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48051.
  • Landén, Amalia H, et al. (författare)
  • Evaluation of tumor-infiltrating lymphocytes and mammographic density as predictors of response to neoadjuvant systemic therapy in breast cancer.
  • 2023
  • Ingår i: Acta oncologica (Stockholm, Sweden). - 1651-226X. ; 62:12, s. 1862-1872
  • Tidskriftsartikel (refereegranskat)abstract
    • Response rates vary among breast cancer patients treated with neoadjuvant systemic therapy (NAST). Thus, there is a need for reliable treatment predictors. Evidence suggests tumor-infiltrating lymphocytes (TILs) predict NAST response. Still, TILs are seldom used clinically as a treatment determinant. Mammographic density (MD) is another potential marker for NAST benefit and its relationship with TILs is unknown. Our aims were to investigate TILs and MD as predictors of NAST response and to study the unexplored relationship between TILs and MD.We studied 315 invasive breast carcinomas treated with NAST between 2013 and 2020. Clinicopathological data were retrieved from medical records. The endpoint was defined as pathological complete response (pCR) in the breast. TILs were evaluated in pre-treatment core biopsies and categorized as high (≥10%) or low (<10%). MD was scored (a-d) according to the breast imaging reporting and data system (BI-RADS) fifth edition. Binary logistic regression and Spearman's test of correlation were performed using SPSS.Out of 315 carcinomas, 136 achieved pCR. 94 carcinomas had high TILs and 215 had low TILs. Six carcinomas had no available TIL data. The number of carcinomas in each BI-RADS category were 37, 122, 112, and 44 for a, b, c, and d, respectively. High TILs were independently associated with pCR (OR: 2.95; 95% CI: 1.59-5.46) compared to low TILs. In the univariable analysis, MD (BI-RADS d vs. a) showed a tendency of higher likelihood for pCR (OR: 2.43; 95% CI: 0.99-5.98). However, the association was non-significant, which is consistent with the result of the multivariable analysis (OR: 2.51; 95% CI: 0.78-8.04). We found no correlation between TILs and MD (0.02; p=.80).TILs significantly predicted NAST response. We could not define MD as a significant predictor of NAST response. These findings should be further replicated.
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48052.
  • Landén, Mikael, 1966, et al. (författare)
  • Brain aging in major depressive disorder: results from the ENIGMA major depressive disorder working group
  • 2021
  • Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 26, s. 5124-5139
  • Tidskriftsartikel (refereegranskat)abstract
    • Major depressive disorder (MDD) is associated with an increased risk of brain atrophy, aging-related diseases, and mortality. We examined potential advanced brain aging in adult MDD patients, and whether this process is associated with clinical characteristics in a large multicenter international dataset. We performed a mega-analysis by pooling brain measures derived from T1-weighted MRI scans from 19 samples worldwide. Healthy brain aging was estimated by predicting chronological age (18–75 years) from 7 subcortical volumes, 34 cortical thickness and 34 surface area, lateral ventricles and total intracranial volume measures separately in 952 male and 1236 female controls from the ENIGMA MDD working group. The learned model coefficients were applied to 927 male controls and 986 depressed males, and 1199 female controls and 1689 depressed females to obtain independent unbiased brain-based age predictions. The difference between predicted “brain age” and chronological age was calculated to indicate brain-predicted age difference (brain-PAD). On average, MDD patients showed a higher brain-PAD of +1.08 (SE 0.22) years (Cohen’s d = 0.14, 95% CI: 0.08–0.20) compared with controls. However, this difference did not seem to be driven by specific clinical characteristics (recurrent status, remission status, antidepressant medication use, age of onset, or symptom severity). This highly powered collaborative effort showed subtle patterns of age-related structural brain abnormalities in MDD. Substantial within-group variance and overlap between groups were observed. Longitudinal studies of MDD and somatic health outcomes are needed to further assess the clinical value of these brain-PAD estimates. © 2020, The Author(s).
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48053.
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48054.
  • Landén, Mikael, 1966, et al. (författare)
  • Compounds with affinity for serotonergic receptors in the treatment of premenstrual dysphoria: a comparison of buspirone, nefazodone and placebo.
  • 2001
  • Ingår i: Psychopharmacology. - 0033-3158. ; 155:3, s. 292-8
  • Tidskriftsartikel (refereegranskat)abstract
    • RATIONALE: It is well established that serotonin reuptake inhibitors (SRIs) are effective for the treatment of premenstrual dysphoria (PMD), but the receptor subtype(s) mediating this effect of serotonin have yet not been identified. OBJECTIVE: In this trial, the possible efficacy of buspirone, a partial 5HT1A receptor agonist, and nefazodone, a combined SRI and 5HT2 receptor antagonist, was evaluated in women with PMD. METHODS: After a three-menstrual-cycle screening phase, patients were randomised to buspirone (n=19), nefazodone (n=22) or placebo (n=22). During the first two treatment cycles, patients were taking the drug during the luteal phase only (mean +/- SD daily dose of buspirone: 21 +/- 6 mg; nefazodone: 228 +/- 54 mg). During the subsequent two cycles, the medication was taken each day of the menstrual cycle (mean daily dose of buspirone: 27 +/- 10 mg; nefazodone: 304 +/- 95 mg). RESULTS: With respect to self-rated global improvement, buspirone (P<0.001) but not nefazodone was significantly superior to placebo. While buspirone appeared to reduce self-rated irritability (visual analogue scale) more effectively than placebo, other self-rated symptoms did not differ markedly between the groups. The side-effects were mild, and sexual dysfunction was not significantly more common in patients given buspirone or nefazodone than in those given placebo. CONCLUSION: It is suggested that buspirone is mildly effective for premenstrual irritability. In patients experiencing sexual dysfunction when treated with an SRI, buspirone may be a useful alternative.
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48055.
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48056.
  • Landén, Mikael, 1966, et al. (författare)
  • Dyslipidemia and high waist-hip ratio in women with self-reported social anxiety.
  • 2004
  • Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530. ; 29:8, s. 1037-46
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous research has indicated that phobic anxiety is associated with coronary heart disease. In this study, the possible association between social anxiety and various anthropometric, metabolic, and endocrine measurements known to be associated with cardiovascular disease were studied in a population-based cohort of 216 women 41-42 years old. Each participant was assessed by means of a DSM-IV based self-report questionnaire regarding social anxiety and related psychiatric diagnoses. Waist-to-hip ratio (WHR), body mass index (BMI), and serum levels of lipids and hormones were assessed. The prevalence of social anxiety was 14% (n=31). The social anxiety group displayed higher serum levels of triglycerides (1.3+/-0.9 vs. 1.0+/-0.5, P=0.003) and low-density lipoprotein (LDL) (3.3+/-0.8 vs. 3.0+/-0.7, P=0.03), but lower high-density lipoprotein (HDL) (1.4+/-0.3 vs. 1.6+/-0.4, P=0.04) and HDL/LDL ratio (0.46+/-0.15 vs. 0.57+/-0.22, P=0.008) than the other women. Serum levels of total testosterone (1.6+/-0.8 vs. 2.2+/-1.1, P=0.013) and free thyroxin (14+/-2 vs. 16+/-4, P=0.04) were lower in subjects confirming social anxiety. While WHR was significantly higher in the social anxiety group (0.83+/-0.06 vs. 0.80+/-0.07, P=0.016), BMI did not differ between the groups. Our data suggest that self-reported social anxiety is associated with two established risk factors for cardiovascular disease: dyslipidemia and increased WHR.
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48057.
  • Landén, Mikael, 1966, et al. (författare)
  • Heart rate variability in premenstrual dysphoric disorder.
  • 2004
  • Ingår i: Psychoneuroendocrinology. - 0306-4530. ; 29:6, s. 733-40
  • Tidskriftsartikel (refereegranskat)abstract
    • Measuring heart rate variability (HRV) is a way to assess the autonomic regulation of the heart. Decreased HRV, indicating reduced parasympathetic tone, has previously been found in depression and anxiety disorders. The objective of this study was to assess HRV in women with premenstrual dysphoric disorder (PMDD). To this end, time domain variables and frequency domain variables were assessed in 28 women with PMDD and in 11 symptom-free controls during both the symptomatic luteal phase and the non-symptomatic follicular phase of the menstrual cycle. Two variables reflecting vagal activity in the time domain, the root mean square of differences of successive normal RR intervals (rMSSD) and standard deviation of normal RR intervals (SDNN) were lower in PMDD patients, but this difference was statistically significant in the follicular phase only. The most important vagal measure in the frequency domain, supine high frequency (HF), also appeared lower in PMDD subjects during the follicular phase. It is suggested that PMDD may be associated with reduced vagal tone compared to controls and that this difference is most apparent in the non-symptomatic follicular phase of the menstrual cycle.
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48058.
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48059.
  • Landén, Mikael, 1966, et al. (författare)
  • Placebo-controlled trial comparing intermittent and continuous paroxetine in premenstrual dysphoric disorder.
  • 2007
  • Ingår i: Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology. - : Springer Science and Business Media LLC. - 0893-133X. ; 32:1, s. 153-61
  • Tidskriftsartikel (refereegranskat)abstract
    • Serotonin reuptake inhibitors (SRIs) do not have to be administered continuously to be effective for premenstrual dysphoric disorder (PMDD), but can be given during luteal phases only. This is of practical importance, but also of theoretical interest since it suggests that the onset of action of SRIs is shorter in PMDD than in, for example depression. In this study, both continuous and intermittent SRI administration was compared with placebo, with the special purpose of analyzing if different PMDD symptoms respond differently depending on the treatment regimen. To this end, women meeting slightly modified DSM-IV criteria for PMDD (mean+/-SD age, 37+/-6.3 years) were treated for three menstrual cycles with paroxetine continuously, paroxetine during the luteal phase only, or placebo, the population completing at least one treatment cycle comprising 55-56 subjects per group. Continuous treatment with paroxetine reduced premenstrual symptoms effectively with a response rate of 85%. The effect size was highest for irritability (1.4) and lowest for lack of energy (0.5). Intermittent treatment was as effective as continuous treatment in reducing irritability, affect lability, and mood swings, but had a somewhat weaker effect on depressed mood and somatic symptoms. The study indicates that the response rate when treating PMDD with SRIs is high, and that irritability is a key target symptom. Symptoms such as irritability, affect lability, and mood swings appear to be more inclined to respond rapidly to SRIs, enabling intermittent treatment, than are, for example, the somatic symptoms.
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48060.
  • Landén, Mikael, 1966, et al. (författare)
  • Respiratory infections during lithium and valproate medication: a within-individual prospective study of 50,000 patients with bipolar disorder
  • 2021
  • Ingår i: International Journal of Bipolar Disorders. - : Springer Science and Business Media LLC. - 2194-7511. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background In vitro studies have demonstrated that lithium has antiviral properties, but evidence from human studies is scarce. Lithium is used as a mood stabilizer to treat patients with bipolar disorder. Here, the aim was to investigate the association between lithium use and the risk of respiratory infections in patients with bipolar disorder. To rule out the possibility that a potential association could be due to lithium's effect on psychiatric symptoms, we also studied the effect of valproate, which is an alternative to lithium used to prevent mood episodes in bipolar disorder. Method We followed 51,509 individuals diagnosed with bipolar disorder in the Swedish Patient register 2005-2013. We applied a within-individual design using stratified Cox regression to estimate the hazard ratios (HRs) of respiratory infections during treated periods compared with untreated periods. Results During follow-up, 5,760 respiratory infections were documented in the Swedish Patient Register. The incidence rate was 28% lower during lithium treatment (HR 0.73, 95% CI 0.61-0.86) and 35% higher during valproate treatment (HR 1.35, 95% CI 1.06-1.73) compared with periods off treatment. Conclusions This study provides real-world evidence that lithium is associated with decreased risk for respiratory infections and suggests that the repurposing potential of lithium for potential antiviral or antibacterial effects is worthy of investigation.
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