD but does not accelerate the worsening over time. Keywords: COPD Assessment Test, CAT, Clinical COPD Questionnaire, CCQ, modified Medical Research Council dyspnea score, mMRC, ischemic heart disease, heart failure

Per-Ola Sundin,1 Ruzan Udumyan,1 Katja Fall,1,2 Scott Montgomery1,3,4 1Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden; 2Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; 3Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital Solna, Karolinska Institutet, Stockholm, Sweden; 4Department of Epidemiology and Public Health, University College, London, UK Background: Although acute onset kidney complications associated with severe infections including pneumonia are well characterized, little is known about possible subsequent delayed risk of chronic kidney disease (CKD). Patients and methods: Associations between hospital admission with pneumonia in adulthood and raised risks of subsequent CKD were evaluated in a cohort of all male residents in Sweden born from 1952 to 1956 (n=284,198) who attended mandatory military conscription examinations in late adolescence (n=264,951) and were followed up through 2009. CKD and pneumonia were identified using Swedish national registers, and their associations were evaluated using Cox regression. Excluding the first year, the subsequent period was divided into ≤5, >5–≤15, and >15 years after hospital admission with pneumonia. Follow-up ended on the date of first incident diagnosis of kidney disease, death, emigration, or December 31, 2009, whichever occurred first. Results: During a median follow-up of 36.7 (interquartile range 35.3–37.9) years from late adolescence, 5,822 men had an inpatient pneumonia diagnosis without contemporaneous kidney disease. Among exposed men, 136 (2.3%) were later diagnosed with CKD compared with 2,749 (1.2%) of the unexposed. The adjusted hazard ratio for CKD in the first year after the first episode of pneumonia was 14.55 (95% confidence interval, 10.41–20.32), identifying early onset kidney complications and possibly pre-existing undiagnosed CKD. Starting follow-up 1 year after pneumonia to reduce the potential influence of surveillance bias and the risk of reverse causation, the adjusted hazard ratio for CKD in the first 5 years of follow-up was 5.20 (95% confidence interval, 3.91–6.93) and then attenuated with increasing time. Conclusion: Pneumonia among inpatients is associated with a persistently increased risk for subsequent CKD, with the highest risk during the years immediately after pneumonia. Health care professionals should be aware of this period of heightened risk to facilitate early diagnosis and secondary preventive interventions. Keywords: pneumonia, kidney disease, end-stage renal disease, inflammation, cohort study

Josefin Sundh,1 Helena Lindgren,2 Mikael Hasselgren,2 Scott Montgomery,3–5 Christer Janson,6 Björn Ställberg,7 Karin Lisspers7 1Department of Respiratory Medicine, School of Medical Sciences, 2Medical Programme, School of Medical Sciences, 3Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, 4Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Stockholm, Sweden; 5Department of Epidemiology and Public Health, University College, London, UK; 6Department of Medical Sciences, Respiratory, Allergy and Sleep Research, 7Department of Public Health and Caring Science, Family Medicine and Preventive Medicine, Uppsala University, Uppsala, Sweden Introduction: Pulmonary rehabilitation is effective in all stages of COPD. The availability and utilization of pulmonary rehabilitation resources, and the characteristics of COPD patients receiving rehabilitation, were investigated in primary and secondary care in central Sweden. Materials and methods: Data on available pulmonary rehabilitation resources were collected using questionnaires, to 14 hospitals and 54 primary health care centers, and information on utilization of different rehabilitation professionals was obtained from questionnaires completed by 1,329 COPD patients from the same centers. Multivariable logistic regression examined associations with having received rehabilitation in the previous year. Results: In primary care, nurse-based asthma/COPD clinics were common (87%), with additional separate access to other rehabilitation professionals. In secondary care, rehabilitation was more often offered as part of a multidisciplinary teamwork (71%). In total, 36% of the patients met an asthma/COPD nurse in the previous year. Utilization was lower in primary than in secondary care for physiotherapists (7% vs 16%), occupational therapists (3% vs 10%), nutritionists (5% vs 13%), and counselors (1% vs 4%). A higher COPD Assessment Test score and frequent exacerbations were associated with higher utilization of all rehabilitation professionals. Conclusion: Pulmonary rehabilitation resources are available but underutilized, and receiving rehabilitation is more common in severe COPD. Treatment recommendations need to be better implemented, especially in mild and moderate COPD. Keywords: multidisciplinary, asthma/COPD nurse, physiotherapist, occupational therapist, nutritionist, counselor

Piotr Kozlowski,1 Scott Montgomery,2–4 Rahel Befekadu,5 Victoria Hahn-Strömberg6 1Department of Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden; 2Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University, Örebro, Sweden; 3Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; 4Department of Epidemiology and Public Health, University College London, London, UK; 5Department of Transfusion Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden; 6Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden Background: Light chain amyloidosis (AL) is a rare deposition disease and is present in 10–15% of patients with myeloma (MM). In contrast to symptomatic AL in MM, presence of bone marrow (BM) amyloid deposits (AD) in MM is not connected to kidney damage. Renal AD but not BM-AD occur mostly in MM with lambda paraprotein (lambda MM). Methods: We investigated amyloid presence in BM clots taken at diagnosis in 84 patients with symptomatic MM and compared disease characteristics in MM with kappa paraprotein (kappa MM)/lambda MM with and without BM-AD. Results: Lambda MM with BM-AD was compared with kappa MM without BM-AD, kappa MM with BM-AD, and lambda MM without BM-AD: lambda MM with BM-AD patients had a significantly higher mean creatinine level (4.23 mg/dL vs 1.69, 1.14, and 1.28 mg/dL, respectively) and a higher proportion presented with severe kidney failure (6/11 [55%] vs 6/32 [19%], 1/22 [5%], and 3/19 [16%], respectively). Proteinuria was more common in lambda MM with BM-AD patients compared with kappa MM without BM-AD patients (8/11 [73%] vs 5/32 [16%], respectively). Conclusion: Kidney damage was more common in lambda MM with BM-AD indicating presence of renal AD. Keywords: plasma cells, neoplasms, amyloidosis, renal insufficiency, proteinuria