Large Particle Fluorescence-Activated Cell Sorting Enables High-Quality Single-Cell RNA Sequencing and Functional Analysis of Adult Cardiomyocytes.
Circ Res. 2019 08 16;125(5):567-569
Authors: Kannan S, Miyamoto M, Lin BL, Zhu R, Murphy S, Kass DA, Andersen P, Kwon C
PMID: 31415233 [PubMed - indexed for MEDLINE]
Cooperation of oncolytic virotherapy with VEGF-neutralizing antibody treatment in IDH wildtype glioblastoma depends on MMP9.
Neuro Oncol. 2019 12 17;21(12):1607-1609
Authors: Wirsching HG, Arora S, Zhang H, Szulzewsky F, Cimino PJ, Quéva C, Houghton AM, Glorioso JC, Weller M, Holland EC
PMID: 31412117 [PubMed - indexed for MEDLINE]
Impact of Telephone-Based Problem-Solving Treatment on the Use of Medical and Psychological Services in the Military.
J Head Trauma Rehabil. 2018 Mar/Apr;33(2):E1-E6
Authors: Richardson JS, Fann JR, Bell KR, Temkin N
Abstract
OBJECTIVE: To explore the impact of problem-solving treatment (PST) for mild traumatic brain injury in active duty service members on the use of medical and psychological services.
PARTICIPANTS: Service members who had a mild traumatic brain injury during their last deployment and enrolled in the CONcussion Treatment After Combat Trauma (CONTACT) study.
DESIGN: Secondary analysis of a randomized clinical trial. Participants were assigned to telephone-based PST, or e-mailed or mailed education only over the course of 6 months.
MAIN MEASURE: Self-reported health service utilization from months 4 through 6 and 10 through 12 after initiation of treatment, using the Cornell Service Index.
RESULTS: In months 4 to 6, participants receiving PST had 6.17 times the odds of an emergency department visit or hospitalization than those receiving education only (95% confidence interval = 1.92-19.8; P value = .0023). These estimates, however, were not significant using a conservative Bonferroni correction (P value threshold < .0014). There were no other significant differences for other medical or psychological services received in months 4 to 6 or 10 to 12.
CONCLUSION: Telephone-based PST was designed to complement clinical care, and this study showed that it may increase emergency department utilization. Future evaluations of PST with more accurate and complete measures of health service utilization are needed.
PMID: 28422894 [PubMed - indexed for MEDLINE]
Improving Provider Readiness for Intimate Partner Violence Screening.
Worldviews Evid Based Nurs. 2019 Jun;16(3):204-210
Authors: Lee ASD, McDonald LR, Will S, Wahab M, Lee J, Coleman JS
Abstract
BACKGROUND: Intimate partner violence (IPV) is a significant public health issue. Healthcare providers (e.g., nurses, advanced practice nurses, physicians, social workers) have a unique opportunity to prevent and reduce IPV through screening and referral. The objective of this project was to determine the impact of education and a brief screening tool integrated into the electronic medical record (EMR) on readiness to screen for IPV.
METHODS: An intervention was implemented that included the EMR integration of a screening tool, creation of an automated resource telephone system and healthcare provider IPV screening and response education. Readiness for screening was evaluated pre- and postintervention using the Domestic Violence Health Care Provider Survey Scale (DVHCPSS), which is scored cumulatively and by each of six domains. An unpaired Student's t test was performed.
RESULTS: Mean age (31-40 years of age) and years of clinical practice (11-15 years) was the same for pre- (n = 96) and postintervention (n = 83) survey respondents. There was an overall significant increase in screening readiness (p = .003) with significant improvement in "professional role resistance/fear of offending the patient" (p < .0001), "blame victim items" (p = .0029), "perceived self-efficacy" (p = .0064), and "victim/provider safety" (p = .003).
LINKING EVIDENCE TO ACTION: Adopting and integrating a validated IPV screening tool into the EMR combined with education was associated with an improvement in overall readiness for IPV screening. Reducing and preventing IPV through universal screening and referral can be accomplished by embedding a standardized readily accessible validated IPV screening tool in the EMR.
PMID: 31012540 [PubMed - indexed for MEDLINE]
Defined neuronal populations drive fatal phenotype in a mouse model of Leigh syndrome.
Elife. 2019 08 12;8:
Authors: Bolea I, Gella A, Sanz E, Prada-Dacasa P, Menardy F, Bard AM, Machuca-Márquez P, Eraso-Pichot A, Mòdol-Caballero G, Navarro X, Kalume F, Quintana A
Abstract
Mitochondrial deficits in energy production cause untreatable and fatal pathologies known as mitochondrial disease (MD). Central nervous system affectation is critical in Leigh Syndrome (LS), a common MD presentation, leading to motor and respiratory deficits, seizures and premature death. However, only specific neuronal populations are affected. Furthermore, their molecular identity and their contribution to the disease remains unknown. Here, using a mouse model of LS lacking the mitochondrial complex I subunit Ndufs4, we dissect the critical role of genetically-defined neuronal populations in LS progression. Ndufs4 inactivation in Vglut2-expressing glutamatergic neurons leads to decreased neuronal firing, brainstem inflammation, motor and respiratory deficits, and early death. In contrast, Ndufs4 deletion in GABAergic neurons causes basal ganglia inflammation without motor or respiratory involvement, but accompanied by hypothermia and severe epileptic seizures preceding death. These results provide novel insight in the cell type-specific contribution to the pathology, dissecting the underlying cellular mechanisms of MD.
PMID: 31403401 [PubMed - indexed for MEDLINE]
Mischaracterization of Spaceflight-Associated Neuro-ocular Syndrome.
JAMA Neurol. 2019 Aug 12;:
Authors: Williams MA, Malm J
PMID: 31403660 [PubMed - as supplied by publisher]
In Reply: The Spectrum of Trigeminal Neuralgia Without Neurovascular Compression.
Neurosurgery. 2019 10 01;85(4):E800-E801
Authors: Magown P, Ko AL, Burchiel KJ
PMID: 31407009 [PubMed - indexed for MEDLINE]
Dual recombinase fate mapping reveals a transient cholinergic phenotype in multiple populations of developing glutamatergic neurons.
J Comp Neurol. 2019 Aug 09;:
Authors: Nasirova N, Quina LA, Agosto-Marlin IM, Ramirez JM, Lambe EK, Turner EE
Abstract
Cholinergic transmission shapes the maturation of glutamatergic circuits, yet the developmental sources of acetylcholine have not been systematically explored. Here we have used Cre-recombinase mediated genetic labeling to identify and map both mature and developing CNS neurons that express choline acetyltransferase (ChAT). Correction of a significant problem with a widely used ChatCre transgenic line ensures that this map does not contain expression artifacts. ChatCre marks all known cholinergic systems in the adult brain, but also identifies several brain areas not usually regarded as cholinergic, including specific thalamic and hypothalamic neurons, the subiculum, the lateral parabrachial nucleus, the cuneate/gracilis nuclei, and the pontocerebellar system. This ChatCre fate map suggests transient developmental expression of a cholinergic phenotype in areas important for cognition, motor control, and respiration. We therefore examined expression of ChAT and the vesicular acetylcholine transporter (VAChT) in the embryonic and early postnatal brain to determine the developmental timing of this transient cholinergic phenotype, and found that it mirrored the establishment of relevant glutamatergic projection pathways. We then used an intersectional genetic strategy combining ChatCre with Vglut2Flp to show that these neurons adopt a glutamatergic fate in the adult brain. The transient cholinergic phenotype of these glutamatergic neurons suggests a homosynaptic source of acetylcholine for the maturation of developing glutamatergic synapses. These findings thus define critical windows during which specific glutamatergic circuits may be vulnerable to disruption by nicotine in utero, and suggest new mechanisms for pediatric disorders associated with maternal smoking, such as sudden infant death syndrome. This article is protected by copyright. All rights reserved.
PMID: 31396962 [PubMed - as supplied by publisher]
Multicenter validation of automated trajectories for selective laser amygdalohippocampectomy.
Epilepsia. 2019 09;60(9):1949-1959
Authors: Vakharia VN, Sparks RE, Li K, O'Keeffe AG, Pérez-García F, França LGS, Ko AL, Wu C, Aronson JP, Youngerman BE, Sharan A, McKhann G, Ourselin S, Duncan JS
Abstract
OBJECTIVE: Laser interstitial thermal therapy (LITT) is a novel minimally invasive alternative to open mesial temporal resection in drug-resistant mesial temporal lobe epilepsy (MTLE). The safety and efficacy of the procedure are dependent on the preplanned trajectory and the extent of the planned ablation achieved. Ablation of the mesial hippocampal head has been suggested to be an independent predictor of seizure freedom, whereas sparing of collateral structures is thought to result in improved neuropsychological outcomes. We aim to validate an automated trajectory planning platform against manually planned trajectories to objectively standardize the process.
METHODS: Using the EpiNav platform, we compare automated trajectory planning parameters derived from expert opinion and machine learning to undertake a multicenter validation against manually planned and implemented trajectories in 95 patients with MTLE. We estimate ablation volumes of regions of interest and quantify the size of the avascular corridor through the use of a risk score as a marker of safety. We also undertake blinded external expert feasibility and preference ratings.
RESULTS: Automated trajectory planning employs complex algorithms to maximize ablation of the mesial hippocampal head and amygdala, while sparing the parahippocampal gyrus. Automated trajectories resulted in significantly lower calculated risk scores and greater amygdala ablation percentage, whereas overall hippocampal ablation percentage did not differ significantly. In addition, estimated damage to collateral structures was reduced. Blinded external expert raters were significantly more likely to prefer automated to manually planned trajectories.
SIGNIFICANCE: Retrospective studies of automated trajectory planning show much promise in improving safety parameters and ablation volumes during LITT for MTLE. Multicenter validation provides evidence that the algorithm is robust, and blinded external expert ratings indicate that the trajectories are clinically feasible. Prospective validation studies are now required to determine if automated trajectories translate into improved seizure freedom rates and reduced neuropsychological deficits.
PMID: 31392717 [PubMed - indexed for MEDLINE]
Anatomical and functional outcomes following switching from aflibercept to ranibizumab in neovascular age-related macular degeneration in Europe: SAFARI study.
Br J Ophthalmol. 2020 04;104(4):493-499
Authors: Gale RP, Pearce I, Eter N, Ghanchi F, Holz FG, Schmitz-Valckenberg S, Balaskas K, Burton BJL, Downes SM, Eleftheriadis H, George S, Gilmour D, Hamilton R, Lotery AJ, Patel N, Prakash P, Santiago C, Thomas S, Varma D, Walters G, Williams M, Wolf A, Zakri RH, Igwe F, Ayan F
Abstract
BACKGROUND/AIMS: Prospective data on switching anti-vascular endothelial growth factors in patients with neovascular age-related macular degeneration (nAMD) who have previously shown no/partial response are limited. This prospective study assessed the effect of switching from aflibercept to ranibizumab on anatomical and functional outcomes in patients with persistent/recurrent disease activity.
METHODS: SAFARI (NCT02161575) was a 6-month, prospective, single-arm study conducted in the UK and Germany. Patients, meeting strict eligibility criteria for one of two subgroups (primary treatment failure or suboptimal treatment response), received 3 monthly intravitreal ranibizumab injections (0.5 mg). Thereafter, ranibizumab was administered pro re nata at monthly visits. The primary endpoint was change from baseline (CfB) to day 90 in central subfield retinal thickness (CSRT). Best-corrected visual acuity (BCVA) and retinal morphology parameters were assessed.
RESULTS: One hundred patients were enrolled (primary treatment failure, 1; suboptimal treatment response, 99). In the overall population, there was a significant CfB in median CSRT of -30.75 µm (95% CI -59.50,-20.50; p<0.0001) to day 90. Improvements were also observed in other quantitative and qualitative optical coherence tomography parameters. In Early Treatment Diabetic Retinopathy Study letters assessed by category, 55% and 59% of patients gained 0-≥15 letters versus baseline at day 90 and day 180, respectively. However, mean improvements in BCVA (CfB) to each time point were small (≤2 letters). No new safety signals were identified.
CONCLUSION: Switching from aflibercept to ranibizumab led to a significant improvement in CSRT, with ~60% experiencing stabilised/improved BCVA. Therefore, patients with nAMD who have shown a suboptimal response to aflibercept may benefit from switching to ranibizumab.
PMID: 31383649 [PubMed - indexed for MEDLINE]
Letter to the Editor. Microsurgery for basilar apex aneurysms in the modern era.
J Neurosurg. 2017 12;127(6):1468-1469
Authors: Morton RP, Kim LJ, Sekhar LN
PMID: 28799878 [PubMed - indexed for MEDLINE]
The benefit zone of full-endoscopic spine surgery.
J Spine Surg. 2019 Jun;5(Suppl 1):S41-S56
Authors: Hasan S, Härtl R, Hofstetter CP
Abstract
Minimally invasive spine procedures have undergone rapid development during the last decade. Efforts to decrease muscle crush injuries during prolonged retraction, avoid significant soft tissue stripping and minimize bony resection are surgical principles that are employed to prevent iatrogenic instability and provide patients with decreased post-operative pain and disability. Full-endoscopic spine surgery represents a tool for the spine surgeon to provide targeted access to spinal pathology utilizing these principles. Endoscopic techniques have seen over 30 years of evolution and innovation, however, early iterations of these techniques largely focused on transforaminal lumbar microdiscectomies. Currently, endoscopic techniques are utilized for approaching pathology in the cervical, thoracic and lumbar spine. There has been a growing body of literature that not only confirms the efficacy of these procedures but also underscores the advantages these procedures offer with respect to less morbidity and safer complication profiles. Endoscopic decompressions have been utilized in the settings of degenerative spinal stenosis, spondylolisthesis, scoliosis, previous fusion, tumor and infection. Furthermore, endoscopic interbody fusion has also been utilized in the lumbar spine as technology continues to advance. As technological innovation continues to facilitate reproducible surgical technique and expand the indications for use, we believe that endoscopic spine surgical techniques will provide surgeons with a more powerful and less morbid approach to spinal pathology that ultimately elevates the standard of care when treating our patients. We present a brief review of the history of endoscopic spine surgery, an overview of current techniques and review current outcomes of endoscopic spine surgical procedures in the context of an invasiveness/complexity index to elucidate the benefit zone of these newer techniques.
PMID: 31380492 [PubMed]
Influence of Commercial and Laboratory Diets on Growth, Body Composition, and Reproduction in the Zebrafish Danio rerio.
Zebrafish. 2019 12;16(6):508-521
Authors: Fowler LA, Williams MB, Dennis-Cornelius LN, Farmer S, Barry RJ, Powell ML, Watts SA
Abstract
The value of the zebrafish (Danio rerio) as a model organism continues to expand. In developing the model, current feeding practice in zebrafish laboratories includes the use of commercially available diets. In this study, we compared outcomes in growth, body composition, and reproduction among zebrafish fed five highly utilized commercial diets and one formulated chemically defined reference diet. Wild-type zebrafish larvae were raised on live feed until 21 days postfertilization and then fed diets for 16 weeks. All fish received a daily ration of >5% of body weight (adjusted biweekly). Growth varied among diets throughout the feeding trial, and at study termination (week 16), significant differences among diets were observed for terminal weight gain, body condition index, body fat deposition, and reproductive outcomes. In addition, the proportion of viable embryos produced from females fed the formulated reference diet was high relative to the commercial diets. These data suggest that metabolic profiles, most likely reflecting nutrient/energy availability, utilization, and allocation, vary relative to diet in zebrafish. Undefined differences in metabolic profiles could result in erroneous predictions of health outcomes and make comparisons among laboratories more challenging. We recommend that dietary standards should be defined for zebrafish to support their common utility in biomedical research.
PMID: 31381491 [PubMed - indexed for MEDLINE]
IMP dehydrogenase-2 drives aberrant nucleolar activity and promotes tumorigenesis in glioblastoma.
Nat Cell Biol. 2019 08;21(8):1003-1014
Authors: Kofuji S, Hirayama A, Eberhardt AO, Kawaguchi R, Sugiura Y, Sampetrean O, Ikeda Y, Warren M, Sakamoto N, Kitahara S, Yoshino H, Yamashita D, Sumita K, Wolfe K, Lange L, Ikeda S, Shimada H, Minami N, Malhotra A, Morioka S, Ban Y, Asano M, Flanary VL, Ramkissoon A, Chow LML, Kiyokawa J, Mashimo T, Lucey G, Mareninov S, Ozawa T, Onishi N, Okumura K, Terakawa J, Daikoku T, Wise-Draper T, Majd N, Kofuji K, Sasaki M, Mori M, Kanemura Y, Smith EP, Anastasiou D, Wakimoto H, Holland EC, Yong WH, Horbinski C, Nakano I, DeBerardinis RJ, Bachoo RM, Mischel PS, Yasui W, Suematsu M, Saya H, Soga T, Grummt I, Bierhoff H, Sasaki AT
Abstract
In many cancers, high proliferation rates correlate with elevation of rRNA and tRNA levels, and nucleolar hypertrophy. However, the underlying mechanisms linking increased nucleolar transcription and tumorigenesis are only minimally understood. Here we show that IMP dehydrogenase-2 (IMPDH2), the rate-limiting enzyme for de novo guanine nucleotide biosynthesis, is overexpressed in the highly lethal brain cancer glioblastoma. This leads to increased rRNA and tRNA synthesis, stabilization of the nucleolar GTP-binding protein nucleostemin, and enlarged, malformed nucleoli. Pharmacological or genetic inactivation of IMPDH2 in glioblastoma reverses these effects and inhibits cell proliferation, whereas untransformed glia cells are unaffected by similar IMPDH2 perturbations. Impairment of IMPDH2 activity triggers nucleolar stress and growth arrest of glioblastoma cells even in the absence of functional p53. Our results reveal that upregulation of IMPDH2 is a prerequisite for the occurance of aberrant nucleolar function and increased anabolic processes in glioblastoma, which constitutes a primary event in gliomagenesis.
PMID: 31371825 [PubMed - indexed for MEDLINE]
Clinical Cancer Advances 2018: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology.
J Clin Oncol. 2018 04 01;36(10):1020-1044
Authors: Heymach J, Krilov L, Alberg A, Baxter N, Chang SM, Corcoran RB, Dale W, DeMichele A, Magid Diefenbach CS, Dreicer R, Epstein AS, Gillison ML, Graham DL, Jones J, Ko AH, Lopez AM, Maki RG, Rodriguez-Galindo C, Schilsky RL, Sznol M, Westin SN, Burstein H
Abstract
A MESSAGE FROM ASCO'S PRESIDENT I remember when ASCO first conceived of publishing an annual report on the most transformative research occurring in cancer care. Thirteen reports later, the progress we have chronicled is remarkable, and this year is no different. The research featured in ASCO's Clinical Cancer Advances 2018 report underscores the impressive gains in our understanding of cancer and in our ability to tailor treatments to tumors' genetic makeup. The ASCO 2018 Advance of the Year, adoptive cell immunotherapy, allows clinicians to genetically reprogram patients' own immune cells to find and attack cancer cells throughout the body. Chimeric antigen receptor (CAR) T-cell therapy-a type of adoptive cell immunotherapy-has led to remarkable results in young patients with acute lymphoblastic leukemia (ALL) and in adults with lymphoma and multiple myeloma. Researchers are also exploring this approach in other types of cancer. This advance would not be possible without robust federal investment in cancer research. The first clinical trial of CAR T-cell therapy in children with ALL was funded, in part, by grants from the National Cancer Institute (NCI), and researchers at the NCI Center for Cancer Research were the first to report on possible CAR T-cell therapy for multiple myeloma. These discoveries follow decades of prior research on immunology and cancer biology, much of which was supported by federal dollars. In fact, many advances that are highlighted in the 2018 Clinical Cancer Advances report were made possible thanks to our nation's support for biomedical research. Funding from the US National Institutes of Health and the NCI helps researchers pursue critical patient care questions and addresses vital, unmet needs that private industry has little incentive to take on. Federally supported cancer research generates the biomedical innovations that fuel the development and availability of new and improved treatments for patients. We need sustained federal research investment to accelerate the discovery of the next generation of cancer treatments. Another major trend in this year's report is progress in precision medicine approaches to treat cancer. Although precision medicine offers promise to people with cancer and their families, that promise is only as good as our ability to make these treatments available to all patients. My presidential theme, "Delivering Discoveries: Expanding the Reach of Precision Medicine," focuses on tackling this formidable challenge so that new targeted therapies are accessible to anyone who faces a cancer diagnosis. By improving access to high-quality care, harnessing big data on patient outcomes from across the globe, and pursuing innovative clinical trials, I am optimistic that we will speed the delivery of these most promising treatments to more patients. Sincerely, Bruce E. Johnson, FASCO ASCO President, 2017 to 2018.
PMID: 29380678 [PubMed - indexed for MEDLINE]
Optimizing Outcome Assessment in Multicenter TBI Trials: Perspectives From TRACK-TBI and the TBI Endpoints Development Initiative.
J Head Trauma Rehabil. 2018 May/Jun;33(3):147-157
Authors: Bodien YG, McCrea M, Dikmen S, Temkin N, Boase K, Machamer J, Taylor SR, Sherer M, Levin H, Kramer JH, Corrigan JD, McAllister TW, Whyte J, Manley GT, Giacino JT, TRACK-TBI Investigators
Abstract
Traumatic brain injury (TBI) is a global public health problem that affects the long-term cognitive, physical, and psychological health of patients, while also having a major impact on family and caregivers. In stark contrast to the effective trials that have been conducted in other neurological diseases, nearly 30 studies of interventions employed during acute hospital care for TBI have failed to identify treatments that improve outcome. Many factors may confound the ability to detect true and meaningful treatment effects. One promising area for improving the precision of intervention studies is to optimize the validity of the outcome assessment battery by using well-designed tools and data collection strategies to reduce variability in the outcome data. The Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, conducted at 18 sites across the United States, implemented a multidimensional outcome assessment battery with 22 measures aimed at characterizing TBI outcome up to 1 year postinjury. In parallel, through the TBI Endpoints Development (TED) Initiative, federal agencies and investigators have partnered to identify the most valid, reliable, and sensitive outcome assessments for TBI. Here, we present lessons learned from the TRACK-TBI and TED initiatives aimed at optimizing the validity of outcome assessment in TBI.
PMID: 29385010 [PubMed - indexed for MEDLINE]
A Canadian genome-wide association study and meta-analysis confirm HLA as a risk factor for peanut allergy independent of asthma.
J Allergy Clin Immunol. 2018 04;141(4):1513-1516
Authors: Asai Y, Eslami A, van Ginkel CD, Akhabir L, Wan M, Yin D, Ellis G, Ben-Shoshan M, Marenholz I, Martino D, Ferreira MA, Allen K, Mazer B, de Groot H, de Jong NW, Gerth van Wijk R, Dubois AEJ, Grosche S, Ashley S, Rüschendorf F, Kalb B, Beyer K, Nöthen MM, Lee YA, Chin R, Cheuk S, Hoffman J, Jorgensen E, Witte JS, Melles RB, Hong X, Wang X, Hui J, Musk AWB, Hunter M, James AL, Koppelman GH, Sandford AJ, Clarke AE, Daley D
PMID: 29325868 [PubMed - indexed for MEDLINE]
Conversion to Chlorhexidine Gluconate for Perioperative Vaginal Preparation: An Evidence-Based Process Improvement Project.
AORN J. 2019 08;110(2):145-152
Authors: Lee ASD
Abstract
Surgical site infections (SSIs) occur during the postoperative period and involve the operative site. To lower the occurrence of SSIs in their patient population, the gynecology SSI prevention committee at a large academic medical institution initiated a process improvement project examining vaginal antiseptic skin prep solutions. Some studies indicate that chlorhexidine gluconate (CHG) is superior to povidone-iodine in the reduction of microbial skin counts and SSIs. After reviewing the available literature, the committee members determined there was an opportunity to make an evidence-based practice change and realize significant cost savings by converting povidone-iodine prepping kits to CHG prepping kits for vaginal procedures. The committee members worked with perioperative and facility leaders to revise the vaginal preparation policy, provide staff member education, and convert to CHG prepping kits. Facility leaders supported this cost-saving conversion for all perioperative units, and the project led to a successful, large-scale, evidence-based process improvement.
PMID: 31355430 [PubMed - indexed for MEDLINE]
If You Listen, I Will Talk: the Experience of Being Asked About Suicidality During Routine Primary Care.
J Gen Intern Med. 2019 10;34(10):2075-2082
Authors: Richards JE, Hohl SD, Whiteside U, Ludman EJ, Grossman DC, Simon GE, Shortreed SM, Lee AK, Parrish R, Shea M, Caldeiro RM, Penfold RB, Williams EC
Abstract
BACKGROUND: Routine population-based screening for depression is an essential part of evolving health care models integrating care for mental health in primary care. Depression instruments often include questions about suicidal thoughts, but how patients experience these questions in primary care is not known and may have implications for accurate identification of patients at risk.
OBJECTIVES: To explore the patient experience of routine population-based depression screening/assessment followed, for some, by suicide risk assessment and discussions with providers.
DESIGN: Qualitative, interview-based study.
PARTICIPANTS: Thirty-seven patients from Kaiser Permanente Washington who had recently screened positive for depression on the 2-item Patient Health Questionnaire [PHQ] and completed the full PHQ-9.
APPROACH: Criterion sampling identified patients who had recently completed the PHQ-9 ninth question which asks about the frequency of thoughts about self-harm. Patients completed semi-structured interviews by phone, which were recorded and transcribed. Directive and conventional content analyses were used to apply knowledge from prior research and elucidate new information from interviews; thematic analysis was used to organize key content overall and across groups based on endorsement of suicide ideation.
KEY RESULTS: Four main organizing themes emerged from analyses: (1) Participants believed being asked about suicidality was contextually appropriate and valuable, (2) some participants described a mismatch between their lived experience and the PHQ-9 ninth question, (3) suicidality disclosures involved weighing hope for help against fears of negative consequences, and (4) provider relationships and acts of listening and caring facilitated discussions about suicidality.
CONCLUSIONS: All participants believed being asked questions about suicidal thoughts was appropriate, though some who disclosed suicidal thoughts described experiencing stigma and sometimes distanced themselves from suicidality. Direct communication with trusted providers, who listened and expressed empathy, bolstered comfort with disclosure. Future research should consider strategies for reducing stigma and encouraging fearless disclosure among primary care patients experiencing suicidality.
PMID: 31346911 [PubMed - indexed for MEDLINE]
Proof of Principle that Molecular Modeling Followed by a Biophysical Experiment Can Develop Small Molecules that Restore Function to the Cardiac Thin Filament in the Presence of Cardiomyopathic Mutations.
ACS Omega. 2019 Apr 30;4(4):6492-6501
Authors: Szatkowski L, Lynn ML, Holeman T, Williams MR, Baldo AP, Tardiff JC, Schwartz SD
Abstract
This article reports a coupled computational experimental approach to design small molecules aimed at targeting genetic cardiomyopathies. We begin with a fully atomistic model of the cardiac thin filament. To this we dock molecules using accepted computational drug binding methodologies. The candidates are screened for their ability to repair alterations in biophysical properties caused by mutation. Hypertrophic and dilated cardiomyopathies caused by mutation are initially biophysical in nature, and the approach we take is to correct the biophysical insult prior to irreversible cardiac damage. Candidate molecules are then tested experimentally for both binding and biophysical properties. This is a proof of concept study-eventually candidate molecules will be tested in transgenic animal models of genetic (sarcomeric) cardiomyopathies.
PMID: 31342001 [PubMed]
