This paper argues that increasing resistance to antimicrobials is an important social externality that has not been captured at the level of economic appraisal. The paper explicitly considers reasons why the externality of antimicrobial resistance has not generally been included as a cost in economic evaluations comparing management strategies for infectious diseases. Four reasons are considered: first, that the absolute cost of antimicrobial resistance is too small to be worth including; second, that there is an implicit discounting of the costs of antimicrobial resistance on the basis of time preference which makes the cost too small to be worth including; third, that there is an implicit discounting of the costs of antimicrobial resistance on the basis of uncertainty which makes the cost too small to be worth including; and fourth, that the costs are too difficult to measure. Although there does not appear to be methodological justification for excluding the costs of antimicrobial resistance, it seems likely that, because of the practical difficulties associated with measuring these costs, they will continue to be ignored. The paper concludes with a discussion of the applicability of standard policy responses used to deal with externalities in other areas of welfare economics.

Bias↗

PubMedDate not supplied

Use of small-diameter capillaries for increasing peptide and protein detection sensitivity in capillary electrophoresis-mass spectrometry.

The use of small ID capillaries is shown to provide a substantial increase in sensitivity for capillary electrophoresis-electrospray ionization/mass spectrometry (CE-ESI/MS). In a comparison using capillaries ranging from either 100 to 10 microns or 50 to 5 microns ID and chemically modified with aminopropylsilane, a 25- to 50-fold increase in sensitivity was observed for both peptide and protein mixtures. This enhanced solute sensitivity allowed the detection of approximately 150 attomoles of melittin (2845 Da) with selected ion monitoring and 600 attomoles of carbonic anhydrase (29,157 Da) while scanning for CE-MS with a quadrupole mass spectrometer. For the protein mixture, mass spectra of sufficient quality for precise molecular weight determination (< or = 0.05%) were obtained for 600 attomole injections using a 5 microns ID capillary. The increase in sensitivity with small capillary diameters can be primarily attributed to a reduced mass flow rate of buffer and other background constituents into the electrospray source, which allows for greater sample ionization efficiency. A model that qualitatively accounts for the results is presented, but quantitative agreement is precluded due to difficulties in accounting for contributions due to a liquid sheath flow used with the electrospray source. The model accounts for the observation that the ESI/MS appears to function as a concentration-sensitive detector under many conditions using large-diameter capillaries. A transition occurs, however, to a regime where the ESI/MS functions as a mass flow-sensitive detector for small-diameter capillaries, where the ESI current is limited by the rate of delivery to the ESI source of charge carrying species in solution. These results suggest peptide and protein analysis at low attomole and subattomole levels should be obtainable with alternative types of mass spectrometers.

Electrophoresis↗

PubMedDate not supplied

Thrombogenesis in experimental microvascular anastomosis.

A large number of microvascular anastomoses, involving both arteriovenous and artery-artery end-to-side and end-to-end anastomoses, were carried out in the rat to develop a temporal and morphologic profile of thrombogenesis. While excellent patency rates were obtained in purely arterial preparations, significant thrombus formation occurred in the arteriovenous preparations, both at the suture line and more distally in the vein. Factors contributing to thrombogenesis in these microvascular anastomoses are discussed.

Anastomosis, Surgical↗

PubMedDate not supplied

Use of ambulatory blood pressure monitoring to compare antihypertensive efficacy and safety of two angiotensin II receptor antagonists, losartan and valsartan. Losartan Trial Investigators.

The efficacy and safety of losartan and valsartan were evaluated in a multicenter, double-blind, randomized trial in patients with mild to moderate essential hypertension. Blood pressure responses to once-daily treatment with either losartan 50 mg (n = 93) or valsartan 80 mg (n = 94) for 6 weeks were assessed through measurements taken in the clinic and by 24-hour ambulatory blood pressure monitoring (ABPM). Both drugs significantly reduced clinic sitting systolic (SiSBP) and diastolic blood pressure (SiDBP) at 2, 4, and 6 weeks. Maximum reductions from baseline in SiSBP and SiDBP on 24-hour ABPM were also significant with the two treatments. The reduction in blood pressure was more consistent across patients in the losartan group, as indicated by a numerically smaller variability in change from baseline on all ABPM measures, which achieved significance at peak (P = .017) and during the day (P = .002). In addition, the numerically larger smoothness index with losartan suggested a more homogeneous antihypertensive effect throughout the 24-hour dosing interval. The antihypertensive response rate was 54% with losartan and 46% with valsartan. Three days after discontinuation of therapy, SiDBP remained below baseline in 73% of losartan and 63% of valsartan patients. Both agents were generally well tolerated. Losartan, but not valsartan, significantly decreased serum uric acid an average 0.4 mg/dL at week 6. In conclusion, once-daily losartan 50 mg and valsartan 80 mg had similar antihypertensive effects in patients with mild to moderate essential hypertension. Losartan produced a more consistent blood pressure-lowering response and significantly lowered uric acid, suggesting potentially meaningful differences between these two A II receptor antagonists.

Analysis of Variance↗

PubMedDate not supplied

Tolerability of long term therapy with enalapril maleate in patients resistant to other therapies and intolerant to captopril.

Patients with severe hypertension and/or congestive heart failure (n = 281) who were unresponsive to other therapies and intolerant to captopril received enalapril treatment (mean dose 19.5 mg/day) under study conditions as part of a Compassionate Use Program. Many of these patients had serious concurrent disorders known to predispose them to a greater risk of adverse experiences and death. The mean duration of enalapril treatment was 29 weeks, with a range of 1 day to approximately 3.5 years. Enalapril was generally well tolerated, and the estimated long term probability of patients terminating enalapril therapy because of adverse effects was low. 20 patients had discontinued captopril treatment because of low white blood cell counts; during subsequent enalapril treatment these reactions resolved in 14 patients, persisted in 2 patients, and could not be evaluated in 4 patients. Captopril-related proteinuria improved or resolved in 9 and persisted in 2 of 15 patients, taste disturbances resolved in 35 and persisted in 2 of 38 patients; and rash resolved in all but 7 of 178 patients during enalapril treatment. 18 patients (6%) discontinued enalapril treatment because of lack of efficacy; 6 of these 18 patients died due to a progression of heart failure, and another 11 patients died for other reasons. The deaths were considered unrelated to therapy with enalapril. Adverse reactions were the reason for discontinuation of enalapril treatment in 53 patients (19%). The most common adverse experiences that resulted in discontinuation of enalapril were: impairment of renal function (5%), hypotension (2%) and rash (2%). No neutropenia, proteinuria, or new taste disturbances were recorded as reasons for discontinuation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMedDate not supplied

Symptom and comorbidity patterns in World War II and Vietnam veterans with posttraumatic stress disorder.

Forty-four veterans with posttraumatic stress disorder (PTSD) from World War II and Vietnam were compared. The groups were comparable on many socioeconomic and combat measures and age at onset of PTSD. Vietnam veterans exhibited more severe PTSD symptoms, higher Hamilton depression scores, and higher scores on the hostility, psychoticism, and "additional symptom" Symptom Checklist-90 (SCL-90) scales. They also had more survivor guilt, impairment of work and interests, avoidance of reminders of trauma, detachment/estrangement from others, startle response, derealization, and suicidal tendencies. Differences were noted between the groups as to the nature of upsetting experiences. Vietnam veterans had a greater lifetime frequency of panic disorder and an earlier age of onset for alcoholism. In other respects, the two groups were diagnostically similar, with PTSD being related to the sequential emergence of psychiatric diagnoses in similar manner for World War II and Vietnam patients.

Adult↗

PubMedDate not supplied

Generalized anxiety disorder patients seek evaluation for cardiological symptoms at the same frequency as patients with panic disorder.

Although panic disorder (PD) and generalized anxiety disorder (GAD) have similar somatic symptoms, panic attacks with chest pain and/or palpitations may seem more likely to be mistaken for heart attacks because of their acute onset. One would therefore expect that PD patients are more likely than GAD patients to seek cardiological consultations. In a survey of 146 PD and 154 GAD patients entering a multi-site drug trial, we found virtually identical rates of such consults. Approximately 50% of each patient group sought medical evaluation for cardiac symptoms. Furthermore, 40% of each group had standard treadmill evaluations and 33% reported having an echocardiogram. This study suggests that future epidemiological studies in cardiology populations should include probes for generalized anxiety disorder.

Anxiety Disorders↗

PubMedDate not supplied

Alterations in consummatory behavior following intracisternal injection of 6-hydroxydopamine.

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Animals↗