Complications of Carotid Interventions for Symptomatic Lesions after Systemic Thrombolysis.

BACKGROUND: Series detailing complications after carotid endarterectomy (CEA) and transfemoral carotid stenting (tfCAS) for patients presenting with neurologic symptoms that are treated with systemic thrombolysis (ST) are sparse. We sought to determine if treatment with ST was associated with a higher rate of post-carotid intervention complications. METHODS: A multispecialty, institutional, prospectively maintained database was queried for symptomatic patients treated with CEA or tfCAS from 2007 to 2019. The primary outcomes of interest were bleeding complications (access/wound complications, hematuria, intracranial hemorrhage) or need for reintervention, stroke, and death. We compared rates of these outcomes between patients who were and were not treated with ST. To adjust for preoperative patient factors and confounding variables, propensity scores for assignment to ST and non-ST were calculated. RESULTS: There were 1,139 patients included (949 [82%] CEA and 190 [17%] tfCAS. All treated lesions were symptomatic (550 [48%] stroke, 603 [52%] transient ischemic attack). Fifty-six patients (5%) were treated with ST. Fifteen of 56 patients also underwent catheter-based intervention for stroke. ST was administered 0 to 1 day preoperatively in 21 (38%) patients, 2 to 6 days preoperatively in 27 (48%) patients, and greater than 6 days preoperatively in 8 (14%) patients. ST patients were more likely to present with stroke (93% vs. 45%; P < 0.001) and have higher preoperative Rankin scores. Unadjusted rate of bleeding/return to operating room was 3% for ST group and 3% for non-ST group (P = 0.60). Unadjusted rate of stroke was 4% for ST group and 3% for the non-ST group (P = 0.91), while perioperative mortality was 5% for ST group and 1% for non-ST group (P = 0.009). After adjusting for patient factors, preoperative antiplatelet/anticoagulation, and operative factors, ST was not associated with an increased odds of perioperative bleeding/return to the operating room (odds ratio 0.37; 95% confidence interval: 0.02-1.63; P = 0.309) or stroke (odds ratio 0.62; 95% confidence interval: 0.16-2.40; P = 0.493). CONCLUSIONS: ST does not convey a higher risk of complications after CEA or tfCAS. After controlling for other factors, patients that received ST had similar rates of local complications and stroke when compared to non-ST patients. Early carotid intervention is safe in patients that have received ST, and delays should be avoided in symptomatic patients given the high risk of recurrent stroke.

Use of Thromboelastography with Platelet Mapping to Identify Prothrombotic Coagulation Profiles in Patients with History of Cardiac Intervention Undergoing Lower Extremity Revascularization.

BACKGROUND: Patients with concomitant coronary and peripheral artery disease (CAD and PAD) are at significant risk for major adverse limb events (MALEs). Prevention of thrombosis in this population is of paramount importance. Identifying prothrombotic coagulation profiles in this cohort may facilitate targeted thromboprophylaxis. We compared coagulation profiles of those with CAD and PAD to those with PAD alone during the perioperative period of lower extremity revascularization. STUDY DESIGN: Patients undergoing lower extremity revascularization underwent thromboelastography-platelet mapping (TEG-PM) analysis preoperatively and at serial intervals for up to 6 months. Coagulation profiles of patients with significant CAD (defined as history of coronary artery bypass graft or percutaneous coronary intervention) and PAD were compared with those with PAD alone. MALE in the postoperative period was recorded. RESULTS: Four hundred seventy-seven TEG-PM samples from 114 patients were analyzed; 28.1% had a history of significant CAD. The incidence of atrial fibrillation was higher in this group. The significant CAD group had lower ADP-platelet inhibition, higher ADP-platelet aggregation, and greater maximum clot strength compared with patients with PAD alone. Patients with significant CAD were more frequently on full-dose anticoagulation, but less frequently on dual antiplatelet therapy; 28.1% of patients with significant CAD developed postoperative MALE compared with 22.9% of patients with PAD alone (p = 0.40). For both groups, patients who developed postoperative MALE demonstrated greater ADP-platelet aggregation and lower ADP-platelet inhibition. CONCLUSIONS: Patients with a history of significant CAD undergoing lower extremity revascularization demonstrated prothrombotic TEG-PM profiles, less frequent use of dual antiplatelet therapy, and greater rates of full-dose anticoagulation. Decreased platelet inhibition was also associated with postoperative MALE. This study underscores the potential utility of viscoelastic assays for coagulation profiling in complex cardiovascular patients.

Reassuring Intraoperative Parameters Do Not Obviate the Need for Infrainguinal Bypass Completion Angiograms.

OBJECTIVE: To determine if routine completion angiography for lower extremity bypasses using vein conduit results in lower rates of postoperative bypass occlusion. SUMMARY OF BACKGROUND DATA: With the increasing availability of on-table angiography and significant advancements in endovascular techniques, some operators routinely perform completion angiograms. The effect of this surgical paradigm has yet to be rigorously compared to the more widespread selective use of completion imaging in the modern era. METHODS: This retrospective cohort study included infrainguinal arterial bypass procedures utilizing vein conduit completed at a single hospital system from 2001 to 2018 and compared postoperative outcomes between bypasses that underwent routine completion angiography versus selective completion angiography. Notably, any bypasses that underwent completion angiography due to intraoperative concerns were excluded from this analysis. RESULTS: 666 bypasses that were performed in 589 patients met inclusion criteria. 126 (16.9%) bypasses were classified into the routine completion angiogram group compared to 540 (81.0%) into the selective completion angiogram group. Patients who underwent routine completion angiograms had a rate of intraoperative reintervention of 22.2%. The routine angiogram group had lower rates of reintervention (3.9% vs 10.0%, P = 0.03) and graft occlusion (2.3% vs 9.2%, P = 0.01) at 1-month postoperatively. CONCLUSION: Lower extremity bypasses using vein conduit that undergo routine completion angiography are associated with lower rates of graft occlusion at 30-days postoperatively. Completion angiography should thus be routinely performed in infrainguinal bypasses that utilize venous conduit.

Factors Influencing Hospital Readmission after Lower Extremity Bypass for Chronic Limb-Threatening Ischemia.

Objectives: Unplanned hospital readmission is a leading source of hospital resource expenditure, and preventing readmission may improve both patient quality of life and healthcare costs. The factors influencing hospital readmission after lower extremity bypass (LEB) for chronic limb-threatening ischemia (CLTI) remain incompletely investigated. Methods: A regional, multi-institutional database was retrospectively reviewed for all patients who underwent LEB for CLTI between 1995 to 2020. The primary outcome was unplanned hospital readmission up to 30 days following bypass. Results: A total of 1315 patients underwent LEB across all institutions, of whom 843 (64.1%) underwent bypass for CLTI. The 30-day hospital readmission rate was 25.3%, and the leading causes of readmission were wound-related complications (51.6%). There was no difference in age, sex, or race between readmitted and non-readmitted patients. Conduit type and bypass target were also similar between groups. Readmitted patients more frequently underwent LEB for tissue loss (58.2% vs 50.2%, P = 0.042). On multivariable analysis, wound infection (odds ratio [OR] 9.1, 95% confidence interval [CI] 6.2-13.2, P < 0.001) and non-infectious wound complications (OR 2.0, 95% CI 1.0-3.9, P = 0.041) were independently associated with hospital readmission. Factors not associated with hospital readmission included patient age, conduit type, distal bypass target, and other medical comorbidities. Conclusions: One quarter of patients are readmitted within 30 days following lower extremity bypass for chronic limb-threatening ischemia. Efforts to mitigate wound infection and non-infectious wound complications may decrease rates of unplanned hospital readmission.

Predicting Arterial Thrombotic Events Following Peripheral Revascularization Using Objective Viscoelastic Data.

Background Peripheral artery disease is endemic in our globally aging population, with >200 million affected worldwide. Graft/stent thrombosis after revascularization is common and frequently results in amputation, major adverse cardiovascular events, and cardiovascular mortality. Optimizing medications to decrease thrombosis is of paramount importance; however, limited guidance exists on how to use and monitor antithrombotic therapy in this heterogeneous population. Thromboelastography with platelet mapping (TEG-PM) provides comprehensive coagulation metrics and may be integral to the next stage of patient-centered thrombophrophylaxis. This prospective study aimed to determine if TEG-PM could predict subacute graft/stent thrombosis following lower extremity revascularization, and if objective cut point values could be established to identify those high-risk patients. Methods and Results We conducted a single-center prospective observational study of patients undergoing lower extremity revascularization. Patients were followed up for the composite end point postoperative graft/stent thrombosis at 1 year. TEG-PM analysis of the time point before thrombosis in the event group was compared with the last postoperative visit in the nonevent group. Cox proportional hazards analysis examined the association of TEG-PM metrics to thrombosis. Cut point analysis explored the predictive capacity of TEG-PM metrics for those at high risk. A total of 162 patients were analyzed, of whom 30 (18.5%) experienced graft/stent thrombosis. Patients with thrombosis had significantly greater platelet aggregation (79.7±15.7 versus 58.5±26.4) and lower platelet inhibition (20.7±15.6% versus 41.1±26.6%) (all P<0.01). Cox proportional hazards analysis revealed that for every 1% increase in platelet aggregation, the hazard of experiencing an event during the study period increased by 5% (hazard ratio, 1.05 [95% CI, 1.02-1.07]; P<0.01). An optimal cut point of >70.8% platelet aggregation and/or <29.2% platelet inhibition identifies those at high risk of thrombosis with 87% sensitivity and 70% to 71% specificity. Conclusions Among patients undergoing lower extremity revascularization, increased platelet reactivity was predictive of subacute postoperative graft/stent thrombosis. On the basis of the cut points of >70.8% platelet aggregation and <29.2% platelet inhibition, consideration of an alternative or augmented antithrombotic regimen for high-risk patients may decrease the risk of postoperative thrombotic events.

Targeting transcription in heart failure via CDK7/12/13 inhibition.

Heart failure with reduced ejection fraction (HFrEF) is associated with high mortality, highlighting an urgent need for new therapeutic strategies. As stress-activated cardiac signaling cascades converge on the nucleus to drive maladaptive gene programs, interdicting pathological transcription is a conceptually attractive approach for HFrEF therapy. Here, we demonstrate that CDK7/12/13 are critical regulators of transcription activation in the heart that can be pharmacologically inhibited to improve HFrEF. CDK7/12/13 inhibition using the first-in-class inhibitor THZ1 or RNAi blocks stress-induced transcription and pathologic hypertrophy in cultured rodent cardiomyocytes. THZ1 potently attenuates adverse cardiac remodeling and HFrEF pathogenesis in mice and blocks cardinal features of disease in human iPSC-derived cardiomyocytes. THZ1 suppresses Pol II enrichment at stress-transactivated cardiac genes and inhibits a specific pathologic gene program in the failing mouse heart. These data identify CDK7/12/13 as druggable regulators of cardiac gene transactivation during disease-related stress, suggesting that HFrEF features a critical dependency on transcription that can be therapeutically exploited.

Differences in Aortic Intramural Hematoma Contrast Attenuation on Multi-Phase CTA Predict Long-Term Aortic Morphologic Change.

BACKGROUND: Evolution of aortic intramural hematoma (IMH) over time may range from resolution to degeneration and is difficult to predict. We sought to measure differences in contrast attenuation between arterial and delayed phase computed tomography angiography (CTA) images within the IMH as a surrogate of hematoma blood flow to predict resolution versus aortic growth and/or adverse outcomes. METHODS: IMH institutional data were gathered from 2005-2020. Hounsfield unit ratio (HUR) was measured as hematoma Hounsfield unit (HU), on delayed phase images divided by HU on arterial phase images on CTA. Aortic growth and effect of HUR was determined using a linear mixed effects model. Freedom from adverse aortic event, defined as the composite of intervention, recurrence of symptoms, radiographic progression, and rupture, was determined using Kaplan-Meier analysis. RESULTS: IMH occurred in 73 patients, of which 27 met the inclusion criteria. HUR ranged from 0.38-1.92 (mean: 0.98). Baseline aortic diameter growth independent of HUR measurement was 0.49 mm/year (95% confidence interval CI: -1.23 to 2.2). With the HUR was introduced into the model, the beta coefficient for time was -5.83 mm/year (95% CI: -10.4 to -1.28 mm/year) and the beta coefficient for the HUR was 5.05 mm/year per one-unit HUR (95% CI: 0.56 to 9.56 mm/year). Thus, an HUR>1.15 would correspond to aortic growth while an HUR<1.15 would correspond to reduction in aortic diameter, consistent with IMH resolution. Aortic adverse events occurred in 13 (48%) patients, 7 (26%) patients had recurrence of symptoms, 8 (30%) required intervention, 5 (18%) progressed to dissection, and 1(4%) had aortic rupture. There was a trend towards an association between higher HUR and composite adverse aortic events (HR 3.2 per 1-unit HUR; 95% CI: 0.6-17.3; P = 0.18). CONCLUSIONS: Increased HUR is associated with increased aortic growth and a trend toward adverse aortic events. Diminished delayed phase enhancement may predict partial or complete IMH resolution. HUR can be used to guide IMH surveillance and treatment.

Improving annual albuminuria testing for individuals with diabetes.

BACKGROUND: Annual albuminuria screening detects the early stages of nephropathy in individuals with diabetes. Because early detection of albuminuria allows for interventions that lower the risk of developing chronic kidney disease, guidelines recommend annual testing for all individuals with type 2 diabetes mellitus and for those with type 1 diabetes for at least 5 years. However, at the Eskind Diabetes Clinic at the Vanderbilt University Medical Center, testing occurred less frequently than desired. METHODS: A quality improvement team first analysed the clinic's processes, identifying the lack of a systematic approach to testing as the likely cause for the low rate. The team then implemented two successive interventions in a pilot of patients seen by nurse practitioners in the clinic. In the first intervention, staff used a dashboard within the electronic health record while triaging each patient, pending an albuminuria order if testing had not been done within the past year. In the second intervention, clinic leadership sent daily reminders to the triage staff. A statistical process control chart tracked monthly testing rates. RESULTS: After 6 months, annual albuminuria testing increased from a baseline of 69% to 82%, with multiple special-cause signals in the control chart. CONCLUSIONS: This project demonstrates that a series of simple interventions can significantly impact annual albuminuria testing. This project's success likely hinged on using an existing workflow to systematically determine if a patient was due for testing and prompting the provider to sign a pended order for an albuminuria test. Other diabetes/endocrinology and primary care clinics can likely implement a similar process and so improve testing rates in other settings. When coupled with appropriate interventions to reduce the development of chronic kidney disease, such interventions would improve patient outcomes, in addition to better adhering to an established quality metric.

The Changing Demographics of Surgical Trainees in General and Vascular Surgery: National Trends over the Past Decade.

OBJECTIVE: Recent initiatives have targeted the issue of gender and ethnic/racial disparities in general surgery and vascular surgery. However, the prevalence of these disparities in general and vascular surgical training programs is unknown. DESIGN: A retrospective analysis was conducted using data from three separate sources, including the US Graduate Medical Education annual report, Electronic Residency Application Service database, and National Resident Matching Program annual report. Demographic information regarding gender distribution and ethnic/racial identity was collected from 328 general surgery residency programs, 59 vascular surgery residency programs, and 100 vascular surgery fellowship programs across the US. The primary outcomes of this study were to evaluate national trends in gender and ethnic diversity in general surgery and vascular surgery training programs, including both traditional fellowship and integrated residency paradigms. RESULTS: From 2011-2020, general surgery residency programs showed a positive trend towards both female applicants (from 31.9%-41.5%) and trainees (from 36.2%-43.1%) (p < 0.0001 each). The proportion of minority trainees decreased, primarily among Black (from 7.2%-5.4%) and Asian trainees (from 21.5%-19.2%) (p < 0.0001 each). Concurrently, the number of vascular integrated residency programs grew from 27 to 59, resulting in a fivefold increase in trainees (from 64-335). Despite this growth, there was no change in the proportion of women applicants or trainees for both vascular integrated residency (24.9% applicants; 36.2% trainees) and fellowship programs (27.4% applicants; 25.9% trainees) over the study period (p = 0.11, 0.89, 0.43, and 0.13 respectively). Moreover, there was no significant change in proportion of minority trainees in both vascular integrated residency and fellowship programs. CONCLUSION: While general surgery programs have expanded in proportion of both female applicants and trainees, racial diversity has decreased. Gender and racial diversity in vascular training has not changed. Future initiatives in general and vascular surgery should focus on recruitment and promotion of proficient women and minority trainees.

Utility of unilateral versus bilateral venous reflux studies for venous insufficiency.

OBJECTIVE: Duplex ultrasonography is the reference standard for diagnosing chronic venous insufficiency. Bilateral venous reflux ultrasound studies are among the most time-consuming and physically demanding tests for vascular ultrasound technologists to perform. Furthermore, if a venous procedure is required, many insurance policies require that a diagnostic venous ultrasound scan for reflux must be performed within 1 year of the procedure. If the intervention is scheduled for >1 year after the ultrasound scan, the insurance company might require a repeat venous ultrasound scan before granting insurance authorization. Hence, ordering bilateral venous duplex ultrasound scans to evaluate for reflux when an intervention might only be performed on one limb within the year could be a waste of time and resources. The aim of the present study was to determine the utility of ordering bilateral vs unilateral studies to evaluate for reflux in patients with suspected chronic venous insufficiency and to determine whether a resource-saving potential exists for vascular laboratories through optimization of the process of ordering venous duplex ultrasound studies. METHODS: A retrospective review of all patients who had undergone bilateral lower extremity ultrasound scanning to evaluate for reflux from January 1, 2016 to December 31, 2016 at the Massachusetts General Hospital vascular laboratory was performed. The demographics, indications for ultrasound scanning, comorbidities, time required to perform the ultrasound study, and interval to intervention were documented. The data were analyzed using SPSS statistical software (IBM Corp, Armonk, NY). RESULTS: During the study period, 13,854 ultrasound studies had been performed in our vascular laboratory, of which 606 (4.4%) had been bilateral ultrasound scans for venous insufficiency. The time allotted for a bilateral study was 2 hours. Of the 606 studies evaluated, 152 (25.1%) showed no evidence of reflux, 284 (46.9%) showed bilateral lower extremity reflux, and 170 (28.1%) showed only venous insufficiency in one leg. Venous ablation, phlebectomy, and/or sclerotherapy were performed for 28.7% of the patients. However only 6.2% of patients had undergone venous procedures on both legs within 1 year after the ultrasound studies. Ablation was the most common procedure performed (54.6%), followed by phlebectomy (27.%) and sclerotherapy (17.9%). Overall, 94.7% of patients had not undergone a venous procedure on both legs within 1 year after the ultrasound studies and, hence, would have required a repeat duplex ultrasound scan to ensure insurance coverage for future procedures. CONCLUSIONS: Most bilateral ultrasound scans for venous insufficiency will not result in an intervention. Thus, most patients (95%) could have undergone a unilateral scan before the initial intervention instead of bilateral duplex ultrasound scanning.

Pulmonary tuberculosis screening in anti-retroviral treated adults living with HIV in Kenya.

BACKGROUND: People living with HIV (PLHIV) who reside in high tuberculosis burden settings remain at risk for tuberculosis disease despite treatment with anti-retroviral therapy and isoniazid preventive therapy (IPT). The performance of the World Health Organization (WHO) symptom screen for tuberculosis in PLHIV receiving anti-retroviral therapy is sub-optimal and alternative screening strategies are needed. METHODS: We enrolled HIV-positive adults into a prospective study in western Kenya. Individuals who were IPT-naïve or had completed IPT > 6 months prior to enrollment were eligible. We evaluated tuberculosis prevalence overall and by IPT status. We assessed the accuracy of the WHO symptom screen, GeneXpert MTB/RIF (Xpert), and candidate biomarkers including C-reactive protein (CRP), hemoglobin, erythrocyte sedimentation rate (ESR), and monocyte-to-lymphocyte ratio for identifying pulmonary tuberculosis. Some participants were evaluated at 6 months post-enrollment for tuberculosis. RESULTS: The study included 383 PLHIV, of whom > 99% were on antiretrovirals and 88% had received IPT, completed a median of 1.1 years (IQR 0.8-1.55) prior to enrollment. The prevalence of pulmonary tuberculosis at enrollment was 1.3% (n = 5, 95% CI 0.4-3.0%): 4.3% (0.5-14.5%) among IPT-naïve and 0.9% (0.2-2.6%) among IPT-treated participants. The sensitivity of the WHO symptom screen was 0% (0-52%) and specificity 87% (83-90%). Xpert and candidate biomarkers had poor to moderate sensitivity; the most accurate biomarker was CRP ≥ 3.3 mg/L (sensitivity 80% (28-100) and specificity 72% (67-77)). Six months after enrollment, the incidence rate of pulmonary tuberculosis following IPT completion was 0.84 per 100 person-years (95% CI, 0.31-2.23). CONCLUSIONS: In Kenyan PLHIV treated with IPT, tuberculosis prevalence was low at a median of 1.4 years after IPT completion. WHO symptoms screening, Xpert, and candidate biomarkers were insensitive for identifying pulmonary tuberculosis in antiretroviral-treated PLHIV.

Comparative Transcriptomics of Ex Vivo, Patient-Derived Endothelial Cells Reveals Novel Pathways Associated With Type 2 Diabetes Mellitus.

In this study low-input RNA-sequencing was used to annotate the molecular identity of endothelial cells isolated and immunopurified with CD144 microbeads. Using this technique, comparative gene expression profiling from healthy subjects and patients with type 2 diabetes mellitus identified both known and novel pathways linked with EC dysfunction. Modeling of diabetes by treating cultured ECs with high glucose identified shared changes in gene expression in diabetic cells. Overall, the data demonstrate how purified ECs from patients can be used to generate new hypotheses about mechanisms of human vascular disease.

Tuberculosis among individuals with community-acquired pneumonia presenting to emergency in Gaborone, Botswana.

Delays in diagnosing Tuberculosis (TB) are associated with increased transmission. TB may present as a clinical syndrome that mimics community-acquired pneumonia (CAP). The aim of this paper was to determine frequency of TB among patients with CAP at a referral hospital in Gaborone, Botswana. We performed a retrospective study of adults presenting with CAP from April 2010-October 2011 to the Emergency Department (ED); we matched this cohort to the National Botswana Tuberculosis Registry (NBTR) to identify individuals subsequently diagnosed with TB. We assessed demographics, time to TB diagnosis, clinical outcomes and performed logistic regressions to identify factors associated with TB diagnosis. We identified 1305 individuals presenting with CAP; TB was subsequently diagnosed in 68 (5.2%). The median time to TB diagnosis was 9.5 days. Forty percent were AFB sputum smear positive and 87% were identified as being HIV-positive. Subsequent diagnosis of TB is common among individuals with CAP at our ED, suggesting that TB may be present at the time of CAP presentation. Given the lack of distinguishing clinical factors between pulmonary TB and CAP, adults presenting with CAP should be evaluated for active TB in Botswana.

Delayed Tibioperoneal Trunk Aneurysm after Atherectomy and Balloon Angioplasty.

True infrapopliteal aneurysms occur very rarely; the majority of reported cases are secondary to trauma or infection. We report the development of a tibioperoneal trunk aneurysm 6 months after atherectomy and angioplasty and describe subsequent open surgical repair via a great saphenous vein bypass graft.

BET bromodomain proteins regulate enhancer function during adipogenesis.

Developmental transitions are guided by master regulatory transcription factors. During adipogenesis, a transcriptional cascade culminates in the expression of PPARγ and C/EBPα, which orchestrate activation of the adipocyte gene expression program. However, the coactivators controlling PPARγ and C/EBPα expression are less well characterized. Here, we show the bromodomain-containing protein, BRD4, regulates transcription of PPARγ and C/EBPα. Analysis of BRD4 chromatin occupancy reveals that induction of adipogenesis in 3T3L1 fibroblasts provokes dynamic redistribution of BRD4 to de novo super-enhancers proximal to genes controlling adipocyte differentiation. Inhibition of the bromodomain and extraterminal domain (BET) family of bromodomain-containing proteins impedes BRD4 occupancy at these de novo enhancers and disrupts transcription of Pparg and Cebpa, thereby blocking adipogenesis. Furthermore, silencing of these BRD4-occupied distal regulatory elements at the Pparg locus by CRISPRi demonstrates a critical role for these enhancers in the control of Pparg gene expression and adipogenesis in 3T3L1s. Together, these data establish BET bromodomain proteins as time- and context-dependent coactivators of the adipocyte cell state transition.

Tuberculosis among individuals with community-acquired pneumonia presenting to emergency in Gaborone, Botswana

Delays in diagnosing Tuberculosis (TB) are associated with increased transmission. TB may present as a clinical syndrome that mimics community-acquired pneumonia (CAP). The aim of this paper was to determine frequency of TB among patients with CAP at a referral hospital in Gaborone, Botswana. We performed a retrospective study of adults presenting with CAP from April 2010-October 2011 to the Emergency Department (ED);we matched this cohort to the National Botswana Tuberculosis Registry (NBTR) to identify individuals subsequently diagnosed with TB. We assessed demographics, time to TB diagnosis, clinical outcomes and performed logistic regressions to identify factors associated with TB diagnosis. We identified 1305 individuals presenting with CAP;TB was subsequently diagnosed in 68 (5.2%). The median time to TB diagnosis was 9.5 days. Forty percent were AFB sputum smear positive and 87% were identified as being HIV-positive. Subsequent diagnosis of TB is common among individuals with CAP at our ED, suggesting that TB may be present at the time of CAP presentation. Given the lack of distinguishing clinical factors between pulmonary TB and CAP, adults presenting with CAP should be evaluated for active TB in Botswana

Impact of total knee replacement practice: cost effectiveness analysis of data from the Osteoarthritis Initiative.

Objectives To evaluate the impact of total knee replacement on quality of life in people with knee osteoarthritis and to estimate associated differences in lifetime costs and quality adjusted life years (QALYs) according to use by level of symptoms.Design Marginal structural modeling and cost effectiveness analysis based on lifetime predictions for total knee replacement and death from population based cohort data.Setting Data from two studies-Osteoarthritis Initiative (OAI) and the Multicenter Osteoarthritis Study (MOST)-within the US health system.Participants 4498 participants with or at high risk for knee osteoarthritis aged 45-79 from the OAI with no previous knee replacement (confirmed by baseline radiography) followed up for nine years. Validation cohort comprised 2907 patients from MOST with two year follow-up.Intervention Scenarios ranging from current practice, defined as total knee replacement practice as performed in the OAI (with procedural rates estimated by a prediction model), to practice limited to patients with severe symptoms to no surgery.Main outcome measures Generic (SF-12) and osteoarthritis specific quality of life measured over 96 months, model based QALYs, costs, and incremental cost effectiveness ratios over a lifetime horizon.Results In the OAI, total knee replacement showed improvements in quality of life with small absolute changes when averaged across levels of confounding variables: 1.70 (95% uncertainty interval 0.26 to 3.57) for SF-12 physical component summary (PCS); -10.69 (-13.39 to -8.01) for Western Ontario and McMaster Universities arthritis index (WOMAC); and 9.16 (6.35 to 12.49) for knee injury and osteoarthritis outcome score (KOOS) quality of life subscale. These improvements became larger with decreasing functional status at baseline. Provision of total knee replacement to patients with SF-12 PCS scores <35 was the optimal scenario given a cost effectiveness threshold of $200 000/QALY, with cost savings of $6974 ($5789 to $8269) and a minimal loss of 0.008 (-0.056 to 0.043) QALYs compared with current practice. These findings were reproduced among patients with knee osteoarthritis from the MOST cohort and were robust against various scenarios including increased rates of total knee replacement and mortality and inclusion of non-healthcare costs but were sensitive to increased deterioration in quality of life without surgery. In a threshold analysis, total knee replacement would become cost effective in patients with SF-12 PCS scores ≤40 if the associated hospital admission costs fell below $14 000 given a cost effectiveness threshold of $200 000/QALY.Conclusion Current practice of total knee replacement as performed in a recent US cohort of patients with knee osteoarthritis had minimal effects on quality of life and QALYs at the group level. If the procedure were restricted to more severely affected patients, its effectiveness would rise, with practice becoming economically more attractive than its current use.