Disruptions to healthcare quality and early child health outcomes: Evidence from health-worker strikes in Kenya.

This paper measures the effects of disruptions to healthcare quality at birth on early child health outcomes in Kenya. To identify impacts, we exploit variation in the timing and location of health-worker strikes at individual hospitals across the country between 1999 and 2014. Using data from Demographic Health Surveys, we find that children born during strikes are more likely to suffer a neonatal death.

Fast acting allosteric phosphofructokinase inhibitors block trypanosome glycolysis and cure acute African trypanosomiasis in mice.

The parasitic protist Trypanosoma brucei is the causative agent of Human African Trypanosomiasis, also known as sleeping sickness. The parasite enters the blood via the bite of the tsetse fly where it is wholly reliant on glycolysis for the production of ATP. Glycolytic enzymes have been regarded as challenging drug targets because of their highly conserved active sites and phosphorylated substrates.

Discovery of a Potent and Orally Bioavailable Cyclophilin Inhibitor Derived from the Sanglifehrin Macrocycle.

Cyclophilins are a family of peptidyl-prolyl isomerases that are implicated in a wide range of diseases including hepatitis C. Our aim was to discover through total synthesis an orally bioavailable, non-immunosuppressive cyclophilin (Cyp) inhibitor with potent anti-hepatitis C virus (HCV) activity that could serve as part of an all oral antiviral combination therapy. An initial lead 2 derived from the sanglifehrin A macrocycle was optimized using structure based design to produce a potent and orally bioavailable inhibitor 3.

A quality improvement project to reduce door-to-electrocardiogram time: A multicenter study.

Objective: To improve compliance with a target door-to-electrocardiogram (EKG) time of 10 minutes or less in patients presenting with symptoms concerning for acute coronary syndrome.

Methods: A pre-post study was performed between January 2014 and May 2016 at five emergency departments (EDs) in Saudi Arabia. Patients who presented to ED with symptoms concerning for acute coronary syndrome were included in the study.

Discovery of Potent Cyclophilin Inhibitors Based on the Structural Simplification of Sanglifehrin A.

Cyclophilin inhibition has been a target for the treatment of hepatitis C and other diseases, but the generation of potent, drug-like molecules through chemical synthesis has been challenging. In this study, a set of macrocyclic cyclophilin inhibitors was synthesized based on the core structure of the natural product sanglifehrin A. Initial compound optimization identified the valine-m-tyrosine-piperazic acid tripeptide (Val-m-Tyr-Pip) in the sanglifehrin core, stereocenters at C14 and C15, and the hydroxyl group of the m-tyrosine (m-Tyr) residue as key contributors to compound potency.

Myocardial ischemia revisited.

Does perioperative myocardial ischemia lead to postoperative myocardial infarction? By Stephen Slogoff and Arthur S. Keats. Anesthesiology 1985; 62:107-14.

Unaccounted blood loss in operations using cardiopulmonary bypass.

Typically, blood loss after operations requiring cardiopulmonary bypass is estimated from the sum of blood on sponges and drapes, in the suction system reservoir, and in chest drainage bottles. Prime of the extracorporeal circuit is usually returned to the patient, but no accounting is made of blood remaining in the circuit. In 50 patients, we examined 25 bubble and 25 membrane oxygenator circuits after completion of cardiopulmonary bypass and after return of all prime to the patients.

Benefits of a glucose-containing priming solution for cardiopulmonary bypass.

Benefits from the use of glucose-containing intravenous and priming solutions during coronary artery bypass operation have not been documented, but an increased risk of postoperative neurologic deficit by hyperglycemia has been suggested. To determine benefits, 107 patients undergoing coronary artery bypass operation were managed identically except that one group (n = 54) received 5% dextrose in lactated Ringer's solution (D5LR) as the sole intravenous and priming solution during operation and a second group (n = 53) received the same solution without glucose (LR). During cardiopulmonary bypass, the D5LR group required significantly less additional crystalloid to maintain safe oxygenator levels and flow (1.

Steal-prone coronary anatomy and myocardial ischemia associated with four primary anesthetic agents in humans.

To examine the relationship between myocardial ischemia in patients with steal-prone coronary anatomy and the administration of isoflurane anesthesia, we reviewed coronary angiograms of 955 patients who had participated in a randomized trial of the use of one of four primary anesthetics for coronary artery bypass operations. Steal-prone anatomy was found in 31.8% of patients who had received enflurane; 40.

Incidence of perioperative myocardial ischemia detected by different electrocardiographic systems.

To determine the extent to which different electrocardiographic systems account for differences in reported incidence of perioperative myocardial ischemia, the authors simultaneously recorded in 109 patients undergoing coronary artery bypass grafting (CABG) the V5 or modified CM5 lead on five ECG systems by means of a specially constructed common V5 lead. The systems included a Spacelabs Alpha 14 Model Series 3200 ECG Cardule at bandwidths of 0.05-125 Hz and 0.

Role of perfusion pressure and flow in major organ dysfunction after cardiopulmonary bypass.

The role of perfusion pressure and flow during cardiopulmonary bypass with moderate hypothermia and hemodilution in the development of new postoperative renal or clinically apparent cerebral dysfunction was examined in 504 adults. Cardiopulmonary bypass flow was targeted at greater than 40 mL.kg-1.

Low activated coagulation time during cardiopulmonary bypass does not increase postoperative bleeding.

The activated coagulation time (ACT) is widely used to monitor adequacy of anticoagulation during cardiopulmonary bypass despite absence of data establishing an ACT below which adverse outcomes occur. For anticoagulation before cardiopulmonary bypass, we administered a single dose of heparin (300 U/kg) to 193 patients and measured ACT and heparin levels at intervals after administration. No additional heparin was administered to any patient.

Randomized trial of primary anesthetic agents on outcome of coronary artery bypass operations.

To examine the role of primary anesthetic agent on outcome of coronary artery bypass grafting operations, 1,012 patients were prospectively randomized to receive enflurane (257), halothane (253), isoflurane (248), or sufentanil (254). Except for administration of the primary anesthetic, anesthesia management was standardized for all patients. The randomized groups did not differ in demographic characteristics, extent of coronary artery disease, chronic antianginal therapy, hemodynamic characteristics including new myocardial ischemia at arrival to the operating room, and surgical characteristics that might influence the rate of postoperative myocardial infarction or death.

Does chronic treatment with calcium entry blocking drugs reduce perioperative myocardial ischemia?

To examine the role of chronic calcium entry blocking drug administration on perioperative myocardial ischemia and, specifically, the frequency of hemodynamically unrelated ischemia, the authors studied 444 patients undergoing coronary artery bypass operations. Before induction of anesthesia, 119 patients who chronically took calcium entry blocking drugs received nifedipine 20 mg or diltiazem 60 mg orally, 74 received calcium entry and beta adrenergic blocking drugs, 71 received beta blocking drugs only, and 180 received neither. New ischemia occurred in 208 (46.

The overstated risk of preoperative hypokalemia.

To examine the relation between preoperative hypokalemia and frequency of intraoperative arrhythmias, Holter monitoring was employed in 447 patients undergoing major cardiac or vascular operations, the group at greatest risk for life-threatening arrhythmias. Based on serum potassium levels measured immediately before surgery, 57% of patients were normokalemic (greater than or equal to 3.6 mEq/L), 34% hypokalemic (3.

Venous admixture to radial artery blood samples during cardiopulmonary bypass.

The possibility that venous blood could be withdrawn through a radial artery cannula when venous pressure is high was examined in 30 patients during cardiopulmonary bypass for coronary artery bypass operation. Progressive desaturation of radial artery blood occurred when venous pressure was equal to arterial pressure. Desaturation not only increased with duration of venous obstruction but also occurred immediately if the arterial tree was emptied after occlusion.

Addition of papaverine to cardioplegia does not reduce myocardial necrosis.

In a randomized, double-blind prospective study involving 495 patients, we investigated whether the addition of papaverine, 60 mg, to our existing regimen of cold cardioplegia would reduce myocardial necrosis during elective coronary artery bypass operations. Twenty-one (4.2%) patients sustained acute postoperative myocardial infarctions (MI), and 7 (1.