COVID-19 vaccine mandate for healthcare workers in the United States: a social justice policy.

INTRODUCTION: Vaccination is the most effective strategy to mitigating COVID-19 and restoring societal function. As the pandemic evolves with no certainty of a herd immunity threshold, universal vaccination of at-risk populations is desirable. However, vaccine hesitancy threatens the return to normalcy, and healthcare workers (HCWs) must embrace their ambassadorial role of shoring up vaccine confidence. Unfortunately, voluntary vaccination has been suboptimal among HCWs in the United States, a priority group for whom immunization is essential for maintaining health system capacity and the safety of high-risk patients in their care. Consequently, some health systems have implemented mandates to improve compliance. AREAS COVERED: This article discusses the ethical and practical considerations of mandatory COVID-19 vaccination policies for HCWs utilizing some components of the World Health Organization's framework and the unique context of a pandemic with evolving infection dynamics. EXPERT OPINION: COVID-19 vaccine mandates for universal immunization of HCWs raise ethical and practical debates about their appropriateness, especially when the vaccines are pending full approval in most jurisdictions. Given the superiority of the vaccines to safety and testing protocols and their favorable safety profile, we encourage health systems to adopt vaccination mandates through participatory processes that address the concerns of stakeholders.

Pressure measurement made by the utilization of ruby sharp-line luminescence.

A rapid, convenient technique for precision pressure measurement in the diamond-anvil high-pressure cell, which makes use of the sharp-line (R-line) luminescence of ruby, has been developed. The observed shift is -0.77 +/-0.03 reciprocal centimeters per kilobar for R(1) and -0.84+/- 0.03 reciprocal centimeters per kilobar for R(2) to lower energy and is approximately linear in the range studied (to 22 kilobars). Line-broadening has been observed in some instances and has been tentatively identified with nonhydrostatic conditions surrounding the ruby sample.

Nitroglycerin and heterogeneity of myocardial blood flow. Reduced subendocardial blood flow and ventricular contractile force.

The effects of both intracoronary and intravenous administration of nitroglycerin on transmural distribution of blood flow in the left ventricle after partial coronary artery occlusion was investigated using two independent methods. In 16 open chest, anesthetized dogs, tubing supplying the cannulated left coronary artery was partially occluded. Strain gauges sutured paralled to superficial and deep fibers of the myocardium separately recorded the contractile force of each layer. With occlusion set so that depression of the deep contractile force was imminent. 12 mug intracoronary nitroglycerin in seven dogs depressed only the deep contractile force without changing systemic hemodynamics. Intravenous administration of 180 mug nitroglycerin in nine dogs resulted in a decrease of deep contractile force and aortic pressure often associated with an increase in superficial contractile force. Distribution of myocardial blood flow during peak coronary flow after intracoronary administration of nitroglycerin or during a decrease in aortic pressure after intravenous nitroglycerin administration was determined by the tissue uptake of an intracoronary bolus of rubidium-(80). This was compared with the uptake of potassium-(42) injected before nitroglycerin. Intravenous or intracoronary administration of nitroglycerin caused a significant reduction in subendocardial blood flow with a decrease in the subendocardial/subepicardial ratio of isotope. These experiments suggest that under conditions of acute partial coronary occlusion, the autoregulatory response results in more fully dilated subendocardial vessels causing them to be less responsive to nitroglycerin. Nitroglycerin may then reduce the vascular resistance in the subepicardial more than the subendocardial vessels, resulting in a "steal" of blood flow from deep to superficial myocardium.

Lateral border zone: quantitation of lateral extension of subendocardial infarction in the dog.

This study was undertaken to quantitate the lateral extension that occurs concomitantly with the transmural extension of a subendocardial infarction. A subendocardial infarct was produced in 12 dogs by a 40 minute temporary coronary artery occlusion. Infarct extension was induced 7 days later by permanent occlusion of the same vessel. Regional myocardial blood flows confirmed that ischemia had been produced with both coronary artery occlusions. The vascular boundaries between the normally perfused and ischemic beds were defined by perfusion with different-colored Microfil solutions. The extent of subendocardial infarction and subsequent transmural and lateral extensions were assessed by point counting of histologic specimens. The initial temporary occlusion produced a 30.0 +/- 4.2% transmural infarct and the subsequent permanent occlusion a 29.2 +/- 3.5% transmural extension in a risk region of 39 +/- 4 g. Lateral extension was not measured in four dogs because the initial subendocardial infarct was patchy with markedly irregular lateral borders. In eight dogs the size of the measured lateral infarct extension from each lateral margin from two histologic sections was 0.63 +/- 0.013 cm2. The area of both lateral extensions was 1.7 +/- 0.1% of the cross-sectional area of its risk region as determined by planimetry. Using a model of the risk region, the mass of the lateral extension was estimated to be 1.4 +/- 0.3 g or 3.5 +/- 0.6% of the region at risk. Thus, at the lateral margin of a subendocardial infarct there is a border zone that is small relative to the size of the region at risk and infarcted myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term therapy with a new cardiotonic agent, WIN 47203: drug-dependent improvement in cardiac performance and progression of the underlying disease.

Seven patients with severe chronic congestive heart failure were treated with a new cardiotonic agent, WIN 47203 (an analog of amrinone), for an average of 7.4 weeks (range 2 to 15). At the initiation of therapy, hemodynamic improvement occurred in all patients as the cardiac index increased from 1.79 +/- 0.39 to 2.30 +/- 0.44 liters/min per m2 (probability [p] less than 0.05) and pulmonary capillary wedge pressure decreased from 24.1 +/- 6.7 to 16.1 +/- 7.8 mm Hg (p less than 0.05). Long-term therapy produced a substantial symptomatic improvement in five of the seven patients. This improvement was fully sustained in two patients and the remaining three experienced a partial return of their symptoms even though the initial hemodynamic improvements at rest remained evident in all seven patients. Withdrawal of WIN 47203 precipitated hemodynamic deterioration in all patients. The cardiac index decreased from 2.25 +/- 0.40 to 1.64 +/- 0.46 liters/min per m2 (p less than 0.05) while the pulmonary capillary wedge pressure increased from 17.1 +/- 7.8 to 23.2 +/- 12.0 mm Hg (p less than 0.05). Stroke volume index after withdrawal was lower than the control level before therapy (17.0 +/- 6.6 versus 20.3 +/- 4.7 ml/m2; p less than 0.05) and pulmonary capillary wedge pressure was similar. During long-term therapy, no undesirable side effects or hematologic changes were observed. Thus, drug-dependent hemodynamic benefits and apparent progression of the underlying cardiac disease were demonstrated during long-term therapy with WIN 47203.

Impaired endothelium-mediated vasodilation in the peripheral vasculature of patients with congestive heart failure.

Impaired endothelial-dependent vasodilation has been demonstrated in two animal models of congestive heart failure and in the coronary circulation of patients with idiopathic dilated cardiomyopathy. To determine whether this impairment contributes to the abnormal peripheral vasomotor tone in patients with congestive heart failure, the local vascular response to intraarterial infusions of graded concentrations (10(-8) M to 10(-5) M) of acetylcholine (an endothelial-dependent vasodilator) and nitroglycerin (a direct-acting vasodilator) was studied in the superficial femoral artery of 19 patients with congestive heart failure (New York Heart Association classes I to IV) and 6 age-matched normal control subjects. The local vascular response was determined from the arterial blood flow velocity pattern obtained by transcutaneous Doppler ultrasonography. Acetylcholine, 10(-5) M, induced a pattern characteristic of vasodilation in all six normal subjects; mean blood flow velocity for the group significantly increased from 11.9 +/- 2.7 to 44.8 +/- 20.9 cm/s (p less than 0.05). In contrast, the same dose of acetylcholine induced a blood flow velocity pattern characteristic of vasodilation in only 4 of the 19 patients with congestive heart failure. Group mean blood flow velocity did not change significantly. Nitroglycerin, 10(-7) M, induced vasodilation in all 6 normal subjects but in only 1 of 19 patients. Nitroglycerin, 10(-5) M, was administered to 10 patients; all 10 demonstrated a pattern characteristic of vasodilation. Thus, acetylcholine-mediated endothelial-dependent vasodilation appears to be impaired in the peripheral vasculature of patients with congestive heart failure. Both endothelial dysfunction and abnormal vascular smooth muscle responsiveness may contribute to abnormal peripheral vasomotor tone.

Outcome and profile of ventricular septal rupture with cardiogenic shock after myocardial infarction: a report from the SHOCK Trial Registry. SHould we emergently revascularize Occluded Coronaries in cardiogenic shocK?

OBJECTIVES: We wished to assess the profile and outcomes of patients with ventricular septal rupture (VSR) in the setting of cardiogenic shock (CS) complicating acute myocardial infarction (MI). BACKGROUND: Cardiogenic shock is often seen with VSR complicating acute MI. Despite surgical therapy, mortality in such patients is high. METHODS: We analyzed 939 patients enrolled in the SHOCK Trial Registry of CS in acute infarction, comparing 55 patients whose shock was associated with VSR with 884 patients who had predominant left ventricular failure. RESULTS: Rupture occurred a median 16 h after infarction. Patients with VSR tended to be older (p = 0.053), were more often female (p = 0.002) and less often had previous infarction (p < 0.001), diabetes mellitus (p = 0.015) or smoking history (p = 0.033). They also underwent right-heart catheterization, intra-aortic balloon pumping and bypass surgery significantly more often. Although patients with rupture had less severe coronary disease, their in-hospital mortality was higher (87% vs. 61%, p < 0.001). Surgical repair was performed in 31 patients with rupture (21 had concomitant bypass surgery); 6 (19%) survived. Of the 24 patients managed medically, only 1 survived. CONCLUSIONS: There is a high in-hospital mortality rate when CS develops as a result of VSR. Ventricular septal rupture may occur early after infarction, and women and the elderly may be more susceptible. Although the prognosis is poor, surgery remains the best therapeutic option in this setting.

Comparative effects of vasodilator drugs on large and small coronary resistance vessels in the dog.

One of the mechanisms whereby nitroglycerin is considered to reduce myocardial ischaemia and spasm is its preferential reduction of resistance of large compared with small coronary arteries. Accordingly, the action of nitroglycerin on these two resistance beds was compared with newer coronary vasodilator drugs. Following intracoronary administration of boluses of each drug, large and small vessel coronary resistance was measured in 14 dogs by recording the pressure drop across each vascular bed while flow was held constant. The dose of each drug was given to reduce small vessel resistance by 30% (range means 27 to 32%) which peaked at 5 to 10 s and declined to 8 to 18% at 1 min when reduction in large vessel resistance was at its maximum. At 1 min the large vessel resistance was decreased 56 +/- 5% by nitroglycerin, 23 +/- 5% by nitroprusside, 8 +/- 4% by perhexiline, 0 +/- 5% by verapamil and increased 8 +/- 5% by nifedipine. Nitroprusside reduced the large vessel resistance significantly less than nitroglycerin (P < 0.001) for an equivalent reduction in small vessel resistance. Perhexiline, verapamil and nifedipine did not significantly reduce large vessel resistance and the discrepancy between these results and their antianginal and antispasm effect in humans was not apparent from these experiments. However, a suitable model of coronary spasm in the dog following ergonovine injection could not be created.

The influence of transient hyperprolactinemia on in vitro fertilization in humans.

Hormonal stimulants of ovarian follicular maturation and anesthesia/surgery were examined for their effects on the concentration of plasma and follicular fluid PRL. Forty-seven patients undergoing in vitro fertilization for the treatment of infertility were selected at random for this prospective study. Patients given human menopausal gonadotropin and clomiphene citrate had significantly higher levels of plasma PRL compared to those given clomiphene only. Anesthesia/surgery elevated plasma PRL levels in all patients, by as much as 50-fold and to as high as 7878 mIU/liter. Follicular fluid PRL levels were correlated with preanesthetic plasma PRL concentrations, but the latter were not correlated with plasma 17 beta-estradiol. Elevated plasma or follicular fluid PRL concentrations had no effect on in vitro fertilization of oocytes or embryonic development. Although not significant, the incidence of pregnancy was highest in the group of patients with the lowest preanesthetic plasma PRL levels.

Long-term amrinone therapy in patients with severe heart failure: drug-dependent hemodynamic benefits despite progression of disease.

Six patients with severe congestive heart failure refractory to conventional therapy, including vasodilators, were treated with oral amrinone for a mean duration of 41 weeks (range 20 to 72 weeks). At initiation of therapy, the cardiac index increased from 1.74 +/- 0.31 to 2.62 +/- 0.52 (mean +/- SD) liters/min/m2 (p less than 0.01) and pulmonary capillary wedge pressure decreased from 26.5 +/- 3.5 to 19.5 +/- 5.4 mm Hg (p less than 0.05). Symptoms were alleviated and exercise capacity increased from 5.9 +/- 2.9 to 11.5 +/- 4.5 minutes (p less than 0.05). During long-term therapy, exercise capacity remained constants in three patients whereas it decreased in three others. All patients demonstrated an increase in heart size. Withdrawal of amrinone therapy precipitated severe symptoms at rest and hemodynamic deterioration in all patients. The cardiac index decreased from 1.87 +/- 0.49 to 1.32 +/- 0.30 liter/min/m2 (p less than 0.05) and pulmonary capillary wedge pressure rose from 20.6 +/- 2.9 to 28.8 +/- 5.6 mm Hg (p less than 0.05). These changes were reversed by reinstitution of therapy. Thus, amrinone-dependent hemodynamic benefits were demonstrated during long-term therapy without tachyphylaxis. In addition, progression of the underlying cardiac disease was observed in every patient.

Thallium-201 accumulation during reperfusion of ischemic myocardium: dependence on regional blood flow rather than viability.

These experiments in dogs were designed to determine whether the use of thallium 201 (TI-201) accumulation in patients during the reperfusion phase after streptokinase lysis of an intracoronary thrombus is a function of coronary blood flow or a function of myocardial viability. The left anterior descending coronary artery was occluded for 60 minutes in open-chest dogs, and the immediate TI-201 accumulation and regional blood flow (MBF) using microspheres was measured in 2 groups: 10 minutes after reperfusion in 9 dogs (group A) and 24 hours after reperfusion in 6 dogs (group B). There was an 80% or greater reduction in MBF in the subendocardium during ischemia in both groups of dogs, and it was inferred that the subendocardium was destined to become necrotic in group A and had become necrotic in group B dogs. The ratio of TI-201 accumulation to MBF in the tissue that had been ischemic was not significantly different from the ratio in normal tissue despite MBF being in the normal range in group A (n = 7, 2 dogs excluded because of reactive hyperemia) and being markedly decreased in group B. Thus, the immediate TI-201 distribution was related to MBF, and caution is recommended in its use to assess myocardial salvage in the early reperfusion phase after streptokinase lysis of intracoronary thrombi. These data suggest that the intramyocardial accumulation of TI-201 is predominantly a passive process and independent of Na-K ATPase.

Failure of dobutamine to increase exercise capacity despite hemodynamic improvement in severe chronic heart failure.

The acute hemodynamic and metabolic effects of dobutamine administered during exercise were studied in 8 patients with severe chronic heart failure. Exercise was performed on an upright bicycle ergometer using a graded protocol. During exercise performed without administration of dobutamine, exhaustion occurred after 4.5 +/- 1.2 minutes of exercise. The cardiac index increased from 1.61 +/- 0.25 to 2.67 +/- 0.59 liters/min/m2 (p less than 0.001), the arteriovenous oxygen difference from 7.8 +/- 1.7 to 12.5 +/- 2.4 ml/100 ml (p less than 0.001), and oxygen uptake from 7.9 +/- 3.0 to 41.2 +/- 15.7 mg/100 ml (p less than 0.001). During exercise performed with the administration of dobutamine, the cardiac index was significantly greater than during the control state, 3.23 +/- 0.78 versus 2.67 +/- 0.59 liters/min/m2 (p less than 0.001), while the arteriovenous oxygen difference was significantly lower, 11.2 +/- 2.1 vs 12.5 +/- 2.4 ml/100 ml (p less than 0.01). The arterial lactate level was not significantly changed, 45.3 +/- 17.6 versus 41.2 +/- 15.7 mg/100 ml. Although the dobutamine level tended to increase maximal oxygen uptake compared with the control period of exercise, 9.1 +/- 1.2 versus 8.5 +/- 1.4 ml/kg/min (p less than 0.05), it did not significantly increase exercise capacity, 4.8 +/- 1.5 versus 4.5 +/- 1.2 min. Thus administration of dobutamine in patients with severe chronic heart failure increased the cardiac index during maximal exercise but failed to increase exercise capacity. Since arteriovenous oxygen difference is reduced, dobutamine probably increases blood flow to the nonexercising tissues and not to the actively metabolizing muscles.

Coronary artery spasm and myocardial infarction in the absence of angiographically demonstrable obstructive coronary disease.

Myocardial infarction due to spasm of an "angiographically normal coronary artery" is rare, and its significance as a cause of myocardial infarction in patients without obstructive coronary disease has not been determined. Two patients are described with transmural myocardial infarction, nonobstructive coronary arteries, and suggestive evidence of coronary vasospasm as the cause of infarction. In one patient, angiography was carried out within 7 days of infarction and the documentation of normal coronary arteries argued strongly against a thromboembolic cause for infarction. This patient also had the combination of asthma, hypereosinophilia, and a systemic disease suggesting an immunologic disturbance with increased autoantibody production. A temporal association was noted between the episodes of asthma and those of coronary spasm during exacerbation of the eosinophilia, which raised the speculative issue of "allergic" coronary vasospasm. It is concluded that spasm of a nonobstructed coronary artery may cause transmural myocardial infarction. Further documentation is required in order to place this association in perspective among the other potential cause of infarction in patients with normal coronary artery anatomy.

New ECG changes associated with a tension pneumothorax: a case report.

This case report reveals new ECG changes associated with a left tension pneumothorax, specifically, PR-segment elevation in the inferior leads and reciprocal PR-segment depression in the aVR lead. A mechanism of atrial injury and/or ischemia is proposed as the cause, and the ECG changes associated with a left tension pneumothorax are briefly reviewed.

Hemodynamic assessment of Lillehei-Kaster tilting disc aortic and mitral prostheses.

Twenty-six patients with Lillehei-Kaster prosthetic heart valves, 15 with aortic and 11 with mitral valves, were catheterized to assess their hemodynamic performance. The calculated effective orifice areas were linearly related to but always less than their actual orifice areas. There was no significant difference in the effective orifice area of the mitral or aortic prostheses of similar size. The aortic prosthesis with an annulus diameter of 21 mm. was found to have a mean effective orifice area of 0.77 sq. cm. Our catheter studies have demonstrated no hemodynamic advantages of the Lillehei-Kaster aortic and mitral prosthetic valves over prosthetic valves.

Improvements in ovarian stimulation for in vitro fertilization.

What are the major improvements in stimulation over recent years? The stimulated cycle has completely superseded the natural cycle since this is the only method of obtaining several embryos. In conventional stimulation, despite an enormous body of literature, no single treatment modality has emerged as superior to other forms of therapy. Undoubtedly it is the experience and habits of individual IVF teams that determine the success of one or another method. Therefore programmed stimulation is an improvement in that it introduces the factors of convenience and simplicity while retaining the clinical efficacy of stimulation by conventional treatment. The analogues of LHRH are still in an early phase of development, but they appear to be associated with a low cancellation rate even in previous poor-responders. Furthermore, preliminary results seem to indicate that this is the first development since the widespread adoption of follicular stimulation, which is associated with an increased pregnancy rate. We are currently involved in trying to associate programmed stimulation and analogue treatment in a bid to combine the advantages of both therapies. Finally, embryo cryopreservation must be mentioned. There is no point in refining our stimulation protocols to obtain many embryos if those surplus to immediate requirement are disposed of. Cryopreservation offers the means of maximizing the pregnancy potential of a single IVF cycle while reducing the possibility of multiple pregnancy.

Hair analysis of cocaine: differentiation between systemic exposure and external contamination.

Cocaine has been shown to accumulate in hair of admitted users. Before using this test to verify cocaine use, however, it is crucial to differentiate between systemic exposure and external contamination from being in contact with crack smoke. In the present studies, the authors document that pyrolysis of crack results in hair accumulation of cocaine, but not its benzoylecgonine metabolite, whereas after admitted cocaine use both species are detectable in hair. External contamination with crack smoke is washable, whereas systemic exposure is not. The authors suggest these two criteria to distinguish systemic exposure from external contamination.

Assessing the early luteal phase in in vitro fertilization cycles: relationships between plasma steroids, endometrial receptors, and endometrial histology.

The corpus luteum-endometrial unit was investigated in in vitro fertilization (IVF) cycles using endocrine, morphologic, and biochemical measurements on the day normally scheduled for embryo transfer (day 16), in 12 stimulated and 4 natural cycles. Advanced endometrial histologic maturity was recorded in 9 of the 12 stimulated cycles. No in-phase endometria were seen when the preovulatory plasma estradiol (E2) was greater than 500 pg/ml or the day 16 plasma progesterone (P) greater than 10 ng/ml in natural or stimulated cycles. Significant negative correlations were noted between both preovulatory E2 and day 16 P and the concentration of cytosolic progesterone receptor (PRc). Advanced endometrial maturity tended to be associated with low concentrations of PRc. Regardless of endometrial maturity, the natural cycle was characterized by low cytosolic E2 receptors (ERc) and high PRc, whereas the concentration of both receptors was usually greatly reduced in stimulated cycles. It is concluded that the advanced endometrial maturation observed in stimulated IVF cycles is a consequence of the production of supraphysiologic levels of sex steroids by the corpus luteum that cause profound modifications of endometrial receptor dynamics.

Evidence for an adverse effect of elevated serum estradiol concentrations on embryo implantation.

Multiple follicular stimulation for IVF may be associated with greatly elevated serum E2 concentrations that are presumed to be antinidatory. This factor was analyzed in 825 consecutive embryo transfer cycles. The pregnancy rate decreased significantly after the transfer of one and two embryos in association with preovulatory E2 levels greater than the 90th percentile for the group (2320 pg/ml). The pregnancy rate did not vary with preovulatory E2 concentration following the transfer of three embryos. Highly significant correlations were noted between preovulatory E2 and early luteal phase concentrations of E2 and P. In a subgroup of 245 cycles, there were no significant relationships between implantation and early luteal phase levels of P or the ratio of E2/P. There was a small but nonsignificant tendency for the pregnancy rate to decrease in association with raised luteal E2. It is concluded that excessive E2 levels at the time of ovulation induction with hCG had an adverse effect on implantation when one or two embryos are transferred, but this may be overcome by the transfer of three embryos. The consequences for embryo transfer are discussed.

An assessment of alternative policies for embryo transfer in an in vitro fertilization-embryo transfer program.

Conventionally, in in vitro fertilization (IVF) programs, all embryos obtained up to three are freshly transferred in the IVF cycle and supernumerary embryos frozen if cryopreservation facilities exist. This study was concerned with assessing alternative policies for embryo transfer (ET). When three or fewer embryos were obtained in the IVF cycle, fresh embryo transfer was either excluded (group I, n = 69) or only one embryo was immediately transferred (group II, n = 46), the remainder being transferred after freezing and thawing. The pregnancy rate in these two policies was compared to that in a control group of patients (group III, n = 115) in whom all the embryos were transferred in the IVF cycle. The ongoing pregnancy rate was similar in all three groups. No multiple pregnancies occurred in groups I and II compared with one in the controls. The consequences of these policies for pregnancy rates and the incidence of multiple gestation are discussed. It is concluded that the deliberate limitation of fresh ET to a maximum of one embryo followed by one or more cycles of thawed frozen ET is not detrimental to the pregnancy rate and is less likely to be associated with multiple gestations. Conversely, this policy increases the workload of the laboratory staff and raises certain ethical questions.