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Background: Clinical recommendations for concussion management encourage reduced cognitive and physical activities immediately after injury, with graded increases in activity as symptoms resolve. Empirical support for the effectiveness of such recommendations is needed. Purpose: To examine whether training medical providers on the Defense and Veterans Brain Injury Center’s Progressive Return to Activity Clinical Recommendation (PRA-CR) for acute concussion improves patient outcomes. Study Design: Cohort study; Level of evidence, 2. Methods: This study was conducted from 2016 to 2018 and compared patient outcomes before and after medical providers received an educational intervention (ie, provider training). Patients, recruited either before or after intervention, were assessed at ≤72 hours, 1 week, 1 month, 3 months, and 6 months after a concussion. The participant population included 38 military medical providers and 106 military servicemembers with a diagnosed concussion and treated by one of the military medical providers: 58 patient participants received care before the intervention (ie, provider training) and 48 received care after intervention. The primary outcome measure was the Neurobehavioral Symptom Inventory. Results: The patients seen before and after the intervention were predominantly male (89.7% and 93.8%, respectively) of military age (mean ± SD, 26.62 ± 6.29 years and 25.08 ± 6.85 years, respectively) and a mean ± SD of 1.92 ± 0.88 days from injury. Compared with patients receiving care before intervention, patients receiving care after intervention had smaller increases in physical activities (difference in mean change; 95% CI, 0.39 to 6.79) and vestibular/balance activities (95% CI, 0.79 to 7.5) during the first week of recovery. Although groups did not differ in symptoms at ≤72 hours of injury ( d = 0.22; 95% CI, –2.21 to 8.07), the postintervention group reported fewer symptoms at 1 week ( d = 0.61; 95% CI, 0.52 to 10.92). Postintervention patients who completed the 6-month study had improved recovery both at 1 month ( d = 1.55; 95% CI, 5.33 to 15.39) and 3 months after injury ( d = 1.10; 95% CI, 2.36 to 11.55), but not at 6 months ( d = 0.35; 95% CI, 5.34 to 7.59). Conclusion: Training medical providers on the PRA-CR for management of concussion resulted in expedited recovery of patients.

Drawing from Australian Aboriginal and Torres Strait Islander perspectives, we conceptualize the association between community participation and continuous quality improvement (CQI) processes in Indigenous primary health care (PHC) services. Indigenous experiences of community participation were drawn from our study identifying contextual factors affecting CQI processes in high-improving PHC services. Using case study design, we collected quantitative and qualitative data at the micro-, meso-, and macro-health system level in 2014 and 2015 in six services in northern Australia. Analyzing qualitative data, we found community participation was an important contextual factor in five of the six services. Embedded in cultural foundations, cultural rules, and expectations, community participation involved interacting elements of trusting relationships in metaphorically safe spaces, and reciprocated learning about each other’s perspectives. Foregrounding Indigenous perspectives on community participation might assist more effective participatory processes in Indigenous PHC including in CQI processes.

Background: Plyometric exercises are frequently used to increase posterior rotator cuff and periscapular muscle strength and simulate demands and positional stresses in overhead athletes. The purpose of this study was to provide descriptive data on posterior rotator cuff and scapular muscle activation during upper extremity plyometric exercises in 90° of glenohumeral joint abduction. Hypothesis: Levels of muscular activity in the posterior rotator cuff and scapular stabilizers will be high during plyometric shoulder exercises similar to previously reported electromyographic (EMG) levels of shoulder rehabilitation exercises. Study Design: Descriptive laboratory study. Methods: Twenty healthy subjects were tested using surface EMG during the performance of 2 plyometric shoulder exercises: prone external rotation (PERP) and reverse catch external rotation (RCP) using a handheld medicine ball. Electrode application included the upper and lower trapezius (UT and LT, respectively), serratus anterior (SA), infraspinatus (IN), and the middle and posterior deltoid (MD and PD, respectively) muscles. A 10-second interval of repetitive plyometric exercise (PERP) and 3 repetitions of RCP were sampled. Peak and average normalized EMG data were generated. Results: Normalized peak and average IN activity ranged between 73% and 102% and between 28% and 52% during the plyometric exercises, respectively, with peak and average LT activity measured between 79% and 131% and between 31% and 61%. SA activity ranged between 76% and 86% for peak and between 35% and 37% for average activity. Muscular activity levels in the MD and PD ranged between 49% and 72% and between 12% and 33% for peak and average, respectively. Conclusion: Moderate to high levels of muscular activity were measured in the rotator cuff and scapular stabilizers during these plyometric exercises with the glenohumeral joint abducted 90°.

Increasing numbers of adults are returning to a diverse array of higher education settings. Institutions that serve this population must consider the meaning of education to these students, their needs, and the modes of instruction most likely to meet those needs. Approaches to education have historically tended toward mechanistic and routine-oriented learning. However, adult learning is best accomplished through more flexible, collaborative, and transformative processes. Adult learning literature over the last several decades has offered challenges and insights into these two approaches. This literature has been rich in its exploration of diverse ideological and conceptual concerns related to the desire to create a more empowering and transformative experience of learning. This article provides a brief historical overview of education and learning as concepts with a focus on the insights of recent adult learning scholarship. The authors will also discuss how the emerging field of restorative practices offers new perspectives on these approaches. As a field that has developed independently of adult learning scholarship, but shares many of its commitments, restorative practices offer a fresh view on adult learning scholarship.

A social marketing campaign promoting hand-washing with soap was implemented to reduce the high burden of infection experienced by Australian Aboriginal children living in remote communities. Epidemiological evidence of effect and other evidence were used to identify the hygiene intervention and health promotion approach for the project. We drew on the findings of: (i) a systematic literature review to identify the intervention for which there is strong effect in similar populations and contexts; and (ii) a narrative literature review to determine our health promotion approach. This process provided practitioners with confidence and understanding so they could address a complex problem in a politically and otherwise sensitive context.

Background: Since Mehta et al. reported the first successful use of regional citrate anticoagulation (RCA) for continuous renal replacement therapy (CRRT) in 1990, RCA is increasingly used for CRRT because it provides filter patency with minimal risk of bleeding. However, RCA has been associated with significant metabolic complications including hypocalcemia, hypernatremia, metabolic alkalosis, and citrate toxicity. Objective: To describe our experience with a newly implemented RCA protocol with acid citrate dextrose formula A (ACD-A) and intravenous calcium gluconate, for use with PrismaFlex CRRT in critically ill patients with acute kidney injury. Methods: A retrospective chart review was conducted from May 1, 2006, until May 1, 2007, in a 16-bed medical-surgical university-affiliated intensive care unit. Data collected included dialysis filter life, patient and circuit metabolic parameters, and units of packed red blood cells transfused. Results: Forty-eight patients received dialysis with citrate (n = 178 fitters). Circuit clotting occurred in 24% of all filters. Mean ± SD filter life was 38.4 ± 25.9 hours, and filter survival at 48 hours was 38.2%. Persistent metabolic alkalosis while on CRRT was identified in 6 of 45 (13.3%) patients. Mild hypocalcemia (ionized calcium Conclusions: We found that anticoagulation of PrismaFlex CRRT with ACD-A and intravenous calcium gluconate provided reasonable filter patency, but with minor metabolic complications. Close monitoring of electrolyte and acid–base balance is required to minimize metabolic derangements.

Background A friction force is generated when moving air contacts the nasal walls, referred to as wall shear stress. This interaction facilitates heat and mass transfer between the mucosa and air, i.e., air-conditioning. The objective of this research was to study the distribution of wall shear stress within the nasal cavity to identify areas that contribute significantly to air-conditioning within the nasal cavity. Methods Three-dimensional computational models of the nasal airways of five healthy subjects (three male and two female subjects) were constructed from nasal CT scans. Numerical simulations of nasal airflow were conducted using the commercial computational fluid dynamics code Fluent 6 (Ansys, Inc., Canonsburg, PA). Wall shear stress was derived from the numerical simulation. Air-conditioning was simulated to confirm the relationship with wall shear stress. Results Nasal airflow simulations predicted high wall shear stress along the anterior aspect of the inferior turbinate, the anteroinferior aspect of the middle turbinate, and within Little's area. Conclusion The airflow simulations indicate that the inferior and middle turbinates and Little's area on the anterior nasal septum contribute significantly to nasal air-conditioning. The concentration of wall shear stress within Little's area indicates a desiccating and potentially traumatic effect of inhaled air that may explain the predilection for spontaneous epistaxis at this site.

ObjectiveThis study determined the pharmacokinetics of intraperitoneal (IP) cefepime in automated peritoneal dialysis (APD) patients.Design and MethodsA prospective pharmacokinetic study was performed in 6 noninfected adult APD patients. All patients were administered a single IP dose of cefepime (15 mg/kg) over a 6-hour dwell. Patients then underwent a fixed APD regimen consisting of the first 6-hour dwell, followed by an 8-hour dialysate-free period and a subsequent series of 3 overnight APD exchanges. Blood and dialysate samples were collected at t = 0, 1, 2, 4, 6 (end of dwell), and 24 hours. Any urine produced during the study period was collected. Cefepime concentrations in serum, dialysate, and urine were determined by liquid chromatography mass spectrometry. Pharmacokinetic parameters were calculated assuming a mono-exponential model.ResultsOne hour after IP administration, serum cefepime levels exceeded the minimum inhibitory concentration (8 μg/mL) for susceptible organisms. The mean serum and dialysate concentrations at 24 hours were 15.8 ± 3.6 and 6.2 ± 2.3 μg/mL respectively. Bioavailability was 84.3% ± 6.2%, volume of distribution 0.34 ± 0.07 L/kg, and serum half-life 13.8 ± 3.2 hours. Total, peritoneal, and renal clearances were 16.5 ± 4.4, 4.3 ± 0.7, and 3.5 ± 2.5 mL/minute, respectively.ConclusionsIP cefepime dosed at 15 mg/kg resulted in adequate serum concentrations in APD patients at 24 hours post dose. Pharmacokinetic predictions suggest that most APD and CAPD patients would achieve adequate serum cefepime concentrations if treated with standard doses of 1000 mg given IP once daily. Patients using APD regimens different from that used in this study, anuric patients, and those with significant residual renal function may require a more individualized approach.

ObjectiveTo determine the impact of dialysate flow rate (DFR) on cefazolin pharmacokinetics (PK) in peritoneal dialysis (PD) patients.MethodsA meta-analysis of published reports, identified by MEDLINE search (1966-2002) and other sources, containing information on cefazolin PK data in PD patients was conducted. Data were analyzed based upon low DFR (≤ 5.50 mL/minute) or high DFR (> 5.50 mL/minute). Data available were from North American (NA) ( n = 45) and Singaporean ( n = 10) patients. Complete data sets were available for 33 patients (CDS patients). Data were analyzed with respect to data origin and data set completeness: all patients (ALL), NA, and CDS. Analysis of log-transformed cefazolin PK data was performed to determine coefficient of determination ( r2) between DFR and cefazolin elimination rate constant (kel), clearance total (ClT), and clearance peritoneal (ClPD). Clearance total data were extrapolated to DFR observed in continuous flow PD.ResultsPublished literature provided data on 55 PD patients (12 high DFR, 43 low DFR). Regardless of data origin (ALL, NA, or CDS), a prominent coefficient of determination ( p < 0.0001) existed between DFR and all cefazolin PK data except ClPD. The p value for DFR correlation to ClPDwas 0.953, 0.011, and 0.036 for ALL, NA, and CDS patients, respectively. Cefazolin ClTand ClPDincreased at higher DFRs.ConclusionThese findings demonstrate that an increased DFR leads to an increased rate of cefazolin clearance in NA PD patients. The impact of Asian descent on cefazolin ClPDwarrants further investigation. Clinicians dosing cefazolin in PD patients using a higher DFR than that used to determine cefazolin PK should use increased doses or prescribe lower/comparable DFRs. Data are not yet available for patients prescribed very high DFRs ( e.g., continuous flow PD); extrapolation of our results demonstrates significant influences on clearance and risk for underdosing.

Urethral metastasis from renal cell carcinoma (RCC) is rare, with only six previously described cases.1–6 The authors report a case which presented eight months post laparoscopic radical nephrectomy with painless, visible haematuria. The epidemiology, potential pathophysiological mechanisms and treatment options are explored.

The efficacy of electrothermal collagen shrinkage in the treatment of patients with anterior cruciate ligament laxity was evaluated. Eighteen patients who had continuity of the anterior cruciate ligament but had symptomatic laxity were treated with arthroscopic electrothermal shrinkage of the anterior cruciate ligament using a monopolar radiofrequency probe. The mean length of follow-up in patients whose stability was maintained was 20.5 months. Seven of the patients had undergone previous reconstruction, four with patellar tendon graft and three with quadrupled hamstring tendon graft. Laxity was chronic in nine patients and acute in nine. The KT-1000 arthrometer results at 1 month postoperatively revealed decreased anterior excursion, with an average side-to-side difference of 1.9 mm. However, 11 patients had a failed result at an average 4.0 months. Of the seven patients with successful results, six had native ligaments and had been treated for acute laxity and one had a patellar tendon graft and had been treated for chronic laxity. Even with the short-term follow-up in our study, it is evident that thermal shrinkage using radiofrequency technology has limited application for patients with anterior cruciate ligament laxity. Although it may be useful in treating patients with an acutely injured native anterior cruciate ligament, further study is needed to see if the ligament stretches out over time or is at increased risk of reinjury.

The use of automated peritoneal dialysis (APD) has increased markedly during the past decade, in response to the need to obtain higher clearances and to accommodate individual lifestyles. Peritonitis rates have been observed to be generally lower in APD as compared with continuous ambulatory peritoneal dialysis (CAPD). Still, peritonitis remains a significant complication of APD. Many questions have been raised regarding the appropriateness of applying, to APD, the therapeutic antibiotic regimens used for treatment of peritonitis in CAPD. The original recommendations for treatment of peritonitis in PD mostly used peritoneal dialysate trough levels based on 2-L CAPD exchanges lasting 4 ‐ 8 hours. Because APD uses shorter, more frequent exchanges, with variable fill volumes, at night, the clearance of many antibiotics is expected to be higher than in CAPD. The use of single daily doses injected intraperitoneally (IP) during the long exchange of CAPD or APD has simplified the administration of antibiotics, and arguably, allows a uniform dose to be used for both modalities. However, the higher clearance of some antibiotics during rapid cycling may reduce tissue concentrations below the therapeutic range. Recent pharmacokinetic studies have shed light on this important subject. Those studies should be used as a base from which to design more effective therapeutic guidelines. INCIDENCE OF PERITONITIS IN APD AND CAPD

The pharmacokinetics of intravenous (IV) vancomycin was studied in automated peritoneal dialysis (APD) patients who received a single IV dose of vancomycin (15 mg/kg total body weight). Dialysate samples were collected at the beginning, middle, and end of dwells 1 – 3 (on-cycler), and at the end of dwells 4 and 5 (off-cycler), for a 24-hour period. Blood samples were collected at the beginning, middle, and end of dwells 1 – 3 (on-cycler), and at the end of dwell 5 (off-cycler) for a 24-hr period. Pharmacokinetics parameters were calculated assuming a one-compartment model. Glomerular filtration rate (GFR) and vancomycin clearance (Cl) values were normalized to 1.73 m2. Ten patients [4 males, 6 females; 47.4 ± 9.9 years of age (mean ± SD)] who had received PD for a median 3.5 months (range 2 – 66 months) were studied. Dwell times were 2.3 ± 0.1 hours on cycler and 7.3 ± 0.1 hours off cycler. Vancomycin half-life was significantly different on-cycler than off-cycler (11.6 ± 5.2 hr vs 62.8 ± 33.0 hr; p < 0.001). Vancomycin total Cl (ClT) was 7.4 ± 2.0 mL/min. Renal Cl (ClR) and PD Cl (ClPD) accounted for 23.6% and 28.0% of ClT, respectively. ClRcorrelated with GFR (ClR= 0.90 GFR – 1.01; r2= 0.79; p = 0.008). Mean vancomycin serum and dialysate end-of-dwell concentrations were above minimum inhibitory concentration of susceptible organisms (5 mg/mL) for the first cycler and the second ambulatory exchanges only.The results of this study suggest that, to provide adequate concentrations for susceptible organisms over a 24-hour period, current intermittent vancomycin dosing recommendations for PD-related peritonitis need to be changed to 35 mg/kg intraperitoneally on day 1, then 15 mg/kg IP thereafter ( i.e., once daily) in APD patients.

ObjectiveThis analysis explores the nutritional status of adult U.S. peritoneal dialysis (PD) patients.DesignThe Peritoneal Dialysis Core Indicators Study is a prospective cross-sectional prevalence survey describing the care provided to a random sample of adult U.S. PD patients.Methods and PopulationPrevalence data were collected from a national random sample of 1381 adult PD patients participating in the United States End Stage Renal Disease (ESRD) program.ResultsThe median age of these patients was 55 years, 61% were Caucasian; the leading cause of ESRD was diabetes mellitus. Age, sex, size, peritoneal permeability, dialysis adequacy, and nutritional indices did not differ between patients on continuous ambulatory PD and patients on automated PD. The dialysis prescriptions employed achieved mean weekly Kt/V urea (wKt/V) and creatinine clearance (wCCr) values of 2.22 ± 0.57 and 67.8 ± 22.5 L/1.73 m2/week, respectively. The PD patients were large, with a mean body weight of 77 ± 21 kg and body mass index (BMI) of 27 ± 8.6 kg/m2. The mean serum albumin of these patients was 3.5 ± 0.51 g/dL, and 43% of values fell below the National Kidney Foundation Dialysis Outcomes Quality Initiative's desired range. The PD patients had a normalized protein equivalent of nitrogen appearance (nPNA) of 1.0 ± 0.57 g/kg/day, a normalized creatinine appearance rate (nCAR) of 17 ± 7.3 mg/kg/day, and an estimated lean body mass (%LBM) of 62% ± 18% of body weight. Serum albumin correlated positively with patient size, nCAR, and nPNA, but negatively with age, the presence of diabetes mellitus, female gender, erythropoietin dose, the creatinine dialysate-to-plasma ratio results of peritoneal equilibration testing, and the dialysis portion of the wCCr. The duration of ESRD experience correlated negatively with both serum albumin and patient size, although these relationships were complex.ConclusionPeritoneal dialysis patients generally have marginal serum albumin levels, a finding incongruent with alternative measures of nutritional status, such as weight, BMI, and creatinine generation. Serum albumin is reduced in patients with high peritoneal permeability ( i.e., rapid transporters) and, because these patients generally have higher than average wCCr values, serum albumin is inversely correlated with the dialysis component of the wCCr. The presumptive nutritional indicators (BMI, %LBM, nPNA, and serum albumin) provide disparate estimates, varying from 10% to 50% for the prevalence of nutritionally stressed PD patients.

Canada’s travel account deficit has decreased significantly since its peak in the early 1990s. Canada’s travel deficit dropped dramatically in 1998. The deceleration in the growth of Canada’s travel deficit is a positive sign in the right direction. Nonetheless, keeping and winning new international visitors will get tougher given growing global economic and financial volatility. In the longer term, the aging of populations in Canada’s major markets will become an increasingly important factor in influencing the direction, rate, and magnitude of its travel account deficit.

Background Use of intermittent antibiotic dosing is increasing in the treatment of peritoneal dialysis (PD)-related peritonitis. We studied the pharmacokinetics of intravenous (IV) piperacillin in automated PD patients. Patients and Methods Eight patients (3 males, 5 females) were recruited and received a single IV dose of piperacillin (35 mg/kg actual body weight). Blood and dialysate samples were collected at the beginning, middle, and end of dwells 1 – 3 (on cycler), and end of dwells 4 – 5 (off cycler) for a 24-hour period. Baseline and 24-hour urine samples (nonanuric patients, n = 7) were collected. Pharmacokinetic parameters were calculated assuming a one-compartment model. Glomerular filtration rate (GFR) and piperacillin clearance (CL) values were normalized to 1.73 m2. Results The patients were 49.5 ± 10.1 years of age (mean ± SD) and had been receiving PD for a median of 3 months (range 2 – 66 months). Dwell times were 2.25 ± 0.06 hours on cycler and 7.26 ± 0.14 hours off cycler. Piperacillin half-life was not statistically different on or off the cycler (on cycler 1.99 ± 0.39 hr, off cycler 4.39 ± 5.4 hr; p = 0.12) and remained insignificant, even accounting for an outlier (on cycler 2.01 ± 0.41 hr, off cycler 2.54 ± 1.48 hr; p = 0.19). Piperacillin total CL (CLT) was 31.29 ± 6.02 mL/minute. Renal CL (CLR) and PD CL (CLPD) accounted for 8.8% and 16.8% of CLT; CLR correlated well with GFR (CLR = 0.86 GFR + 0.1; p < 0.000 03). Mean piperacillin serum and dialysate end-of-dwell concentrations were above minimum inhibitory concentration of susceptible organisms (8 μg/mL) for the three cycler exchanges only. Serum and dialysate concentrations predicted using a one-compartment model suggest that IV piperacillin 4000 mg would provide adequate concentrations for susceptible organisms over a 12-hour period. Conclusion The current IV piperacillin dosing recommendations of 4000 mg every 12 hours for PD-related peritonitis are appropriate for patients on automated PD. Intermittent intraperitoneal piperacillin is not recommended.

Objective To identify correlations between the pharmacokinetic variables that describe drug disposition in peritoneal dialysis (PD) patients and the measures used to assess dialysis adequacy. Design and Methods This retrospective study re-evaluated data collected during previous pharmacokinetic studies for intraperitoneally administered cefazolin, ceftazidime, and gentamicin in continuous ambulatory peritoneal dialysis (CAPD) patients, and intravenous cefazolin and tobramycin in automated PD patients. Pharmacokinetic variables were compared to creatinine clearance (CCr), Kt/V, and peritoneal equilibration test data using the Pearson product correlation coefficient ( r). Results Prominent correlations were found between renal CCr and renal Kt/V, with renal clearances of CAPD cefazolin and ceftazidime, and automated PD tobramycin and cefazolin ( r values ranged from 0.698 to 0.986; p < 0.05). Conclusion These findings support current peritonitis treatment recommendations that patients with residual renal function may require higher doses or more frequent drug administration.

Department of Medicine,1 Hennepin County Medical Center, University of Minnesota Medical School, Minneapolis, Minnesota; Albany College of Pharmacy,2 Albany, New York, U.S.A.; Department of Peritoneal Dialysis,3 Academic Medical Center, Amsterdam, The Netherlands; Manchester Royal Infirmary,4 Manchester, United Kingdom; Vanderbilt University Medical Center,5 Nashville, Tennessee; Baxter Healthcare Corporation,6 McGaw Park, Illinois, U.S.A.; Renal Division,7 Jikei-kai University, School of Medicine, Tokyo, Japan; University of Pittsburgh Medical Center,8 Pittsburgh, Pennsylvania, U.S.A.; Renal Division,9 Department of Medicine, Evangelic School of Medicine, Curitiba Parana, Brazil; University of Toronto,10 Toronto Hospital, Toronto, Ontario, Canada

Infection causes significant morbidity and mortality in end-stage renal disease patients. Despite recommendations to the contrary, vancomycin is often used empirically. Antibiograms may aid in the choice of empiric antibiotic therapy. We developed an antibiogram and determined the susceptibility of various microorganisms to cefazolin, gentamicin, and vancomycin. Retrospective review of culture results and susceptibility data from a 21-month time period were used to determine microorganism frequency of identification and antimicrobial sensitivity. A total of 362 microorganisms were identified and 285 cultures performed in 171 patients (144 hemodialysis; 27 peritoneal dialysis). Predominant organisms were coagulase-negative staphylococci (39.8%) and Staphylococcus aureus (24.6%). Gram-positive organisms accounted for 73.5% of isolates. Methicillin-resistant S. aureus and vancomycin-resistant Enterococcus were identified 3.8% and 2.3% of time, respectively. Gram-positive and negative microorganisms were frequently susceptible to cefazolin and gentamicin. Antibiogram interpretation indicates that cefazolin alone or in combination with gentamicin may be appropriate empiric antibiotic therapy in our outpatient dialysis center.

Objective To investigate the pharmacokinetic parameters of intermittent intraperitoneal (IP) cefazolin, and recommend a cefazolin dosing regimen in continuous ambulatory peritoneal dialysis (CAPD) patients. Design Prospective nonrandomized open study. Setting CAPD outpatient clinic in Albany, New York. Patients Seven volunteer CAPD patients without peritonitis. Three of the patients were nonanuric while 4 were anuric. Interventions Cefazolin (15 mg/kg total body weight) was given to each patient during the first peritoneal exchange. Blood and dialysate samples were collected at times 0, 0.5, 1, 2, 3, 6 (end of the first antibiotic-containing dwell), 24, and 48 hours after the administration of IP cefazolin. Urine samples were collected in nonanuric patients over the study period. Results The mean ± SD amount of cefazolin dose absorbed from the dialysate after the 6-hour dwell was 69.7% ± 8.0% of the administered dose. The cefazolin absorption rate constant from dialysate to serum was 0.21 ± 0.1 /hr (absorption half-life 3.5 ± 0.8 hr). The mean serum concentrations reached at 24 and 48 hours were 52.4 ± 3.7 mg/L and 30.3 ± 5.9 mg/L, respectively. The mean dialysate cefazolin concentrations reached at 24 and 48 hours were 15.1 ± 3.4 mg/L and 7.9 ± 1.4 mg/L, respectively. The cefazolin serum elimination rate constant was 0.02 ± 0.01 /hr (elimination half-life 31.5 ± 8.8 hr). The total cefazolin body clearance was 3.4 ± 0.6 mL/min. In the 3 nonanuric patients the mean renal clearance of cefazolin was 0.6 ± 0.4 mL/min. The peritoneal clearance of cefazolin was 1.0 ± 0.3 mL/min. The systemic volume of distribution of cefazolin was 0.2 ± 0.05 L/kg. No statistical difference was detected in pharmacokinetic parameters between anuric and nonanuric patients, although this may be due to the small number of patients in each group. Conclusion A single daily dose of cefazolin dosed at 15 mg/kg actual body weight in CAPD patients is effective in achieving serum concentration levels greater than the minimum inhibitory concentration for sensitive organisms over 48 hours, and dialysate concentration levels over 24 hours. Caution is warranted in extrapolation of dosing recommendations to patients who maintain a significant degree of residual renal function.

ObjectiveThe 1996 Peritoneal Dialysis Core Indicators Study illustrates the conduct of peritoneal dialysis in the United States during 1996.Design and Patient PopulationThe survey is a medical records audit of 1317 randomly selected adult U.S.A. Medicare patients using peritoneal dialysis during 1996.Outcome MeasuresAbstracted data included basic demographic characteristics, dialysis prescription, delivered dialysis dose, residual renal function, serum albumin, hematocrit, anemia management, and patient status.ResultsThe survey included 785 patients using continuous ambulatory peritoneal dialysis (CAPD) and 423 using automated peritoneal dialysis (APD) primarily in the form of continuous cycling peritoneal dialysis (CCPD). Except for the prescription mechanics and a greater likelihood that African-Americans would use CAPD, the groups did not differ substantially from one another. Evaluation of patient weight (W), body mass index (BMI), residual renal function, average serum albumin, protein equivalent of nitrogen appearance (nPNA), and dialysis efficiency as weekly fractional urea nitrogen removal (wKt/V urea) and weekly creatinine clearance (wCrCI) revealed a picture of reasonable dialysis delivery and marginal protein nutrition. Additionally, there was little evidence that “dialysis efficiency,” over the range assessed, had a major influence on nutritional status. Despite a tendency toward obesity (body weight = 76.6 ± 20.0 kg and BMI = 27 ± 7), 47% of patients had an average serum albumin below “normal” (3.5 g/dL by bromcresol green) and 70% had a nPNA below 1.0 g/kg/day.ConclusionsPeritoneal dialysis patients appear to have marginal protein reserves despite surfeit energy stores.

Objective To review and compare the risks of nonnarcotic analgesic toxicities in adults and estimate the relative healthcare costs of these toxicities, since direct comparison of costs is not possible. Data Sources A MEDLINE search of the literature from 1969 to 1995 was used to identify pertinent data. Additional references were identified from articles obtained in the search. Information was obtained from prospective, retrospective, controlled, and uncontrolled studies; case reports; and review articles. Data Extraction Estimates of annual US costs of toxicities were extrapolated and synthesized from data from diagnosis-related groups, published information about the incidence of toxicity, or local data. Data Synthesis Chronic use of nonsteroidal antiinflammatory drugs (NSAIDs) is associated with a high incidence of acute renal toxicity and gastrointestinal toxicity. The most common problems associated with acetaminophen use are hepatotoxicity after acute ingestion of large doses (>10 g) or habitual use of smaller doses (Conclusions Intermittent use of most nonnarcotic analgesics produces a small risk of chronic renal or hepatic toxicity. Gastrointestinal toxicity, especially upper gastrointestinal bleeding, remains a significant problem with NSAIDs and aspirin. Acetaminophen remains the nonnarcotic analgesic of choice for intermittent use by most patient groups. The toxicities associated with NSAIDs constitute about 72.6% of the total toxicities (costs $1.86 billion) caused by NSAIDs, acetaminophen, and aspirin.

The recommendations provided in this document represent a distillation of various experiences, as well as data obtained from published studies in the setting of substantial changes in antibiotic sensitivity. It is hoped that this revised compilation will provide a basis upon which future developments and advances can be made in the therapeutic approach to infectious complications of peritoneal dialysis.

Objective This study aimed to investigate the pharmacokinetic characteristics of once-daily intraperitoneal (IP) gentamicin in continuous ambulatory peritoneal dialysis (CAPD) patients. Design Prospective, nonrandomized, open study. Setting CAPD outpatient clinic in a teaching hospital. Patients Ten volunteer CAPD patients without peritonitis. Interventions Each patient received a single IP dose of 0.6 mg/kg of gentamicin. Blood and dialysate samples were collected at 0,0.5,1, 2, 3,6 (end of first dwell), and 24 hours after the administration of IP gentamicin. Any urine produced over the 24hour study period was also collected. The dialysate concentration/time data were fitted to a monoexponential curve for all patients. Results The bioavailability was 56±11% over a six hour dwell. The mean serum elimination half-life (t1/2) was 35.8 hours. The volume of distribution was 0.23±0.08 L/kg. Equilibration of gentamicin across the peritoneal membrane was rapid, with a t½ equilibration of 4.5 hours. The peritoneal clearance was 5.74±1.5 mL/min. Patients with residual renal function had significantly higher systemic gentamicin clearances (7.36±1.46 mL/min) than those of anuric patients (4.76±1.08 mL/min, p < 0.024). Conclusion Currently recommended doses of oncedaily IP gentamicin for the treatment of peritonitis may not produce the desired therapeutic serum and dialysate concentrations over 24 hours for effective treatment of peritonitis.

Objective This study aimed to compare the correlations between KTN and creatinine clearance (Ccr) calculated by different methods and to determine and compare the correlations between KTN and Ccr. Design Nonrandomized, retrospective analysis of data. Setting Continuous ambulatory peritoneal dialysis (CAPD) outpatient clinic in a teaching hospital. Patients All patients were included for analysis if the data collection was complete for the calculations of KTN and Ccr using five different methods. Interventions Volume of distribution for urea (V) was estimated by four methods: Watson nomogram, ideal body weight (IBW), actual body weight, and total body surface area. Ccr was determined by five methods: Dialysate Ccr was calculated by creatinine (Cr) uncorrected and corrected for the presence of glucose; urinary Ccr was calculated using urinary Cr alone and the average urinary clearance of urea and Cr; and by the Cockcroft and Gault method. Main Outcome Measures Correlations between KTN and Ccr. Results Sixty-three data sets were collected from 52 CAPD patients. The correlations between weekly KTN and Ccr normalized to 1.73 m2 body surface area were found to be highly variable from one method to another (r2 = 0.012 -0.494). For obese patients (20% above IBW), KTN values obtained were more variable using the Watson nomogram compared to the IBW and BSA methods. Conclusion KT/V calculated using the Watson nomogram and the Ccr determined using average of urinary urea and creatinine clearance gave the best correlation (r2 = 0.49).

Objective: To describe a program of creatinine clearance–based dosage adjustment of 10 renally eliminated antimicrobial agents and to discuss the utility of such a program in a hospital as a method of quality assurance (by ensuring that patients with renal impairment receive generally accepted dosage adjustments), based on pharmacodynamic principles. Methods: Consecutive patients prescribed any of 10 targeted renally eliminated antibiotics were included. Recommendations for dosage adjustment were made to the prescriber based on a calculated creatinine clearance. Additional adjustments in drug therapy were performed, including dosage recommendations of nontargeted drugs, simplification of antibiotic regimens, and conversion of intravenous to oral therapy. A cost analysis was performed. Results: During a 6-month study period, 160 dosage changes (7.6% of total number screened) were recommended in 137 patients receiving the targeted antimicrobial agents. Prescribers accepted 147 recommendations (91.9%). A dosage change recommendation was necessary more than 12% of the time for acyclovir, ceftazidime, and imipenem/cilastatin. A cost avoidance of $11 702.08 was realized. Ancillary drug recommendations that were offered and accepted during the program realized a cost avoidance of $6613.75. Conclusions: This dosage adjustment program using pharmacodynamic principles was successful in optimization of dosing, potential minimization of morbidity caused by excessive dosing, and demonstration of direct and potentially indirect cost avoidance. A dosing program for patients with renal impairment would be of benefit to other clinicians and institutions seeking to optimize patient care.

Objective The primary literature was reviewed to determine the stability of drug additives in peritoneal dialysis solutions. Data Sources A MEDLINE search and retrieval, covering the period 1981 to 1994, was undertaken to identify relevant original literature. Additional references were identified from citations within the original literature. Non-English literature was excluded unless an English abstract was provided. Study Selection Forty-nine studies were identified. Of these, 24 were directly related to drug stability, 13 were related to the clinical use of the drug additives but included no stability data, and 12 examined other, nonstability aspects of in vitroactivity of antibiotics, additives, or drug adsorption in peritoneal dialysis bags and tubing. Data Extraction Data included concentrations of drug additives and dialysate solutions, duration and temperatures of storage conditions, types of assay, and whether they were stability-indicating. Results Stability was defined as the duration of time that the drug concentration remained at 90% or more of the original concentration. Stability was examined under a large variety of conditions. Thirty-one drugs were identified from 20 manuscripts as single-drug additives. Most beta-Iactams were stable for 1 –2 weeks in a refrigerator and for several days at room temperature. Aminoglycosides were stable for 1 –2 days at room temperature. Glycopeptides were stable for several weeks refrigerated or at room temperature. Prolonged storage at room temperature resulted in instability of cefotaxime, ceftazidime, ceftriaxone, and miconazole. Eleven drugs were identified from seven manuscripts as drug combination studies and showed similar stability as single agents. Dialysate concentration appeared to have minimal effect on stability. Conclusions Drug additives in peritoneal dialysate, singly or combined, should be avoided unless data are available to support their stability. Additives should be made as close as possible to the time of the exchange. Alternatively, additives should be stored refrigerated, then warmed prior to use. The practice of preparing numerous bags at one time should be avoided. Finally, stability data do not indicate sterile integrity of the dialysate.

Continuous ambulatory peritoneal dialysis (CAPD) continues to grow as a treatment modality for end-stage renal disease (ESRD). The high cost of care, multiplicity of drugs used by each patient, high cost of individual drugs, and high incidence of complications, make this patient population a challenging area for clinical pharmacy input. This article discusses the mechanics of CAPD, together with patient selection criteria, monitoring of the dialysis prescription, and infectious complications. The potential for research involving clinical pharmacists is discussed. Apart from studies on the pharmacokinetic disposition of drugs administered to CAPD patients, there remains a relative lack of information on many aspects of drug therapy. Recommendations for areas of continued study include the optimization of antibiotic therapy for peritonitis and exit-site infections, use of the intraperitoneal route for systemic effects of drugs, quality-of-life investigations, and stability studies of drugs in dialysate.

The quinolone class of antibiotics is enjoying a recent resurgence in interest and use due to the development of improved compounds. Norfloxacin, ciprofloxacin, and, most recently, ofloxacin have been marketed. Enoxacin and other agents are in various stages of investigation. These newer compounds are often used for indications not successfully treated by the original quinolones, or in some cases, not optimally treated with any previously available oral antibiotic. A potential problem with the increasing use of quinolone-type antibiotics for systemic illness is the chelation and inactivation of these compounds by several cations. One outcome of these potential interactions is a possible reduction in bioavailability and effectiveness of quinolone compounds. A review of the literature on quinolone-cation interactions, in vivo and in vitro significance, and recommendations to avoid potential problems are provided.

Fifty-nine patients returned a confidential mailed questionnaire, to determine their procedures for disposal of CAPO waste including bags, fluids and needles, and to assess their instruction and opinions on health risks from their wastes. Patients came predominantly from rural communities. Sixty four percent used disposal boxes for used needles, 80% discarded drained bags in the garbage without wrapping them in plastic and 7 to 17% of patients discarded needles straight to the garbage, depending on circumstances. Thirty seven percent did not recall receiving instruction on waste disposal, and of those who did, instructions came predominantly from nurses. Twenty of 32 patients who had suffered peritonitis disposed of their bags during peritonitis in the same manner as when they did not have peritonitis. Most patients (61%) felt issues dealing with CAPO waste disposal were “important” or “very important”, but fewer “agreed” or “strongly agreed” that it posed a health risk to others (16%) or to the environment (10%). Inconsistencies in methods of disposal and potential risks of infection dictate that guidelines must be developed to deal with these issues.

Ceftizoxime is a third-generation, semisynthetic cephalosporin that has activity against many grampositive and gram-negative micro-organisms. In the treatment of continuous ambulatory peritoneal dialysis (CAPD) peritonitis, ceftizoxime is usually reserved for organisms which show in vitro susceptibility once the organism has been cultured (1). The pharmacokinetics of ceftizoxime have been previously studied in CAPD patients without peritonitis (2). However, there are no pharmacokinetic data or efficacy studies of ceftizoxime in patients with peritonitis. We report dialysate and serum levels following the use of intraperitoneal (IP) ceftizoxime for the treatment of peritonitis caused by Serratia marcescens.

Large scale surveys have demonstrated that mild hypophosphataemia ( < O·70 mmol/L) is a relatively common finding among hospital inpatients, with an incidence of 2-3070. 1,2 Most patients are asymptomatic and do not require phosphate replacement therapy. Severe hypophosphataemia «0· 30 mmol/L), in contrast, is an uncommon finding,2,3 and frequently results in significant adverse effects. Severe hypophosphataemia is often multifactorial in origin and parenteral phosphate replacement may be required. Factors which may contribute to hypophosphataemia include reduced phosphate intake, increased phosphate loss and a shift of phosphate into cells." Reduced phosphate intake may occur during starvation and phosphate reabsorption may be prevented by certain antacids. Increased urinary phosphate loss occurs in vitamin D resistant rickets, oncogenic hypophosphataemia and other renal tubular disorders. An intracellular phosphate shift is a common finding following refeeding of malnourished subjects, and also occurs during respiratory alkalosis, dextrose infusion and treatment of diabetic ketoacidosis. We report an unusual case in which recurrent severe symptomatic hypophosphataemia was caused by a shift of phosphate into a rapidly growing clone of tumour cells.

La publicite sous toutes ses formes a eu un impact important a tous niveaux, et fut meme utilisee par le ministere de l'enseignement de New York pour diffuser et mettre en valeur la technologie de l'informatique.

A 34-year-old man took a mixed overdose of multiple lipid-soluble drugs. He did not respond to maximal medical therapy but improved after the introduction of Intralipid. The possible mechanisms of action and potential adverse consequences of using Intralipid in this context are reviewed.

Experience in the use of subcutaneous erythropoietin (EPO) in 32 continuous ambulatory peritoneal dialysis (CAPD) patients is presented. All patients were treated with oral iron supplements. The total and mean +/- SD durations of EPO treatment were 466 weeks and 14.6 +/- 10.1 weeks respectively. Twenty-two patients started treatment with normal or elevated iron stores; 10 had an initial iron saturation less than 20%. The initial hematocrit was 23.8 +/- 3.7%. Thirteen patients reached a steady-state hematocrit by the end of the study period, when the mean +/- SD hematocrit for all 32 patients was 34.1 +/- 3.6%. All patients responded to EPO. The initial dose of EPO was 147.1 +/- 53.8 U/kg/week. Maintenance dose was 72 +/- 36 U/kg/week.