Derivation of the uncontrolled donation after circulatory determination of death protocol for New York city.

Evidence from Europe suggests establishing out-of-hospital, uncontrolled donation after circulatory determination of death (UDCDD) protocols has potential to substantially increase organ availability. The study objective was to derive an out-of-hospital UDCDD protocol that would be acceptable to New York City (NYC) residents. Participatory action research and the SEED-SCALE process for social change guided protocol development in NYC from July 2007 to September 2010. A coalition of government officials, subject experts and communities necessary to achieve support was formed. Authorized NY State and NYC government officials and their legal representatives collaboratively investigated how the program could be implemented under current law and regulations. Community stakeholders (secular and religious organizations) were engaged in town hall style meetings. Ethnographic data (meeting minutes, field notes, quantitative surveys) were collected and posted in a collaborative internet environment. Data were analyzed using an iterative coding scheme to discern themes, theoretical constructs and a summary narrative to guide protocol development. A clinically appropriate, ethically sound UDCDD protocol for out-of-hospital settings has been derived. This program is likely to be accepted by NYC residents since the protocol was derived through partnership with government officials, subject experts and community participants.

Kidney and cardiovascular protection with SGLT2 inhibitors: lessons from cardiovascular outcome trials and CREDENCE.

The burden of diabetic kidney disease is rising rapidly worldwide, and new therapies are of vital importance to reduce the risk of kidney failure and major cardiovascular events. Of the newer glucose-lowering agents, sodium-glucose co-transporter 2 (SGLT2) inhibitors have shown exciting potential in preventing these adverse events. The results of several large cardiovascular outcome trials, a single dedicated kidney outcome trial and a dedicated heart failure trial, demonstrate substantial clinical benefits for several different SGLT2 inhibitors. Emerging evidence raises the possibility that these benefits may extend to those with non-diabetic chronic kidney disease. This review summarises the current evidence for SGLT2 inhibitor benefits and harms, and examines which patients are most likely to gain from these therapies.

Gaseous constituents in the plume from eruptions of mount st. Helens.

Measurements in the stratosphere of gaseous constituents in the plume of Mount St. Helens were obtained during five flights of the NASA U-2 aircraft between 19 May and 17 June 1980. Mixing ratios from gas chromatographic measurements on samples acquired about 24 hours after the initial eruption show considerable enhancement over nonvolcanic concentrations for sulfur dioxide (more than 1000 times), methyl chloride (about 10 times), and carbon disulfide (more than 3 times). The mixing ratio of carbonyl sulfide was comparable to nonvolcanic mixing ratios although 3 days later it was enhanced two to three times. Ion chromatography measurements on water-soluble constituents are also reported. Very large concentrations of chloride, nitrate, and sulfate ions were measured, implying large mixing ratios for the water-soluble gaseous constituents from which the anions are derived. Measurements of radon-222 present in the plume are also reported.

Ketorolac tromethamine as compared with morphine sulfate for treatment of postoperative pain.

Ketorolac tromethamine, a nonnarcotic, prostaglandin synthesis-inhibiting analgesic, was compared with morphine sulfate for relief of moderate to severe postoperative pain. The 155 patient participants received single intramuscular doses of either ketorolac, 10, 30, or 90 mg, or morphine, 6 or 12 mg, administered in a double-blind, randomized fashion. Pain scores (verbal and visual analog) were recorded at baseline and assessed at 30 minutes and then hourly to 6 hours. Pain relief was rated at the same times. Ketorolac, 90 and 30 mg, was rated significantly better than morphine, 6 mg, at each assessment interval after 1 hour. Ketorolac, 90 and 30 mg, was rated similarly to morphine, 12 mg, for the first 3 hours and better than morphine, 12 mg, 4 hours after injection. There were no serious side effects reported. The only side effect reported in more than 3% of patients was 8% somnolence with morphine. This study shows ketorolac to be a safe and effective analgesic for relief of postoperative pain.

Comparison of intranasal midazolam and sufentanil premedication in pediatric outpatients.

BACKGROUND: Intranasally administered midazolam was compared with sufentanil as a premedicant for 60 patients, aged 1/2 to 6 years, undergoing outpatient surgery of 2 hours or less. METHODS: Thirty minutes before anesthetic induction (halothane in 50% nitrous oxide/oxygen), patients were randomly assigned to receive either intranasal midazolam (0.2 mg/kg) or sufentanil (2 microg/kg). A "blinded" observer evaluated preoperative emotional state, response to premedication, induction, and emergence from anesthesia and side effects. RESULTS: Children who had not previously cried were more likely to cry when midazolam was administered compared with sufentanil (71% versus 20%, p = 0.0031). Of 31 midazolam patients, 20 experienced nasal irritation. Approximately 15 to 20 minutes after drug administration, most patients in both groups could be comfortably separated from their parents. The sufentanil group appeared to be more sedated and more cooperative during induction of anesthesia. Vital signs and oxygen saturation did not change significantly with either medication before or after surgery, although two sufentanil patients had a moderate reduction in ventilatory compliance after anesthetic induction. Sufentanil was associated with more nausea and vomiting than midazolam (34% versus 6%, p < 0.02). CONCLUSION: Both intranasal midazolam and sufentanil provide rapid, safe, and effective sedation in small children before anesthesia for ambulatory surgery. Sufentanil provided somewhat better conditions for induction and emergence. Midazolam causes more nasal irritation during instillation, and sufentanil causes more postoperative nausea and vomiting. Both drugs enabled patients to be separated from their parents with a minimum of distress. Patients in the midazolam group were discharged approximately 40 minutes earlier (p <0.005).

Pharmacokinetics and pharmacodynamics of vecuronium administered by bolus and infusion during halothane or balanced anesthesia.

Vecuronium was administered to two patient groups as a single intravenous dose, 60 micrograms/kg, combined with an infusion, 1 microgram/min/kg. Anesthesia was maintained for the first group with a halothane-nitrous oxide technique; the second group received fentanyl-barbiturate-tranquilizer-nitrous oxide. As the infusion ended, plasma vecuronium concentrations were 0.34 (+/- 0.10) microgram/ml for the halothane group and 0.32 (+/- 0.07) microgram/ml for the fentanyl group, associated with 93% (+/- 8) and 88% (+/- 10) twitch depression, respectively. Vecuronium plasma concentration-time data were combined with the simultaneous intensities of neuromuscular blockade to model the kinetic-dynamic values for each patient. For the halothane group the steady-state volume was 0.21 (+/- 0.04) L/kg, the clearance was 2.9 (+/- 0.1) ml/min/kg, and the elimination half-life was 100 (+/- 36) minutes; for the fentanyl group these were 0.20 (+/- 0.08) L/kg, 3.2 (+/- 0.1) ml/min/kg, and 84 (+/- 43) minutes, respectively. Plasma concentrations associated with 50% blockade averaged 0.2 microgram/ml for both groups. Neither the pharmacokinetics nor the pharmacodynamics of vecuronium in humans differed between these two patient groups.

Antibody used to identify penicillin-binding protein 2' in methicillin-resistant strains of Staphylococcus aureus (MRSA).

Polyclonal antibodies were raised against the membrane-bound penicillin-binding protein (PBP 2') present in methicillin-resistant strains of Staphylococcus aureus (MRSA) and were used to detect its presence in membranes from strains grown under varying conditions for the expression of resistance. The antibody preparation reacted with another membrane protein from methicillin-sensitive S. aureus (MSSA) which migrated to the same position as PBP 2' on SDS gel electrophoresis. Pretreatment of the antisera with membranes of sensitive strains removed antibodies recognising high-Mr proteins common to both MRSA and MSSA: the residual antibody then reacted specifically with PBP 2'. Antisera pretreated in this manner can be used as a probe for the definitive identification of MRSA strains.

How you look determines what you find: severity of illness and variation in blood transfusion for hip fracture.

PURPOSE: Utilization report cards are commonly used to assess hospitals. However, in practice, they rarely account for differences in patient populations among hospitals. Our study questions were: (1) How does transfusion utilization for hip fracture patients vary among hospitals? (2) What patient characteristics are associated with transfusion and how do those characteristics vary among hospitals? (3) Is the apparent pattern of variation of utilization among hospitals altered by controlling for these patient characteristics? SUBJECTS AND METHODS: We included consecutive hip fracture patients aged 60 years or older who underwent surgical repair between 1982 and 1993 in 19 hospitals from four states, excluding those who refused blood transfusion, had multiple trauma, metastatic cancer, multiple myeloma, an above the knee amputation, or were paraplegic or quadriplegic. The outcome of interest was postoperative blood transfusion. "Trigger hemoglobin" was the lowest hemoglobin recorded before transfusion or recorded at any time during the week before or after surgery for patients who were not transfused. RESULTS: There was considerable variation in transfusion among hospitals postoperatively (range 31.2% to 54.0%, P = 0.001). Trigger hemoglobin also varied considerably among hospitals. In unadjusted analyses, four of nine teaching and two of nine nonteaching hospitals had postoperative transfusion rates significantly higher than the reference (teaching) hospital, while one nonteaching hospital had a lower rate. In an analysis controlling for trigger hemoglobin and multiple clinical variables, one of nine teaching and four of nine nonteaching hospitals had rates higher than the reference hospital, while four teaching hospitals and one nonteaching hospital had lower rates. CONCLUSIONS: The apparent pattern of variation of transfusion among hospitals varies according to how one adjusts for relevant patient characteristics. Utilization report cards that fail to adjust for these characteristics may be misleading.

Pharmacokinetics and pharmacodynamics of sedatives and analgesics in the treatment of agitated critically ill patients.

The pharmacokinetics and pharmacodynamics of sedatives and analgesics are significantly altered in the critically ill. These changes may account for the large differences in drug dosage requirements compared with other patient populations. Drugs that in other settings may be considered short-acting often have significantly altered onset and duration of action in critically ill patients, necessitating a change in dosage. Of the benzodiazepines, lorazepam is the drug whose parameters are the least likely to be altered in critical illness. The presence of active metabolites with other benzodiazepines complicates their use during periods of prolonged use. Similarly, the presence of active metabolites of morphine and pethidine (meperidine) warrants caution in patients with renal insufficiency. The fewer cardiovascular effects seen with high-potency opioids, such as fentanyl and sufentanil, increase their usefulness in haemodynamically compromised patients. The pharmacodynamics of propofol are not significantly altered in the critically ill. Ketamine should be used with a benzodiazepine to prevent the emergence of psychomimetic reactions. Lower sedative doses of benzodiazepines and anaesthetics may not provide reliable amnesia. Barbiturates and propofol probably do not induce hyperalgesia and lack intrinsic analgesic activity. The antipsychotic agent haloperidol has a calming effect on patients and administration to the point of sedation is generally not necessary. Combinations of sedatives and analgesics are synergistic in producing sedation. The costs of sedation and analgesia are very variable and closely linked to the pharmacokinetics and pharmacodynamics of the drug. Monitoring of sedation and analgesia is difficult in uncooperative patients in the intensive care unit. In the future, specific monitoring tools may assist clinicians in the regulation of infusions of sedative and analgesic agents.

Foamy changes of placental cells in probable beta glucuronidase deficiency associated with hydrops fetalis.

Mucopolysaccharidosis type VII (MPS VII, beta glucuronidase deficiency) has been described in association with non-immune hydrops fetalis. Three consecutive pregnancies in an itinerant family, which resulted in stillbirths caused by non-immune hydrops are described. The parents were closely related and there was a strong family history of storage disorders. The main clue to the diagnosis, however, came from the presence of pronounced foamy cytoplasmic change in the villous Hofbauer cells of the placenta. This raised the possibility of an inherited metabolic storage disorder. The parents were subsequently shown to have beta glucuronidase activities in the heterozygous range in leucocytes and fibroblasts which suggested that the non-immune hydrops was caused by beta glucuronidase deficiency.

Immunological detection of penicillin-binding protein 2' in clinical isolates of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis.

The additional penicillin-binding protein (PBP 2') that is important in determining intrinsic resistance in methicillin-resistant strains of Staphylococcus aureus (MRSA) has been detected immunologically in strains from a variety of world-wide locations. This additional protein has also been definitively identified both immunologically and as a PBP in methicillin-resistant strains of S. epidermidis (MRSE). The assay described is rapid, specific and sensitive and has been used to detect PBP 2' in S. haemolyticus but not in beta-lactam resistant Streptococci.

Characterisation of a monoclonal antibody and its use in the immunoaffinity purification of penicillin-binding protein 2' of methicillin-resistant Staphylococcus aureus.

The additional penicillin-binding protein (PBP) 2' that is important in determining intrinsic resistance in methicillin-resistant strains of Staphylococcus aureus (MRSA) has been purified by affinity chromatography using monoclonal antibodies. Monoclonal antibody 1/423.10.351 reacted in ELISA with detergent extracts of membranes from resistant organisms, but not in immunoblots with PBP 2' separated by SDS-PAGE. Immunoprecipitation experiments showed that antibody 1/423.10.351 reacted with PBP 2' in detergent extracts. The latter antibody, covalently coupled to protein A-Sepharose through the Fc region, served as an affinity matrix to purify PBP 2'. The PBP was detected in immunoblots using a second monoclonal antibody, 2/401.43. Conjugation of this antibody with alkaline phosphatase afforded more rapid detection of PBP 2' for the immunological detection of PBP 2' both in affinity-purified fractions and in resistant strains.

Cost analysis of propofol versus thiopental induction anesthesia in outpatient laparoscopic gynecologic surgery.

This study investigated the cost of propofol versus thiopental anesthesia in 243 patients who underwent outpatient laparoscopic gynecologic surgery. Patients records were analyzed for medication use, duration of surgery, anesthesia, recovery room stay, and associated costs. Despite the higher drug cost for propofol, the total mean cost was $273.00 less per patient for patients receiving propofol induction anesthesia. Extension of these data translates into cost savings of approximately $7900.00 if propofol had been used for all patients. Although the duration of surgery for the propofol group was shorter by nearly 12 minutes, the anesthesia duration and recovery room stay were both longer for the thiopental group, reflecting the longer duration of action of thiopental. Although the realized cost savings of drugs, surgery, anesthesia, and recovery time when propofol versus thiopental is used for outpatient laparoscopic gynecologic surgery are relatively small on an individual patient basis, cost savings may become more significant if larger patient populations are studied.

Pharmacoeconomic analysis of sevoflurane versus isoflurane anesthesia in elective ambulatory surgery.

This study investigated the economic aspects of sevoflurane and isoflurane anesthesia in 47 healthy women undergoing elective ambulatory surgery, as part of a randomized, prospective clinical trial. Patient records were analyzed for anesthetic; duration of surgery, anesthesia, and recovery room stay; and associated charges. Sevoflurane is shorter acting than isoflurane, but it was not associated with a shorter duration of anesthesia or surgical unit stay, or earlier hospital discharge. Total charges associated with sevoflurane anesthesia were greater than those for isoflurane ($2641 and $2230, respectively) and primarily related to prolonged anesthesia and surgical unit stay. A minor decrease in recovery room charges ($15) associated with earlier discharge was observed with sevoflurane (p>0.05), but the agent was not associated with lower hospital charges. Larger trials and assessment of other patient populations may show sevoflurane to be more pharmacoeconomically advantageous than isoflurane.

A double-blind, placebo-controlled evaluation of intranasal metoclopramide in the prevention of postoperative nausea and vomiting.

Nausea and vomiting are common complaints in the postoperative period and contribute to patient distress and delay of discharge for outpatient surgical procedures. Laparoscopic procedures are associated with a high incidence of postoperative nausea and vomiting (PONV) episodes. Parenteral use of metoclopramide prevents and treats PONV. The intranasal route provides rapid and complete absorption of metoclopramide without many of the adverse effects observed with parenteral administration of the drug. We performed a prospective, double-blinded, randomized, placebo-controlled study to evaluate the safety and efficacy of metoclopramide 20 mg administered intranasally for emetic prophylaxis in laparoscopic surgery patients. The results from 109 patients enrolled in the study showed that this intranasal dose of metoclopramide may be ineffective in preventing the occurrence of PONV. The poor performance of the intranasal metoclopramide formulation in this study cannot be attributed to patient-specific and perioperative factors. It may be due to an inadequate dose or slow absorption of the drug. The small sample size, however, may also have been a factor.

Evaluation of the safety and efficacy of ketorolac versus morphine by patient-controlled analgesia for postoperative pain.

STUDY OBJECTIVE: To compare ketorolac tromethamine with morphine for pain management after major abdominal surgery. DESIGN: Double-blind, randomized study. SETTING: Hospital recovery room and postoperative surgical unit. PATIENTS: One hundred ninety-one patients with at least moderate pain after major abdominal surgery. INTERVENTIONS: Patients received ketorolac by patient-controlled analgesia (PCA) bolus alone (Ket B), ketorolac by bolus plus infusion (Ket I), or morphine by PCA bolus (morphine), with injectable morphine available for supplementation. MEASUREMENTS AND MAIN RESULTS: Levels of sedation, pain intensity, pain relief, and adverse events were recorded at baseline, at 2, 4, and 6 hours, and at termination. Supplemental morphine was required by 71% of Ket B patients, 67% of Ket I patients, and 38% of morphine patients (p < or = 0.001 for Ket B vs morphine). Although patients receiving ketorolac required more supplemental morphine than the morphine group (6.0 mg Ket I, 6.2 mg Ket B, 4.0 mg morphine), there was a large morphine-sparing effect in both ketorolac groups (total morphine 6.0 mg Ket I, 6.2 mg Ket B, 33.3 mg morphine). Overall pain relief scores were similar for morphine and Ket I groups, and were lower for Ket B than for morphine (p = 0.002). There were no differences among groups in numbers of patients with adverse events. CONCLUSION: Ketorolac may be effective when administered by PCA device, and has a clear morphine-sparing effect.

Retrospective analysis of postoperative nausea and vomiting to determine antiemetic activity of droperidol added to propofol: a possible drug interaction.

Propofol decreases the frequency of postoperative nausea and vomiting. We investigated whether its antiemetic activity could be improved further by coadministration of droperidol. We retrospectively reviewed the records of 266 women who underwent laparoscopic operations with nitrous oxide anesthesia and thiopental or propofol induction. The records were screened for frequency and time of occurrence of nausea and vomiting, concurrent drug use, duration of surgery, and times of recovery room admission and discharge. The combination of droperidol and thiopental decreased the frequency of nausea and vomiting over droperidol plus propofol, propofol alone, and thiopental alone. The addition of droperidol to propofol anesthesia doubled the frequency of multiple nausea and vomiting episodes, suggesting a possible interaction between the drugs. We cannot recommend that droperidol be added to propofol anesthesia for prophylaxis of postoperative nausea and vomiting.

The effects of sevoflurane and isoflurane on recovery from outpatient surgery.

This randomized, open-label study compared the investigational inhalational anesthetic sevoflurane with isoflurane in 47 healthy women undergoing elective ambulatory surgery. The women were randomized to receive either sevoflurane or isoflurane in 60% nitrous oxide-oxygen. Induction with thiopental 3-6 mg/kg was followed by vecuronium 0.1 mg/kg and fentanyl 0-200 micrograms. Duration of anesthesia, time to emergence, orientation, length of stay in the surgical unit, and hospital discharge were recorded. The emergence, length of stay, and discharge times after discontinuation of sevoflurane were 9.7 +/- 0.7, 120.6 +/- 8.0, and 244 +/- 15 minutes, respectively, and for isoflurane were 11.9 +/- 1.4, 106.8 +/- 7.1, and 282 +/- 24 minutes, respectively (NS). The isoflurane group had a higher frequency of postoperative cough. At the end of surgery, the sevoflurane group received a deeper level of anesthesia (minimum alveolar concentration 1.5 vs 1.3), however, these patients were oriented earlier (13.6 +/- 1.1 min vs 17.0 +/- 1.5 min isoflurane; p = 0.02) after discontinuation of anesthesia, although this difference is of little clinical significance.

The relationship between price of services, quality of care, and patient time costs for general dental practice.

OBJECTIVE: To examine the relationships between price of services, quality of care, and patient time costs in private practices of general dentists. DATA SOURCE/STUDY SETTING: In October 1992, a 3.7 percent sample of eligible general dentists in part-time or full-time private practice in 1991 was randomly drawn from a sampling frame tailored from data gathered by the 1991-1992 American Dental Association Distribution of Dentists census of all United States dentists. DATA COLLECTION: A mail survey was used to collect data on dentist demographic characteristics, dental practice characteristics practice finances, and insurance. The survey was completed and returned by 3,048 general dentists (77 percent response rate). Local area population characteristics were obtained from secondary sources. STUDY DESIGN: Two-stage least squares regression was used to evaluate the structural relationships between price of services, quality of care, and time costs to patients. Structural equations were estimated for four different quality of care measures and two time costs. PRINCIPAL FINDINGS: Price of services and quality of care were significantly related to each other. Higher quality of care was associated with higher price of services and, reciprocally, higher price of services was associated with higher quality of care. Shorter waits for a new patient appointment were associated with higher prices. Higher price of services, lower quality of care, and longer waits for a new patient appointment were related to shorter in-office waiting time. CONCLUSIONS: The implication of these findings is that if price of services is constrained, then the quality of care provided by the dentist may also be reduced.