Coronary reperfusion in primates. Serial electrocardiographic and histologic assessment.

After acute coronary occlusion in primates, the time period during which reperfusion results in significant salvage of reversibly injured myocardium was investigated. In 23 monkeys, the left anterior descending coronary artery was occluded from 1 to 6 h; and in 5 others, occlusion was maintained for the 1-wk study. Unipolar epicardial electrocardiograms were monitored from mapping points on the anterior and lateral left venticle. S-T segment elevation (S-T upward arrow) and R + S wave amplitude (RS) were measured before occlusion and at regular intervals during occlusion and reperfusion. Summated S-T upward arrow (SigmaS-T upward arrow) and summated RS (SigmaRS), computed for mapping points demonstrating greater than 2 mV S-T upward arrow, were used as serial measures of electrical injury. SigmaS-T upward arrow peaked within 2-h postocclusion and then gradually declined throughout the period of occlusion suggesting the progress of infarction within the area of injury. After reperfusion SigmaS-T upward arrow rapidly declined to near cnotrol values indicating the extent of reversible injury. During the period of occlusion, the magnitude of voltage loss in SigmaS-T upward arrow as a percent of maximum SigmaS-T upward arrow was proportional to the duration of occlusion, though the rate of loss decreased with increasing time of occlusion. Reperfusion after 6 h of occlusion resulted in reversal of only a small remaining component of the maximum current of injury. The voltage decrease in SigmaRS (from control values) was proportional to the duration of occlusion, though the decrease was accelerated during the first 2-h postocclusion. Whereas reperfusion interrupted the decline in SigmaRS, a consistent increase in SigmaRS postreperfusion was observed only after occlusion of 1 h. With respect to reperfusion groups, significance in SigmaS-T upward arrow voltage loss as a percent of maximum SigmaS-T upward arrow was demonstrated between 2-h and 4-h, 4- and 6-h, and 6-h and chronically ligated animals. Significance in SigmaRS voltage loss as a percent of control SigmaRS was demonstrated between 2- and 4-h, and 4- and 6-h reperfusion groups. Hearts were excised at 7 days for histological assessment of infarct size. Planimetric determination of left ventricular areas and areas of necrosis using slides made from 10 serial cross sections were used in estimating the percent of left ventricle infarcted. A significant reduction in infarct size was demonstrated between reperfused animals at 2 h and the 4- and 6-h reperfusion groups. A trend was noted suggesting increasing infarct size up to 6 h after experimental occlusion.

Regional myocardial blood flow in experimental myocardial infarction after pretreatment with aspirin.

The effects of aspirin on myocardial blood flow in an area of ischemia were studied in 12 baboons. In each, a diagonal branch of the left anterior descending coronary artery was ligated. Six of the baboons received aspirin (2 X 600 mg orally, 12 hours and 1 hour before ligation); the other six did not receive aspirin and served as a control group. The extent of myocardial ischemia was delineated with an electrode wire grid on the surface of the anterior left ventricular wall. The maximal area circumscribed by electrodes with 2 mV or more ST segment elevation was compared with the area of reduced myocardial blood flow. Myocardial blood flow was measured with the radioactive microspheres method using strontium-85-labeled carbonized spheres. Two areas of reduced myocardial blood flow were noted, one with severely reduced flow in the center of the myocardial infarct (0 to 49% of noninfarcted myocardium) and another with mild to moderately reduced myocardial blood flow at the border of the myocardial infarct (50 to 90% of noninfarcted myocardium). Myocardial blood flow in the border area (margins of ST elevation area) for the total wall was 85 +/- 8% of normal in the aspirin-treated animals and 40 +/- 4% in the control group (p less than 0.01); for the epicardium it was 67 +/- 10% of normal in noninfarcted myocardium after aspirin and 37 +/- 5% for the control group (p less than 0.05); and for the endocardium it was 78 +/- 8% of normal in noninfarcted myocardium after aspirin and 39 +/- 6% in the control group (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Failure of mannitol to reduce myocardial infarct size in the baboon.

OBJECTIVE: The aim was to determine whether mannitol, previously shown to have several myocardial protective properties, could reduce the myocardial infarct size after coronary occlusion in the baboon. METHODS: Anaesthetised baboons underwent a 2 h transient coronary artery occlusion. Each was randomised into one of two groups receiving either mannitol (n = 6) or no adjunct (n = 8). Mannitol (20%) was given at a rate of 0.4 ml.min-1 x kg-1 starting at 105 min postocclusion until reperfusion was allowed at 2 h, and at a rate of 0.2 ml.min-1 x kg-1 thereafter, until a total of 500 ml had been delivered. Changes in the ST segments were recorded with epicardial wires. The animals were killed at 24 h postocclusion and the hearts excised. Silicone microvascular dye was injected into the previously occluded coronary artery to delineate the perfusion bed. The hearts were fixed in formalin, sliced, and mounted on slides. Using planimetry the ratios of the mean volume of infarct to the mean volume of the perfusion bed (VI/VPB) were calculated and compared. RESULTS: The VI/VPB for the mannitol treated group was 71.7(SEM 14.0)% and for the control group, 65.6(6.9)% (NS). No significant difference was noted in the mean summated ST segment elevations between the two groups. CONCLUSIONS: Mannitol does not reduce myocardial infarct size or ischaemia in the baboon.

Quantitative effect of a single large dose of methylprednisolone on infarct size in baboons.

Despite numerous studies directed at determining the ability of glucocorticoids to minimise myocardial ischaemic damage following acute coronary occlusion, there remains no clear consensus concerning their usefulness. Within an ischaemic region, glucocorticoids produce membrane stabilising effects which decrease the autolytic effects of marked cellular swelling and lysosomal membrane rupture. Their use has also been associated with a decreased cellular lysis due to infiltrating inflammatory cells and with an increase in collateral blood flow. The use of glucocorticoids has remained clinically attractive due to experimental observations regarding these local actions; however, the potential of these actions to enhance long-term viability of ischaemic myocardium has remained uncertain. A major problem in the comparison of the extent of infarction between treated and untreated animals has been the variability in infarct size that results from coronary artery ligation at any given anatomical site. In the experimental baboon model which we have employed, we have previously shown that the ultimate epicardial area of infarction, as well as the volume of infarction as assessed histologically at 7 days post occlusion, shows a good linear relationship to the area of ischaemic injury at 1-hour post occlusion, as assessed by high resolution epicardial ST segment mapping. In this way animals may serve as their own controls and as long as an intervention is initiated at 1 h or later post occlusion, then the epicardial area or transmural volume of histologically assessed infarction at 7 days can be compared with the predicted epicardial area or transmural volume of infarction and hence determine the effect of that intervention in altering infarct size. This experimental model does not rely on a comparison of the absolute magnitude of infarcts between treated and untreated animals and, therefore, avoids the error introduced by the inherent variability in infarct size between animals after coronary occlusion.

Infarct distribution in subhuman primates after acute coronary occlusion.

The extent of epicardial, endocardial and septal infarct was determined in 24 monkeys and five baboons 1 week after acute left anterior descending or diagonal branch coronary artery ligation. All 24 Macaca cynmologous monkeys had non-dominant left anterior descending coronary arteries. A snare ligature was placed just distal to the first diagonal branch for varying time periods (1, 2, 4, and 6 h followed by reperfusion or left in place permanently). In five baboons a chronic ligature was placed around a diagonal branch. All animals lived and were killed a week later. Histological mapping and planimetry of serial cross-sections were employed to quantify the extent and distribution of the infarct. All infarcts were transmural. The extent of epicardial infarct was significantly greater than the extent of endocardial infarct for 2 h ligations (3.5 +/- 0.87% of the left ventricle versus 2.4 +/- 0.58% of the left ventricle, P less than 0.05), the chronic left anterior descending coronary artery ligations (5.4 +/- 1.06% of the left ventricle versus 4.5 +/- 0.92% of the left ventricle, P less than 0.05 and for the chronic diagonal branch ligations (4.06 +/- 0.66% of the right ventricle + left ventricle versus 2.64 +/- 0.51+ of the right ventricle + left ventricle, P less than 0.02). It is evident, however, that the magnitude of this epicardial preponderance was not great and that, in general, the infarcts were transmural and rectangular in configuration.

Reduction in infarct size by synchronized selective coronary venous retroperfusion of arterialized blood.

The effectiveness of selective synchronized pulsatile coronary venous retroperfusion for the temporary metabolic support of a region of acutely ischemic myocardium has previously been demonstrated. This study was designed to determine the degree of reduction in ultimate infarct size that may be achieved when coronary venous retroperfusion initiated early after coronary occlusion is combined with later anterograde reperfusion. In 10 baboons, the proximal left anterior descending coronary artery was occluded for 4 hours at which time anterograde reperfusion was restored. In five baboons (Group A), coronary venous retroperfusion was initiated 15 minutes after occlusion. Five baboons (Group B) underwent an identical procedure without coronary venous retroperfusion. Epicardial electrograms were recorded from 24 sites overlying the ischemic region. At 24 hours, hearts were excised and serial transverse sections of the left ventricle were stained with nitroblue tetrazolium for stereometric determination of infarct size. In Group A 12 +/- 5.4 percent (mean +/- standard error of the mean) of epicardial sites with S-T segment elevation at 15 minutes after occlusion showed subsequent Q waves, compared with 96 +/- 2.3 percent in Group B (p less than 0.01). In Group A 4.8 +/- 1.7 percent of the left ventricular mass was infarcted, compared with 30.6 +/- 4.2 percent in Group B (p less than 0.01). The results demonstrated the effectiveness of coronary venous retroperfusion in preserving ischemic myocardium such that anterograde reperfusion resulted in a mean reduction of 84 percent in ultimate infarct size.

Failure of nifedipine therapy to reduce myocardial infarct size in the baboon.

The value of nifedipine in reducing the ultimate size of an infarct associated with a period of coronary occlusion followed by reperfusion was assessed. Eight baboons were administered a bolus dose of nifedipine, 5 micrograms/kg intravenously, and then a maintenance dose of 30 micrograms/kg per hour was begun 1 hour before occlusion. This regimen resulted in an 8.5 +/- 1.2 percent (mean +/- standard error) decrease in mean arterial pressure. The left anterior descending coronary artery was occluded for 2 hours and then perfusion restored. At 2 hours after reperfusion the nifedipine infusion was discontinued. Eight control baboons underwent an identical protocol without nifedipine therapy. At 24 hours after occlusion, microvascular dyes were injected into the left anterior descending coronary artery and adjacent arteries to delineate the perfusion bed of the previously occluded artery. The volume of infarction was determined with planimetry and compared with the volume of the perfusion bed of the occluded artery. The area of infarction was always contained within the perfusion bed of the occluded artery. The mean percent of the perfusion bed with infarction was 50.1 +/- 5.8 in the control group and 41.7 +/- 9.5 in the treated group (difference not significant; p greater than 0.05). In both control and treated groups of baboons hemorrhage occurred only within the region of infarction. In both groups electron microscopy revealed large electron-dense granules within the mitochondria. In conclusion nifedipine therapy during a 2 hour period of coronary occlusion followed by reperfusion did not result in any significant reduction in ultimate infarct size in the baboon.

Quantitative assessment in infarct size reduction by coronary venous retroperfusion in baboons.

Initial favorable reports in which coronary venous retroperfusion was begun after acute coronary artery occlusion have demonstrated a reversal of ischemic injury and improved left ventricular function. However, little information has been generated to document the extent to which retroperfusion may decrease ultimate histologically determined infarct size. The objective of the present study was to evaluate the effectiveness of retroperfusion in reducing infarct size by using an accurate quantitative method in which infarct size was related to the size of the anatomic perfusion bed of the occluded artery (region at risk for infarction). In an experimental group of 5 baboons, the left anterior descending coronary artery was occluded and coronary venous retroperfusion started 1 hour after occlusion. After a 4-hour period of occlusion, retroperfusion was discontinued and anterograde perfusion was simultaneously restored. A control group of 5 baboons underwent an identical procedure without retroperfusion. Twenty-four hours after occlusion, hearts were excised and the previously occluded left anterior descending coronary artery as well as the adjacent arteries were infected with microvascular dye to delineate the perfusion bed of the occluded artery. Planimetry of serial corss-sections of the left ventricle enabled the size of the perfusion bed of the occluded artery and size of the infarct to be determined. The mean percentage of the perfusion bed infarcted in the control group was 94.1 +/- 0.9 (mean +/- standard error) and in the retroperfused group was 57.4 +/- 3.5 (p less than 0.001). Hence, the results demonstrated that when retroperfusion was initiated after 1 hour of coronary occlusion, the mean percentage of the perfusion bed salvaged was increased by 36.7%.

Trypanosome infections of the tsetse fly Glossina pallidipes in the Luangwa Valley, Zambia.

Trypanosome infections of Glossina pallidipes were investigated at a site in the Luangwa Valley, Zambia between June 1991 and September 1992. Almost 3700 flies were captured, dissected, screened for trypanosome infection, and aged using both wing fray and (for females) ovarian categories. DNA probes were used to identify midgut infections. Prevalences of mature infections were 6.2% Trypanosoma vivax-type and 3.1% T. congolense-type (including low prevalances of T. brucei, T. simiae and another Nannomonas species). The prevalence of infection increased with age. For both types of infection this relationship could be described by a simple 'catalytic' model which generates estimates of per capita rates of infection. Prevalences varied significantly with time independently of any changes in the age structure of the tsetse population. This may reflect temporal variation in the per capita rates of infection.

Does intravenous glutamine prevent bacterial translocation in hemorrhagic shock?

Bacterial translocation across the gut wall may be associated with insult to the latter. In this situation, intestinal flora can enter the blood stream and lymph nodes and be transported to other organs. Glutamine is a nonessential amino acid not presently included in total parenteral nutrition (TPN) preparations. The use of glutamine-enriched TPN in the rat has resulted in a significant reduction in bacterial translocation. This study attempted to evaluate the role of glutamine in preventing bacterial translocation following hemorrhagic shock in a rat model. Forty Sprague-Dawley rats were equally divided into two groups. The controls were given TPN solution, while the treated group had glutamine instead of the standard alanine present in TPN. Hemorrhagic shock was induced in both groups and blood cultures were performed. Glutamine-treated rats did not show a significant difference in survival suggesting that it is of no particular value in severe hemorrhagic shock in rats.

Aneurysm of the thoracic aorta. Review of 260 cases.

In a 1980 review of the natural history and treatment of 176 thoracic aortic aneurysms, we noted the high incidence of rupture (47% overall) in 135 patients not treated surgically. Since that original study we have added another 84 patients to our series and have noted a complete change in management such that most patients are now treated surgically. We now have 260 patients in our series, 126 of whom were treated surgically. Sixty-seven were emergency operations and 59 were elective. Surgical mortality was 8% for elective resection and 33% for emergency operation. Over the past 5 years these figures have improved to 5% surgical mortality for elective resection and 16% surgical mortality for emergency resection. The 5 year survival rates for the entire series were 50% for patients treated with elective operation, 30% for combined emergency and elective operation groups, and 21% for nonsurgically treated patients. Abdominal aortic aneurysm was present in 74 patients (28%) and 23 of these patients had undergone a prior resection of an abdominal aortic aneurysm. This series documents the improved survival of patients with aneurysms of the thoracic aorta who are treated with prompt surgical intervention. It also further substantiates earlier findings of a high incidence of aneurysms of the abdominal aorta in this patient population.

Hemorrhagic infarction and coronary reperfusion.

Coronary ligation experiments were performed on 23 primates. Some of the experiments were followed by reperfusion after periods of occlusion of from 1 to 6 hours. Hemorrhage into the infarct was noted in all animals and was greatest following reperfusion after 4 hours of occlusion or longer. Hemorrhage increases the measured infarct size to the point that it is actually larger than that seen with ligation alone. However, this increase is accounted for by the larger amount of intramyocardial hemorrhage. Hemorrhage is greatest in the center of the infarct and decreases at the margins. It appears that hemorrhage occurs into necrotic muscle and does not occur significantly at the margins of the infarct where damage to otherwise viable myocardium might result.

Surgical treatment of lung cancer in patients over the age of 70 years.

Eighty patients of 70 years of age with lung cancer have been treated since 1964. Forty-eight received no therapy or chemotherapy and/or irradiation. Mean survival was 3.5 to 10 months, and only three (6%) survived for 2 years. Twenty-two of 32 patients selected for thoracotomy underwent resection for cure (70%). The operative mortality rate was 18% for resection, and 64% of the patients survived for at least 2 years. The incidence of exploratory thoracotomy decreased in the last 5 years of the study with the introduction of more rigorous preoperative evaluation. The poor survival rate without resection and the favorable survival rate following recovery from resection support the continued use of surgical resection for lung cancer in elderly patients, despite an increased operative risk.

Surgical resection of giant metastatic leiomyosarcoma of the heart.

A 44-year-old woman underwent a hysterectomy for leiomyosarcoma in 1969. Cardiac invasion was detected in 1981 but the tumor was considered inoperable. In 1985, 16 years after hysterectomy, malignant tamponade developed as a result of a massive tumor arising from the left ventricle. Emergency decompression by median sternotomy and tube thoracostomy was followed a week later by tumor resection and simultaneous excision of a lung metastasis with the aid of cardiopulmonary bypass. The cardiac tumor weighed 719 gm. A residual pelvic tumor found on a computed tomographic scan was subsequently removed. She is alive and well 22 months after the operation. Aggressive surgical resection of cardiac and other metastases of this slowly growing tumor can be lifesaving.

Distribution and severity of atherosclerosis in the coronary arteries.

A postmortem study of 93 human hearts was undertaken. Gross inspection was used to determine the degree of atherosclerosis and postmortem coronary angiography to estimate the degree of luminal narrowing. The findings indicate the following: (1) There is high correlation between the estimates of luminal narrowing in the gross specimen and the presence of significant atherosclerosis. (2) Approximately 30 per cent of vessels with significant proximal disease will have significant distal coronary artery disease. (3) When one coronary artery is involved with severe proximal atherosclerosis, either of the other two vessels are likely to be involved, with a frequency of 75 per cent ormore. (4) When significant distal disease is present the proximal vessel is nearly always involved. (5) Patient selection prior to referral to surgery may be partly responsible for the over 90 per cent operability rate in patients undergoing coronary artery bypass grafting.

Ventricular septal defect and aortic insufficiency. Surgical treatment.

Twenty-five patients with ventricular septal defect (VSD) associated with aortic insufficiency (AI) have been since 1964. Of these patients, one died suddenly without operation; in 2 patients, AI developed in the late postoperative period following VSD closure; and in 3 others, AI developed shortly after VSD closure. The remaining 19 patients are discussed in detail. The VSD was subpulmonic in 13 (68 per cent) and subcristal in 6 (32 per cent). Primary suture of the VSD was undertaken in 13 patients and patch closure in 6. Seven patients had aortic valvuloplasty and 2 had aortic valve replacement. There were no surgical deaths, and the long-term follow-up shows that VSD closure alone has been sufficient to arrest progression of AI in patients with mild insufficiency, particularly in those with subpulmonic VSD. Valvuloplasty, when necessary, was more effective when done at an early age.

Acute thrombotic obstruction with Björk-Shiley valves: diagnostic and surgical considerations.

Eight patients have had thrombotic obstruction of a prosthetic valve since 1971, six mitral valves and two aortic. All eight patients had a Björk-Shiley valve. During the same period 159 Björk-Shiley valves were placed, 85 in the mitral and 74 in the aortic area. This represents a valve thrombotic occlusive incidence of 4.4 percent in our series, 5.9 percent of mitral and 2.7 percent of aortic prostheses. Among the six patients with mitral prostheses only one survived. The two patients with occluded aortic valves survived. The onset of symptoms was very abrupt in most patients and progressed very rapidly. Acute pulmonary edema was observed in five patients. Anticoagulation was considered inadequate in all patients. Aspirin or dipyridamole was being used in seven patients at the time of thrombosis. The data indicate a high frequency of thrombotic occlusion of Björk-Shiley valves in the absence of full anticoagulation with warfarin derivatives and emphasizes the urgent need for surgery once valve thrombosis is suspected.

Effect of left ventricular--to--aortic bypass on infarct size and infarct microcirculation in baboons.

A major diagonal branch of the left anterior descending coronary artery (LAD) was acutely occluded in 17 baboons. Complete left ventricular (LV) decompression was achieved with a left heart bypass (LHB) system in six baboons while 11 baboons served as untreated controls. In the treated group, LHB was initiated after 30 minutes of coronary occlusion. For a period of 6 hours after occlusion, aortic pressure, LV pressure, left atrial pressure, and cardiac output were monitored. During the same monitoring period, electrograms were recorded from a high resolution matrix of fixed epicardial electrodes. Regional myocardial blood flow was determined prior to and at intervals following the initiation of LHB with radioactive microspheres. Infarct size was assessed histologically from serial cross sections of the left ventricle. The degree of salvage achieved by LHB was assessed by comparing the epicardial area of infarction 6 hours after occlusion (AI) to the area of epicardial St-segment elevation (STE) 30 minutes after occlusion (maxAST). In the LHB-treated group, 40.0% +/- 8.1% (SEM) of maxAST showed subsequent infarction; in the control group, 79.8% +/- 2.7% of maxAST showed eventual infarction (p less than 0.01). STE overlying the region of ischemia in the LHB-treated group did not undergo the spontaneous decline observed in the control group, which is normally associated with the progression of necrosis. Regional myocardial blood flow did not change significantly in the ischemic region during the period of occlusion following LHB. LHB. The results suggest that LHB is capable of substantial salvage of acutely ischemic myocardium by reducing myocardial work and thus reducing myocardial oxygen requirements.

Effects of perfluorocarbon exchange transfusion on reducing myocardial infarct size in a primate model of ischemia-reperfusion injury: a prospective, randomized study.

BACKGROUND: This study was undertaken to test the hypothesis that perfluorocarbons were able to reduce myocardial infarct size in a baboon model of ischemia-reperfusion injury. Exchange transfusion of perfluorocarbons has been shown to reduce myocardial infarct size in the dog, who, unlike the baboon, has an extensive collateral circulation. METHODS: After 15 minutes of occlusion of the left anterior descending coronary artery, 14 baboons were bled to attain a hematocrit of 24% to 26% and were simultaneously transfused, six with Fluosol-DA 20% emulsion and eight with FC-43 emulsion. After 2 hours of ligation, the coronary arteries were reperfused. Baboons were killed 24 hours after ligation, and the hearts were excised. Microvascular dye was infused into the coronary artery to delineate its perfusion bed. Ratios of the mean volume of infarct to the mean volume of perfusion bed were calculated and compared by use of planimetry. A similar protocol was followed in two other groups of baboons except that lactated Ringer's solution was infused into six of them, whereas eight had no exchange transfusions. RESULTS: The ratios of the mean volume of infarct to the mean volume of perfusion bed of the four groups were as follows: Fluosol-DA, 38.1% +/- 7.5%; FC-43, 37.7% +/- 8.3%; lactated Ringer's, 46.9% +/- 10.5%; controls, 65.6% +/- 6.9%. Statistical significance was reached when comparing both perfluorocarbon-treated groups with the controls (p < 0.05 for both groups) but not significant when comparing them with the Ringer's lactate-treated group. CONCLUSIONS: Results suggest that the beneficial effects of exchange transfusion with the perfluorocarbons may be primarily due to hemodilution.

Variations in pediatric pneumonia and bronchitis/asthma admission rates. Is appropriateness a factor?

OBJECTIVE: To explore through a pilot study the relationship between appropriateness (medical necessity) and variations in pediatric hospital admission rates across several communities in the Boston (Mass) area for two common pediatric conditions with extremely variable admission rates: pneumonia and bronchitis/asthma. DESIGN: We identified five communities in the greater Boston area with high, average, and below-average ratios of observed to expected admissions for the study conditions. Diagnosis-specific, criteria-based utilization review instruments were developed by community-based pediatricians and applied by trained nurse reviewers to medical records. ADMISSIONS STUDIED: All admissions for pneumonia (diagnosis related group [DRG] 91) and bronchitis/asthma (DRG 98) of study area residents younger than 18 years to participating hospitals during fiscal year 1986. OUTCOME MEASURES: For each area, we calculated age-adjusted admission rates, age-adjusted observed to expected ratios, and rates of inappropriate admissions. We tested the hypothesis that admission rates and inappropriateness rates were directly related. RESULTS: We deemed 9.4% of pneumonia admissions and 4.4% of bronchitis/asthma admissions inappropriate. Rates of inappropriate admissions were not significantly associated with admission rates in this local pilot study for either study condition at P < .05. However, in one community both rates were high for both conditions. Feedback of findings to the key local hospital there resulted in sharp decreases in admission rates for DRGs 91 and 98 in subsequent years. CONCLUSIONS: Our results suggest that higher pediatric admission rates may not be associated with higher rates of inappropriateness. Further research is needed, with a larger number of communities, to differentiate practice patterns more precisely and explore patient and family preferences.