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The COVID-19 pandemic has had an unprecedented and disruptive impact on people's health and lives worldwide. In addition to burdening people's health in the short-term in the form of infection, illness, and mortality, there has been an enormous negative impact on clinical research. Clinical trials experienced challenges in ensuring patient safety and enrolling new patients throughout the pandemic. Here, we investigate and quantify the negative impact that the COVID-19 pandemic has industry-sponsored clinical trials, both in the USA and worldwide. We find a negative correlation between the severity of the COVID-19 pandemic and clinical trial screening rate, with the relationship being strongest during the first three months of the pandemic compared to the entire duration of the pandemic. This negative statistical relationship holds across therapeutic areas, across states in the USA despite the heterogeneity of responses at the state-level, and across countries. This work has significant implications for the management of clinical trials worldwide in response to the fluctuating severity of COVID-19 moving forward and for future pandemics.
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COVID-19 , Humanos , Pandemias/prevenção & controle , SARS-CoV-2 , Segurança do PacienteAssuntos
Glândulas Suprarrenais/patologia , Insuficiência Adrenal/patologia , Histoplasmose/patologia , Hiperpigmentação/patologia , Debilidade Muscular/patologia , Glândulas Suprarrenais/diagnóstico por imagem , Insuficiência Adrenal/diagnóstico por imagem , Insuficiência Adrenal/tratamento farmacológico , Insuficiência Adrenal/microbiologia , Idoso , Antifúngicos/uso terapêutico , Diagnóstico Diferencial , Fadiga/microbiologia , Feminino , Glucocorticoides/uso terapêutico , Histoplasmose/diagnóstico por imagem , Histoplasmose/tratamento farmacológico , Humanos , Hiperpigmentação/microbiologia , Mineralocorticoides/uso terapêutico , Debilidade Muscular/diagnóstico por imagem , Debilidade Muscular/microbiologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Redução de PesoRESUMO
The U.S. Department of Veterans Affairs (VA) is implementing two trauma-focused, evidence-based psychotherapies (TF-EBPs) for posttraumatic stress disorder (PTSD): cognitive processing therapy and prolonged exposure therapy (PE). Veterans with PTSD often do not receive these treatments, and little is known about the reasons veterans may not receive TF-EBPs. The aim of this qualitative study was to summarize clinician-reported reasons in medical records for nonreceipt of TF-EBPs. All veterans (N = 63) identified through PTSD screening who were newly engaged in mental health care and received individual evaluations in a PTSD specialty clinic in fiscal year 2008 were included in the sample. Content analysis of electronic medical records revealed multiple potential reasons for nonreceipt of TF-EBPs including referral to other PTSD treatments, other clinical priorities, poor engagement in care, practical barriers, negative beliefs, and receipt of care in other settings. Eight veterans (13%) initiated TF-EBPs. Further interventions to promote engagement in PTSD treatment are warranted.
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Documentação , Registros Eletrônicos de Saúde , Serviços de Saúde Mental , Psicoterapia/métodos , Transtornos de Estresse Pós-Traumáticos/terapia , Adulto , Instituições de Assistência Ambulatorial , Prática Clínica Baseada em Evidências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Estresse Pós-Traumáticos/psicologia , Estados Unidos , United States Department of Veterans Affairs , Veteranos/psicologia , Adulto JovemRESUMO
The increased use of personal or VA-loaned computers and mobile devices for at-home telehealth has generated a need for support from a peer technical consultant who can troubleshoot technical issues.
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OBJECTIVES: The first Home-Based Telemental pilot program (HBTMH) in the Department of Veterans Affairs addresses the significant challenge of access to mental health treatment for rural veterans. Though the feasibility of telemental healthcare in clinic-based settings has been well documented, the feasibility of telemental health via webcam and computer in a patient's home or other non-clinic settings is unknown. METHODS: The HBTMH program, established in December 2009 at the Portland VA Medical Center, delivers a wide range of mental health services into the homes and other non-clinic settings of rural veterans via webcam, secure and encrypted software and veteran-owned personal computers. The program adhered to a Standard Operating Procedure (SOP) Manual, evaluated patients with the Assessment for Suitability for Home Based Telemental Health (ASH-25), utilized a Patient Support Person (PSP), and incorporated a peer technical consultant to provide assistance to veterans. The authors describe satisfaction and safety survey results from the initial 40 veterans enrolled. RESULTS: Survey results support the feasibility and safety of using webcams, secure/encrypted software and veteran-owned personal computers for the delivery of mental health services into the home. Veterans report high levels of satisfaction and perceived safety with home-based telemental health. RESULTS also suggest fewer no-show appointments in home-based telemental health compared to clinic-based telemental health. CONCLUSIONS: The authors discuss the strength and limitations of the program as well as potential areas of future research.
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Transtornos Mentais/terapia , Satisfação do Paciente , Psicoterapia/métodos , Telemedicina/métodos , Veteranos/psicologia , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Psicoterapia/instrumentação , População Rural , Telemedicina/instrumentação , Estados Unidos , United States Department of Veterans Affairs/organização & administraçãoRESUMO
OBJECTIVE: To describe non-lymphoma hematological malignancies in systemic lupus erythematosus (SLE). METHODS: A large SLE cohort was linked to cancer registries. We examined the types of non-lymphoma hematological cancers. RESULTS: In 16,409 patients, 115 hematological cancers [including myelodysplastic syndrome (MDS)] occurred. Among these, 33 were non-lymphoma. Of the 33 non-lymphoma cases, 13 were of lymphoid lineage: multiple myeloma (n = 5), plasmacytoma (n = 3), B cell chronic lymphocytic leukemia (B-CLL; n = 3), precursor cell lymphoblastic leukemia (n = 1) and unspecified lymphoid leukemia (n = 1). The remaining 20 cases were of myeloid lineage: MDS (n = 7), acute myeloid leukemia (AML; n = 7), chronic myeloid leukemia (CML; n = 2) and 4 unspecified leukemias. Most of these malignancies occurred in female Caucasians, except for plasma cell neoplasms (4/5 multiple myeloma and 1/3 plasmacytoma cases occurred in blacks). CONCLUSIONS: In this large SLE cohort, the most common non-lymphoma hematological malignancies were myeloid types (MDS and AML). This is in contrast to the general population, where lymphoid types are 1.7 times more common than myeloid non-lymphoma hematological malignancies. Most (80%) multiple myeloma cases occurred in blacks; this requires further investigation.
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Neoplasias Hematológicas/complicações , Lúpus Eritematoso Sistêmico/complicações , Adulto , Idoso , Estudos de Coortes , Feminino , Neoplasias Hematológicas/diagnóstico , Humanos , Incidência , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: We explore preliminary clinical effectiveness and feasibility of an intervention utilizing collaborative care components and behavioral activation (BA) to treat comorbid chronic pain and posttraumatic stress disorder (PTSD). DESIGN: Descriptive, including pre- and posttreatment assessment results. SETTING: Portland Veterans Affairs Medical Center. PARTICIPANTS: Fifty-eight Iraq and Afghanistan veterans with chronic pain and PTSD symptoms. INTERVENTIONS: Veterans participated in a biopsychosocial evaluation and up to eight BA sessions using a collaborative approach involving primary care, mental health, and other clinicians. A physiatrist assisted the psychologist in providing recommendations to primary care providers. OUTCOME MEASURES: Participants were administered pre- and posttreatment measures of PTSD, pain severity, pain interference, mental health, quality of life, satisfaction, and global ratings of change with the purpose of assessing progress and improving quality. RESULTS: Of the 58 participants, 30 completed treatment. Common recommendations included physical therapy and exercise programs, pain medication or pain medication adjustments, and additional diagnostic workups, such as imaging. Participants who completed the program showed significant improvements on measures of PTSD, pain severity, and pain interference. Improvements were also evident on measures of mental health and quality of life. Overall, participants were satisfied with the program, and on average reported feeling "somewhat better." CONCLUSIONS: These findings suggest that a collaborative approach that includes BA is feasible and a potentially effective treatment for comorbid chronic pain and PTSD.
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Comportamento/efeitos dos fármacos , Manejo da Dor/métodos , Dor/complicações , Transtornos de Estresse Pós-Traumáticos/complicações , Veteranos/psicologia , Adulto , Terapia Comportamental , Lesões Encefálicas/complicações , Dor Crônica/complicações , Terapia Combinada , Avaliação da Deficiência , Feminino , Humanos , Masculino , Saúde Mental , Dor/psicologia , Medição da Dor , Qualidade de Vida , Estudos Retrospectivos , Fatores Socioeconômicos , Transtornos de Estresse Pós-Traumáticos/psicologia , Inquéritos e Questionários , Resultado do TratamentoRESUMO
People with chronic pain and comorbid posttraumatic stress disorder (PTSD) report more severe pain and poorer quality of life than those with chronic pain alone. This study evaluated the extent to which associations between PTSD and chronic pain interference and severity are mediated by pain-related coping strategies and depressive symptoms. Veterans with chronic pain were divided into 2 groups, those with (n=65) and those without (n=136) concurrent PTSD. All participants completed measures of pain severity, interference, emotional functioning, and coping strategies. Those with current PTSD reported significantly greater pain severity and pain interference, had more symptoms of depression, and were more likely to meet diagnostic criteria for a current alcohol or substance use disorder (all p-values <.01). Participants with PTSD reported more use of several coping strategies, including guarding, resting, relaxation, exercise/stretching, and coping self-statements. Illness-focused pain coping (i.e., guarding, resting, and asking for assistance) and depressive symptoms jointly mediated the relationship between PTSD and both pain interference (total indirect effect=0.194, p<.001) and pain severity (total indirect effect=0.153, p=.004). Illness-focused pain coping also evidenced specific mediating effects, independent of depression. In summary, specific pain coping strategies and depressive symptoms partially mediated the relationship between PTSD and both pain interference and severity. Future research should examine whether changes in types of coping strategies after targeted treatments predict improvements in pain-related function for chronic pain patients with concurrent PTSD.
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Adaptação Psicológica/fisiologia , Dor Crônica/complicações , Dor Crônica/psicologia , Depressão/etiologia , Depressão/reabilitação , Negociação , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/psicologia , Idoso , Dor Crônica/epidemiologia , Estudos Transversais , Depressão/epidemiologia , Feminino , Hospitais de Veteranos/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: The objective was to examine differences by age in mental health treatment initiation in Veterans Health Administration (VA) primary care patients after positive posttraumatic stress disorder (PTSD) screens. METHODS: This was a retrospective cohort study of 71,039 veterans who were administered PTSD screens during primary care encounters in 2007 at four Pacific Northwest VA medical center sites and who had no specialty mental health clinic visits or PTSD diagnoses recorded in the year before screening. Main outcome measures were attendance of any specialty mental health clinic visits or receipt of any antidepressant medication in the year after a positive PTSD screen. RESULTS: Older veterans, compared with veterans less than 30 years old, were less likely to attend any specialty mental health visits after positive PTSD screens [adjusted odds ratios (ORs) ranged from .57 to .12, all P<.001], and veterans 75 years and older were less likely to receive any antidepressant medication (adjusted OR=.56, P<.001). CONCLUSIONS: Initiation of mental health treatment among veterans who screen positive for PTSD varies significantly by age. Further research should examine whether this is due to differences in base rates of PTSD, treatment preferences, provider responses to screens or other age-related barriers to mental health treatment.
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Antidepressivos/uso terapêutico , Serviços de Saúde Mental/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Atenção Primária à Saúde/estatística & dados numéricos , Transtornos de Estresse Pós-Traumáticos/terapia , Veteranos/estatística & dados numéricos , Adulto , Fatores Etários , Idoso , Assistência Ambulatorial/estatística & dados numéricos , Estudos de Coortes , Feminino , Humanos , Masculino , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Noroeste dos Estados Unidos/epidemiologia , Estudos Retrospectivos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Estados Unidos/epidemiologia , United States Department of Veterans Affairs/estatística & dados numéricos , Veteranos/psicologiaRESUMO
OBJECTIVES: This study described utilization of specialty treatment for posttraumatic stress disorder (PTSD) at U.S. Department of Veterans Affairs (VA) facilities among veterans of Operation Enduring Freedom (OEF), in Afghanistan, or of Operation Iraqi Freedom (OIF), in Iraq, and non-OEF-OIF veterans recently diagnosed as having PTSD. It also identified predictors of receiving minimally adequate specialty treatment, defined as attending at least nine clinic visits within 365 days of screening positive for PTSD. METHODS: VA administrative data were obtained for 869 veterans who screened positive for PTSD between November 7, 2006, and September 30, 2008, received a diagnosis of PTSD, and visited a PTSD specialty clinic operated by the VA in the Pacific Northwest at least once within a year of screening positive. RESULTS: A total of 286 (33%) of the 852 veterans for whom complete data were available received minimally adequate specialty treatment; OEF-OIF veterans were less likely than non-OEF-OIF veterans to receive minimally adequate specialty treatment (29% versus 36%, p=.021) and attended fewer mean±SD visits to a PTSD clinic (8.2±11.4 versus 9.9±13.5, p=.045). Predictors of receiving minimally adequate specialty treatment included attending a PTSD clinic visit within 30 days of a positive screen, living in an urban location, and having psychiatric comorbidities. CONCLUSIONS: Most veterans with new PTSD diagnoses who initiated VA PTSD specialty care did not receive minimally adequate specialty treatment. Future studies should examine factors that lead to premature discontinuation of PTSD treatment and to what extent specialty treatment for PTSD is necessary.
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Serviços de Saúde Mental/estatística & dados numéricos , Transtornos de Estresse Pós-Traumáticos/terapia , United States Department of Veterans Affairs/estatística & dados numéricos , Veteranos/estatística & dados numéricos , Adulto , Campanha Afegã de 2001- , Feminino , Humanos , Guerra do Iraque 2003-2011 , Modelos Logísticos , Masculino , Fatores Socioeconômicos , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Estados Unidos , Veteranos/psicologiaRESUMO
The objective of this cross-sectional study was to assess group differences between veterans with and without posttraumatic stress disorder (PTSD) in mindful awareness and mindful non-judging. The relationships between mindfulness and PTSD symptom clusters were also evaluated. Three age and gender-matched groups, 1)15 combat veterans with PTSD, 2)15 combat veterans without PTSD, and 3) 15 non-combat veterans without PTSD, completed the Mindful Attention Awareness Scale and the Accept without Judgment scale. PTSD status was determined with the Clinician Administered PTSD Scale and excluded disorders screened with the Structured Clinical Interview for DSM-IV. Mindfulness scale group differences were assessed with analysis of variance. Mindfulness and the PTSD symptom clusters relationships were assessed with hierarchical regression analysis. There were group differences on mindful non-judging (F(2,44)=7.22, p=.002) but not mindful awareness (p>.05). Combat exposure accounted for significant variation in PTSD symptoms (hyper-arousal 47%; numbing-avoiding 32%; re-experiencing 23%). Mindfulness accounted for a significant percentage variance of PTSD symptoms (re-experiencing 32%; numbing-avoiding 19%, hyper-arousal 16%), beyond combat exposure effects, although only mindful non-judging was significant in the model. This study confirms in a clinical sample that mindful non-judging is associated with PTSD symptoms and could represent a meaningful focus for treatment.
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Imagery rehearsal therapy (IRT) may help reduce residual nightmares and posttraumatic stress disorder (PTSD) symptoms in veterans after trauma-focused PTSD treatment. Fifteen male U.S. veterans with PTSD and trauma-related nightmares, who had not previously completed trauma-focused PTSD treatment, attended 6 IRT group sessions. No benefits were observed immediately posttreatment. At 3- and 6-month follow-up, however, trauma-related nightmare frequency (nights/week) decreased (p < .01). The number of trauma-related nightmares/week (p < .01), number of total nightmares/week (p < .05), and PTSD symptoms (p < .05) also decreased at 3 months. The overall F test for time was significant (p < .05) for nightmare severity and fear of sleep. No effects were found on measures of the impact of nightmares, sleep quality, or depression. Clinical and research implications are discussed.
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Sonhos/psicologia , Imagens, Psicoterapia , Transtornos de Estresse Pós-Traumáticos/terapia , Veteranos/psicologia , Adulto , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos , GuerraRESUMO
Protein Kinase Balpha(PKBalpha, or Akt1) is believed to play a crucial role in programmed cell death, cancer progression and the insulin-signaling cascade. The protein is activated by phosphorylation at multiple sites and subsequently phosphorylates and activates eNOS. Free cysteine residues of the protein may capture reactive, endogenously produced nitric oxide (NO) as S-nitrosothiols. Site-specific detection of S-nitrosylated cysteine residues, usually at low stoichiometry, has been a major challenge in proteomic research largely due to the lack of mass marker for S-nitrosothiols that are very labile under physiologic conditions. In this report we describe a sensitive and specific MS method for detection of S-nitrosothiols in PKB alpha/Akt1 in rat soleus muscle. PKB alpha/Akt1 was isolated by immunoprecipitation and 2D-gel electrophoresis, subjected to in-gel tryptic digestion, and cysteinyl nitrosothiols were reacted with iodoacetic acids [2-C(12)/C(13) = 50/50] under ascorbate reduction conditions. This resulted in the production of relatively stable carboxymethylcysteine (CMC) immonium ions (m/z 134.019 and m/z 135.019) within a narrow argon collision energy (CE = 30 +/- 5 V) in the high MS noise region. In addition, free and disulfide-linked cysteine residues were converted to carboxyamidomethylcysteines (CAM). Tryptic S-nitrosylated parent ion was detected with a mass accuracy of 50 mDa for the two CMC immonium ions at the triggered elution time during capillary liquid chromatography (LC) separation. A peptide containing Cys(296) was discriminated from four co-eluting tryptic peptides under lock mass conditions (m/z 785.8426). S-nitrosothiol in the tryptic peptide, ITDFGLBKEGIK (B: CAM, [M + 2H](2+) = 690.86, Found: 690.83), is believed to be present at a very low level, since the threshold for the CMC immonium trigger ions was set at 3 counts/s in the MS survey. The high levels of NO that are produced under stress conditions may result in increased S-nitrosylation of Cys(296) which blocks disulfide bond formation between Cys(296) and Cys(310) and suppresses the biological effects of PKB alpha/Akt1. With the procedures developed here, this process can be studied under physiological and pathological conditions.
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Cromatografia Líquida/métodos , Músculo Esquelético/enzimologia , Espectrometria de Massas por Ionização por Electrospray/métodos , Animais , Eletroforese em Gel Bidimensional , Privação de Alimentos , Músculo Esquelético/química , Nanotecnologia , Ratos , S-Nitrosotióis/químicaRESUMO
Reversible phosphorylation of proteins functions as a biological switching network for activation and inhibition of downstream biological processes. Since phosphorylations of these sites are often transient processes, and hence sub-stoichiometric, systematic characterization of phosphorylation sites is a formidable challenge. In this work, a new approach was developed to pinpoint phosphotyrosine sites on tyrosine-containing peptides. This required (1) the development of a new and highly sensitive nano-electrospray assembly and (2) validation of the concept that the specificity and detection limit for trace levels of phosphotyrosine immonium ion in peptide mixtures from protein digests can be increased by varying the collision energy. With our method, an automatic tandem mass spectrometric analysis of peptides eluted from a C(18) capillary liquid chromatographic column is triggered by a positive confirmation of phosphotyrosine immonium ion in a time-of-flight mass spectrometric survey. The approach was tested by analyzing the phosphorylation of human IRS-1 peptides that interact with the Src-homology 2 domain and mixtures of these peptides with tryptic digests of bovine serum albumin and horse heart myoglobin.