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Vitamin K antagonists (VKAs) are frequently prescribed to patients with congenital heart disease (CHD) for atrial arrhythmias or Fontan palliation, but there is a paucity of data regarding time spent in the therapeutic range (TTR). We sought to determine the TTR in patients with CHD and atrial arrhythmias or Fontan palliation prescribed VKAs and explore associations with thromboembolic and bleeding events.

The anti-inflammatory agent colchicine is gaining interest as a treatment for coronary artery disease. However, the effects of colchicine in atherosclerotic animal models are mostly unknown. This study aimed to evaluate colchicine in a rabbit model of atherosclerosis.

Evidence suggests a role for excessive inflammation in COVID-19 complications. Colchicine is an oral anti-inflammatory medication beneficial in gout, pericarditis, and coronary disease. We aimed to investigate the effect of colchicine on the composite of COVID-19-related death or hospital admission.

Purpose: The effect of direct laryngoscopy using a Macintosh blade (MAC) vsGlideScope™ videolaryngoscopy using a Spectrum LoPro blade (GVL) on nociceptive stimulation has not been quantitatively studied. This study used the new nociception level (NOL) index to compare the nociceptive response induced by GVL or MAC during laryngoscopy with or without intubation. Methods: Patients underwent two laryngoscopies at four-minute intervals (L1, L2), one with GVL and the other with MAC (first randomization). A third laryngoscopy (L3) followed by tracheal intubation was performed four minutes after L2 (GVL or MAC, second randomization). Nociception was quantitatively assessed by NOL and standard hemodynamic parameters (heart rate [HR] and mean arterial pressure). For the crossover design, blade comparisons accounted for sequence and blade type. A possible carryover effect between laryngoscopies was assessed. Results: In the 50 patients randomized, there was no carryover effect from one laryngoscopy to the next for all analyzed parameters. Nociception level index peak values were higher with MAC than GVL. Analysis of ΔNOL showed a lower nociceptive response with GVL for L1+L2 combined. Mean peak NOL values were significantly higher after L3+intubation than after L1+L2, for both GVL and MAC groups. Analysis of ΔHR values did not show a significant difference between GVL and MAC for any laryngoscopy. Conclusion: Laryngoscopy alone with GVL induces less nociception than with MAC. The NOL was more sensitive than HR at detecting nociceptive responses to MAC vsGVL. Additionally, and irrespective of which technique/blade was used, the combination of laryngoscopy + tracheal intubation produced a much greater nociceptive response than the laryngoscopy alone. Trial registration: www.clinicaltrials.gov (NCT03277872); registered 29 August 2017.

Compelling evidence showing a link between atrial fibrillation (AF) and cognitive decline and dementia is accumulating.

BACKGROUND:Comorbidity indexes derived from administrative databases are essential tools of research in global health. We sought to develop and validate a novel cardiac-specific comorbidity index, and to compare its accuracy with the generic Charlson–Deyo and Elixhauser comorbidity indexes.METHODS:We derived the cardiac-specific comorbidity index from consecutive patients who were admitted to hospital at a tertiary-care cardiology hospital in Quebec. We used logistic regression analysis and incorporated age, sex and 22 clinically relevant comorbidities to build the index. We compared the cardiac-specific comorbidity index with refitted Charlson–Deyo and Elixhauser comorbidity indexes using the C-statistic and net reclassification improvement to predict in-hospital death, and the Akaike information criterion to predict length of stay. We validated our findings externally in an independent cohort obtained from a provincial registry of coronary disease in Alberta.RESULTS:The novel cardiac-specific comorbidity index outperformed the refitted generic Charlson–Deyo and Elixhauser comorbidity indexes for predicting in-hospital mortality in the derivation population (n= 10 137): C-statistic 0.95 (95% confidence interval [CI] 0.94–0.9) v. 0.81 (95% CI 0.77–0.84) and 0.86 (95% CI 0.82–0.89), respectively. In the validation population (n= 17 877), the cardiac-specific comorbidity index was similarly better: C-statistic 0.92 (95% CI 0.89–0.94) v. 0.76 (95% CI 0.71–0.81) and 0.82 (95% CI 0.78–0.86), respectively, and also numerically outperformed the Charlson–Deyo and Elixhauser comorbidity indexes for predicting 1-year mortality (C-statistic 0.78 [95% CI 0.76–0.80] v. 0.75 [95% CI 0.73–0.77] and 0.77 [95% CI 0.75–0.79], respectively). Similarly, the cardiac-specific comorbidity index showed better fit for the prediction of length of stay. The net reclassification improvement using the cardiac-specific comorbidity index for the prediction of death was 0.290 compared with the Charlson–Deyo comorbidity index and 0.192 compared with the Elixhauser comorbidity index.INTERPRETATION:The cardiac-specific comorbidity index predicted in-hospital and 1-year death and length of stay in cardiovascular populations better than existing generic models. This novel index may be useful for research of cardiology outcomes performed with large administrative databases.

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Aim:To evaluate the impact of AGTR1A1166C (rs5186) on the response to candesartan in patients with heart failure. Materials & methods:Prospective, multicentre, open-label study. We studied 299 symptomatic patients with heart failure presenting a left ventricular ejection fraction ≤40. Results:Reductions in the primary end points of natriuretic peptides were not significantly associated with AGTR1A1166C. Nevertheless, carrying the 1166C allele was associated with a greater compensatory increase in renin activity (p  0.037) after 16 weeks of treatment with candesartan and a more modest effect on aldosterone concentrations (p  0.022). Conclusion:AGTR11166C carriers may experience a greater long-term compensatory renin–angiotensin–aldosterone system activation following treatment with candesartan. Whether these associations ultimately influence clinical outcomes requires investigation.Clinicaltrials.gov: NCT00400582

Vascular inflammation is increased in patients with psoriasis. This randomized, double-blind, multicenter study evaluated the effects of tumor necrosis factor-α antagonist adalimumab on vascular inflammation in patients with psoriasis. A total of 107 patients were randomized (1:1) to receive adalimumab for 52 weeks or placebo for 16 weeks followed by adalimumab for 52 weeks. Vascular inflammation was assessed with positron emission tomography-computed tomography. There were no differences in the change from baseline in vessel wall target-to-background ratio (TBR) from the ascending aorta (primary endpoint) (adalimumab: TBR = 0.002, 95% confidence interval [CI] = –0.048 to 0.053; placebo: TBR = –0.002, 95% CI = –0.053 to 0.049; P = 0.916) and the carotids (adalimumab: TBR = 0.031, 95% CI = –0.005 to 0.066; placebo: TBR = 0.018, 95% CI = –0.019 to 0.055; P = 0.629) at week 16 between adalimumab and placebo. After 52 weeks of treatment with adalimumab there was no significant change from start of treatment in TBR from the ascending aorta (TBR = –0.006, 95% CI = –0.049 to 0.038; P = 0.796), but there was an increase in TBR in carotids (TBR = 0.027, 95% CI = 0.000 to 0.054; P = 0.046). This study showed no difference over 16 weeks in vascular inflammation in patients treated with a tumor necrosis factor-α antagonist or placebo and a modest increase in vascular inflammation in carotids after 52 weeks of treatment with adalimumab.

AbstractBackground:Mitral regurgitation (MR) is a common valvular heart disorder requiring intervention once it becomes severe. Transcatheter mitral repair with the MitraClip device is a safe and effective therapy for selected patients denied surgery. The authors sought to evaluate the clinical outcomes and economic impact of this therapy compared to medical management in heart-failure patients with symptomatic mitral regurgitation.Methods and results:The study was comprised of two phases; an observational study of patients with heart failure and mitral regurgitation treated with either medical therapy or the MitraClip, and an economic model. Results of the observational study were used to estimate parameters for the decision model, which estimated costs, and benefits in a hypothetical cohort of patients with heart failure and moderate-to-severe mitral regurgitation treated with either standard medical therapy or MitraClip. The cohort of patients treated with the MitraClip was propensity matched to a population of heart failure patients, and their outcomes compared. At a mean follow-up of 22 months, all-cause mortality was 21% in the MitraClip cohort and 42% in the medical management cohort (p = .007). The decision model demonstrated that MitraClip increased life expectancy from 1.87–3.60 years and quality-adjusted life years (QALY) from 1.13–2.76 years. The incremental cost was $52,500 Canadian dollars, corresponding to an incremental cost-effectiveness ratio (ICER) of $32,300.00 per QALY gained. Results were sensitive to the survival benefit.Conclusion:In heart failure patients with symptomatic moderate–severe mitral regurgitation, therapy with the MitraClip is associated with superior survival and is cost-effective compared to medical therapy.

The management of paediatric asthma exacerbations is based on trials in children of all ages. Recent studies from 2009 raised the possibility that preschoolers (younger than 6 years) with viral-induced wheezing and children exposed to tobacco smoke might be at an increased risk of treatment failure. The study objective was to identify factors associated with management failure in children presenting to the emergency department with moderate or severe asthma exacerbations.

Polymorphisms in the adenylate cyclase 9 (ADCY9) gene influence the benefits of the cholesteryl ester transfer protein (CETP) modulator dalcetrapib on cardiovascular events after acute coronary syndrome. We hypothesized that Adcy9inactivation could improve cardiac function and remodeling following myocardial infarction (MI) in absence of CETP activity.

Clinical evidence has suggested that the oat-soluble fiber β-glucan might have lipid-lowering effects.

AbstractObjectiveTo determine whether a nursing intervention delivered at emergency department (ED) discharge would reduce ED revisits.MethodA randomized study was conducted in the ED of a tertiary cardiac hospital in Montreal, Quebec. Between November 2006 and March 2010, 3,795 patients were assessed for eligibility based on two risk factors for ED revisits (=1 ED visit in the past year and =6 medications); 132 were randomized to the experimental group (EG) and 133 to the control group (CG). The intervention included one nurse-patient meeting before leaving the ED, with two additional telephone contacts over the next 2 weeks. The primary outcome was time to ED revisits within 30 days after discharge. Secondary outcomes included time to ED revisits over 90, 180, and 365 days and hospitalizations over 30, 90, 180, and 365 days.ResultsA planned interim analysis that stopped the study with half of the planned sample showed that the time to ED revisits was similar in both groups at 30 days (p=0.81; revisits: 18.2% in EG, 19.6% in CG), 90 days (p=0.44), 180 days (p=0.98), and 365 days (p=0.75). The only difference identified was a lower hospitalization proportion at 180 days in the EG group (13.6% v. 24.1%; p=0.038).ConclusionsThese findings are consistent with previous research showing that few ED-based interventions are successful in reducing ED returns. Factors other than those targeted by the intervention, including an improvement in usual care, may explain the findings.

This study sought to assess the prognostic value of physical examination in a modern treated heart failure population.

Background:Persistent postoperative pain continues to be an underrecognized complication. We examined the prevalence of and risk factors for this type of pain after cardiac surgery.Methods:We enrolled patients scheduled for coronary artery bypass grafting or valve replacement, or both, from Feb. 8, 2005, to Sept. 1, 2009. Validated measures were used to assess (a) preoperative anxiety and depression, tendency to catastrophize in the face of pain, health-related quality of life and presence of persistent pain; (b) pain intensity and interference in the first postoperative week; and (c) presence and intensity of persistent postoperative pain at 3, 6, 12 and 24 months after surgery. The primary outcome was the presence of persistent postoperative pain during 24 months of follow-up.Results:A total of 1247 patients completed the preoperative assessment. Follow-up retention rates at 3 and 24 months were 84% and 78%, respectively. The prevalence of persistent postoperative pain decreased significantly over time, from 40.1% at 3 months to 22.1% at 6 months, 16.5% at 12 months and 9.5% at 24 months; the pain was rated as moderate to severe in 3.6% at 24 months. Acute postoperative pain predicted both the presence and severity of persistent postoperative pain. The more intense the pain during the first week after surgery and the more it interfered with functioning, the more likely the patients were to report persistent postoperative pain. Pre-existing persistent pain and increased preoperative anxiety also predicted the presence of persistent postoperative pain.Interpretation:Persistent postoperative pain of nonanginal origin after cardiac surgery affected a substantial proportion of the study population. Future research is needed to determine whether interventions to modify certain risk factors, such as preoperative anxiety and the severity of pain before and immediately after surgery, may help to minimize or prevent persistent postoperative pain.

Psoriasis is a chronic inflammatory disease associated with increased risks of myocardial infarction and stroke. Systemic treatments for moderate to severe psoriasis can reduce skin and joint inflammation; however, their effects on vascular inflammation are unknown.

Radiofrequency catheter ablation in immature hearts has been associated with marked enlargement of lesions over time, with potential for related late adverse events. It remains unknown whether cryothermal ablation lesions display a similar pattern of growth.

Vascular inflammation can lead to plaque instability and acute coronary syndromes (ACS). Viruses produce potent immunomodulating proteins that regulate key inflammatory pathways. A myxoma virus–derived serpin Serp-1 reduces inflammatory cell invasion and plaque growth in vascular injury models. Our objective was to evaluate the safety and efficacy of Serp-1 in patients with ACS undergoing percutaneous coronary intervention.

Recent improvements in multidetector computed tomography (MDCT) with 64-slice scanners have allowed acquisition of a coronary study in 5 s to 6 s, with good temporal and spatial resolution. Previous studies have reported an underestimation of plaque burden by MDCT. Whether shorter scan times can allow correct assessment of plaque volume requires comparison with intravascular ultrasound (IVUS).

Increased production of reactive oxygen species plays an essential role in the pathogenesis of several diseases, including cardiac hypertrophy. In our search to identify redox-sensitive targets that contribute to redox signaling, we found that protein tyrosine phosphatase 1B (PTP1B) was reversibly oxidized and inactivated in hearts undergoing hypertrophy. Cardiomyocyte-specific deletion of PTP1B in mice (PTP1B cKO mice) caused a hypertrophic phenotype that was exacerbated by pressure overload. Furthermore, we showed that argonaute 2 (AGO2), a key component of the RNA-induced silencing complex, was a substrate of PTP1B in cardiomyocytes and in the heart. Our results revealed that phosphorylation at Tyr393and inactivation of AGO2 in PTP1B cKO mice prevented miR-208b–mediated repression of thyroid hormone receptor–associated protein 1 (THRAP1; also known as MED13) and contributed to thyroid hormone–mediated cardiac hypertrophy. In support of this conclusion, inhibiting the synthesis of triiodothyronine (T3) with propylthiouracil rescued pressure overload–induced hypertrophy and improved myocardial contractility and systolic function in PTP1B cKO mice. Together, our data illustrate that PTP1B activity is cardioprotective and that redox signaling is linked to thyroid hormone responsiveness and microRNA-mediated gene silencing in pathological hypertrophy.

Chronic hyperglycemia plays a role in the pathogenesis of coronary artery disease (CAD); however, the cut-off level beyond which glycemia becomes detrimental is still controversial. Postprandial glycemia may be a stronger CAD risk factor than fasting glycemia in patients without documented heart disease.

In the present study, we evaluated circulating pro-inflammatory mediators and markers of oxidative stress in patients with decompensated CHF (congestive heart failure) and assessed whether clinical recompensation by short-term inotropic therapy influences these parameters. Patients with worsening CHF (n=29, aged 61.9±2.7 years), NYHA (New York Heart Association) class III–IV, and left ventricular ejection fraction of 23.7±1.8% were studied. Controls comprised age-matched healthy volunteers (n=15; 54.1±3.2 years). Plasma levels of cytokines [IL (interleukin)-6 and IL-18], chemokines [MCP-1 (monocyte chemotactic protein-1)], adhesion molecules [sICAM (soluble intercellular adhesion molecule), sE-selectin (soluble E-selectin)], systemic markers of oxidation [TBARS (thiobarbituric acid-reactive substances), 8-isoprostaglandin F2α and nitrotyrosine] and hs-CRP (high-sensitivity C-reactive protein) were measured by ELISA and colorimetric assays at admission and 30 days following 72-h milrinone (n=15) or dobutamine (n=14) infusion. Plasma IL-6, IL-18, sICAM, E-selectin, hs-CRP and oxidative markers were significantly higher in patients on admission before inotropic treatment compared with controls (P<0.05). Short-term inotropic support improved clinical status as assessed by NYHA classification and by the 6-min walk test and significantly decreased plasma levels of IL-6, IL-18, sICAM, hs-CRP and markers of oxidation (P<0.05) at 30 days. The effects of milrinone and dobutamine were similar. In conclusion, our results demonstrate that patients with decompensated CHF have marked systemic inflammation and increased production of oxygen free radicals. Short-term inotropic support improves functional status and reduces indices of inflammation and oxidative stress in patients with decompensated CHF.

Background: To determine the rate of progression of dilation of the aortic root in adults with a bicuspid aortic valve. Methods: We reviewed retrospectively the transthoracic echocardiograms of 50 adults with a bicuspid aortic valve. Each patient had had at least two examinations made 12 months apart. Measurements were taken at four levels: at the basal attachment of the leaflets of the valve within the left ventricular outflow tract, at the widest point of the sinuses of Valsalva, at the sinutubular junction, and in the ascending aorta 1 cm beyond the sinutubular junction. Results: Progressive dilation occurred at all levels, ranging from 0.3 mm/yr at the basal attachment within the left ventricular outflow tract to 1.0 mm/yr, 1 cm beyond sinutubular junction. These rates of dilation were greater than the reported rate of 0.8 mm per decade in the normal population. The rate of dilation found in the ascending aorta 1 cm beyond the sinutubular junction was significantly greater than at the other sites (p = 0.005). The 21 patients with baseline measurements greater than 34 mm had a significantly higher rate of progression (p = 0.007). Sex, age, and the degree of valvar obstruction or regurgitation did not significantly influence the rate of progression of dilation. Conclusion: There is a significantly higher rate of dilation of the aortic root in adults with a bicuspid aortic valve when compared to the normal population. Periodic evaluation of the ascending aorta is essential in these patients, even after replacement of the aortic valve. Other imaging modalities should be considered if the region beyond the sinutubular junction is not well visualized by transthoracic echocardiography.

Objective:Pulmonary hypertension is commonly found in patients undergoing valvular surgery and can be worsened by cardiopulmonary bypass. Inhaled epoprostenol (prostacyclin) has been used for the treatment of pulmonary hypertension, but its effects compared with those of placebo on hemodynamics, oxygenation, echocardiographic examination, and platelet function have not been studied during cardiac surgery. Methods:Twenty patients with pulmonary hypertension undergoing cardiac surgery were randomized in a double-blind study to receive inhaled epoprostenol (60 μg) or placebo. The inhalation occurred after induction of anesthesia and before surgical incision. The effects on left and right systolic and diastolic cardiac functions evaluated by means of pulmonary artery catheterization and transesophageal echocardiography, as well as oxygenation and platelet aggregation, were studied. Results:Inhalation of epoprostenol significantly reduced indexed right ventricular stroke work from 10.7 ± 4.57 g · m · m−2to 7.8 ± 3.94 g · m · m−2(P=.003) and systolic pulmonary artery pressure from 48.4 ± 18 mm Hg to 38.9 ± 11.9 mm Hg (P=.002). The effect was correlated with the severity of pulmonary hypertension (r= 0.76, P=.01) and was no longer apparent after 25 minutes. There was no significant effect on systemic arterial pressures, left ventricular function, arterial oxygenation, platelet aggregation, and surgical blood loss. Conclusion:Inhaled epoprostenol reduces pulmonary pressure and improves right ventricular stroke work in patients with pulmonary hypertension undergoing cardiac surgery. A dose of 60 μg is hemodynamically safe, and its effect is completely reversed after 25 minutes. We did not observe any evidence of platelet dysfunction or an increase in surgical bleeding after administration of inhaled epoprostenol.

To describe the red blood cell transfusion practices of pediatric intensivists.

OBJECTIVE: To study the effect of patching on the speed of reepithelialization, slit-lamp signs of epithelial wound healing, and patient discomfort following a corneal abrasion. METHODS: Forty-eight eyes of 46 patients with corneal erosion sparing Bowman membrane were randomized into 2 groups: with or without patching. Slit-lamp examination and photographs of the fluorescein-stained cornea were performed on a daily basis until reepithelialization was complete. Photographs were analyzed using computer-assisted planimetry. RESULTS: No statistically significant difference was found between patched (n=25) and nonpatched (n=22) eyes for the mean size of the initial erosion (patched eyes, 23.7 mm2; nonpatched eyes, 18.9 mm2; P=.42), linear speed of reepithelialization (reduction over time of the radius of the largest circle included in the erosion: patched eyes, 0.0375 mm/h; nonpatched eyes, 0.0353 mm/h; P=.78), and surface speed of reepithelialization (reduction over time of the erosion area: patched eyes, 0.6510 mm2/h; nonpatched eyes, 0.5657 mm2/h; P=.60). The power to detect a 12-hour delay of epithelial closure was 95%. There were no significant differences between the 2 groups for pain, analgesia, insomnia, aspect of the epithelial border, intensity and duration of stromal edema, Descemet folds, anterior uveitis, and filaments. CONCLUSIONS: Patching a corneal erosion does not significantly accelerate reepithelialization and does not alter the epithelial wound healing pattern. It does not reduce the incidence and severity of inflammation nor relieve pain when compared with treatment without patching.

The authors attempted to determine the relative importance of factors that influence bleeding during and after spinal fusion. Data from 30 ASA I patients with idiopathic scoliosis were prospectively collected and analyzed. Intraoperative bleeding was 1971 ± 831 ml (mean ± SD) (61.5 ± 27% of estimated blood volume (EBV) and correlated with the number of fused vertebrae (r = 0.66, P < 0.0001) and the duration of surgery (r = 0.46, P = 0.0105). There was no correlation between intraoperative bleeding and the Cobb curve angle (43 to 86°), the mean arterial blood pressure (MAP) (63 to 86 mmHg), the central venous pressure (CVP), the quantity of epinephrine infiltrated, muscle relaxants or opioids used, nor in the type of opioids used, the minimal body temperature or whether stored or autologous blood was used. Postoperative bleeding was 1383 ± 369 ml (43.1 ± 11.7% of EBV) and correlated with the length of time the Hemovac drain was in place (r = 0.40, P = 0.0285) and MAP (r = 0.40, P = 0.0285). There was no correlation between postoperative and intraoperative bleeding nor in the number of fused vertebrae. Six patients had greater postoperative than intraoperative bleeding. The total bleeding (intra-plus postoperative) was 3347 ± 920 ml (104.2 ± 30.6 of EBV) and correlated with the number of fused vertebrae (r = 0.63, P = 0.0001) and with the duration of surgery (r = 0.42, P = 0.0208). We conclude that the number of fused vertebrae is the key factor in predicting intraoperative and total bleeding. Postoperative bleeding is considerable (up to 76.9% of EBV). No other factors allow for adequate prediction of postoperative bleeding and these patients must be kept under strict surveillance after surgery.

OBJECTIVE: To evaluate the therapeutic effects of anterior stromal punctures (ASP) in patients with bullous keratopathy (BK). PATIENTS AND METHODS: Twenty-seven patients awaiting penetrating keratoplasty with a diagnosis of BK were examined. They were seen before treatment with ASP and 1, 4, and 12 weeks after treatment. The examination included slitlamp examination, photography of the cornea, ultrasonic pachymetry, central esthesiometry, and pneumotonometry. Subjective evaluations of pain, discomfort, and photophobia were also done using a visual scale model. Photographs were analyzed by computer-assisted planimetry and used to measure the corneal surface covered by bullae and microcysts. Pretreatment and posttreatment values (mean±SEM) were compared using the Student paired t test. RESULTS: At 3 months, a significant reduction in pain was noted. A decrease in the mean corneal surface covered by bullae (BKPreASP=2733±553 μm2; BK3mo=1006±356 μm2, P=.004) was observed. A decrease in the esthesiometry (E) measurement (EPreASP=3.5±0.4 cm; E3mo=1.3±0.3 cm, P&lt;.001), an increase in corneal thickness ([CT] CTPreASP=869±24 μm; CT3mo=902±21 μm, P&lt;.001), and a decrease in the number of quadrants through which iris (I) details could be seen (IPreASP=1.7±0.3; I3mo=1.2±0.3, P=.015) were also noted. These findings corroborate the clinical observation of increased subepithelial fibrosis following ASP. CONCLUSIONS: Anterior stromal punctures reduce bullae formation and alleviate pain in patients with BK, and they constitute a valuable alternative to penetrating keratoplasty should surgery be delayed or contraindicated.

Reduction of inflammation with colchicine has emerged as a therapeutic option for secondary prevention of cardiovascular disease (CVD) in patients with coronary artery disease (CAD). Our objective was to consolidate evidence from randomized controlled trials (RCTs) evaluating the efficacy and safety of low-dose colchicine for secondary prevention of CVD among patients with CAD on standard medical therapy.