When to start antiretroviral therapy in children aged 2-5 years: a collaborative causal modelling analysis of cohort studies from southern Africa

BACKGROUND There is limited evidence on the optimal timing of antiretroviral therapy (ART) initiation in children 2-5 y of age. We conducted a causal modelling analysis using the International Epidemiologic Databases to Evaluate AIDS-Southern Africa (IeDEA-SA) collaborative dataset to determine the difference in mortality when starting ART in children aged 2-5 y immediately (irrespective of CD4 criteria), as recommended in the World Health Organization (WHO) 2013 guidelines, compared to deferring to lower CD4 thresholds, for example, the WHO 2010 recommended threshold of CD4 count <750 cells/mm(3) or CD4 percentage (CD4%) <25%. METHODS AND FINDINGS ART-naïve children enrolling in HIV care at IeDEA-SA sites who were between 24 and 59 mo of age at first visit and with ≥1 visit prior to ART initiation and ≥1 follow-up visit were included. We estimated mortality for ART initiation at different CD4 thresholds for up to 3 y using g-computation, adjusting for measured time-dependent confounding of CD4 percent, CD4 count, and weight-for-age z-score. Confidence intervals were constructed using bootstrapping. The median (first; third quartile) age at first visit of 2,934 children (51% male) included in the analysis was 3.3 y (2.6; 4.1), with a median (first; third quartile) CD4 count of 592 cells/mm(3) (356; 895) and median (first; third quartile) CD4% of 16% (10%; 23%). The estimated cumulative mortality after 3 y for ART initiation at different CD4 thresholds ranged from 3.4% (95% CI: 2.1-6.5) (no ART) to 2.1% (95% CI: 1.3%-3.5%) (ART irrespective of CD4 value). Estimated mortality was overall higher when initiating ART at lower CD4 values or not at all. There was no mortality difference between starting ART immediately, irrespective of CD4 value, and ART initiation at the WHO 2010 recommended threshold of CD4 count <750 cells/mm(3) or CD4% <25%, with mortality estimates of 2.1% (95% CI: 1.3%-3.5%) and 2.2% (95% CI: 1.4%-3.5%) after 3 y, respectively. The analysis was limited by loss to follow-up and the unavailability of WHO staging data. CONCLUSIONS The results indicate no mortality difference for up to 3 y between ART initiation irrespective of CD4 value and ART initiation at a threshold of CD4 count <750 cells/mm(3) or CD4% <25%, but there are overall higher point estimates for mortality when ART is initiated at lower CD4 values. Please see later in the article for the Editors' Summary.

S9511: a Southwest Oncology Group phase II study of trimetrexate, 5-fluorouracil, and leucovorin in unresectable or metastatic adenocarcinoma of the stomach.

OBJECTIVE: The primary objective of this trial was to evaluate the response rate for trimetrexate in conjunction with 5-FU and leucovorin (LV) (= TFL) in the treatment of advanced gastric cancer in a phase II, cooperative group setting. METHODS: Patients with locally advanced, unresectable, or metastatic adenocarcinoma of the stomach received trimetrexate 110 mg/m IV over 60 minutes day 1, followed by 5-FU 500 mg/m IV bolus and LV 200 mg/m IV over 60 minutes day 2, followed by oral LV 15 mg every 6 hours x 7 doses, all weekly for 6 weeks followed by 2 weeks of rest, continued until progression. RESULTS: Characteristics for 37 eligible patients: median age 63 (range: 23-83); male/female: 69% of 31%; performance status 0/1/2 15/20/1. The confirmed response rate was 19%, and median overall survival was 6 months. Two patients died as a result of therapy, 1 because of infection without significant neutropenia, and 1 due to perforation of a responding gastric lesion. Seventy-two percent experienced grades 3 and 4 toxicity, most commonly diarrhea, fatigue, and lymphopenia. CONCLUSIONS: This regimen achieves response rates comparable to other 5-FU-based regimens, when used in treatment of incurable gastric cancer. Toxicity appears manageable.

Radiographic bone level changes of implant-supported restorations in edentulous and partially dentate patients: 5-year results.

PURPOSE To evaluate and compare crestal bone level changes and peri-implant status of implant-supported reconstructions in edentulous and partially dentate patients after a minimum of 5 years of loading. MATERIALS AND METHODS All patients who received a self-tapping implant with a microstructured surface during the years 2003 and 2004 at the Department of Prosthodontics, University of Bern, were included in this study. The implant restorations comprised fixed and removable prostheses for partially and completely edentulous patients. Radiographs were taken immediately after surgery, at impression making, and 1 and 5 years after loading. Crestal bone level (BIC) was measured from the implant shoulder to the first bone contact, and changes were calculated over time (ΔBIC). The associations between pocket depth, bleeding on probing (BOP), and ΔBIC were assessed. RESULTS Sixty-one implants were placed in 20 patients (mean age, 62 ± 7 years). At the 5-year follow-up, 19 patients with 58 implants were available. Implant survival was 98.4% (one early failure; one patient died). The average ΔBIC between surgery and 5-year follow-up was 1.5 ± 0.9 mm and 1.1 ± 0.6 mm for edentulous and partially dentate patients, respectively. Most bone resorption (50%, 0.7 mm) occurred during the first 3 months (osseointegration) and within the first year of loading (21%, 0.3 mm). Mean annual bone loss during the 5 years of loading was < 0.12 mm. Mean pocket depth was 2.6 ± 0.7 mm. Seventeen percent of the implant sites displayed BOP; the frequency was significantly higher in women. None of the variables were significantly associated with crestal bone loss. CONCLUSION Crestal bone loss after 5 years was within the normal range, without a significant difference between edentulous and partially dentate patients. In the short term, this implant system can be used successfully for various prosthetic indications.

Eighty percent of patients with surgical hip dislocation for femoroacetabular impingement have a good clinical result without osteoarthritis progression at 10 years

BACKGROUND We previously reported the 5-year followup of hips with femoroacetabular impingement (FAI) that underwent surgical hip dislocation with trimming of the head-neck junction and/or acetabulum including reattachment of the labrum. The goal of this study was to report a concise followup of these patients at a minimum 10 years. QUESTIONS/PURPOSES We asked if these patients had (1) improved hip pain and function; we then determined (2) the 10-year survival rate and (3) calculated factors predicting failure. METHODS Between July 2001 and March 2003, we performed surgical hip dislocation and femoral neck osteoplasty and/or acetabular rim trimming with labral reattachment in 75 patients (97 hips). Of those, 72 patients (93 hips [96%]) were available for followup at a minimum of 10 years (mean, 11 years; range, 10-13 years). We used the anterior impingement test to assess pain and the Merle d'Aubigné-Postel score to assess function. Survivorship calculation was performed using the method of Kaplan and Meier and any of the following factors as a definition of failure: conversion to total hip arthroplasty (THA), radiographic evidence of worsening osteoarthritis (OA), or a Merle d'Aubigné-Postel score less than 15. Predictive factors for any of these failures were calculated using the Cox regression analysis. RESULTS At 10-year followup, the prevalence of a positive impingement test decreased from preoperative 95% to 38% (p < 0.001) and the Merle d'Aubigné-Postel score increased from preoperative 15.3 ± 1.4 (range, 9-17) to 16.9 ± 1.3 (12-18; p < 0.001). Survivorship of these procedures for any of the defined failures was 80% (95% confidence interval, 72%-88%). The strongest predictors of failure were age > 40 years (hazard ratio with 95% confidence interval, 5.9 [4.8-7.1], p = 0.002), body mass index > 30 kg/m(2) (5.5 [3.9-7.2], p = 0.041), a lateral center-edge angle < 22° or > 32° (5.4 [4.2-6.6], p = 0.006), and a posterior acetabular coverage < 34% (4.8 [3.7-5.6], p = 0.006). CONCLUSIONS At 10-year followup, 80% of patients with FAI treated with surgical hip dislocation, osteoplasty, and labral reattachment had not progressed to THA, developed worsening OA, or had a Merle d'Aubigné-Postel score of less than 15. Radiographic predictors for failure were related to over- and undertreatment of acetabular rim trimming.

Twelve percent of hips with a primary cam deformity exhibit a slip-like morphology resembling sequelae of slipped capital femoral epiphysis

BACKGROUND In some hips with cam-type femoroacetabular impingement (FAI), we observed a morphology resembling a more subtle form of slipped capital femoral epiphysis (SCFE). Theoretically, the morphology in these hips should differ from hips with a primary cam-type deformity. QUESTIONS/PURPOSES We asked if (1) head-neck offset; (2) epiphyseal angle; and (3) tilt angle differ among hips with a slip-like morphology, idiopathic cam, hips after in situ pinning of SCFE, and normal hips; and (4) what is the prevalence of a slip-like morphology among cam-type hips? METHODS We retrospectively compared the three-dimensional anatomy of hips with a slip-like morphology (29 hips), in situ pinning for SCFE (eight hips), idiopathic cam deformity (171 hips), and 30 normal hips using radial MRI arthrography. Normal hips were derived from 17 asymptomatic volunteers. All other hips were recruited from a series of 277 hips (243 patients) seen at a specialized academic hip center between 2006 and 2010. Forty-one hips with isolated pincer deformity were excluded. Thirty-six of 236 hips had a known cause of cam impingement (secondary cam), including eight hips after in situ pinning of SCFE (postslip group). The 200 hips with a primary cam were separated in hips with a slip-like morphology (combination of positive fovea sign [if the neck axis did not intersect with the fovea capitis] and a tilt angle [between the neck axis and perpendicular to the basis of the epiphysis] exceeding 4°) and hips with an idiopathic cam. We evaluated offset ratio, epiphyseal angle (angle between the neck axis and line connecting the center of the femoral head and the point where the physis meets the articular surface), and tilt angle circumferentially around the femoral head-neck axis. Prevalence of slip-like morphology was determined based on the total of 236 hips with cam deformities. RESULTS Offset ratio was decreased anterosuperiorly in idiopathic cam, slip-like, and postslip (eg, 1 o'clock position with a mean offset ranging from 0.00 to 0.14; p < 0.001 for all groups) compared with normal hips (0.25 ± 0.06 [95% confidence interval, 0.13-0.37]) and increased posteroinferiorly in slip-like (eg, 8 o'clock position, 0.5 ± 0.09 [0.32-0.68]; p < 0.001) and postslip groups (0.55 ± 0.12 [0.32-0.78]; p < 0.001) and did not differ in idiopathic cam (0.32 ± 0.09 [0.15-0.49]; p = 0.323) compared with normal (0.31 ± 0.07 [0.18-0.44]) groups. Epiphyseal angle was increased anterosuperiorly in the slip-like (eg, 1 o'clock position, 70° ± 9° [51°-88°]; p < 0.001) and postslip groups (75° ± 13° [49°-100°]; p = 0.008) and decreased in idiopathic cam (50° ± 8° [35°-65°]; p < 0.001) compared with normal hips (58° ± 8° [43°-74°]). Posteroinferiorly, epiphyseal angle was decreased in slip-like (eg, 8 o'clock position, 54° ± 10° [34°-74°]; p < 0.001) and postslip (44° ± 11° [23°-65°]; p < 0.001) groups and did not differ in idiopathic cam (76° ± 8° [61°-91°]; p = 0.099) compared with normal (73° ± 7° [59°-88°]) groups. Tilt angle increased in slip-like (eg, 2/8 o'clock position, 14° ± 8° [-1° to 30°]; p < 0.001) and postslip hips (29° ± 10° [9°-48°]; p < 0.001) and decreased in hips with idiopathic cam (-7° ± 5° [-17° to 4°]; p < 0.001) compared with normal (-1° ± 5° [-10° to 8°]) hips. The prevalence of a slip-like morphology was 12%. CONCLUSIONS The slip-like morphology is the second most frequent pathomorphology in hips with primary cam deformity. MRI arthrography of the hip allows identifying a slip-like morphology, which resembles hips after in situ pinning of SCFE and distinctly differs from hips with idiopathic cam. These results support previous studies reporting that SCFE might be a risk factor for cam-type FAI.

Long-term Outcome After Monosegmental L4/5 Stabilization for Degenerative Spondylolisthesis With the Dynesys Device.

STUDY DESIGN Retrospective analysis of prospectively collected clinical data. OBJECTIVE To assess the long-term outcome of patients with monosegmental L4/5 degenerative spondylolisthesis treated with the dynamic Dynesys device. SUMMARY OF BACKGROUND DATA The Dynesys system has been used as a semirigid, lumbar dorsal pedicular stabilization device since 1994. Good short-term results have been reported, but little is known about the long-term outcome after treatment for degenerative spondylolisthesis at the L4/5 level. METHODS A total of 39 consecutive patients with symptomatic degenerative lumbar spondylolisthesis at the L4/5 level were treated with bilateral decompression and Dynesys instrumentation. At a mean follow-up of 7.2 years (range, 5.0-11.2 y), they underwent clinical and radiographic evaluation and quality of life assessment. RESULTS At final follow-up, back pain improved in 89% and leg pain improved in 86% of patients compared with preoperative status. Eighty-three percent of patients reported global subjective improvement. Ninety-two percent would undergo the surgery again. Eight patients (21%) required further surgery because of symptomatic adjacent segment disease (6 cases), late-onset infection (1 case), and screw breakage (1 case). In 9 cases, radiologic progression of spondylolisthesis at the operated segment was found. Seventy-four percent of operated segments showed limited flexion-extension range of <4 degrees. Adjacent segment pathology, although without clinical correlation, was diagnosed at the L5/S1 (17.9%) and L3/4 (28.2%) segments. In 4 cases, asymptomatic screw loosening was observed. CONCLUSIONS Monosegmental Dynesys instrumentation of degenerative spondylolisthesis at L4/5 shows good long-term results. The rate of secondary surgeries is comparable to other dorsal instrumentation devices. Residual range of motion in the stabilized segment is reduced, and the rate of radiologic and symptomatic adjacent segment degeneration is low. Patient satisfaction is high. Dynesys stabilization of symptomatic L4/5 degenerative spondylolisthesis is a possible alternative to other stabilization devices.

(Supplement) Regeneration of Pinus sylvestris, disturbance residuals and soil properties 5 years after a mixed-severity wildfire in the inner Italian Alps

We analyzed the abundance of Scots pine regeneration in a 257 ha wildfire in an inner-alpine forest. We sampled regeneration, percent soil cover by classes, physical and chemical properties of topsoils (A horizon, 0-5 cm) under four fire severity levels (unburned, moderate, moderate/high, high severity). 5 plots per severity level, circular (R= 3m). Analysis methods for soil properties as described in the paper.

Landsat derived percent vegetation cover of Israel (as of 2003)

Wildfires are part of the Mediterranean ecosystem, however, in Israel all wildfires are human caused, either intentionally or un-intentionally. In this study we aimed to develop and test a new method for mapping fire scars from MODIS imagery, to examine the temporal and spatial patterns of wildfires in Israel in the 2000s and to examine the factors controlling Israel's wildfire regime. To map the fires we used two 'off-the-shelf' MODIS fire products as our basis-the 1 km MODIS Collection 5 fire hotspots, the 500 m MCD45A1 burnt areas-and we created a new set of fire scar maps from the 250 m MOD13Q1 product. We carried out a cross comparison of the three MODIS based wildfire scar maps and evaluated them independently against the wild fire scars mapped from 30 m Landsat TM imagery. To examine the factors controlling wildfires we used GIS layers of rainfall, land use, and a Landsat-based national vegetation map. Wildfires occurred in areas where annual rainfall was above 250 mm, mostly in areas with herbaceous vegetation. Wildfire frequency was especially high in the Golan Heights and in the foothills of the Judean mountains, and a high correspondence was found between military training zones and the spatial distribution of fire scars. The use of MODIS satellite images enabled us to map wildfires at a national scale due to the high temporal resolution of the sensor. Our MOD13Q1 based mapping of fire scars adequately mapped large (>1 km**2) fires with accuracies above 80%. Such large fires account for a large proportion of all fires, and pose the greatest threats. This database can aid managers in determining wildfire risks in space and in time.

Stable C and N isotopes and percent C as well as N composition of plankton from the North Atlantic

Elemental C and N percent composition and natural abundance of stable C and N isotopes of plankton species and/or size-fractions collected in several cruises on the N Atlantic Ocean from Greenland to Norway and around Iceland. Determinations included key copepod and krill species. Lipid extraction was performed in some samples to determine carbón isotope depletion factors.

Census of calcareous nannofossil taxa expressed as percent of total number of individuals counted, ODP Legs 113, 114, 119, 120

Quantitative analysis of upper Eocene-upper Oligocene calcareous nannofossil assemblages from five Ocean Drilling Program sites in the Atlantic and Indian Ocean sectors of the Southern Ocean reveals an abrupt increase in cool-water taxa at the top of magnetic Subchron C13R ca. 35.9 Ma, coincident with an enrichment of ~1? d18O in the planktonic foraminifers at these sites. The synchrony of the abrupt increase in cool-water taxa in the Southern Ocean renders this event a useful biostratigraphic datum at southern high latitudes. This earliest Oligocene cool-water taxa increase was the sharpest and largest during the late Eocene-late Oligocene interval and indicates a drop in surface-water temperature of more than 3°C in the Southern Ocean. This suggests that the earliest Oligocene d18O shift represents primarily a temperature signal; a small portion (~0.2?) is attributable to a global ice-volume increase.