Inuit wellness: A better understanding of the principles that guide actions and an overview of practices.

By imposing non-Inuit ways of doing within households and communities, colonization has created a rift between generations and impacted the transmission of Inuit practices and knowledge. Inuit care-providers continue to support their fellow community members with individual and collective approaches to wellbeing. The objectives and design of the current project were developed with community members who play an active role in mobilization and wellness. Inuit and non-Inuit research assistants conducted 14 individual interviews and 2 group interviews (total of 19 participants) with key informants involved in community wellness work. Then an Elder (third author) shared her knowledge regarding traditional practices. In this study we describe three underlying principles regarding wellness practices as well as five approaches and the mechanisms by which these approaches seem to impact personal and collective wellbeing. This study highlights how Inuit culture and knowledge can support children, family and community wellbeing in the ways of being together and of taking care of each other. The study responds to an expressed desire named by our partners to document Inuit approaches as well as the principles and practices underlying such approaches and how they are related to self-determination.

The evolution of percutaneous nephrolithotomy: Analysis of a single institution experience over 25 years.

INTRODUCTION: Over time, the incidence of nephrolithiasis has risen significantly, and patient populations have become increasingly complex. Our study aimed to determine the impact of changes in patient demographics on percutaneous nephrolithotomy (PCNL) outcomes. METHODS: A retrospective analysis of a prospectively collected database was carried out from 1990-2015. Patient demographics, comorbidities, stone and procedure characteristics were analyzed. Multivariate logistic regression was used to evaluate differences in operative duration, complications, stone-free rate, and length of stay. RESULTS: A total of 2486 patients with a mean age of 54±15 years, body mass index (BMI) of 31±8, and stone surface area of 895±602 mm2 were analyzed; 47% of patients had comorbidities, including hypertension (22%), diabetes mellitus (14%), and cardiac disease (13%). Complication rate was 19%, including a 2% rate of major complications (Clavien grade III-V). There was a statistically significant increase in patient age, BMI, and comorbidities over time, which was correlated with an increased complication rate (odds ratio [OR] 1.15; p=0.010). The overall transfusion rate was 1.0% and remained stable (p=0.131). With time, both OR duration (mean Δ 16 minutes; p<0.001) and hospital length of stay (mean Δ 2.4 days; p<0.001) decreased significantly. Stone-free rate of 1873 patients with available three-month followup was 87% and decreased significantly over time (OR 1.09; p<0.001), but was correlated with an increased use of computed tomography (CT) scans for followup imaging. CONCLUSIONS: Despite an increasingly complex patient population, PCNL remains a safe and effective procedure with a high stone-free rate and low risk of complications.

Four Months of Rifampin or Nine Months of Isoniazid for Latent Tuberculosis in Adults.

BACKGROUND: A 9-month regimen of isoniazid can prevent active tuberculosis in persons with latent tuberculosis infection. However, the regimen has been associated with poor adherence rates and with toxic effects. METHODS: In an open-label trial conducted in nine countries, we randomly assigned adults with latent tuberculosis infection to receive treatment with a 4-month regimen of rifampin or a 9-month regimen of isoniazid for the prevention of confirmed active tuberculosis within 28 months after randomization. Noninferiority and potential superiority were assessed. Secondary outcomes included clinically diagnosed active tuberculosis, adverse events of grades 3 to 5, and completion of the treatment regimen. Outcomes were adjudicated by independent review panels. RESULTS: Among the 3443 patients in the rifampin group, confirmed active tuberculosis developed in 4 and clinically diagnosed active tuberculosis developed in 4 during 7732 person-years of follow-up, as compared with 4 and 5 patients, respectively, among 3416 patients in the isoniazid group during 7652 person-years of follow-up. The rate differences (rifampin minus isoniazid) were less than 0.01 cases per 100 person-years (95% confidence interval [CI], -0.14 to 0.16) for confirmed active tuberculosis and less than 0.01 cases per 100 person-years (95% CI, -0.23 to 0.22) for confirmed or clinically diagnosed tuberculosis. The upper boundaries of the 95% confidence interval for the rate differences of the confirmed cases and for the confirmed or clinically diagnosed cases of tuberculosis were less than the prespecified noninferiority margin of 0.75 percentage points in cumulative incidence; the rifampin regimen was not superior to the isoniazid regimen. The difference in the treatment-completion rates was 15.1 percentage points (95% CI, 12.7 to 17.4). The rate differences for adverse events of grade 3 to 5 occurring within 146 days (120% of the 4-month planned duration of the rifampin regimen) were -1.1 percentage points (95% CI, -1.9 to -0.4) for all events and -1.2 percentage points (95% CI, -1.7 to -0.7) for hepatotoxic events. CONCLUSIONS: The 4-month regimen of rifampin was not inferior to the 9-month regimen of isoniazid for the prevention of active tuberculosis and was associated with a higher rate of treatment completion and better safety. (Funded by the Canadian Institutes of Health Research and the Australian National Health and Medical Research Council; ClinicalTrials.gov number, NCT00931736 .).

Transplantation of pediatric renal allografts from donors less than 10 kg.

Few transplant programs use kidneys from donors with body weight (BW) < 10 kg. We hypothesized that pediatric en bloc transplants from donors with BW < 10 kg would provide similar transplant outcomes to larger grafts. All pediatric en bloc renal transplants performed at our center between 2001 and 2017 were reviewed (N = 28). Data were stratified by smaller (donor BW < 10 kg; n = 11) or larger donors (BW > 10 kg; n = 17). Renal volume was assessed during follow-up with ultrasound. Demographic characteristics were similar between the 2 groups of recipients. After mean follow-up of 44 months (smaller donors) and 124 months (larger donors), graft and patient outcomes were similar between groups. Serum creatinine at 1, 3, and 5 years was no different between groups. At 1 day posttransplant, mean total renal volume in the smaller donors was 28 ± 9 mm3 vs 45 ± 12 mm3 (P < .01). By 3 weeks, it was 53 ± 19 mm3 (smaller donors) versus 73 ± 19 mm3 (larger donors) (P = NS). Complication rates were similar between both groups with 1 case of venous thrombosis in the smaller group. With experience, outcomes are equivalent to those from larger pediatric donors.

KIM-1 Is a Potential Urinary Biomarker of Obstruction: Results from a Prospective Cohort Study.

INTRODUCTION: Partial or complete obstruction of the urinary tract is a common and challenging urological condition that may occur in patients of any age. Serum creatinine is the most commonly used method to evaluate global renal function, although it has low sensitivity for early changes in the glomerular filtration rate or unilateral renal pathology. Hence, finding another measurable parameter that reflects the adaptation of the renal physiology to these circumstances is important. Several recent studies have assessed the use of new biomarkers of acute kidney injury (AKI), but the information among patients with stone disease and those with obstructive uropathy is limited. MATERIAL AND METHODS: A prospective cohort study was conducted to determine the urinary levels of kidney injury molecule-1 (KIM-1), Total and Monomeric neutrophil gelatinase-associated lipocalin (NGAL) in patients with hydronephrosis secondary to renal stone disease, congenital ureteropelvic junction obstruction or ureteral stricture. Comparison between patients with hydronephrosis and no hydronephrosis was carried out along with correlation analysis to detect factors associated with biomarker expression. RESULTS: Urinary levels of KIM-1 significantly decreased after hydronephrosis treatment in patients with unilateral obstruction (1.19 ng/mL vs 0.76 ng/mL creatinine, p = 0.002), additionally KIM-1 was significantly higher in patients with hydronephrosis compared to stone disease patients without radiological evidence of obstruction (1.19 vs 0.64, p = 0.006). Total and Monomeric NGAL showed a moderate correlation with the presence of leukocyturia. We found that a KIM-1 value of 0.735 ng/mg creatinine had a sensitivity of 75% and specificity of 67% to predict the presence of hydronephrosis in preoperative studies (95% CI 0.58-0.87, p = 0.006). CONCLUSION: Our results show that KIM-1 is a promising biomarker of subclinical AKI associated with hydronephrosis in urological patients. NGAL values were influenced by the presence of leukocyturia, limiting its usefulness in this population.

Natural History of Residual Fragments After Percutaneous Nephrolithotomy: Evaluation of Factors Related to Clinical Events and Intervention.

OBJECTIVE: To determine the natural history of residual fragments (RF) after percutaneous nephrolithotomy in long-term patient follow-up and to identify possible predictive factors for future intervention. MATERIALS AND METHODS: We assessed all patients from 2006 to 2013 with postoperative computed tomography scan revealing RF, who did not undergo second-look nephroscopy or immediate ancillary procedures, and with at least 12 months of clinical follow-up. We evaluated factors associated with clinical, radiological, and surgical outcomes. Kaplan-Meier curves were used to calculate the proportion of asymptomatic and treatment-free patients during follow-up. RESULTS: From 781 percutaneous nephrolithotomies performed, 202 patients underwent postoperative computed tomography scan and 44 patients with residual stones were included in the analysis. Mean follow-up was 57.9 months. A total of 24 patients (54.5%) developed at least 1 clinical outcome, and 32 (72.7%) patients had a surgical intervention. Only 4 patients had radiological evidence of stone passage. Multivariate analysis found that RF >4 mm and struvite or apatite stones were significant predictors for surgical intervention. The 5-year estimated probability to remain intervention free was 29%. CONCLUSION: Despite the size of the RF, the vast majority of patients required an intervention during long-term follow-up. We identified that RFs of diameter >4 mm associate with the need for a surgical therapy, but the rate of clinical events was not affected by the size or location of the stones. Struvite or apatite composition stones had an increased risk of intervention during follow-up. Spontaneous passage was an uncommon event in this cohort.

Assessing the Magnitude of Effect of Bone Structures on Shockwave Lithotripsy Fragmentation: Results from an In Vitro Study.

INTRODUCTION: Several anatomic and clinical factors have been implicated in the failure rates of shock wave lithotripsy (SWL), including the attenuating effects of bony structures. We designed an in vitro model that incorporates the lumbar spine, including vertebral bodies and transverse processes along the pathway of shockwaves, to mimic the clinical scenario during SWL of upper ureteral stones. We hypothesized that the presence of bone structures in the SWL pathway significantly affects the fragmentation rate. MATERIALS AND METHODS: An ordnance gelatin (OG) model was conceptualized and created to allow a pig's lumbar spine to be embedded within it. Artificial urinary calculi weighing 2 ± 0.1 g (1.2-cm diameter) were prepared using BegoStone plaster. The trial was divided into two arms: group 1 models had OG only and served as the control and group 2 models had the bone embedded in the gelatin with stone wells placed above the transverse processes. Twenty-four stones per group were subjected to SWL using the STORZ MODULITH SLX-F2 lithotripter, using the same treatment parameters. Fragments were sieved through 2- and 4-mm filters, and the fragmentation coefficients (FC) were calculated. The Mann-Whitney test was used to compare FC between the two groups. RESULTS: The mean fragmentation rate of group 1 was statistically significantly higher compared with group 2 using a 4-mm sieve (43% vs 0.62%, p < 0.001) and the 2-mm filter (18% vs 0.52%, p < 0.001). CONCLUSIONS: The presence of bone structures dramatically reduces the fragmentation rate of phantom stones using an OG in vitro model. The OG model is inexpensive and simple to use to simulate clinical situations during SWL.

Epidemic History and Iatrogenic Transmission of Blood-borne Viruses in Mid-20th Century Kinshasa.

BACKGROUND: The human immunodeficiency virus type 1 (HIV-1) pandemic was ignited in Léopoldville (now known as Kinshasa), in the former Belgian Congo. Factors that jump-started its early expansion remain unclear. Nonlethal hepatitis C virus (HCV) and human T-cell lymphotropic virus (HTLV-1) can be used to investigate past iatrogenic transmission. METHODS: We undertook a cross-sectional study of elderly inhabitants of Kinshasa, with serological assays, amplification, and sequencing. Risk factors were assessed through logistic regression. Phylogenetic methods reconstructed the genetic history of HCV. RESULTS: A total of 217 of 839 participants (25.9%) were HCV seropositive; 26 (3.1%) were HTLV-1-seropositive. Amplification products were obtained from 118 HCV-seropositive participants; subtypes 4k (in 47 participants) and 4r (in 38) were most common. Independent risk factors for HCV subtype 4r seropositivity were intramuscular tuberculosis therapy, intravenous injections at hospital A, intravenous injections before 1960, and injections at a colonial-era venereology clinic. Intravenous injections at hospital B and antimalarials were associated with HCV subtype 4k seropositivity. Risk factors for HTLV-1 seropositivity included intravenous injections at hospitals C or D and transfusions. Evolutionary analysis of viral sequences revealed independent exponential amplification of HCV subtypes 4r and 4k from the 1950s onward. CONCLUSIONS: Iatrogenic transmission of HCV and HTLV-1 occurred in mid-20th century Kinshasa, at the same time and place HIV-1 emerged. Iatrogenic routes may have contributed to the early establishment of the pandemic.

Robotic Proximal Ureteropyelostomy After Unsuccessful Endourologic Management of Complicated Proximal Ureteral Stone Disease.

We present a clinical case of a 66-year-old female with a left ureteropelvic junction impacted renal calculi associated with a tortuous ureter. After a failed combined retrograde and antegrade endoscopic procedure, a robot-assisted laparoscopic ureteropyelostomy was successful.

Hypothermic machine perfusion improves Doppler ultrasonography resistive indices and long-term allograft function after renal transplantation: a single-centre analysis.

OBJECTIVES: To evaluate whether hypothermic machine perfusion (HMP) of transplanted kidneys can improve long-term renal allograft function compared with static cold storage (CS). METHODS: We evaluated whether graft Doppler ultrasonography resistive indices improved with the use of HMP compared with CS preservation, and examined whether these improvements were predictive of long-term graft function. A total of 30 kidney transplants (15 pairs) were examined. One of the kidney pairs was placed on CS and transplanted first (CS group, n = 15). The other kidney of each pair was placed on HMP and transplanted after the CS group (HMP group, n = 15). Doppler ultrasonography was performed on days 1 and 7 after transplantation and resistive indices were evaluated. The estimated glomerular filtration rate (eGFR) was monitored for 24 months after transplantation. RESULTS: Despite longer cold ischaemia times, kidneys maintained with HMP had lower resistive indices (P = 0.005) with correspondingly higher eGFR throughout the follow-up. Subgroup analysis showed that the HMP-induced improvement in postoperative eGFR was greatest in kidneys obtained from donation after cardiac death (DCD), even at 2 years after transplantation (P = 0.008). CONCLUSIONS: HMP of transplant kidneys appears to improve vascular resistance after transplantation and has a positive impact on long-term allograft function compared with CS in the population of recipients of DCD kidneys.

Donation after cardiac death pediatric en bloc renal transplantation.

PURPOSE: Use of small pediatric kidneys obtained from extremely young donors after cardiac death has been limited. This potential organ source remains under used by transplant teams. MATERIALS AND METHODS: We reviewed all renal transplants at our institution from 2000 to 2013 to identify recipients of an en bloc pair of kidneys from deceased pediatric donors younger than 4 years. The outcomes of donation after cardiac death en bloc allografts were compared with neurological determination of death en bloc allografts. RESULTS: A total of 21 recipients of en bloc renal allografts were identified, of which 4 organ pairs were obtained through donation after cardiac death. Mean ± SD donor age was 20.6 ± 11.6 months and weight was 12.4 ± 3.7 kg. Delayed allograft function occurred in 2 of 4 recipients of allografts obtained from donation after cardiac death en bloc and 3 of 17 recipients of allografts from neurological determination of death en bloc. One year after transplantation mean ± SD glomerular filtration rates were similar, at 80.7 ± 15.3 and 85.7 ± 33.4 ml/minute/1.73 m(2) in the cardiac and neurological allograft groups, respectively (difference not significant). Surgical complications occurred in 3 patients, and no allograft was lost to thrombosis. CONCLUSIONS: We report successful transplantation of a small cohort of pediatric en bloc kidneys obtained through donation after cardiac death from donors younger than 4 years. Outcomes at 1 year are comparable to those in neurological determination of death en bloc allograft recipients.

Percutaneous nephrolithotomy in patients with urinary tract abnormalities.

BACKGROUND AND PURPOSE: Patients with urinary tract abnormalities are at an increased risk of stone formation. Percutaneous nephrolithotomy (PCNL) plays an important role in the treatment of this patient population; however, outcomes are less well defined compared with patients with normal urinary tract anatomy. Our objective was to evaluate the influence of urinary tract abnormalities on intraoperative and postoperative outcomes with PCNL. PATIENTS AND METHODS: We report on a single-center prospective database of 2284 consecutive PCNLs in 1935 patients from 1990 to 2012. For the purposes of this analysis, patients were categorized by the presence or absence of a urinary tract abnormality. Multivariable analyses were used to identify independent predictors of the length of hospital stay, operative time, complications, and residual stones at discharge and 3 months. RESULTS: A urinary tract abnormality was present in 14.4% (n=330) of the cohort. On univariable analysis, patients with urinary tract abnormalities were more likely to present with urinary tract infection (28% vs 19%, P<0.001) and less likely to present with hematuria (13% vs 19%, P<0.02). On multivariable regression, a urinary tract abnormality was predictive of residual stone at discharge, need for a secondary procedure, but did not increase the risk of residual stone at 3 months or the development of complications. Operative time and hospital stay were only moderately prolonged. CONCLUSION: Patients with urinary tract abnormalities who undergo PCNL have a higher risk of residual stones at discharge and need for secondary procedures, but comparable complication rates, operative time, and hospital stay.

Debilitating lower urinary tract symptoms in the post-renal transplant population can be predicted pretransplantation.

BACKGROUND: Overactive bladder and benign prostatic hyperplasia commonly cause lower urinary tract symptoms (LUTS) in the renal transplant (RTx) population. These LUTS may be masked by low urine output and may pose risk to renal allografts after RTx. Our purpose was to determine the frequency and severity of LUTS in RTx patients and to determine if patients at highest risk for LUTS could be predicted by validated questionnaires or other pre-RTx characteristics. METHODS: All patients who underwent RTx between 2005 and 2010 were asked to complete the validated Overactive Bladder Questionnaire based on patient symptoms before RTx and at 6 and 12 months after RTx. Male patients also completed the International Prostate Symptom Score survey. Patient, donor, and RTx characteristics and outcome data were collected. RESULTS: Of 466 RTx recipients, 23.8% responded and 89 patients were eligible for participation in the study. LUTS were common both before and after RTx as measured by the Overactive Bladder Questionnaire and International Prostate Symptom Score. Pre-RTx survey scores were predictive of moderate to severe post-RTx LUTS (relative risk, 4.1-18.0; P≤0.05). Low urine output of less than 250 mL per day was also predictive of moderate to severe post-RTx LUTS (relative risk, 2.9-5.9; P<0.02). CONCLUSIONS: Validated questionnaires and low urine output before transplantation may be used to identify patients at highest risk for LUTS after RTx. Identification of at risk patients would allow earlier initiation of treatment strategies to improve patient quality of life.

Cost analysis of two follow-up strategies for localized kidney cancer: a Canadian cohort comparison.

INTRODUCTION: The cost of surveillance strategies in patients after radical nephrectomy for localized primary renal cell carcinoma (RCC) has not been evaluated. We compared the costs of 2 different surveillance strategies, the new Canadian Urological Association (CUA) guidelines and the old strategy implemented in our institution. METHODS: Seventy-five patients who underwent radical nephrectomy for primary non-metastatic renal cancer were retrospectively reviewed. The direct cost of surveillance was determined and compared with the theoretical cost which would have been accrued using the CUA guidelines. RESULTS: Our mean follow-up was 31.1 (SD ± 20.4) months. The overall and disease-free survival endpoints were 87.7% and 85.2%, respectively. Total medical costs were higher for our old institutional surveillance strategy than the CUA guidelines ($181 861 vs. $135 054). For the complete follow-up of 75 patients, a cost-savings of $46 806 could have been achieved following the CUA guidelines (p = 0.002). Of recurrences, 7 of 8 were detected by routine screening, only 1 recurrence was identified by symptoms. The cost per recurrence detected in our old protocol was $9 812.92. The increased cost of our institution was due to more visits with basic testing, symptomatic investigation, and follow-up of imaging tests. The median percent cost attributable to these extra tests was 15% (range 0 to 59). CONCLUSION: Based on our results, we endorse the new CUA surveillance strategy in RCC follow-up as appropriate and cost effective in comparison with previous follow-up strategies used at our institution.

Impact of treatment completion, intolerance and adverse events on health system costs in a randomised trial of 4 months rifampin or 9 months isoniazid for latent TB.

RATIONALE: Treatment for latent tuberculosis infection with isoniazid for 9 months (9INH) has poor completion and serious adverse events, while treatment for 4 months with daily rifampin (4RIF) has significantly higher completion and fewer adverse events. OBJECTIVES: To compare the health system costs of 4RIF and 9INH. METHODS: In a randomised trial conducted in five Canadian centres, one Brazilian and one Saudi Arabian centre, consenting subjects were randomised to receive 4RIF or 9INH. Health system costs were estimated from healthcare utilisation including scheduled and unscheduled visits, investigations and drugs. All activities for all subjects were evaluated using financial information from 2007 from the Montreal Chest Institute. Costs were expressed in Canadian dollars. RESULTS: Total health system cost per patient allocated to 4RIF was $854 compared with $970 for 9INH (p<0.0001). The average cost per patient for the 328 of 420 (78%) who completed 4RIF therapy was $1094 compared with $1625 for the 254 of 427 (60%) completing 9INH (p<0.0001). Costs were modestly increased in patients with minor intolerance and substantially increased if the treating physician stopped treatment because of possible adverse events. Total costs related to management of adverse events with 9INH were $48 142 compared with $25 684 for 4RIF (p=0.008). Using these data, incremental cost-effectiveness analyses showed that 4RIF would be cost saving and prevent more cases within 2 years if efficacy exceeded 74%, and cost saving if efficacy exceeded 65%. CONCLUSIONS: The 4RIF regimen was significantly cheaper per patient completing treatment because of better completion and fewer adverse events.

Profiles of neurological outcome prediction among intensivists.

BACKGROUND: Advances in intensive care medicine have increased survival rates of patients with critical neurological conditions. The focus of prognostication for such patients is therefore shifting from predicting chances of survival to meaningful neurological recovery. This study assessed the variability in long-term outcome predictions among physicians and aimed to identify factors that may account for this variability. METHODS: Based on a clinical vignette describing a comatose patient suffering from post-anoxic brain injury intensivists were asked in a semi-structured interview about the patient's specific neurological prognosis and about prognostication in general. Qualitative research methods were used to identify areas of variability in prognostication and to classify physicians according to specific prognostication profiles. Quantitative statistics were used to assess for associations between prognostication profiles and physicians' demographic and practice characteristics. RESULTS: Eighteen intensivists participated. Functional outcome predictions varied along an evaluative dimension (fair/good-poor) and a confidence dimension (certain-uncertain). More experienced physicians tended to be more pessimistic about the patient's functional outcome and more certain of their prognosis. Attitudes toward quality of life varied along an evaluative dimension (good-poor) and a "style" dimension (objective-subjective). Older and more experienced physicians were more likely to express objective judgments of quality of life and to predict a worse quality of life for the patient than their younger and less experienced counterparts. CONCLUSIONS: Various prognostication profiles exist among intensivists. These may be dictated by factors such as physicians' age and clinical experience. Awareness of these associations may be a first step to more uniform prognostication.

Adverse events with 4 months of rifampin therapy or 9 months of isoniazid therapy for latent tuberculosis infection: a randomized trial.

BACKGROUND: Treatment of latent tuberculosis infection with isoniazid for 9 months is complicated by poor patient adherence and the need for close follow-up of side effects, especially hepatotoxicity. Shorter and safer regimens are needed. OBJECTIVE: To compare the frequency of adverse events and treatment completion in 2 treatment regimens for latent tuberculosis infection. DESIGN: Multicenter, randomized, open-label trial. SETTING: Tuberculosis clinics located in university hospitals in Canada, Brazil, and Saudi Arabia. PATIENTS: 847 patients without a contraindication for rifampin and requiring treatment for latent tuberculosis infection. INTERVENTION: Four months of daily rifampin therapy or 9 months of daily isoniazid therapy. MEASUREMENTS: Grade 3 to 4 drug-related adverse events resulting in drug discontinuation (primary outcome), and on-time treatment completion, grade 1 to 2 drug-related adverse events, and changes in liver enzymes and hematologic variables (secondary outcomes). RESULTS: Seventeen of 422 participants who started isoniazid therapy developed grade 3 to 4 adverse events compared with 7 of 418 who started rifampin therapy (risk difference [rifampin minus isoniazid], -2.3% [95% CI, -5% to -0.1%]; P = 0.040). Grade 3 or 4 hepatitis occurred in 16 of 422 isoniazid recipients compared with 3 of 418 rifampin recipients (risk difference, -3.1% [CI, -5% to -1%]; P = 0.003). Grade 1 or 2 adverse events attributed to study drugs occurred with similar frequency. Asymptomatic reduction in platelet and leukocyte counts were more frequent in rifampin recipients. More patients completed rifampin treatment (78%) than isoniazid treatment (60%) (difference, 18% [CI, 12% to 24%]; P < 0.001]). LIMITATION: The study did not measure efficacy, and the open-label design may increase the chance of bias in ascertainment of adverse events. CONCLUSION: Treatment of latent tuberculosis with 4 months of rifampin leads to fewer serious adverse events and better adherence than 9 months of isoniazid. These findings justify a large-scale trial to compare the efficacy of rifampin with that of isoniazid.

Estimating thymic function through quantification of T-cell receptor excision circles.

Analysis of immune reconstitution is of major importance in clinical settings such as following bone marrow transplantation or during anti-retroviral treatment of HIV-infected patients. In these patients, thymic function is essential for the reconstitution of a diversified T-cell receptor (TCR) repertoire. During thymopoiesis, several genetic rearrangements lead to the generation of fully functional TCR. By-products of these processes, the T-cell receptor excision circles (TRECs), are present in cells exported from the thymus but do not replicate during mitosis; they can thus be used as molecular markers for recent thymic emigrants. We demonstrate how thymic function can be assessed in a quantitative and noninvasive fashion in humans by estimating intrathymic precursor T-cell proliferation through the quantification of distinct TREC molecules in peripheral blood cells.