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  • Global Landscape Review of Serotype-Specific Invasive Pneumococcal Disease Surveillance among Countries Using PCV10/13: The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) Project.

    Deloria Knoll, Maria; Bennett, Julia C; Garcia Quesada, Maria; Kagucia, Eunice W; Peterson, Meagan E; Feikin, Daniel R; Cohen, Adam L; Hetrich, Marissa K; Yang, Yangyupei; Sinkevitch, Jenna N; et al. (MDPI, 2021-04-02)
    Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon. Keywords: global; invasive pneumococcal disease; pneumococcal conjugate vaccines; pneumococcal meningitis; surveillance.
  • Serotype Distribution of Remaining Pneumococcal Meningitis in the Mature PCV10/13 Period: Findings from the PSERENADE Project.

    Garcia Quesada, Maria; Yang, Yangyupei; Bennett, Julia C; Hayford, Kyla; Zeger, Scott L; Feikin, Daniel R; Peterson, Meagan E; Cohen, Adam L; Almeida, Samanta C G; Ampofo, Krow; et al. (MDPI, 2021-04-01)
    Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5-7 years with primary series uptake above 70%. The distribution was estimated using a multinomial Dirichlet regression model, stratified by PCV product and age. In PCV10-using sites (N = 8; cases = 1141), PCV10 types caused 5% of cases <5 years of age and 15% among ≥5 years; the top serotypes were 19A, 6C, and 3, together causing 42% of cases <5 years and 37% ≥5 years. In PCV13-using sites (N = 32; cases = 4503), PCV13 types caused 14% in <5 and 26% in ≥5 years; 4% and 13%, respectively, were serotype 3. Among the top serotypes are five (15BC, 8, 12F, 10A, and 22F) included in higher-valency PCVs under evaluation. Other top serotypes (24F, 23B, and 23A) are not in any known investigational product. In countries with mature vaccination programs, the proportion of pneumococcal meningitis caused by vaccine-in-use serotypes is lower (≤26% across all ages) than pre-PCV (≥70% in children). Higher-valency PCVs under evaluation target over half of remaining pneumococcal meningitis cases, but questions remain regarding generalizability to the African meningitis belt where additional data are needed.
  • Fetal descent in nulliparous women assessed by ultrasound: a longitudinal study.

    Hjartardóttir, Hulda; Lund, Sigrún H; Benediktsdóttir, Sigurlaug; Geirsson, Reynir T; Eggebø, Torbjørn M; 1Department of Obstetrics and Gynecology, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland. Electronic address: huldahja@landspitali.is. 2deCODE genetics, Reykjavik, Iceland. 3Department of Obstetrics and Gynecology, Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland; Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 4National Center for Fetal Medicine, Department of Obstetrics and Gynecology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway; Department of Obstetrics and Gynecology, Stavanger University Hospital, Stravanger, Norway; Institute of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway. (Elsevier, 2020-10-08)
    Background: Ultrasound measurements offer objective and reproducible methods to measure the fetal head station. Before these methods can be applied to assess labor progression, the fetal head descent needs to be evaluated longitudinally in well-defined populations and compared with the existing data derived from clinical examinations. Objective: This study aimed to use ultrasound measurements to describe the fetal head descent longitudinally as labor progressed through the active phase in nulliparous women with spontaneous onset of labor. Study design: This was a single center, prospective cohort study at the Landspitali - The National University Hospital of Iceland, Reykjavik, Iceland, from January 2016 to April 2018. Nulliparous women with a single fetus in cephalic presentation and spontaneous labor onset at a gestational age of ≥37 weeks, were eligible. Participant inclusion occurred during admission for women with an established active phase of labor or at the start of the active phase for women admitted during the latent phase. The active phase was defined as an effaced cervix dilated to at least 4 cm in women with regular contractions. According to the clinical protocol, vaginal examinations were done at entry and subsequently throughout labor, paired each time with a transperineal ultrasound examination by a separate examiner, with both examiners being blinded to the other's results. The measurements used to assess the fetal head station were the head-perineum distance and angle of progression. Cervical dilatation was examined clinically. Results: The study population comprised 99 women. The labor patterns for the head-perineum distance, angle of progression, and cervical dilatation differentiated the participants into 75 with spontaneous deliveries, 16 with instrumental vaginal deliveries, and 8 cesarean deliveries. At the inclusion stage, the cervix was dilated 4 cm in 26 of the women, 5 cm in 30 of the women, and ≥6 cm in 43 women. One cesarean and 1 ventouse delivery were performed for fetal distress, whereas the remaining cesarean deliveries were conducted because of a failure to progress. The total number of examinations conducted throughout the study was 345, with an average of 3.6 per woman. The ultrasound-measured fetal head station both at the first and last examination were associated with the delivery mode and remaining time of labor. In spontaneous deliveries, rapid head descent started around 4 hours before birth, the descent being more gradual in instrumental deliveries and absent in cesarean deliveries. A head-perineum distance of 30 mm and angle of progression of 125° separately predicted delivery within 3.0 hours (95% confidence interval, 2.5-3.8 hours and 2.4-3.7 hours, respectively) in women delivering vaginally. Although the head-perineum distance and angle of progression are independent methods, both methods gave similar mirror image patterns. The fetal head station at the first examination was highest for the fetuses in occiput posterior position, but the pattern of rapid descent was similar for all initial positions in spontaneously delivering women. Oxytocin augmentation was used in 41% of women; in these labors a slower descent was noted. Descent was only slightly slower in the 62% of women who received epidural analgesia. A nonlinear relationship was observed between the fetal head station and dilatation. Conclusion: We have established the ultrasound-measured descent patterns for nulliparous women in spontaneous labor. The patterns resemble previously published patterns based on clinical vaginal examinations. The ultrasound-measured fetal head station was associated with the delivery mode and remaining time of labor. Keywords: angle of progression; cesarean delivery; fetal head position; fetal head station; head-perineum distance; transabdominal ultrasound; transperineal ultrasound.
  • Changes in Invasive Pneumococcal Disease Caused by Serotype 1 Following Introduction of PCV10 and PCV13: Findings from the PSERENADE Project.

    Bennett, Julia C; Hetrich, Marissa K; Garcia Quesada, Maria; Sinkevitch, Jenna N; Deloria Knoll, Maria; Feikin, Daniel R; Zeger, Scott L; Kagucia, Eunice W; Cohen, Adam L; Ampofo, Krow; et al. (MDPI, 2021-03-27)
    Streptococcus pneumoniae serotype 1 (ST1) was an important cause of invasive pneumococcal disease (IPD) globally before the introduction of pneumococcal conjugate vaccines (PCVs) containing ST1 antigen. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project gathered ST1 IPD surveillance data from sites globally and aimed to estimate PCV10/13 impact on ST1 IPD incidence. We estimated ST1 IPD incidence rate ratios (IRRs) comparing the pre-PCV10/13 period to each post-PCV10/13 year by site using a Bayesian multi-level, mixed-effects Poisson regression and all-site IRRs using a linear mixed-effects regression (N = 45 sites). Following PCV10/13 introduction, the incidence rate (IR) of ST1 IPD declined among all ages. After six years of PCV10/13 use, the all-site IRR was 0.05 (95% credibility interval 0.04-0.06) for all ages, 0.05 (0.04-0.05) for <5 years of age, 0.08 (0.06-0.09) for 5-17 years, 0.06 (0.05-0.08) for 18-49 years, 0.06 (0.05-0.07) for 50-64 years, and 0.05 (0.04-0.06) for ≥65 years. PCV10/13 use in infant immunization programs was followed by a 95% reduction in ST1 IPD in all ages after approximately 6 years. Limited data availability from the highest ST1 disease burden countries using a 3+0 schedule constrains generalizability and data from these settings are needed.
  • Vitamin D status and association with gestational diabetes mellitus in a pregnant cohort in Iceland.

    Magnusdottir, Kristin S; Tryggvadottir, Ellen A; Magnusdottir, Ola K; Hrolfsdottir, Laufey; Halldorsson, Thorhallur I; Birgisdottir, Bryndis E; Hreidarsdottir, Ingibjorg T; Hardardottir, Hildur; Gunnarsdottir, Ingibjorg; 1Unit for Nutrition Research, Landspitali University Hospital and Faculty of Food Science and Nutrition, University of Iceland, Reykjavik, Iceland. 2Institution of Health Science Research, University of Akureyri and Akureyri Hospital, Akureyri, Iceland. 3Centre for Fetal Programming, Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. 4Department of Obstetrics and Gynecology, Landspitali University Hospital, Reykjavík, Iceland. 5Faculty of Medicine, University of Iceland, Reykjavík, Iceland. (Swedish Nutrition Foundation, 2021-03-23)
    Background: Vitamin D deficiency has been associated with an increased risk of gestational diabetes mellitus (GDM), one of the most common pregnancy complications. The vitamin D status has never previously been studied in pregnant women in Iceland. Objective: The aim of this research study was to evaluate the vitamin D status of an Icelandic cohort of pregnant women and the association between the vitamin D status and the GDM incidence. Design: Subjects included pregnant women (n = 938) who attended their first ultrasound appointment, during gestational weeks 11-14, between October 2017 and March 2018. The use of supplements containing vitamin D over the previous 3 months, height, pre-pregnancy weight, and social status were assessed using a questionnaire, and blood samples were drawn for analyzing the serum 25‑hydroxyvitamin D (25OHD) concentration. Information regarding the incidence of GDM later in pregnancy was collected from medical records. Results: The mean ± standard deviation of the serum 25OHD (S-25OHD) concentration in this cohort was 63±24 nmol/L. The proportion of women with an S-25OHD concentration of ≥ 50 nmol/L (which is considered adequate) was 70%, whereas 25% had concentrations between 30 and 49.9 nmol/L (insufficient) and 5% had concentrations < 30 nmol/L (deficient). The majority of women (n = 766, 82%) used supplements containing vitamin D on a daily basis. A gradual decrease in the proportion of women diagnosed with GDM was reported with increasing S-25OHD concentrations, going from 17.8% in the group with S-25OHD concentrations < 30 nmol/L to 12.8% in the group with S-25OHD concentrations ≥75 nmol/L; however, the association was not significant (P for trend = 0.11). Conclusion: Approximately one-third of this cohort had S-25OHD concentrations below adequate levels (< 50 nmol/L) during the first trimester of pregnancy, which may suggest that necessary action must be taken to increase their vitamin D levels. No clear association was observed between the vitamin D status and GDM in this study. Keywords: cod liver oil; gestational diabetes mellitus; nutritional status; pregnancy; supplements; vitamin D.
  • Effects of intensive upright mobilisation on outcomes of mechanically ventilated patients in the intensive care unit: a randomised controlled trial with 12-months follow-up

    Amundadottir, Olof R.; Jónasdóttir, Rannveig J.; Sigvaldason, Kristinn; Gunnsteinsdottir, Ester; Haraldsdottir, Brynja; Sveinsson, Thorarinn; Sigurdsson, Gisli H.; Dean, Elizabeth; a School of Health Sciences, University of Iceland, Reykjavik, Iceland b Department of Physiotherapy, Landspitali–The National University Hospital of Iceland, Reykjavik, Iceland c Department of Anaesthesiology and Intensive Care Medicine, Landspitali–The National University Hospital of Iceland, Reykjavik, Iceland d Department of Physical Therapy, Faculty of Medicine, The University of British Columbia, Vancouver, Canada (Taylor & Francis, 2021-03-04)
    Objective: To examine effects of intensive upright mobilisation on short- and long-term outcomes in critically ill mechanically ventilated patients. Methods: A randomised controlled trial compared patient outcomes after intensive twice-daily (n = 29) or daily mobilisation (n = 21). Patients in the intensive care unit (ICU), mechanically ventilated for over 48 hours, were randomly assigned to one of the two groups. Outcomes were duration of mechanical ventilation, ICU and hospital lengths of stay; health-related quality of life and physical function. Results: The twice-daily mobilisation group began upright mobilisation on day seven of ICU stay, and were mobilised upright on 31% of ICU days compared with the daily mobilisation group, who began upright mobilisation on day eight (p >= .05), and mobilised upright on 22% of ICU days (p = .03). No difference between groups was observed for any variable of interest across time-points over one year. Conclusions: The intensive twice-daily mobilisation group neither started upright mobilisation early nor yielded superior short- or long-term outcomes compared to the daily mobilisation group. Both groups showed poor physical health-related quality of life and exercise capacity one year after ICU discharge. Our findings support the need for targeted and tailored upright mobilisation in the ICU and after discharge.
  • Effect of Obstructive Sleep Apnea and Positive Airway Pressure Therapy on Cardiac Remodeling as Assessed by Cardiac Biomarker and Magnetic Resonance Imaging in Nonobese and Obese Adults.

    Xu, Liyue; Keenan, Brendan T; Maislin, David; Gislason, Thorarinn; Benediktsdóttir, Bryndís; Gudmundsdóttir, Sigrun; Gardarsdottir, Marianna; Staley, Bethany; Pack, Frances M; Guo, Xiaofeng; et al. (Lippincott, Williams & Wilkins, 2021-01-19)
    It is unknown whether obesity modifies the effect of obstructive sleep apnea (OSA) and positive airway pressure (PAP) therapy on cardiac remodeling and NT-proBNP (N-terminal pro-B-type natriuretic peptide) levels. We compared NT-proBNP and cardiac magnetic resonance imaging in adults without OSA (n=56) and nonobese (n=73; body mass index <30 kg/m2) and obese (n=136; body mass index ≥30 kg/m2) adults with OSA. We also investigated these traits in nonobese (n=45) and obese (n=78) participants with OSA adherent to 4 months of PAP treatment. At baseline, left ventricular mass to end-diastolic volume ratio, a measure of left ventricular concentricity, was greater in both nonobese and obese participants with OSA compared with those without OSA. Participants with OSA and obesity exhibited reduced phasic right atrial function. No significant differences in baseline NT-proBNP were observed across groups. The effect of PAP treatment on NT-proBNP and left atrial volume index was significantly modified by obesity. In nonobese participants, PAP therapy was associated with a decrease in NT-proBNP (P<0.0001) without a change in left atrial volume index, whereas in obese participants, PAP was associated with an increase in left atrial volume index (P=0.006) without a change in NT-proBNP. OSA was associated with left ventricular concentric remodeling independent of obesity and right atrial dysfunction in participants who were obese. PAP treatment was associated with reduced NT-proBNP in nonobese participants with OSA, but left atrial enlargement in obese participants with OSA, suggesting that PAP-induced reduction in BNP release (which is known to occur during obstructive apnea episodes) may lead to volume retention in obese participants with OSA. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01578031.
  • Lifelong Reduction in LDL (Low-Density Lipoprotein) Cholesterol due to a Gain-of-Function Mutation in LDLR

    Bjornsson, Eythor; Gunnarsdottir, Kristbjorg; Halldorsson, Gisli H; Sigurdsson, Asgeir; Arnadottir, Gudny A; Jonsson, Hakon; Olafsdottir, Eva F; Niehus, Sebastian; Kehr, Birte; Sveinbjörnsson, Gardar; et al. (Lippincott Williams & Wilkins, 2020-12-14)
    Background: Loss-of-function mutations in the LDL (low-density lipoprotein) receptor gene (LDLR) cause elevated levels of LDL cholesterol and premature cardiovascular disease. To date, a gain-of-function mutation in LDLR with a large effect on LDL cholesterol levels has not been described. Here, we searched for sequence variants in LDLR that have a large effect on LDL cholesterol levels. Methods: We analyzed whole-genome sequencing data from 43 202 Icelanders. Single-nucleotide polymorphisms and structural variants including deletions, insertions, and duplications were genotyped using whole-genome sequencing-based data. LDL cholesterol associations were carried out in a sample of >100 000 Icelanders with genetic information (imputed or whole-genome sequencing). Molecular analyses were performed using RNA sequencing and protein expression assays in Epstein-Barr virus-transformed lymphocytes. Results: We discovered a 2.5-kb deletion (del2.5) overlapping the 3' untranslated region of LDLR in 7 heterozygous carriers from a single family. Mean level of LDL cholesterol was 74% lower in del2.5 carriers than in 101 851 noncarriers, a difference of 2.48 mmol/L (96 mg/dL; P=8.4×10-8). Del2.5 results in production of an alternative mRNA isoform with a truncated 3' untranslated region. The truncation leads to a loss of target sites for microRNAs known to repress translation of LDLR. In Epstein-Barr virus-transformed lymphocytes derived from del2.5 carriers, expression of alternative mRNA isoform was 1.84-fold higher than the wild-type isoform (P=0.0013), and there was 1.79-fold higher surface expression of the LDL receptor than in noncarriers (P=0.0086). We did not find a highly penetrant detrimental impact of lifelong very low levels of LDL cholesterol due to del2.5 on health of the carriers. Conclusions: Del2.5 is the first reported gain-of-function mutation in LDLR causing a large reduction in LDL cholesterol. These data point to a role for alternative polyadenylation of LDLR mRNA as a potent regulator of LDL receptor expression in humans. Keywords: cardiovascular disease; genetics; lipids; microRNA; polyadenylation.
  • Acute Kidney Injury After Acute Repair of Type A Aortic Dissection.

    Helgason, Dadi; Helgadottir, Solveig; Ahlsson, Anders; Gunn, Jarmo; Hjortdal, Vibeke; Hansson, Emma C; Jeppsson, Anders; Mennander, Ari; Nozohoor, Shahab; Zindovic, Igor; et al. (Elsevier, 2020-09-19)
    Background: The aim of this study was to examine the incidence, risk factors, and outcomes of patients with acute kidney injury (AKI) after surgery for acute type A aortic dissection (ATAAD) using the Nordic Consortium for Acute Type A Aortic Dissection registry. Methods: Patients who underwent ATAAD surgery at 8 Nordic centers from 2005 to 2014 were analyzed for AKI according to the RIFLE criteria. Patients who died intraoperatively, those who had missing baseline or postoperative serum creatinine, and patients on preoperative renal replacement therapy were excluded. Results: AKI occurred in 382 of 941 patients (40.6%), and postoperative dialysis was required for 105 patients (11.0%). Renal malperfusion was present preoperatively in 42 patients (5.1%), of whom 69.0% developed postoperative AKI. In multivariable analysis patient-related predictors of AKI included age (per 10 years; odds ratio [OR], 1.30; 95% confidence interval [CI], 1.15-1.48), body mass index >30 kg/m2 (OR, 2.16; 95% CI, 1.51-3.09), renal malperfusion (OR, 4.39; 95% CI, 2.23-9.07), and other malperfusion (OR, 2.10; 95% CI, 1.55-2.86). Perioperative predictors were cardiopulmonary bypass time (per 10 minutes; OR, 1.04; 95% CI, 1.02-1.07) and red blood cell transfusion (OR per transfused unit, 1.08; 95% CI, 1.06-1.10). Rates of 30-day mortality were 17.0% in the AKI group compared with 6.6% in the non-AKI group (P < .001). In 30-day survivors AKI was an independent predictor of long-term mortality (hazard ratio, 1.86; 95% CI; 1.24-2.79). Conclusions: AKI is a common complication after surgery for ATAAD and independently predicts adverse long-term outcome. Of note one-third of patients presenting with renal malperfusion did not develop postoperative AKI, possibly because of restoration of renal blood flow with surgical repair. Mortality risk persists beyond the perioperative period, indicating that close clinical follow-up of these patients is required.
  • Pubertal development and risk of premenstrual disorders in young adulthood.

    Lu, Donghao; Aleknaviciute, Jurate; Bjarnason, Ragnar; Tamimi, Rulla M; Valdimarsdóttir, Unnur A; Bertone-Johnson, Elizabeth R; 1Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 2Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 3Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. 4Department of Psychiatry, Erasmus MC University Medical Center, Rotterdam, The Netherlands. 5Faculty of Medicine, University of Iceland and Children's Medical Centre, Landspitali University Hospital, Reykjavik, Iceland. 6Department of Population Health Sciences, Weill Cornell Medicine, New York, NY, USA. 7Center of Public Health Sciences, Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 8Department of Biostatistics and Epidemiology, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, MA, USA. 9Department of Health Promotion and Policy, School of Public Health and Health Sciences, University of Massachusetts Amherst, Amherst, MA, USA. (Oxford University Press, 2021-01)
    Study question: Is pubertal timing associated with risk of premenstrual disorders (PMDs) in young adulthood? Summary answer: Late pubertal development is associated with decreased premenstrual symptom burden and risk of PMDs in young adulthood. What is known already: PMDs, including premenstrual syndrome and premenstrual dysphoric disorder, may begin during the teenage years. Few risk factors in early life have been identified for PMD development. Study design, size, duration: A prospective cohort study of 6495 female participants during 1996-2013. Participants/materials, setting, methods: We included participants from the Growing Up Today Study (GUTS). Pubertal development was indicated by the timing of menarche, breast and pubic hair growth. Self-reported age at menarche was longitudinally assessed at enrollment (in 1996/2004 for GUTS I/II) and onwards, and classified as early (age ≤ mean - SD, 11.64 years), normative and late menarche (age ≥ mean + SD, 13.95 years). Timing of pubic hair and breast growth were assessed multiple times during follow-up via Tanner scales, and classified into early, normative and late development according to mean ± SD. Using a validated questionnaire based on the Calendar of Premenstrual Experiences, we assessed premenstrual symptoms and identified probable cases of PMDs in 2013. We examined the associations of timing of pubertal development with premenstrual symptom score and disorders using multivariable linear and logistic regressions, respectively. Main results and the role of chance: In 2013 (mean age = 26), 1001 (15.4%) individuals met criteria for a PMD. An inverse association was found between age at menarche and premenstrual symptom z-score (β -0.05 per year, 95% CI -0.07 to -0.03) and risk of PMDs (odds ratio (OR) 0.93 per year, 95% CI 0.88 to 0.99). Compared to individuals with normative menarche, individuals with late menarche had a lower risk of PMDs (OR 0.73, 95% CI 0.59 to 0.91), while individuals with early menarche had comparable odds (OR 0.98, 95% CI 0.81 to 1.18). Moreover, early growth of pubic hair was associated with increased premenstrual symptoms (z-score β 0.09 per year, 95% CI 0.02 to 0.17) and PMD risk (OR 1.28, 95% CI 1.04 to 1.56), independent of age at menarche. No associations were noted for breast development. Limitations, reasons for caution: One major limitation is some misclassification of menarche due to recall. We, however, showed robust association among participants who were premenarcheal at baseline. Wider implications of the findings: Our findings suggest that pubertal timing, particularly timing of menarche, is inversely associated with the risk of developing premenstrual symptoms in young adulthood, and that women with later menarche have significantly lower risk of PMDs. Information on PMDs should be provided to teenage girls and their parents. If these findings are confirmed in independent populations, prevention strategies and early detection programs may be considered for women with early pubertal development. Study funding/competing interest(s): The work is supported by the National Institutes of Health and Swedish Research Council. Trial registration number: N/A. Keywords: menarche; premenstrual disorders; premenstrual dysphoric disorder; premenstrual syndrome; pubertal development.
  • Use of psychiatric medication in three Arctic nursing homes: association with dementia and psychiatric symptoms.

    Gisladottir, Sigurveig; Sigurdardottir, Arun K; Hjaltadottir, Ingibjörg; 1Fossahlid Nursing Home, Health Care Institution of Eastern Iceland. 2University of Akureyri, School of Health Sciences, Akureyri, Iceland. 3Akureyri Hospital, Akureyri, Iceland. 4Faculty of Nursing, University of Iceland. 5Division of Clinical Services Landspítali, National University Hospital, Reykjavik, Iceland. (Taylor & Francis, 2021-04)
    As more people reaches advanced age, more people experience cognitive impairment and dementia. Dementia is a degenerative disease in which behavioural and psychological symptoms frequently occur, resulting in admissions to nursing homes (NHs), where the most common treatment has been medical treatment. The aim was to compare three rural Arctic NHs in Iceland in their use of psychiatric medication, type of dementia among residents, level of cognitive impairment and selected quality indicators, as well as considering national data, for the period 2016-2018. Data from the interRAI-MDS 2.0 evaluation were used. Residents with severe cognitive impairment used more antipsychotic medications, and residents with mild and severe cognitive impairment used more antidepressants than residents with no cognitive impairment did. Diagnoses of Alzheimer's Disease and Related Dementias (ADRD) are more common in the capital area and the national average than they are in the rural NHs. This indicates need for diagnostic assessments of ADRD to be conducted in rural areas. Benchmarking is beneficial for local and national regulatory bodies to find areas for improvement. The NHs did not have a lower quality of care compared with the whole country, but areas for improvement were identified. One of the NHs has already started this process. Keywords: Nursing homes; arctic areas; dementia; psychiatric medication.
  • Mild Stage 1 post-operative acute kidney injury: association with chronic kidney disease and long-term survival.

    Long, Thorir Einarsson; Helgason, Dadi; Helgadottir, Solveig; Sigurdsson, Gisli Heimir; Palsson, Runolfur; Sigurdsson, Martin Ingi; Indridason, Olafur Skuli; 1Faculty of Medicine, University of Iceland, Reykjavik, Iceland. 2Internal Medicine Services, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 3Department of Anesthesia and Intensive Care, Akademiska University Hospital, Uppsala, Sweden. 4Division of Anesthesia and Intensive Care Medicine, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. 5Division of Nephrology, Landspitali-The National University Hospital of Iceland, Reykjavik, Iceland. (Oxford University Press, 2020-02-10)
    Pre- and post-operative SCr values were available for 47 333 (42%) surgeries. Of those, 1161 (2.4%) had mild Stage 1 AKI and 2355 (5%) more severe forms of AKI. Mild Stage 1 AKI was associated with both incident CKD and progression of pre-existing CKD (P < 0.001). After exclusion of post-operative deaths within 30 days, mild Stage 1 AKI was not associated with worse 1-year survival in patients with preserved kidney function (94% versus 94%, P = 0.660), and same was true for patients with pre-operative CKD (83% versus 82%, P = 0.870) compared with their matched individuals. Conclusions. Mild Stage 1 AKI is associated with development and progression of CKD, but not with inferior 1-year survival. These findings support the inclusion of a small absolute increase in SCr in the definition of AKI.
  • Body weight changes and longitudinal associations with cognitive decline among community-dwelling older adults.

    Eymundsdottir, Hrafnhildur; Ramel, Alfons; Geirsdottir, Olof G; Skuladottir, Sigrun S; Gudmundsson, Larus S; Jonsson, Palmi V; Gudnason, Vilmundur; Launer, Lenore; Jonsdottir, Maria K; Chang, Milan; et al. (Wiley, 2021-02-20)
    Introduction: We aim to investigate the longitudinal associations between changes in body weight (BW) and declines in cognitive function and risk of mild cognitive impairment (MCI)/dementia among cognitively normal individuals 65 years or older. Methods: Data from the Age Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik Study) including 2620 participants, were examined using multiple logistic regression models. Cognitive function included speed of processing (SP), executive function (EF), and memory function (MF). Changes in BW were classified as; weight loss (WL), weight gain (WG), and stable weight (SW). Results: Mean follow-up time was 5.2 years and 61.3% were stable weight. Participants who experienced WL (13.4%) were significantly more likely to have declines in MF and SP compared to the SW group. Weight changes were not associated with EF. WL was associated with a higher risk of MCI, while WG (25.3%) was associated with a higher dementia risk, when compared to SW. Discussion: Significant BW changes in older adulthood may indicate impending changes in cognitive function. Keywords: APOE ε4; body weight changes; cognitive function; dementia; executive function; memory function; mild cognitive impairment; nutrition; speed of processing.
  • Fertug kona með hósta og brjóstverk - Tilfelli mánaðarins

    Haukur Kristjánsson; Jón Gunnlaugur Jónasson; Per Martin Silverborn; Sigríður Ólína Haraldsdóttir; Tómas Guðbjartsson; 1 Landspítali, 2 meinafræðideild Landspítala, 3 læknadeild Háskóla Íslands, 4 hjartaog lungnaskurðdeild Sahlgrenska háskólasjúkrahússins, Gautaborg, Svíþjóð, 5 lungnadeild Landspítala, 6 hjarta- og lungnaskurðdeild Landspítala. (Læknafélag Íslands, 2021-06)
  • Fjölþætt svæðisbundið verkjaheilkenni - Yfirlitsgrein

    Kristján G. Guðmundsson; Reykjalundur (Læknafélag Íslands, 2021-06)
    Verkjaheilkennið er oftast í útlim með miklum hamlandi verkjum og breyttri skynjun, oft með snertiviðkvæmni (allodyniu). Þroti er oft samfara, ásamt litabreytingum á húð, breyttri svitamyndun og skertri hreyfigetu. Einkennin eru raunar fjölþætt og mismunandi. Verkirnir eru oftast til komnir eftir áverka og eru langt umfram upphaflega áverkann. Sjúkdómurinn er fátíður, og taldist nýgengi hans vera um 5,5 á 100.000 íbúa í erlendri rannsókn. Nýgengi sjúkdómsins hér á landi í gagnagrunnum Embættis landlæknis reyndist vera 1,3 á hverja 100.000 íbúa á ári sem vekur grun um að sjúkdómurinn gæti verið vangreindur. Orsök sjúkdómsins er óþekkt. Talið er að um sé að ræða bólgusvörun eftir áverka sem leiðir til sjálfsofnæmisviðbragða. Þá er einnig rætt um verkjanæmingu í taugakerfinu. Bæði er um að ræða breytingar í úttaugakerfi og í miðtaugakerfi, meðal annars með tilfærslu á virkni svæða í heilaberki sem hafa að gera með sársaukaviðbrögð. Við greiningu er stuðst við skilmerki alþjóðafélagsins um verkjarannsóknir. Þverfagleg teymisvinna er talin vera markvissasta meðferðin þar sem unnið er eftir sálfélagslíkamlega módelinu. Einn þáttur í meðferð langt gengins sjúkdóms er speglameðferð. Lyfjameðferð sjúkdómsins er svipuð og við taugaverkjum. Vegna bólguviðbragða er hægt að nota bólgueyðandi lyf eða stera. Einnig er ábending á bisfosfonöt, einkum ef um beinþynningu er að ræða. NMDA-antagonistar eins og ketamín hafa einnig verið notaðir. Þá hefur raförvun bakhorns mænu með rafstreng virst gera gagn. Oftast gengur sjúkdómurinn yfir á nokkrum misserum, en í hluta tilfella er hann þrálátur og hamlandi, jafnvel árum og áratugum saman.
  • Langtímaárangur viðgerða vegna hrörnunartengds míturlokuleka á Íslandi

    Árni Steinn Steinþórsson; Árni Johnsen; Martin Ingi Sigurðsson; Sigurður Ragnarsson; Tómas Guðbjartsson; 1 Læknadeild Háskóla Íslands, 2 svæfinga- og gjörgæsludeild, 3 hjarta- og lungnaskurðdeild Landspítala, 4 hjarta- og lungnaskurðdeild háskólasjúkrahússins í Lundi, Svíþjóð. (Læknafélag Íslands, 2021-06)
    INNGANGUR Hrörnunartengdur míturlokuleki er helsta ábendingin fyrir míturlokuviðgerð á Vesturlöndum. Tilgangur rannsóknarinnar var að kanna langtímalifun og fylgikvilla míturlokuviðgerða vegna hrörnunartengds leka á Íslandi. EFNI OG AÐFERÐIR Rannsóknin var afturskyggn og náði til 101 sjúklings (meðalaldur 57,7 ár, 80,2% karlar) sem gengust undir míturlokuviðgerð vegna hrörnunartengds leka á Landspítala 2004-2018. Skráðar voru ábendingar fyrir aðgerð, niðurstöður hjartaómunar fyrir aðgerð og aðgerðartengdir þættir. Snemmkomnir (<30 daga) og síðkomnir fylgikvillar voru skráðir og reiknuð 30 daga dánartíðni. Langtímalifun og MACCE (major adverse cardiac and cerebrovascular event) frí lifun var áætluð með aðferð Kaplan-Meier og borin saman við almennt þýði af sama kyni og aldri. Miðgildi eftirfylgdartíma var 83 mánuðir. NIÐURSTÖÐUR Að meðaltali voru gerðar 6,7 (bil 1-14) míturlokuviðgerðir árlega og fengu 99% sjúklinga gervihring. Brottnám á aftara blaði var framkvæmt í 82,2% tilfella og Gore-Tex® gervistög notuð hjá 64,4% sjúklinga. Alvarlegir fylgikvillar greindust hjá 28,7% sjúklinga, algengastir voru hjartadrep tengt aðgerð (11,9%) og enduraðgerð vegna blæðingar (8,9%). Þrjátíu daga dánarhlutfall var 2%, miðgildi dvalar á gjörgæslu einn dagur og heildarlegutími 8 dagar. Einn sjúklingur þurfti enduraðgerð síðar vegna endurtekins míturlokuleka. Fimm ára lifun eftir aðgerð var 93,5% (95%-ÖB: 88,6-98,7) og 10 ára lifun 85,3% (95%-ÖB: 76,6- 94,9). Fimm ára MACCE-frí lifun var 91,1% (95%-ÖB: 85,3-97,2) og eftir 10 ár 81,0% (95%-ÖB: 71,6-91,6). Ekki reyndist marktækur munur á heildarlifun rannsóknarhópsins samanborið við samanburðarþýðið (p=0,135, log-rank próf). ÁLYKTUN Árangur míturlokuviðgerða vegna hrörnunartengds leka er sambærilegur við árangur á stærri hjartaskurðdeildum erlendis. Almennt farnast þessum sjúklingum ágætlega til lengri tíma þrátt fyrir að snemmkomnir fylgikvillar séu tíðir
  • Störf sjálfstætt starfandi sálfræðinga í samkomubanni í mars og apríl 2020

    Hafrún Kristjánsdóttir; Linda Bára Lýðsdóttir; María Kristín Jónsdóttir (Sálfræðingafélag Íslands, 2020)
    Í byrjun árs 2020 skall heimsfaraldur SARS-CoV-2 (COVID-19) skyndilega á í vestrænum ríkjum. Þann 28. febrúar greindist fyrsti Íslendingurinn með COVID-19 og í mars var sett á samkomubann hérlendis. Leiða má að því líkur að slíkur faraldur hafi áhrif á andlega líðan fólks en engu að síður hafa erlendar rannsóknir sýnt að áhrif fyrstu bylgju á líðan almennings voru ekki mikil. Markmið þessarar rannsóknar var að kanna áhrif samkomubanns hér á landi í mars og apríl 2020 á störf sjálfstætt starfandi sálfræðinga. Alls tóku 98 sálfræðingar þátt í rannsókninni. Lagðar voru fyrir 36 spurningar sem sneru að eftirspurn eftir viðtölum, formi viðtala, mati sálfræðinga á líðan skjólstæðinga sinna og geðheilsu þjóðarinnar. Einnig var spurt um áhrif líðanar sálfræðinga á getu þeirra til þess að sinna meðferð og áhrif samkomubanns vegna COVID-19 á tekjur þeirra. Niðurstöður þessarar rannsóknar bentu til þess að eftirspurn eftir sálfræðiviðtölum hafi dregist saman í fyrstu bylgju faraldursins. Breyting varð á formi viðtala; viðtölum í lokuðu rými fækkaði en fjarviðtölum fjölgaði. Um þriðjungur sjálfstætt starfandi sálfræðinga taldi að geðheilsa skjólstæðinga sinna hefði versnað á tímabilinu. Mikill meirihluti taldi að COVID-19 myndi hafa áhrif á geðheilsu þjóðarinnar. Líðan sálfræðinga hafði, að þeirra mati, lítil áhrif á getu til þess að sinna meðferð. Vegna minni eftirspurnar lækkuðu tekjur hjá miklum meirihluta þátttakenda. Ljóst er að samkomubann í mars og apríl hafði áhrif á störf sálfræðinga. Ekki er vitað hvort samkomubann vegna þriðju bylgju COVID-19 muni hafa sambærileg áhrif og er frekari rannsókna þörf. Efnisorð: SARS-CoV-2, COVID-19, sálfræðingar, líðan, fjarþjónusta.
  • Þunglyndiskvarði fyrir börn (Children’s Depression Inventory) - Kerfisbundið yfirlit yfir próffræðilega eiginleika íslenskrar útgáfu

    Guðrún M. Jóhannesdóttir; Linda R. Jónsdóttir; Guðmundur Á. Skarphéðinsson; Háskóli Íslands (Sálfræðingafélag Íslands, 2020)
    Þunglyndiskvarði fyrir börn (e. Children‘s Depression Inventory (CDI)) er notaður til skimunar á þunglyndiseinkennum barna og er í töluverðri notkun hérlendis. Markmið þessarar greinar er að meta próffræðilega eiginleika kvarðans í íslenskum úrtökum með kerfisbundnu yfirliti. Af 2.873 heimildum, sem höfundar skimuðu, stóðu 28 heimildir eftir um próffræðilega eiginleika CDI á Íslandi. Niðurstöður voru almennt svipaðar og erlendis. Eins og búast mátti við mældist meðaltal hærra í klínískum úrtökum en almennum og stúlkur skoruðu hærra en drengir. Innra samræmi heildartölu CDI var nokkuð hátt bæði í almennu og klínísku úrtaki. Samleitniréttmæti kom vel út þar sem CDI var með háa fylgni við aðra þunglyndiskvarða en niðurstöður rannsókna á aðgreiningarréttmæti voru ekki allar á sama máli þar sem fylgni CDI sýndi í sumum tilvikum háa fylgni við kvíðakvarða en í öðrum lága fylgni. Í einni rannsókn með innlagnarúrtaki úr BUGL kom í ljós að forspárréttmæti CDI var gott við alvarlega þunglyndisgreiningu DSM-IV en ekki við þunglyndisgreiningu ICD-10. Niðurstöður tveggja leitandi þáttagreininga sýndu að atriði hlóðust á þrjá þætti en ekki fimm eins og niðurstöður í stöðlunarúrtaki bentu til. Þörf er á frekari rannsóknum á forspárréttmæti, til dæmis á heilsugæslustöðvum og á göngudeildarúrtaki á BUGL. Mikilvægt er að kanna forspárréttmæti betur til að kanna notagildi til skimunar á börnum með þunglyndi. Einnig er þörf á frekari rannsóknum á staðfestandi þáttagreiningu og engar rannsóknir fundust á endurtektaráreiðanleika í íslensku úrtaki. Almennt virðast próffræðilegir eiginleikar CDI vera viðunandi miðað við sambærilega kvarða sem notaðir eru hérlendis. Helstu styrkleikar eru innra samræmi og hátt samleitniréttmæti. Efnisorð: þunglyndiskvarði fyrir börn, þunglyndi, Children’s Depression Inventory, CDI, kerfisbundið yfirlit, próffræðilegir eiginleikar, íslensk börn.
  • Hugfræði og skynjunarvísindi í íslömskum vísindaheimi miðalda

    Árni Kristjánsson; Háskóli Íslands (Sálfræðingafélag Íslands, 2020)
    Aristóteles sagði að maðurinn mæti sjónskynjun öðrum skynfærum meira. Í gegnum heimspekiog vísindasöguna hefur miklum tíma verið varið í rannsóknir á sjónskynjun og eru rannsóknir og kenningar Keplers oft nefndar sem upphafspunktur nútímasjónskynjunarvísinda. En í þeirri frásögn er horft fram hjá merku framlagi vísindamanna innan íslamska menningarheimsins á miðöldum. Íslamskir vísindamenn varðveittu ekki einungis þekkingu Forn-Grikkja, heldur bættu þeir miklu við hana. Vísindamenn eins og Ibn-Ishaq, Al-Kindí, Avicenna og þó sér í lagi Alhazen lögðu mikið af mörkum til skilnings á sjónskynjun og vísindagrein þeirri sem nú er kölluð hugfræði og höfðu mikil áhrif á sporgöngumenn sína á endurreisnartímanum, þar á meðal Kepler. Raunar er Bók um ljósfræði eftir Alhazen eitthvert merkasta rit um sjónskynjun sem komið hefur út. Alhazen kynnti til sögunnar hugmyndir um hvernig sólarljós endurvarpast í umhverfinu og berst inn í augað og hvernig ímynd varpast á ljósnæm svæði innan augans, auk þess sem bókin er líklega fyrsta heildstæða ritið um sálfræði skynjunar. Víðfræg lausn Keplers á gátunni um endurvarp ljóss á sjónbotninn endurspeglar áhrif Alhazens úr ritum vísindamanna á 13. og 14. öld sem höfðu aðgang að hugmyndum hans. Efnisorð: saga sálfræðinnar, íslömsk sálfræði, skynjunarvísindi.
  • Algengi líkamsskynjunarröskunar á Íslandi

    Hrefna Harðardóttir; Arna Hauksdóttir; Heiðrún Hlöðversdóttir; Unnur Anna Valdimarsdóttir; Andri Steinþór Björnsson; Háskóli Íslands (Sálfræðingafélag Íslands, 2021)
    Líkamsskynjunarröskun (LSR; e. body dysmorphic disorder) er geðröskun sem einkennist af þráhyggju um útlitsgalla sem er ekki til staðar. Þessum hugsunum fylgir mikil vanlíðan og skerðing á virkni. Megintilgangur rannsóknarinnar var að (a) meta algengi LSR í almennu úrtaki á Íslandi og (b) bera saman bakgrunn og klínísk einkenni þeirra sem skimast með LSR við þá sem skimast með almenna kvíðaröskun (AKR) og þátttakendur sem ekki skimast með einkenni þessara geðraskana (samanburðarhópur). Þátttakendur voru 854. Alls skimuðust 34 (4%) þátttakendur með LSR (88% konur) og 50 (6%) með AKR (64% konur). Þátttakendur sem skimuðust með LSR voru líklegri til að vera einhleypir, atvinnulausir og í veikindaleyfi eða öryrkjar en þátttakendur án LSR eða AKR. Þeir sem skimuðust með LSR sýndu jafnframt fleiri einkenni þunglyndis og streitu en einstaklingar í samanburðarhópi og voru líklegri til að hafa sjálfsvígshugsanir og að hafa gert tilraun til sjálfsvígs. Að jafnaði var ekki munur á hópunum sem skimuðust með LSR og AKR en þó var hærra hlutfall einstaklinga, sem skimuðust með LSR, sem hafði gert sjálfsvígstilraun. Niðurstöður benda til þess að LSR sé algeng geðröskun í almennu þýði sem hafi margvísleg neikvæð áhrif á líf fólks. Það er mikilvægt að auka þekkingu meðal almennings og heilbrigðisstarfsfólks á LSR, helstu einkennum hennar og viðeigandi meðferð við röskuninni. Efnisorð: líkamsskynjunarröskun, útlitsgallar, algengi, skimun, almenn kvíðaröskun.

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