Predictors and Characteristics of Opioid Utilization >15 Days Following Total Knee Arthroplasty.

BACKGROUND: America is amid an opioid epidemic, best characterized by liberal prescribing practices; widespread opioid misuse, abuse, and diversion; and rising rates of prescription-related opioid overdose. While many contributors to opioid overprescribing exist, orthopedic surgery is identified as a key driver. The purpose of this study is to determine predictors of ongoing opioid use >15 days post-total knee arthroplasty (TKA) and those patients prescribed >1350 morphine milligram equivalents (MMEs) in the 15 days following surgery. METHODS: A retrospective cohort study was conducted in patients undergoing TKA (January 2016-December 2017) in an integrated healthcare system. Outcomes of interest were patient and clinical characteristics. RESULTS: A total of 621 patients were included in the study. The majority were female (57.6%), were non-Hispanic/Latino white (92.3%), and from metropolitan areas (64.3%) with fewer than 110,000 population. Mean age was 66.3. Being female (odds ratio [OR] = 1.547, P = .092), having a higher body mass index (OR = 1.043, P = .036), and receipt of more postdischarge prescriptions in the 60-day follow-up period (OR = 8.815, P < .0001) were associated with a greater likelihood of receipt of opioid prescriptions for more than 15 days. Older patients (OR = 0.954, P = .01) and those discharged to home (OR = 0.478, P = .045) were less likely to receive >1350 MME; longer length of stay (OR = 1.447, P = .013) was more likely in those prescribed >1350 MMEs. CONCLUSION: Several predictors were associated with longer duration and higher doses of opioid prescriptions post-TKA. Further research is needed to ascertain the challenges of opioid prescribing from both the metropolitan surgical team and rural healthcare provider perspective.

Efficacy and Safety of Percutaneous Microwave Ablation and Cementoplasty in the Treatment of Painful Spinal Metastases and Myeloma.

BACKGROUND AND PURPOSE: Painful spinal metastases are a common cause of cancer-related morbidity. Percutaneous ablation presents an attractive minimally invasive alternative to conventional therapies. We performed a retrospective review of 69 patients with 102 painful spinal metastases undergoing microwave ablation and cementoplasty to determine the efficacy and safety of this treatment. MATERIALS AND METHODS: Procedures were performed between January 2015 and October 2016 with the patient under general anesthesia using image guidance for 102 spinal metastases in 69 patients in the following areas: cervical (n = 2), thoracic (n = 50), lumbar (n = 34), and sacral (n = 16) spine. Tumor pathologies included the following: multiple myeloma (n = 10), breast (n = 27), lung (n = 12), thyroid (n = 6), prostate (n = 5), colon (n = 4), renal cell (n = 3), oral squamous cell (n = 1), and adenocarcinoma of unknown origin (n = 1). Procedural efficacy was determined using the visual analog scale measured preprocedurally and at 2-4 weeks and 20-24 weeks postprocedure. Tumor locoregional control was assessed on follow-up cross-sectional imaging. Procedural complications were recorded to establish the safety profile. RESULTS: The median ablation time was 4 minutes 30 seconds ± 7 seconds, and energy dose, 4.1 ± 1.6 kJ. Median visual analog scale scores were the following: 7.0 ± 1.8 preprocedurally, 2 ± 1.6 at 2-4 weeks, and 2 ± 2.1 at 20-24 weeks. Eight patients died within 6 months following the procedure. Follow-up imaging in the surviving patients at 20-24 weeks demonstrated no locoregional progression in 59/61 patients. Two complications were documented (S1 nerve thermal injury and skin burn). CONCLUSIONS: Microwave ablation is an effective and safe treatment technique for painful spinal metastases. Further studies may be helpful in determining the role of microwave ablation in locoregional control of metastases.

Ceftriaxone attenuates acute cocaine-evoked dopaminergic neurotransmission in the nucleus accumbens of the rat.

BACKGROUND AND PURPOSE: Ceftriaxone is a ß-lactam antibiotic and glutamate transporter activator that reduces the reinforcing effects of psychostimulants. Ceftriaxone also reduces locomotor activation following acute psychostimulant exposure, suggesting that alterations in dopamine transmission in the nucleus accumbens contribute to its mechanism of action. In the present studies we tested the hypothesis that pretreatment with ceftriaxone disrupts acute cocaine-evoked dopaminergic neurotransmission in the nucleus accumbens. EXPERIMENTAL APPROACH: Adult male Sprague-Dawley rats were pretreated with saline or ceftriaxone (200 mg kg(-1) , i.p. × 10 days) and then challenged with cocaine (15 mg kg(-1) , i.p.). Motor activity, dopamine efflux (via in vivo microdialysis) and protein levels of tyrosine hydroxylase (TH), the dopamine transporter and organic cation transporter as well as α-synuclein, Akt and GSK3ß were analysed in the nucleus accumbens. KEY RESULTS: Ceftriaxone-pretreated rats challenged with cocaine displayed reduced locomotor activity and accumbal dopamine efflux compared with saline-pretreated controls challenged with cocaine. The reduction in cocaine-evoked dopamine levels was not counteracted by excitatory amino acid transporter 2 blockade in the nucleus accumbens. Pretreatment with ceftriaxone increased Akt/GSK3ß signalling in the nucleus accumbens and reduced levels of dopamine transporter, TH and phosphorylated α-synuclein, indicating that ceftriaxone affects numerous proteins involved in dopaminergic transmission. CONCLUSIONS AND IMPLICATIONS: These results are the first evidence that ceftriaxone affects cocaine-evoked dopaminergic transmission, in addition to its well-described effects on glutamate, and suggest that its ability to attenuate cocaine-induced behaviours, such as psychomotor activity, is due in part to reduced dopaminergic neurotransmission in the nucleus accumbens.

Impact of analgesic modality on stress response following laparoscopic colorectal surgery: a post-hoc analysis of a randomised controlled trial.

BACKGROUND: Epidural analgesia is perceived to modulate the stress response after open surgery. This study aimed to explore the feasibility and impact of measuring the stress response attenuation by post-operative analgesic modalities following laparoscopic colorectal surgery within an enhanced recovery after surgery (ERAS) protocol. METHODS: Data were collected as part of a double-blinded randomised controlled pilot trial at two UK sites. Patients undergoing elective laparoscopic colorectal resection were randomised to receive either thoracic epidural analgesia (TEA) or continuous local anaesthetic infusion to the extraction site via wound infusion catheter (WIC) post-operatively. The aim of this study was to measure the stress response to the analgesic modality by measuring peripheral venous blood samples analysed for serum concentrations of insulin, cortisol, epinephrine and interleukin-6 at induction of anaesthesia, at 3, 6, 12 and 24 h after the start of operation. Secondary endpoints included mean pain score in the first 48 h, length of hospital stay, post-operative complications and 30-day re-admission rates. RESULTS: There was a difference between the TEA and WIC groups that varies across time. In the TEA group, there was significant but transient reduced level of serum epinephrine and a higher level of insulin at 3 and 6 h. In the WIC, there was a significant reduction of interleukin-6 values, especially at 12 h. There was no significant difference observed in the other endpoints. CONCLUSIONS: There is a significant transient attenuating effect of TEA on stress response following laparoscopic colorectal surgery and within ERAS as expressed by serum epinephrine and insulin levels. Continuous wound infusion with local anaesthetic, however, attenuates cytokine response as expressed by interleukin-6.

A multidisciplinary approach to the management of atypical osseous epithelioid hemangioendothelioma.

Hemangioendothelioma is a rare vascular tumor of intermediate malignant potential. Though epithelioid hemangioendothelioma (EH) is commonly found in soft tissues, it has been known to be present in skeletal tissues. The authors present a case of a 50-year-old woman diagnosed with EH of the iliac bone and acetabulum, who experienced pathological fracture at presentation. This report describes a multidisciplinary approach to the management that includes initial incisional biopsy, curettage, and bone grafting, followed by Intensity Modulated Radiation Therapy. The patient finally underwent hemipelvic resection with allograft reconstruction after recurrence. Histopathological study revealed osseous EH of low mitotic activity that stained positively for CD31, CD34, vimentin, and Factor VIII. Herein, the authors discuss the imaging characteristics, histopathological aspects, cytogenetic findings, and the radiobiological behavior of osseous EH. After an aggressive multidisciplinary intervention, the patient is able to achieve local control with no evidence of distal metastatic disease.

Henipavirus microsphere immuno-assays for detection of antibodies against Hendra virus.

Hendra and Nipah viruses (HeV and NiV) are closely related zoonotic pathogens of the Paramyxoviridae family. Both viruses belong to the Henipavirus genus and cause fatal disease in animals and humans, though only HeV is endemic in Australia. In general and due to the acute nature of the disease, agent detection by PCR and virus isolation are the primary tools for diagnostic investigations. Assays for the detection of antibodies against HeV are fit more readily for the purpose of surveillance testing in disease epidemiology and to meet certification requirements in the international movement of horses. The first generation indirect ELISA has been affected by non-specific reactions which must be resolved using virus neutralisation serology conducted at laboratory bio-safety level 4 containment (PC4). Recent developments have enabled improvements in the available serology assays. The production of an expressed recombinant truncated HeV G protein has been utilised in ELISA and in Luminex-based multiplexed microsphere assays. In the latter format, two Luminex assays have been developed for use in henipavirus serology: a binding assay (designed for antibody detection and differentiation) and a blocking assay (designed as a surrogate for virus neutralisation). Equine and canine field sera were used to evaluate the two Luminex assays relative to ELISA and virus neutralisation serology. Results showed that Luminex assays can be effective as rapid, sensitive and specific tests for the detection of HeV antibody in horse and dog sera. The tests do not require PC4 containment and are appropriate for high throughput applications as might be required for disease investigations and other epidemiological surveillance. Also, the results show that the Luminex assays detect effectively HeV vaccine-induced antibodies.

Rectal impalement injury through the pelvis, abdomen and thorax.

Impalement rectal injuries with intraperitoneal organ injuries are rare. It is even rarer for such injuries to result in pelvic, abdominal and thoracic internal injuries. We present the case of a 39-year-old man who was admitted after an assault where a broken broomstick was inserted forcibly into his rectum. Surgery revealed penetration through the rectum, dome of the bladder, mesentery, liver and right lung. The patient survived following management by a multispecialty surgical team. Our literature review identified four similar cases with one fatality only. Prognosis seems to be good in these types of injuries provided there is an early presentation, the penetrating object is left in situ before the operation and, most importantly, there is an organised team approach to deal with the various injuries.

Obesity-dependent metabolic signatures associated with nonalcoholic fatty liver disease progression.

Our understanding of the mechanisms by which nonalcoholic fatty liver disease (NAFLD) progresses from simple steatosis to steatohepatitis (NASH) is still very limited. Despite the growing number of studies linking the disease with altered serum metabolite levels, an obstacle to the development of metabolome-based NAFLD predictors has been the lack of large cohort data from biopsy-proven patients matched for key metabolic features such as obesity. We studied 467 biopsied individuals with normal liver histology (n=90) or diagnosed with NAFLD (steatosis, n=246; NASH, n=131), randomly divided into estimation (80% of all patients) and validation (20% of all patients) groups. Qualitative determinations of 540 serum metabolite variables were performed using ultraperformance liquid chromatography coupled to mass spectrometry (UPLC-MS). The metabolic profile was dependent on patient body-mass index (BMI), suggesting that the NAFLD pathogenesis mechanism may be quite different depending on an individual's level of obesity. A BMI-stratified multivariate model based on the NAFLD serum metabolic profile was used to separate patients with and without NASH. The area under the receiver operating characteristic curve was 0.87 in the estimation and 0.85 in the validation group. The cutoff (0.54) corresponding to maximum average diagnostic accuracy (0.82) predicted NASH with a sensitivity of 0.71 and a specificity of 0.92 (negative/positive predictive values=0.82/0.84). The present data, indicating that a BMI-dependent serum metabolic profile may be able to reliably distinguish NASH from steatosis patients, have significant implications for the development of NASH biomarkers and potential novel targets for therapeutic intervention.

Genetic association study of CYP1A1 polymorphisms identifies risk haplotypes in nonsmall cell lung cancer.

Lung cancer remains a leading cause of disease globally, with smoking being the largest single cause. Phase I enzymes, including cytochrome P(450), family 1, subfamily A, polypeptide 1 (CYP1A1), are involved in the activation of carcinogens, such as polycyclic aromatic hydrocarbons, to reactive intermediates that are capable of binding covalently to DNA to form DNA adducts, potentially initiating the carcinogenic process. The aim of the present study was to investigate the association of CYP1A1 gene polymorphisms and haplotypes with lung cancer risk. A case-control study was carried out on 1,040 nonsmall cell lung cancer (NSCLC) cases and 784 controls to investigate three CYP1A1 variants, CYP1A1*2A (rs4646903; thymidine to cytosine substitution at nucleotide 3801 (3801T>C)), CYP1A1*2C (rs1048943; 2455A>G; substitution of isoleucine 462 with valine (exon 7)) and CYP1A1*4 (rs1799814; 2453C>A; substitution of threonine 461 with asparagine (exon 7)) using PCR restriction fragment length polymorphism methods. The CYP1A1*2A and CYP1A1*2C variants were significantly over-represented in NSCLC cases compared with controls, whereas the CYP1A1*4 variant was under-represented. CYP1A1 haplotypes (in allele order CYP1A1*4, CYP1A1*2C, CYP1A1*2A) CGC and CGT were associated with an increased risk of lung cancer, whereas AAT was associated with decreased lung cancer risk in this population. The present study has identified risk haplotypes for CYP1A1 in NSCLC and confirmed that CYP1A1 polymorphisms are a minor risk factor for NSCLC.

Pediatric Scoliosis Surgery - the association between preoperative risk factors and postoperative complications with emphasis on cerebral palsy children.

Scoliosis repair surgery is a common procedure. Our study's first goal was to compare pre- and postoperative parameters between the cerebral palsy (CP) and idiopathic scoliosis (IS) children. The second goal was to establish possible associations between preoperative parameters that could predict the outcome of spinal surgery and the incidence of early postoperative complications. A retrospective record review of all children who underwent scoliosis operative surgery between 1998 and 2007 was conducted. Of the 141 children included, 21 were CP and 120 were IS. The CP children attended surgery with significantly lower weight and pulmonary reserves and had larger curves and fusions compared to the IS children. CP children had a significantly higher rate of major complications, especially pulmonary and neurological, and a higher rate of delayed extubations. In addition, young age at surgery and posterior spinal fusion correlated with a more favorable immediate postoperative prognosis among the IS population. CP children attended surgery in worse physical condition and in turn had a poorer immediate and short-term postoperative prognosis than IS children. Young age at surgery and posterior fusions revealed protective characteristics among the IS population.

Selenium supplementation for critically ill adults.

BACKGROUND: Selenium is a trace mineral essential to human health, which has an important role in the immune response, defence against tissue damage and thyroid function. Improving selenium status could help protect against overwhelming tissue damage and infection in critically ill adults. OBJECTIVES: This review assessed the effects of selenium supplementation including the selenium-containing compound, ebselen, on adults recovering from critical illness. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library, Issue 2, 2003), MEDLINE, (1966 to July 2003), EMBASE (1980 to Week 30 2003),CAB NAR (1973 to March 2003), BIOSIS (1985 to July 2003), CINAHL (1982 to July 2003), HEALTHSTAR (1975 to September 2002), Current Controlled Trials, and reference lists. We contacted investigators, and handsearched four journals. Date of the most recent search: December 2003. SELECTION CRITERIA: Randomized trials of selenium or ebselen supplementation by any route, in adults with critical illness (including burns, head injury, brain haemorrhage, cerebrovascular accident and surgery). DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. We sought additional information as required from trialists. We also undertook pooling of data for outcomes and selected exploratory analyses were undertaken. MAIN RESULTS: Seven randomized trials involving813participants were included. The quality of trials, as reported, was poor, particularly for allocation concealment. The availability of outcome data was limited and trials involving selenium supplementation, were small. Thus the results must be interpreted with caution. Because of heterogeneity, results are presented for the random effects models. Four selenium trials showed no statistically significant difference in mortality (relative risk (RR) 0.52, 95% confidence interval (CI) 0.20 to 1.34). Three trials of ebselen also showed no statistically significant difference in mortality (RR 0.83, 95% CI 0.51 to 1.35). One trial of selenium found no statistically significant difference between groups for participants developing infection (RR 1.33, 95% CI 0.55 to 3.24). Three trials of ebselen provided data for participants developing infections (pyrexia, respiratory infections or meningitis), which was not statistically significant (RR 0.60, 95% CI 0.36 to 1.02). No clear evidence emerged for the benefits of selenium or ebselen supplementation for the outcomes of days on a ventilator, length of intensive care unit stay, length of hospital stay or quality of life. REVIEWERS' CONCLUSIONS: There is insufficient evidence to recommend supplementation of critically ill patients with selenium or ebselen. Trials are required which overcome the defects of the reviewed studies, particularly inadequate size and methodology. This review will be updated when four ongoing trials are completed.

Effect of systemic matrix metalloproteinase inhibition on periodontal wound repair: a proof of concept trial.

BACKGROUND: The adjunctive use of matrix metalloproteinase (MMP) inhibitors with scaling and root planing (SRP) promotes new attachment in patients with periodontal disease. This pilot study was designed to examine aspects of the biological response brought about by the MMP inhibitor low dose doxycycline (LDD) combined with access flap surgery (AFS) on the modulation of periodontal wound repair in patients with severe chronic periodontitis. METHODS: Twenty-four subjects were enrolled into a 12-month, randomized, placebo-controlled, double-masked trial to evaluate clinical, biochemical, and microbial measures of disease in response to 6 months therapy of either placebo capsules + AFS or LDD (20 mg b.i.d.) + AFS. Clinical measures including probing depth (PD), clinical attachment levels (CAL), and bleeding on probing (BOP) as well as gingival crevicular fluid bone marker assessment (ICTP) and microbial DNA analysis (levels and proportions of 40 bacterial species) were performed at baseline and 3, 6, 9, and 12 months. RESULTS: Patients treated with LDD + AFS showed more potent reductions in PD in surgically treated sites of >6 mm (P<0.05, 12 months). Furthermore, LDD + AFS resulted in greater reductions in ICTP levels compared to placebo + AFS. Rebounds in ICTP levels were noted when the drug was withdrawn. No statistical differences between the groups in mean counts were found for any pathogen tested. CONCLUSIONS: This pilot study suggests that LDD in combination with AFS may improve the response of surgical therapy in reducing probing depth in severe chronic periodontal disease. LDD administration also tends to reduce local periodontal bone resorption during drug administration. The use of LDD did not appear to contribute to any significant shifts in the microbiota beyond that of surgery alone.

Use of block copolymers of poly(ortho esters) and poly (ethylene glycol) micellar carriers as potential tumour targeting systems.

Amphiphilic AB and ABA block copolymers have been prepared from poly (ortho esters) and poly (ethylene glycol). Such block copolymers readily form micellar dispersions in water, or buffers. The CMC is in the range of 3 x 10(-4)-5 x 10(-4) g/l which is a value low enough to assure retention of micelle integrity upon intravenous injection. The size, as determined by dynamic light scattering was in the 40-70 nm range. The micelles can be stored in lyophilized form for at lest 8 months and easily reconstituted to the original properties. The micelles are stable in PBS at pH 7.4 and 37 degrees C for 3 days and in a citrate buffer at pH 5.5 and 37 degrees C for 2 h. Stability in the presence of bovine serum albumin depends on the structure of the block copolymer and especially the length of the POE block.

Factors associated with continued participation in mammography screening.

BACKGROUND: Relatively little is known about factors that predict ongoing participation in mammography screening at regular intervals. Members of managed care plans have access to this preventive service; yet, many still do not receive it routinely. METHODS: Using administrative data from HIP Health Plan of New York, a group model HMO, 24,215 women ages 50-80 years identified as having a screening mammogram during the baseline period were followed for 2 years to determine demographic and utilization factors that might be related to having a subsequent mammogram within the recommended time interval. RESULTS: Of the 24,215 women with an index mammogram, 71.8;pc had a subsequent screening mammogram within 2 years. Women ages 65-74 years and those with Medicare coverage had the highest mammogram rates among the age and coverage categories. Number of primary care and gynecology physician visits was strongly related to having a subsequent mammogram. The average (mean) time between index and subsequent mammogram was 14.4 months. CONCLUSION: The significance of health plan visits in subsequent mammography underscores the importance of physician-patient communication in a managed care plan and the integration of health plan members into the HMO delivery system. Even in this environment with equal access for all types of coverage, Medicaid members were less likely to receive this preventive service.

A randomized intervention to improve ongoing participation in mammography.

OBJECTIVE: To test the effectiveness of interventions intended to increase rates of regular breast cancer screening, according to recommended guidelines. STUDY DESIGN: A randomized controlled trial of 2 outreach interventions (a mail reminder and a telephone reminder plus appointment scheduling) compared with a routine publicity campaign to encourage continued participation in mammography screening. PARTICIPANTS AND METHODS: Participants were 1908 women aged 50 to 75 years continuously enrolled in a large group-model HMO during the study who underwent a bilateral mammogram during the first quarter of 1994 and no subsequent mammogram during the next 18 to 21 months. Data were obtained from health plan administrative data files supplemented by medical chart review. Women were randomly assigned to receive (1) a mail reminder, (2) a telephone reminder, or (3) routine publicity on mammography for all women. The outcome measure was a mammogram received after the intervention period and within 2 years of the initial mammogram date. RESULTS: Bivariate and multivariate statistical analyses showed that participation was significantly higher for women contacted by telephone than through routine publicity. Mail reminders were no more effective than a routine publicity campaign. Primary care physician and gynecologist visits increased the likelihood of a subsequent mammogram for women in all intervention groups. CONCLUSIONS: Telephone contact by regular health plan staff was more successful than publicity in encouraging continued participation in mammography screening in women enrolled in a group-model managed health care plan. Because mailings did not influence participation in mammography screening, health plans should be cautious about investing in member mailings without first evaluating their effectiveness in the context of existing outreach efforts.

A double-blind, randomized comparison of i.v. lorazepam versus midazolam for sedation of ICU patients via a pharmacologic model.

BACKGROUND: Benzodiazepines, such as lorazepam and midazolam, are frequently administered to surgical intensive care unit (ICU) patients for postoperative sedation. To date, the pharmacology of lorazepam in critically ill patients has not been described. The aim of the current study was to characterize and compare the pharmacokinetics and pharmacodynamics of lorazepam and midazolam administered as continuous intravenous infusions for postoperative sedation of surgical ICU patients. METHODS: With Institutional Review Board approval, 24 consenting adult surgical patients were given either lorazepam or midazolam in a double-blind fashion (together with either intravenous fentanyl or epidural morphine for analgesia) through target-controlled intravenous infusions titrated to maintain a moderate level of sedation for 12-72 h postoperatively. Moderate sedation was defined as a Ramsay Sedation Scale score of 3 or 4. Sedation scores were measured, together with benzodiazepine plasma concentrations. Population pharmacokinetic and pharmacodynamic parameters were estimated using nonlinear mixed-effects modeling. RESULTS: A two-compartment model best described the pharmacokinetics of both lorazepam and midazolam. The pharmacodynamic model predicted depth of sedation for both midazolam and lorazepam with 76% accuracy. The estimated sedative potency of lorazepam was twice that of midazolam. The predicted C50,ss (plasma benzodiazepine concentrations where P(Sedation > or = ss) = 50%) values for midazolam (sedation score [SS] > or = n, where n = a Ramsay Sedation Score of 2, 3, ... 6) were 68, 101, 208, 304, and 375 ng/ml. The corresponding predicted C50,ss values for lorazepam were 34, 51, 104, 152, and 188 ng/ml, respectively. Age, fentanyl administration, and the resolving effects of surgery and anesthesia were significant covariates of benzodiazepine sedation. The relative amnestic potency of lorazepam to midazolam was 4 (observed). The predicted emergence times from sedation after a 72-h benzodiazepine infusion for light (SS = 3) and deep (SS = 5) sedation in a typical patient were 3.6 and 14.9 h for midazolam infusions and 11.9 and 31.1 h for lorazepam infusions, respectively. CONCLUSIONS: The pharmacology of intravenous infusions of lorazepam differs significantly from that of midazolam in critically ill patients. This results in significant delays in emergence from sedation with lorazepam as compared with midazolam when administered for ICU sedation.

Therapeutic drug monitoring: do the improved outcomes justify the costs?

In the 30 years that therapeutic drug monitoring (TDM) has moved from an abstract consideration to a routine intervention, issues remain over justifying the benefits in the light of the ever-increasing competition for budgetary resources. Resolving the issues is constrained by various methodological concerns. These include considerations such as: (i) the changed environment of knowledge and practice during the generation in which TDM has been used and evaluated; (ii) the predominance of studies using system-related rather than patient-centred outcomes; (iii) using a timeframe for analysis that is too short; (iv) a lack of rigour in many of the pharmacoeconomic analyses; and (v) excessive use of a site-specific rather than a societal perspective. Current observation suggests that the greatest benefit of TDM accrues from targeted or specialty populations: those with severely decompensated renal function, those at the extremes of age, and those using immunosuppressive, some antineoplastic, some psychotherapeutic and some anticonvulsant drugs. In these situations, safe and humane practice considers TDM a necessity without respect to cost. But for many routine situations with drugs for which TDM has commonly been used in the past, present reliance on the intervention may have become excessive in the light of today's knowledge base of practitioners.

Factors influencing mammography use among women in Medicare managed care.

This article presents findings about the mammography screening experience of Medicare members of a health maintenance organization (HMO). Based on a mail survey of 309 women, we assessed factors that may be facilitators or barriers to this service for older women. The results indicate that these respondents generally are receiving timely mammograms; over three-quarters (79 percent) reported having a mammogram in the past 2 years. Multivariate analysis showed that women who were younger (under 75 years of age), believed in the importance of screening, had been told by a physician to obtain a mammogram, and were more satisfied with their physician and more likely to report mammography use.