RESUMO
OBJECTIVE: The United States Preventative Services Task Force guidelines for screening for abdominal aortic aneurysms (AAA) are broad and exclude many at risk groups. We analyzed a large AAA screening database to examine the utility of a novel machine learning (ML) model for predicting individual risk of AAA. METHODS: We created a ML model to predict the presence of AAAs (>3 cm) from the database of a national nonprofit screening organization (AAAneurysm Outreach). Participants self-reported demographics and comorbidities. The model is a two-layered feed-forward shallow network. The ML model then generated AAA probability based on patient characteristics. We evaluated graphs to determine significant factors, and then compared those graphs with a traditional logistic regression model. RESULTS: We analyzed a cohort of 10,033 patients with an AAA prevalence of 2.74%. Consistent with logistic regression analysis, the ML model identified the following predictors of AAA: Caucasian race, male gender, advancing age, and recent or past smoker with recent smoker having a more profound affect (P < .05). Interestingly, the ML model showed body mass index (BMI) was associated with likelihood of AAAs, especially for younger females. The ML model also identified a higher than predicted risk of AAA in several groups, including female nonsmokers with cardiac disease, female diabetics, those with a family history of AAA, and those with hypertension or hyperlipidemia at older ages. An elevated BMI conveyed a higher than expected risk in male smokers and all females. The ML model also identified a complex relationship of both diabetes mellitus and hyperlipidemia with gender. Family history of AAA was a more important risk factor in the ML model for both men and women too. CONCLUSIONS: We successfully developed an ML model based on an AAA screening database that unveils a complex relationship between AAA prevalence and many risk factors, including BMI. The model also highlights the need to expand AAA screening efforts in women. Using ML models in the clinical setting has the potential to deliver precise, individualized screening recommendations.
Assuntos
Aneurisma da Aorta Abdominal , Hiperlipidemias , Humanos , Masculino , Feminino , Estados Unidos , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/epidemiologia , Fatores de Risco , Prevalência , Aprendizado de Máquina , Assistência ao Paciente , Hiperlipidemias/complicações , Programas de Rastreamento , Ultrassonografia/efeitos adversosRESUMO
A 50-year-old patient presented with a stroke. An ascending aortic mass noted by computed tomography was attached to the aortic wall and was found to be thrombus at surgery. Pathologic examination revealed an intraluminal thrombus attached to a focal segment of intimal fragmentation. Sectioning of the aortic wall revealed what were findings consistent with what would be noted with a previously unrecognized traumatic ascending aortic deceleration injury. To our knowledge, this is the first case of a late presentation of deceleration aortic injury, presenting with a thrombus within the ascending aorta.
Assuntos
Doenças da Aorta , Trombose , Aorta/diagnóstico por imagem , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/etiologia , Desaceleração , Humanos , Pessoa de Meia-Idade , Trombose/diagnóstico por imagem , Trombose/etiologia , Tomografia Computadorizada por Raios XRESUMO
OBJECTIVE: The U.S. Preventative Services Task Force guidelines for abdominal aortic aneurysm (AAA) screening are based mainly on studies of older Caucasian males from non-U.S. POPULATIONS: This study was designed to analyze the findings of a large, all-inclusive AAA screening program in the United States. METHODS: Screening events were held nationally by a U.S. nonprofit organization between 2001 and 2017. AAA screening was offered regardless of risk profile. Participants filled out a demographics form with known comorbidities. Significant risk factors were determined using logistic regression with backward stepwise variable selection. Odds ratios (OR) are reported with 95% confidence intervals (CIs). RESULTS: A total of 9457 screened participants (47% male) were analyzed. The mean age was 67 ± 9 years with 40.8% between 65 and 75 years old. Most participants were Caucasian (83.4%), followed by African American (13.1%). Screened risk factors included hypertension (58.1%), hyperlipidemia (54.9%), smoking (52.0%), cardiac disease (29.2%), diabetes mellitus (18.4%), a family history of AAA (22.4%) or brain aneurysms (8.6%), and body mass index (26.9 ± 5.28). Overall, 267 participants (2.82%) were found to have an AAA (>3 cm). Those ages 65 to 75 had a prevalence of 2.98%. In a fully adjusted, multivariate logistic regression, there was an increased risk of AAA in males (OR, 3.24; 95% CI, 2.39-4.40), current smokers (OR, 3.28; 95% CI, 2.36-4.54), previous smokers (OR, 1.86; 95% CI, 1.41-2.47), cardiac disease (OR, 1.30; 95% CI, 1.01-1.68), family history of AAA (OR, 1.60; 95% CI, 1.20-2.14), and advancing age (P < .0001). Female ever smokers 65 to 75 years old had a prevalence of 1.7%. Male smokers 45 to 54 and 55 to 64 years old had a prevalence of 3.37% and 4.43%, respectively. There was an increased risk of AAA in females with morbid obesity (OR, 5.54; 95% CI, 1.34-22.83 in never smokers and OR, 5.61; 95% CI, 1.04-30.15 in smokers), female smokers with hypertension (OR, 3.22; 95% CI, 1.21-8.58), males with cardiac disease (OR, 2.06; 95% CI, 1.08-3.90 in never smokers and OR, 1.48; 95% CI, 1.05-2.09), male smokers with a family history of AAA (OR, 1.69; 95% CI, 1.61-2.46), and current smokers (OR, 6.33; 95% CI, 2.62-15.24 for females and OR, 2.50; 95% CI, 1.70-3.65 for males). CONCLUSIONS: This study shows that there remain high-risk groups outside the current guidelines that would likely benefit from AAA screening. Risk factors for AAA include male gender, smoking, cardiac disease, family history of AAA, and advancing age. The most significant risk factor is current smoking status.
Assuntos
Aneurisma da Aorta Abdominal/epidemiologia , Programas de Rastreamento/métodos , Medição de Risco/métodos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Sexuais , Estados Unidos/epidemiologiaRESUMO
A 70-year-old male underwent transthoracic (TTE) and transesophageal (TEE) echocardiography for a stroke. A bicuspid aortic valve was suspected by TTE, but TEE revealed a normally functioning quadricuspid aortic valve. A quadricuspid aortic valve may be more common than generally thought, as it may not be readily diagnosed by TTE, and may remain functionally normal.
Assuntos
Estenose da Valva Aórtica , Doença da Válvula Aórtica Bicúspide , Válvula Aórtica Quadricúspide , Idoso , Valva Aórtica/diagnóstico por imagem , Ecocardiografia Transesofagiana , Humanos , Masculino , Valva MitralRESUMO
Orleans Parish in Louisiana is in the midst of an exponentially increasing number of patient admissions with COVID-19 and respiratory symptoms. Patients have been described having CT findings most consistent with an early-stage (<7 days from symptoms onset) or an advanced stage (8-14 days from symptoms onset). We describe and illustrate those early and advanced stage CT findings from patients with documented COVID-19 who have been admitted to University Medical Center in New Orleans, Louisiana.
Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico por imagem , Pneumonia Viral/diagnóstico por imagem , Tomografia Computadorizada por Raios X , COVID-19 , Humanos , Louisiana , Pandemias , SARS-CoV-2RESUMO
Partial anomalous pulmonary venous connection is defined by one or more of the pulmonary veins draining to the heart into a location other than the left atrium. Depending on the location of the anomalous venous connection, they can be categorized as supracardiac, infracardiac, cardiac, and mixed types. In some cases, there is no hemodynamic consequence; in others, it can result in tricuspid regurgitation, right heart dilation, and pulmonary hypertension. Frequently, the reason for referral can be asymptomatic right heart dilation of unknown significance. Diagnosis is often difficult by transthoracic echocardiogram unless there is a high index of suspicion, and the appropriate views are obtained. Cardiac CT (computed tomography) or cardiac MRI (magnetic resonance imaging) can provide more precise anatomic detail as needed. The current article reviews the etiology and pathophysiology of partial anomalous pulmonary venous connection, and also reviews the current knowledge on their treatment.
Assuntos
Ecocardiografia/métodos , Imageamento por Ressonância Magnética/métodos , Veias Pulmonares/anormalidades , Síndrome de Cimitarra/diagnóstico por imagem , Síndrome de Cimitarra/fisiopatologia , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Feminino , Humanos , Veias Pulmonares/diagnóstico por imagem , Adulto JovemRESUMO
A 39-year-old male commercial diver developed cutis marmorata after a dive. He had a full recovery after therapy in a hyperbaric oxygen chamber. Transthoracic echocardiography revealed an atrial septal aneurysm and a large shunt during normal respirations. This form of decompression sickness may progress to type II DCS, thus is important to identify and treat. Cutis marmorata as a result of diving is highly associated with an atrial septal defect or a large patent foramen ovale. It is particularly important to assess these patients for a right-to-left shunt as part of a medical evaluation prior to returning to diving.
Assuntos
Doença da Descompressão/complicações , Mergulho , Ecocardiografia/métodos , Forame Oval Patente/complicações , Dermatopatias Vasculares/diagnóstico por imagem , Dermatopatias Vasculares/etiologia , Adulto , Humanos , Oxigenoterapia Hiperbárica , Masculino , Dermatopatias Vasculares/terapiaRESUMO
A 63-year-old female with multiple cardiovascular risk factors presented with a nontypical chest pain syndrome. Myocardial perfusion imaging (MPI) with a regadenoson (Lexiscan) Technetium Tc99 m (Sestamibi) stress test was interpreted as normal. The patient's chest pain syndrome continued, and subsequently, she presented to the emergency room. Cardiac computed tomographic angiography (CCTA) revealed a partially calcified left main coronary artery (LMCA) plaque with mild positive remodeling, having low attenuation (68 Hounsfield units-HU) in the noncalcified portion. In addition, a significant proximal left anterior descending coronary artery (LAD) noncalcified plaque was also noted. These lesions were hemodynamically significant by CCTA fractional flow reserve (FFRCT ) as evidenced by a significant drop across the LMCA, followed by the LAD and circumflex (CX) vessels. Stenting of the stenosis was performed with resolution of symptoms. The phenomenon of "balanced ischemia" was not readily detected with a regadenoson Technetium Tc99 m perfusion stress test but was readily documented by FFRCT .
Assuntos
Angiografia por Tomografia Computadorizada/métodos , Estenose Coronária/diagnóstico por imagem , Teste de Esforço , Reserva Fracionada de Fluxo Miocárdico , Isquemia Miocárdica/diagnóstico , Purinas , Pirazóis , Tecnécio Tc 99m Sestamibi , Agonistas do Receptor A2 de Adenosina , Angiografia Coronária/métodos , Estenose Coronária/complicações , Estenose Coronária/cirurgia , Diagnóstico Diferencial , Reações Falso-Negativas , Feminino , Humanos , Pessoa de Meia-Idade , Isquemia Miocárdica/etiologia , Valor Preditivo dos Testes , Compostos Radiofarmacêuticos , StentsRESUMO
A patient's coronary artery calcium score (CACS) is a strong independent predictor of cardiovascular risk. Used in conjunction with traditional measures of risk, the CACS helps the clinician discuss cardiovascular (CV) risk and recommend therapies with the patient. We present several cases in which measurement of the CACS and traditional risk factors were used to help guide the clinician-patient conversation and guide therapies.
Assuntos
Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico , Vasos Coronários/diagnóstico por imagem , Medição de Risco/métodos , Calcificação Vascular/diagnóstico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Coronary computed tomography angiography (CCTA) has been an established noninvasive method for detection of coronary artery disease (CAD). Although CCTA has had a high sensitivity and negative predictive value for CAD detection, specificity for obstructive CAD has been relatively low, partly due to coronary calcium, imaging artifacts, and other factors leading to an overestimation of stenosis severity. A relatively new noninvasive method of calculation of fractional flow reserve (FFR) using CCTA (FFRCT ) data has been developed. This noninvasive method yields similar results to invasive FFR measurement, improving specificity for noninvasively detecting lesion-specific ischemia thus helping guide revascularization.
Assuntos
Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Estenose Coronária/diagnóstico , Vasos Coronários/diagnóstico por imagem , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Estenose Coronária/fisiopatologia , Vasos Coronários/fisiopatologia , Humanos , Curva ROC , Índice de Gravidade de DoençaRESUMO
Grade I diastolic dysfunction (DD) is generally associated with a normal mean left atrial pressure (LAP) and normal left ventricular end-diastolic pressure (LVEDP). The first hemodynamic alteration seen in DD, however, is the development of an elevated LVEDP with a persistent normal LAP. This is manifested by echocardiography as a continued mitral pulsed wave (PW) E/A <0.8 (Grade I DD), but with evidence of an elevated LVEDP. Such findings include alterations in PV flow, mitral PW inflow response to Valsalva maneuver, and also the presence of a B-bump on the mitral M-mode tracing. When assessing diastolic function, it may be clinically helpful to assess for this early hemodynamic manifestation of DD.
Assuntos
Velocidade do Fluxo Sanguíneo/fisiologia , Ecocardiografia Doppler/métodos , Átrios do Coração/diagnóstico por imagem , Valva Mitral/diagnóstico por imagem , Veias Pulmonares/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico , Pressão Ventricular/fisiologia , Pressão Sanguínea/fisiologia , Diástole , Átrios do Coração/fisiopatologia , Humanos , Valva Mitral/fisiopatologia , Veias Pulmonares/fisiopatologia , Disfunção Ventricular Esquerda/fisiopatologia , Função Ventricular Esquerda/fisiologiaRESUMO
The actions of hydrogen sulfide (H2S) on the heart and vasculature have been extensively reported. However, the mechanisms underlying the effects of H2S are unclear in the anesthetized rat. The objective of the present study was to investigate the effect of H2S on the electrocardiogram and examine the relationship between H2S-induced changes in heart rate (HR), mean arterial pressure (MAP), and respiratory function. Intravenous administration of the H2S donor Na2S in the anesthetized Sprague-Dawley rat decreased MAP and HR and produced changes in respiratory function. The administration of Na2S significantly increased the RR interval at some doses but had no effect on PR or corrected QT(n)-B intervals. In experiments where respiration was maintained with a mechanical ventilator, we observed that Na2S-induced decreases in MAP and HR were independent of respiration. In experiments where respiration was maintained by mechanical ventilation and HR was maintained by cardiac pacing, Na2S-induced changes in MAP were not significantly altered, whereas changes in HR were abolished. Coadministration of glybenclamide significantly increased MAP and HR responses at some doses, but methylene blue, diltiazem, and ivabradine had no significant effect compared with control. The decreases in MAP and HR in response to Na2S could be dissociated and were independent of changes in respiratory function, ATP-sensitive K+ channels, methylene blue-sensitive mechanism involving L-type voltage-sensitive Ca2+ channels, or hyperpolarization-activated cyclic nucleotide-gated channels. Cardiovascular responses observed in spontaneously hypertensive rats were more robust than those in Sprague-Dawley rats.NEW & NOTEWORTHY H2S is a gasotransmitter capable of producing a decrease in mean arterial pressure and heart rate. The hypotensive and bradycardic effects of H2S can be dissociated, as shown with cardiac pacing experiments. Responses were not blocked by diltiazem, ivabradine, methylene blue, or glybenclamide.
Assuntos
Pressão Arterial/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Sulfeto de Hidrogênio/farmacologia , Sulfetos/farmacologia , Animais , Canais de Cálcio Tipo L/efeitos dos fármacos , Estimulação Cardíaca Artificial , Eletrocardiografia/efeitos dos fármacos , Glibureto/farmacologia , Hipoglicemiantes/farmacologia , Canais KATP/efeitos dos fármacos , Masculino , Bloqueadores dos Canais de Potássio/farmacologia , Ratos , Ratos Endogâmicos SHR , Ratos Sprague-Dawley , Respiração ArtificialRESUMO
Nonalcoholic fatty liver disease may range from simple steatosis to fibrosis and cirrhosis. It is associated with the development of coronary artery calcification and appears to be an independent predictor of future adverse cardiovascular events. As the presence of a fatty liver appears to portray an independent increased risk, it may be beneficial to note this on coronary artery calcium scoring reports. Determination of fatty liver is relatively easy to perform. We discuss the method used by the Multi-Ethnic Study of Atherosclerosis (MESA) study for determination of fatty liver from CT coronary artery calcium scoring acquisitions, which may be implemented in clinical analysis.
Assuntos
Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Calcificação Vascular/diagnóstico por imagem , Doença da Artéria Coronariana/complicações , Humanos , Calcificação Vascular/complicaçõesRESUMO
As a result of improvements in congenital heart surgery, there are more adults alive today with congenital heart disease (CHD) than children. Individuals with cardiac birth defects may be able to participate in physical activities but require proper cardiovascular evaluation. The American Heart Association and American College of Cardiology released guidelines in 2015 for athletes with cardiovascular abnormalities. The guidelines express that although restriction from competitive athletics may be indicated for some, the majority of individuals with CHD can and should engage in some form of physical activity. This case study demonstrates the importance of combining all aspects of history, physical examination, ECG, and imaging modalities to evaluate cardiac anatomy and function in young athletes with complex CHD.
Assuntos
Atletas , Eletrocardiografia/métodos , Cardiopatias Congênitas/cirurgia , Coração/fisiologia , Imageamento por Ressonância Magnética/métodos , Exame Físico/métodos , Adulto , Coração/diagnóstico por imagem , Cardiopatias Congênitas/diagnóstico por imagem , Humanos , Masculino , Adulto JovemRESUMO
A 59-year-old male presented to the emergency room with symptoms of chest tightness and palpitations. Following conversion of atrial fibrillation to sinus rhythm, he had deep symmetrical T-wave changes on his electrocardiogram. Symptoms resolved almost immediately, and his initial troponin was negative. He underwent cardiac CT angiography utilizing an emergency room triage protocol which resulted in a diagnosis of nonobstructive coronary artery disease and apical hypertrophic cardiomyopathy. Following a hospital stay of less than 24 hours, he was discharged to outpatient follow-up on medical management and has remained asymptomatic over 6 months. This case presentation illustrates an example of the diversity of pathology that presents in emergency rooms with symptoms consistent with acute coronary syndrome.
Assuntos
Síndrome Coronariana Aguda/diagnóstico por imagem , Cardiomiopatia Hipertrófica/diagnóstico por imagem , Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Doença da Artéria Coronariana/diagnóstico por imagem , Cardiomiopatia Hipertrófica/complicações , Doença da Artéria Coronariana/etiologia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Quantification of computed tomography (CT) noise helps in determination of radiation dosage requirements for adequate image quality. Clinical methods used include calculation of the standard deviation (SD) of a selected region of interest (ROI). In industry, wavelet decomposition has been used for image compression while removing high-frequency noise. We evaluated a cohort of 74 consecutive patients referred for coronary artery calcium scoring and quantitated noise within a 16×16 ROI in the ascending aorta using the traditional SD method and also using a two-dimensional dyadic wavelet decomposition method. Clinically, noise has been shown to be proportional to patient weight and also body mass index (BMI), which is a derived value from height and weight. Noise for both methods was plotted against patient parameters of height, weight, waist circumference and calculated BMI. A regression line was calculated and coefficient of determination (CoD) calculated for each. The CoD was better for height, weight, and waist circumference using the wavelet method as compared to the traditional SD method. The wavelet method of quantification of image noise may be an improved method as compared to the SD method. This method could help further refine an imaging system's determination of radiation dosage requirements to obtain a satisfactory quality image.
Assuntos
Algoritmos , Modelos Teóricos , Tomografia Computadorizada por Raios X/métodos , Índice de Massa Corporal , Humanos , Doses de RadiaçãoRESUMO
A young female developed progressive dyspnea on minimal exertion. Echocardiography demonstrated a large right heart with severe pulmonary hypertension. Cardiac computed tomographic angiography then demonstrated a superior sinus venosus atrial septal defect with an anomalous right upper pulmonary venous drainage. Echo and CCTA were complementary in making a proper diagnosis.
Assuntos
Angiografia por Tomografia Computadorizada/métodos , Angiografia Coronária/métodos , Ecocardiografia/métodos , Comunicação Interatrial/diagnóstico por imagem , Imagem Multimodal/métodos , Veias Pulmonares/diagnóstico por imagem , Anormalidades Múltiplas/diagnóstico por imagem , Adulto , Diagnóstico Diferencial , Feminino , HumanosRESUMO
BACKGROUND: Radiofrequency ablation of the renal arteries (RF-ABL) has been shown to decrease blood pressure (BP) in drug-resistant hypertensive patients who receive antihypertensive drug therapy. However, there remain questions regarding how RF-ABL influences BP independent of drug therapy and whether complete renal denervation is necessary to maximally lower BP. To study these questions, we examined the cardiovascular, sympathetic, and renal effects produced by RF-ABL of the proximal renal arteries in spontaneously hypertensive rats (SHR) with established hypertension. METHODS: SHR were instrumented (telemetry) for measurement of systolic/diastolic BP (SBP/DBP). Rats then underwent Sham-ABL or RF-ABL adjacent to the renal ostium and BP was recorded for 8 weeks. Changes in sympathetic activity, 24-hour water/sodium excretion, and levels of urinary angiotensinogen (AGT), plasma renin activity, and kidney renin content (KRC) were measured in SHR. RESULTS: Compared with Sham-ABL, RF-ABL produced a sustained decrease in BP. At 8 weeks, SBP/DBP was 171±6/115±3 and 183±4/129±3mm Hg for RF-ABL and Sham-ABL SHR, respectively. Correlating with the reduction in BP, RF-ABL significantly decreased the low frequency/total and low frequency/high frequency of BP variability and attenuated the hypotensive response to chlorisondamine. Kidney norepinephrine levels were markedly decreased at 8 weeks in RF-ABL vs. Sham-ABL SHR. There were no group differences in 24-hour sodium/water excretion or urinary AGT excretion rate (6 weeks) or plasma renin activity or KRC (8 weeks). In other studies, concurrent RF-ABL plus surgical denervation initially decreased BP to a greater level than RF-ABL alone, but thereafter the reduction in BP between groups was not different. CONCLUSIONS: In hypertensive SHR, bilateral RF-ABL of the proximal renal arteries produced a sustained decease in sympathetic activity and BP without changes in sodium/water excretion or activity of the systemic/renal renin-angiotensin system.
Assuntos
Ablação por Cateter , Hipertensão/cirurgia , Rim/irrigação sanguínea , Inibição Neural , Artéria Renal/inervação , Simpatectomia/métodos , Sistema Nervoso Simpático/cirurgia , Angiotensinogênio/urina , Animais , Pressão Sanguínea , Modelos Animais de Doenças , Hipertensão/fisiopatologia , Masculino , Natriurese , Norepinefrina/metabolismo , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Renina/sangue , Sistema Renina-Angiotensina , Sistema Nervoso Simpático/metabolismo , Sistema Nervoso Simpático/fisiopatologia , Fatores de Tempo , MicçãoRESUMO
Late cardiac perforation by a right ventricular (RV) pacemaker lead may be a challenge to diagnose. Echocardiography often will not adequately demonstrate lead tip migration, but chest computed tomography (CT) readily identifies the lead and tip location. A patient presented one month after dual-chamber pacemaker implantation with fever, sepsis and failure of RV pacer lead capture. Echocardiography demonstrated vegetations on the RV lead and a pericardial effusion, but the lead tip location could not be identified. CT identified the tip as having migrated through the pericardium into the anterior mediastinum. These complimentary echo and CT findings helped make a diagnosis and direct patient therapy.