The Importance of Early Diagnosis and Treatment of Postpartum Depression

Postpartum depression (PPD) is a major depressive episode following childbirth that can have serious consequences affecting the family. Consequences range from marital problems and issues with child development to maternal suicide and infantcide. Depression in mothers can lead to cognitive and social impairment in the child as well as paternal postpartum depression in the father. Due to the severity of these problems, it is important to diagnose and treat mothers as soon as possible. There are several symptoms that are evident in mothers suffering from PPD that lead to diagnosis. Symptoms are similar to those of major depressive episodes, but they occur 24 hours to several months postpartum. Treatment options for PPD include psychotherapy as well as tricyclic antidepressants and selective serotonin reuptake inhibitors. While these medications have been shown to be the most effective pharmacological options, more research needs to be conducted to establish their effects on the infants. The possibility of preventative therapy also needs to be addressed to minimize the long-term effects of the disorder

Treatment Options for Seasonal Affective Disorder

Many patients who have undiagnosed Seasonal Affective Disorder (SAD) may come into the pharmacy to try to self-treat their symptoms with over-the-counter and herbal drugs. Often, patients don\u27t recognize their symptoms as a true depressive disorder since they are not constant. The pharmacist has the opportunity to talk to these patients, educate them on the disease state and explain that they do have options, both pharmacologic and non-pharmacologic. It also is important for pharmacists to point out any interactions that the herbal or over-the-counter medications may have with other medications and to refer patients to their physician for further treatment. Currently, the Diagnostic and Statistical Manual for Mental Disorders (DSM) IV does not recognize SAD as a separate disorder but rather a specifier of Major Depressive Disorder (MDD). However, there are currently recommendations to include SAD as a distinct disorder in DSM V, which is to be released in May 2013

The Use of Propranolol in the Treatment of Posttraumatic Stress Disorder

This article examines the rising issue of post-traumatic stress disorder (PTSD) and possible treatment options. PTSD is a behavioral disorder resulting from memory formation and association with a traumatic event. A search of the published literature reveals several positive studies and case reports suggesting that propranolol, a beta adrenergic receptor antagonist, may be useful for both treatment and prevention of PTSD. Additionally, current studies are being completed in different population groups to determine the overall effectiveness and mechanism by which propranolol is able to provide relief from certain symptoms common to the disorder. This article discusses the medical evidence and possible treatment role of propranolol for patients suffering from PTSD

Quantifying n-Photon Indistinguishability with a Cyclic Integrated Interferometer

We report on a universal method to measure the genuine indistinguishability of n photons—a crucial parameter that determines the accuracy of optical quantum computing. Our approach relies on a low-depth cyclic multiport interferometer with N=2n modes, leading to a quantum interference fringe whose visibility is a direct measurement of the genuine n-photon indistinguishability. We experimentally demonstrate this technique for an eight-mode integrated interferometer fabricated using femtosecond laser micromachining and four photons from a quantum dot single-photon source. We measure a fourphoton indistinguishability up to 0.81 +- 0.03. This value decreases as we intentionally alter the photon pairwise indistinguishability. The low-depth and low-loss multiport interferometer design provides an original path to evaluate the genuine indistinguishability of resource states of increasing photon number

Genomic landscape of follicular lymphoma across a wide spectrum of clinical behaviors

While some follicular lymphoma (FL) patients do not require treatment or experience prolonged responses, others relapse early, and little is known about genetic alterations specific to patients with a particular clinical behavior. We selected 56 grade 1–3A FL patients according to their need of treatment or timing of relapse: never treated (n = 7), non-relapsed (19), late relapse (14), early relapse or POD24 (11), and primary refractory (5). We analyzed 56 diagnostic and 12 paired relapse lymphoid tissue biopsies and performed copy number alteration (CNA) analysis and next generation sequencing (NGS). We identified six focal driver losses (1p36.32, 6p21.32, 6q14.1, 6q23.3, 9p21.3, 10q23.33) and 1p36.33 copy-neutral loss of heterozygosity (CN-LOH). By integrating CNA and NGS results, the most frequently altered genes/regions were KMT2D (79%), CREBBP (67%), TNFRSF14 (46%) and BCL2 (40%). Although we found that mutations in PIM1, FOXO1 and TMEM30A were associated with an adverse clinical behavior, definitive conclusions cannot be drawn, due to the small sample size. We identified common precursor cells harboring early oncogenic alterations of the KMT2D, CREBBP, TNFRSF14 and EP300 genes and 16p13.3-p13.2 CN-LOH. Finally, we established the functional consequences of mutations by means of protein modeling (CD79B, PLCG2, PIM1, MCL1 and IRF8). These data expand the knowledge on the genomics behind the heterogeneous FL population and, upon replication in larger cohorts, could contribute to risk stratification and the development of targeted therapies.This study was supported by Marató TV3-Cancer (201904-30 to SB), Fundación Asociación Española Contra el Cancer AECC/CIBERONC: PROYE18020BEA (to SB), Generalitat de Catalunya Suport Grups de Recerca AGAUR (2021-SGR-01293 to S.B.), Fondo de Investigaciones Sanitarias, Instituto de Salud Carlos III, “Cofinanciado por la Unión Europea” and Fondos FEDER: European Regional Development Fund “Una manera de hacer Europa”: PI17/01061 (SB), PI19/00887 (ALG and EG), INT20/00050 to AL-G). CL is supported by postdoctoral Beatriu de Pinós grant from Secretaria d’Universitats i Recerca del Departament d’Empresa i Coneixement de la Generalitat de Catalunya and by Marie Sklodowska-Curie COFUND program from H2020 (2018-BP-00055). EC is an Academia Researcher of the “Institució Catalana de Recerca i Estudis Avançats” of the Generalitat de Catalunya. This work was mainly developed at the Centre Esther Koplowitz (CEK), Barcelona, Spain.Peer reviewe

A gene-expression profiling score for prediction of outcome in patients with follicular lymphoma: a retrospective training and validation analysis in three international cohorts

Patients with follicular lymphoma (FL) have heterogeneous outcomes. Predictor models able to distinguish, at diagnosis, patients at high versus low risk of progression are still needed. A training set of fresh-frozen tumour biopsies was prospectively obtained from 160 untreated patients with high-tumour-burden follicular lymphoma enrolled in the phase 3 randomised PRIMA trial, in which rituximab maintenance was evaluated after rituximab plus chemotherapy induction (median follow-up 6·6 years [IQR 6·0-7·0]). RNA of sufficient quality was obtained for 149 of 160 cases, and Affymetrix U133 Plus 2.0 microarrays were used for gene-expression profiling. We did a multivariate Cox regression analysis to identify genes with expression levels associated with progression-free survival independently of maintenance treatment in a subgroup of 134 randomised patients. Expression levels from 95 curated genes were then determined by digital expression profiling (NanoString technology) in 53 formalin-fixed paraffin-embedded samples of the training set to compare the technical reproducibility of expression levels for each gene between technologies. Genes with high correlation (>0·75) were included in an L2-penalised Cox model adjusted on rituximab maintenance to build a predictive score for progression-free survival. The model was validated using NanoString technology to digitally quantify gene expression in 488 formalin-fixed, paraffin-embedded samples from three independent international patient cohorts from the PRIMA trial (n=178; distinct from the training cohort), the University of Iowa/Mayo Clinic Lymphoma SPORE project (n=201), and the Barcelona Hospital Clinic (n=109). All tissue samples consisted of pretreatment diagnostic biopsies and were confirmed as follicular lymphoma grade 1-3a. The patients were all treated with regimens containing rituximab and chemotherapy, possibly followed by either rituximab maintenance or ibritumomab-tiuxetan consolidation. We determined an optimum threshold on the score to predict patients at low risk and high risk of progression. The model, including the multigene score and the threshold, was initially evaluated in the three validation cohorts separately. The sensitivity and specificity of the score for the prediction of the risk of lymphoma progression at 2 years were assessed on the combined validation cohorts. FINDINGS: In the training cohort, the expression levels of 395 genes were associated with a risk of progression. 23 genes reflecting both B-cell biology and tumour microenvironment with correlation coefficients greater than 0·75 between the two technologies and sample types were retained to build a predictive model that identified a population at an increased risk of progression (p<0·0001). In a multivariate Cox model for progression-free survival adjusted on rituximab maintenance treatment and Follicular Lymphoma International Prognostic Index 1 (FLIPI-1) score, this predictor independently predicted progression (adjusted hazard ratio [aHR] of the high-risk group compared with the low-risk group 3·68, 95% CI 2·19-6·17 [p<0·0001]). The 5-year progression-free survival was 26% (95% CI 16-43) in the high-risk group and 73% (64-83) in the low-risk group. The predictor performances were confirmed in each of the individual validation cohorts (aHR comparing high-risk to low-risk groups 2·57 [95% CI 1·65-4·01] in cohort 1; 2·12 [1·32-3·39] in cohort 2; and 2·11 [1·01-4·41] in cohort 3). In the combined validation cohort, the median progression-free survival was 3·1 years (95% CI 2·4-4·8) in the high-risk group and 10·8 years (10·1-not reached) in the low-risk group (p<0·0001). The risk of lymphoma progression at 2 years was 38% (95% CI 29-46) in the high-risk group and 19% (15-24) in the low-risk group. In a multivariate analysis, the score predicted progression-free survival independently of anti-CD20 maintenance treatment and of the FLIPI score (aHR for the combined cohort 2·30, 95% CI 1·72-3·07). INTERPRETATION: We developed and validated a robust 23-gene expression-based predictor of progression-free survival that is applicable to routinely available formalin-fixed, paraffin-embedded tumour biopsies from patients with follicular lymphoma at time of diagnosis. Applying this score could allow individualised therapy for patients according to their risk category

EZH2 alterations in follicular lymphoma: biological and clinical correlations

International audienceThe histone methyltransferase EZH2 has an essential role in the development of follicular lymphoma (FL). Recurrent gain-of-function mutations in EZH2 have been described in 25% of FL patients and induce aberrant methylation of histone H3 lysine 27 (H3K27). We evaluated the role of EZH2 genomic gains in FL biology. Using RNA sequencing, Sanger sequencing and SNP-arrays, the mutation status, copy-number and gene-expression profiles of EZH2 were assessed in a cohort of 159 FL patients from the PRIMA trial. Immunohistochemical (IHC) EZH2 expression (n = 55) and H3K27 methylation (n = 63) profiles were also evaluated. In total, 37% of patients (59/159) harbored an alteration in the EZH2 gene (mutation n = 46, gain n = 23). Both types of alterations were associated with highly similar transcriptional changes, with increased proliferation programs. An H3K27me3/me2 IHC score fully distinguished mutated from wild-type samples, showing its applicability as surrogate for EZH2 mutation analysis. However, this score did not predict the presence of gains at the EZH2 locus. The presence of an EZH2 genetic alteration was an independent factor associated with a longer progression-free survival (hazard ratio 0.58, 95% confidence interval 0.36–0.93, P = 0.025). We propose that the copy-number status of EZH2 should also be considered when evaluating patient stratification and selecting patients for EZH2 inhibitor-targeted therapies

Clinical reappraisal of SHORT syndrome with PIK3R1 mutations: towards recommendation for molecular testing and management

International audienceSHORT syndrome has historically been defined by its acronym: short stature (S), hyperextensibility of joints and/or inguinal hernia (H), ocular depression (O), Rieger abnormality (R) and teething delay (T). More recently several research groups have identified PIK3R1 mutations as responsible for SHORT syndrome. Knowledge of the molecular etiology of SHORT syndrome has permitted a reassessment of the clinical phenotype. The detailed phenotypes of 32 individuals with SHORT syndrome and PIK3R1 mutation, including eight newly ascertained individuals, were studied to fully define the syndrome and the indications for PIK3R1 testing. The major features described in the SHORT acronym were not universally seen and only half (52%) had 4 or more of the classic features. The commonly observed clinical features of SHORT syndrome seen in the cohort included IUGR \textless 10(th) percentile, postnatal growth restriction, lipoatrophy and the characteristic facial gestalt. Anterior chamber defects and insulin resistance or diabetes were also observed but were not as prevalent. The less specific, or minor features of SHORT syndrome include teething delay, thin wrinkled skin, speech delay, sensorineural deafness, hyperextensibility of joints and inguinal hernia. Given the high risk of diabetes mellitus, regular monitoring of glucose metabolism is warranted. An echocardiogram, ophthalmological and hearing assessments are also recommended

The Role of Practice Research Networks (PRN) in the Development and Implementation of Evidence: The Northern Improving Access to Psychological Therapies PRN Case Study

Practice research networks (PRNs) can support the implementation of evidence based practice in routine services and generate practice based evidence. This paper describes the structure, processes and learning from a new PRN in the Improving Access to Psychological Therapies programme in England, in relation to an implementation framework and using one study as a case example. Challenges related to: ethics and governance processes; communications with multiple stakeholders; competing time pressures and linking outcome data. Enablers included: early tangible outputs and impact; a collaborative approach; engaging with local research leads; clarity of processes; effective dissemination; and committed leadership

Utilization of mechanical power and associations with clinical outcomes in brain injured patients: a secondary analysis of the extubation strategies in neuro-intensive care unit patients and associations with outcome (ENIO) trial

Background: There is insufficient evidence to guide ventilatory targets in acute brain injury (ABI). Recent studies have shown associations between mechanical power (MP) and mortality in critical care populations. We aimed to describe MP in ventilated patients with ABI, and evaluate associations between MP and clinical outcomes. Methods: In this preplanned, secondary analysis of a prospective, multi-center, observational cohort study (ENIO, NCT03400904), we included adult patients with ABI (Glasgow Coma Scale ≤ 12 before intubation) who required mechanical ventilation (MV) ≥ 24&nbsp;h. Using multivariable log binomial regressions, we separately assessed associations between MP on hospital day (HD)1, HD3, HD7 and clinical outcomes: hospital mortality, need for reintubation, tracheostomy placement, and development of acute respiratory distress syndrome (ARDS). Results: We included 1217 patients (mean age 51.2&nbsp;years [SD 18.1], 66% male, mean body mass index [BMI] 26.3 [SD 5.18]) hospitalized at 62 intensive care units in 18 countries. Hospital mortality was 11% (n = 139), 44% (n = 536) were extubated by HD7 of which 20% (107/536) required reintubation, 28% (n = 340) underwent tracheostomy placement, and 9% (n = 114) developed ARDS. The median MP on HD1, HD3, and HD7 was 11.9&nbsp;J/min [IQR 9.2-15.1], 13&nbsp;J/min [IQR 10-17], and 14&nbsp;J/min [IQR 11-20], respectively. MP was overall higher in patients with ARDS, especially those with higher ARDS severity. After controlling for same-day pressure of arterial oxygen/fraction of inspired oxygen (P/F ratio), BMI, and neurological severity, MP at HD1, HD3, and HD7 was independently associated with hospital mortality, reintubation and tracheostomy placement. The adjusted relative risk (aRR) was greater at higher MP, and strongest for: mortality on HD1 (compared to the HD1 median MP 11.9&nbsp;J/min, aRR at 17&nbsp;J/min was 1.22, 95% CI 1.14-1.30) and HD3 (1.38, 95% CI 1.23-1.53), reintubation on HD1 (1.64; 95% CI 1.57-1.72), and tracheostomy on HD7 (1.53; 95%CI 1.18-1.99). MP was associated with the development of moderate-severe ARDS on HD1 (2.07; 95% CI 1.56-2.78) and HD3 (1.76; 95% CI 1.41-2.22). Conclusions: Exposure to high MP during the first week of MV is associated with poor clinical outcomes in ABI, independent of P/F ratio and neurological severity. Potential benefits of optimizing ventilator settings to limit MP warrant further investigation