Assessing polymyalgia rheumatica activity when C-reactive protein is unavailable or uninterpretable.

Objective: The PMR activity score (PMR-AS) includes the CRP value, which may be lacking or invalid owing to anti-IL-6 therapy. Our objective was to develop alternatives to PMR-AS that do not require CRP. Methods: We used the Club Rhumatisme et Inflammation (CRI; 89 patients with PMR) and the Tolerance and Efficacy of tocilizumab iN pOlymyalgia Rheumatica (TENOR; 20 patients with recent-onset PMR naive to glucocorticoid who received three tocilizumab infusions, at weeks 0, 4 and 8, followed by prednisone from weeks 12 to 24) cohorts. In the CRI cohort, we evaluated correlations between PMR-AS items to select the best item for imputing CRP. Then we calculated the PMR-AS with (PMR-AS) and without (clin-PMR-AS) CRP and we used the linear regression between PMR-AS and clin-PMR-AS to obtain CRP-imputed (CRP-imp) PMR-AS. Finally, we evaluated agreement between clin-PMR-AS, CRP-imp PMR-AS, PMR-AS and ESR-PMR-AS in the TENOR cohort during tocilizumab therapy. Results: In the CRI cohort, agreement between PMR-AS and clin-PMR-AS was excellent (κ = 0.90). Linear regression between PMR-AS and clin-PMR-AS [CRP-imp PMR-AS = 1.12(clin-PMR-AS)+0.26] allowed us to build the CRP-imp PMR-AS. Mean (s.d.) values were as follows: 8.40 (9.76) for PMR-AS, 7.24 (8.58) for clin-PMR-AS and 7.84 (9.61) for CRP-imp PMR-AS. CRP-imp PMR-AS agreed more closely with PMR-AS than did clin-PMR-AS. The results in the TENOR cohort confirmed that CRP-imp PMR-AS or ESR-PMR-AS could be used. Conclusion: Alternatives to the PMR-AS obtained without CRP can be used to monitor PMR activity in everyday practice in patients without available CRP values and in those receiving IL-6 antagonist therapy.

Automatic versus manual oxygen administration in the emergency department.

Oxygen is commonly administered in hospitals, with poor adherence to treatment recommendations.We conducted a multicentre randomised controlled study in patients admitted to the emergency department requiring O2 ≥3 L·min-1 Patients were randomised to automated closed-loop or manual O2 titration during 3 h. Patients were stratified according to arterial carbon dioxide tension (PaCO2 ) (hypoxaemic PaCO2 ≤45 mmHg; or hypercapnic PaCO2 >45-≤55 mmHg) and study centre. Arterial oxygen saturation measured by pulse oximetry (SpO2 ) goals were 92-96% for hypoxaemic, or 88-92% for hypercapnic patients. Primary outcome was % time within SpO2 target. Secondary endpoints were hypoxaemia and hyperoxia prevalence, O2 weaning, O2 duration and hospital length of stay.187 patients were randomised (93 automated, 94 manual) and baseline characteristics were similar between the groups. Time within the SpO2 target was higher under automated titration (81±21% versus 51±30%, p<0.001). Time with hypoxaemia (3±9% versus 5±12%, p=0.04) and hyperoxia under O2 (4±9% versus 22±30%, p<0.001) were lower with automated titration. O2 could be weaned at the end of the study in 14.1% versus 4.3% patients in the automated and manual titration group, respectively (p<0.001). O2 duration during the hospital stay was significantly reduced (5.6±5.4 versus 7.1±6.3 days, p=0.002).Automated O2 titration in the emergency department improved oxygenation parameters and adherence to guidelines, with potential clinical benefits.

Risk of recurrent venous thromboembolism in COPD patients: results from a prospective cohort study.

We aimed to assess the risk of recurrent venous thromboembolism (VTE) in patients with chronic obstructive pulmonary disease (COPD) following cessation of anticoagulation therapy.In a prospective cohort of 1468 patients with a documented episode of VTE, followed for up to 5 years after cessation of anticoagulation therapy, the diagnosis of COPD was confirmed in 136. The main outcome was recurrent VTE. The secondary outcome was overall mortality. Univariate and multivariate analyses were performed to identify the risk factors of recurrence.Of the 1468 patients included, recurrent VTE was observed in 306 (34 with COPD and 272 without) during a median follow-up period of 36.5 months. The incidence rate of recurrent VTE was 9.1% (95% CI 6.5-12.8) for COPD patients and 7.0% (95% CI 6.2-7.9) for non-COPD patients. COPD was not associated with an increased risk of VTE recurrence on univariate or multivariate analyses (hazard ratio: 1.0 (95% CI 0.7-1.4)). The risk of death, adjusted for demographic and clinical characteristics, showed no increase in COPD patients, as compared to non-COPD patients.In patients with COPD who had an acute episode of VTE, the risk of recurrent VTE was not any higher than that in non-COPD patients.

Efficacy of first-line tocilizumab therapy in early polymyalgia rheumatica: a prospective longitudinal study.

BACKGROUND: Glucocorticoids are the cornerstone treatment of polymyalgia rheumatica (PMR) but induce adverse events. OBJECTIVES: To evaluate the efficacy and safety of first-line tocilizumab in PMR. METHODS: In a prospective open-label study (ClinicalTrials.gov: NCT01713842), 20 glucocorticoid-free patients fulfilling Chuang's PMR criteria, with symptom onset within the last 12 months and a PMR activity score (PMR-AS) >10, each received three tocilizumab infusions at 4-week intervals, without glucocorticoids, followed by oral prednisone from weeks 12 to 24 (0.15 mg/kg if PMR-AS ≤10 and 0.30 mg/kg otherwise). The primary end point was the proportion of patients with PMR-AS≤10 at week 12. RESULTS: Baseline median PMR-AS was 36.6 (IQR 30.4-43.8). At week 12, all patients had PMR-AS≤10 and received the low prednisone dosage. Median PMR-AS at weeks 12 and 24 was 4.5 (3.2-6.8) and 0.95 (IQR 0.4-2), respectively (p<0.001 vs baseline for both time points). No patient required rescue treatment. Positron emission tomography-CT showed significant improvements. The most common adverse events were transient neutropenia (n=3) and leucopenia (n=5); in one patient, the second tocilizumab infusion was omitted due to leucopenia. CONCLUSIONS: Tocilizumab monotherapy is effective in recent-onset PMR. Randomised controlled trials are warranted. TRIAL REGISTRATION NUMBER: NCT01713842.

Glucose transporter 1-expressing proinflammatory monocytes are elevated in combination antiretroviral therapy-treated and untreated HIV+ subjects.

Monocyte activation during HIV-1 infection is associated with increased plasma levels of inflammatory markers and increased risk for premature development of age-related diseases. Because activated monocytes primarily use glucose to support cellular metabolism, we hypothesized that chronic monocyte activation during HIV-1 infection induces a hypermetabolic response with increased glucose uptake. To test this hypothesis, we evaluated glucose transporter 1 (Glut1) expression and glucose uptake by monocyte subpopulations in HIV-seropositive (HIV(+)) treatment-naive individuals (n = 17), HIV(+) individuals on combination antiretroviral therapy with viral loads below detection (n = 11), and HIV-seronegative (HIV(-)) individuals (n = 16). Surface expression of Glut1 and cellular uptake of the fluorescent glucose analog 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2 deoxyglucose were analyzed by flow cytometry on monocyte subpopulations. Irrespective of treatment status, monocytes from HIV(+) persons had significantly increased surface expression of Glut1 compared with those from HIV(-) controls. Nonclassical (CD14(+)CD16(++)) and intermediate (CD14(++)CD16(+)) monocyte subpopulations showed higher Glut1 expression than did classical (CD14(++)CD16(-)) monocytes. Intermediate monocytes from treatment-naive HIV(+) individuals also showed increased uptake of 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2 deoxyglucose compared with those from HIV(-) controls. Our results show that HIV infection is associated with increased glucose metabolism in monocytes and that Glut1 expression by proinflammatory monocytes is a potential marker of inflammation in HIV-infected subjects. However, the possibility exists whereby other Gluts such as Glut3 and Glut4 may also support the influx of glucose into activated and inflammatory monocyte populations.

Actigraphy is not a reliable method for measuring sleep patterns in neonates.

AIM: Polysomnography is the gold standard for studying sleep, but it is complex to use, and this can be problematic in clinically unstable preterm infants. We evaluated the reliability of actigraphy and polysomnography in detecting sleep-wake patterns in newborn infants. METHODS: A prospective, monocentric study was conducted that measured the sleep patterns of 48 infants: 24 late preterm neonates born at 34-36 weeks of gestational age and 24 term neonates. We used both polysomnography and the Actiwatch Mini during a three-hour period and then compared the results from the two methods. RESULTS: The baseline measurements for the preterm and terms groups were as follows: gestational age (34.5 weeks and 39.2 weeks), birthweight (2368 g and 3393 g) and age (6.4 days and 0.72 days). With the Actiwatch Mini, sensitivity for the late preterm and full-term infants was 78% and 87% for the leg actigraph and 78% and 93% for the arm actigraph. For specificity, the respective figures were 42% and 31% for the leg and 34% and 20% for the arm. CONCLUSION: Actigraphy using the Actiwatch Mini was not a reliable method for measuring sleep patterns in healthy late preterm and term neonates a few days after birth.

MRI investigation of radiating pain in the lower limbs: value of an additional sequence dedicated to the lumbosacral plexus and pelvic girdle.

OBJECTIVE: In some cases, sciatica-like symptoms radiating through the buttock, anterior thigh, or leg result from spinal root compression in an extraspinal location or from injury to the pelvic girdle. It has been suggested that adding a coronal STIR sequence dedicated to the lumbosacral plexus and pelvis to the routine MRI protocol can provide a good depiction of disorders of this type. MATERIALS AND METHODS: Two hundred nine patients with sciatica-like symptoms of suspected lumbar origin were included in the study. Disorders responsible for symptoms involving extraspinal compression of the lumbosacral plexus or pelvic girdle were retrospectively noted and correlated with age, sex, location of pain, referring physician, presence of discoradicular impingement liable to explain symptoms, and history of neoplasia. RESULTS: An extraspinal cause of symptoms was depicted in 12 cases (5.7%), including three cases of extraspinal compression and nine differential diagnoses in the pelvic region. Prevalence of an extraspinal cause of pain was significantly correlated with the absence of discoradicular impingement in the spine (p=0.046). A higher prevalence of extraspinal compression of the lumbosacral plexus (p=0.029) was seen in patients 60 years old or older, whereas no other feature was statistically associated with an extraspinal cause of pain. CONCLUSION: Because of its short acquisition time and subsequent low cost, the additional coronal STIR sequence should be performed in the routine MRI investigation of sciatica-like symptoms when no discoradicular impingement is seen in the spine to depict an extraspinal cause of symptoms.

Does midazolam enhance pain control in prehospital management of traumatic severe pain?

PURPOSE: Midazolam comedication with morphine is a routine practice in pre and postoperative patients but has not been evaluated in prehospital setting. We aimed to evaluate the comedication effect of midazolam in the prehospital traumatic adults. METHODS: A prehospital prospective randomized double-blind placebo-controlled trial of intravenous morphine 0.10 mg/kg and midazolam 0.04 mg/kg vs morphine 0.10 mg/kg and placebo. Pain assessment was done using a validated numeric rating scale (NRS). The primary end point was to achieve an efficient analgesic effect (NRS≤3) 20 minutes after the baseline. The secondary end points were treatment safety, total morphine dose required until obtaining NRS≤3, and efficient analgesic effect 30 minutes after the baseline. FINDINGS: Ninety-one patients were randomized into midazolam (n=41) and placebo (n=50) groups. No significant difference in proportion of patients with a pain score≤3 was observed between midazolam (43.6%) and placebo (45.7%) after 20 minutes (P=.849). Secondary end points were similar in regard with proportion of patients with a pain score≤3 at T30, the side effects and adverse events except for drowsiness in midazolam vs placebo, 43.6% vs 6.5% (P<.001). No significant difference in total morphine dose was observed, that is, midazolam (14.09 mg±6.64) vs placebo (15.53 mg±6.27) (P=.315). CONCLUSIONS: According to our study, midazolam does not enhance pain control as an adjunctive to morphine regimen in the management of trauma-induced pain in prehospital setting. However, such midazolam use seems to be associated with an increase in drowsiness.

Inhibition of telomerase activity by human immunodeficiency virus (HIV) nucleos(t)ide reverse transcriptase inhibitors: a potential factor contributing to HIV-associated accelerated aging.

BACKGROUND: Human immunodeficiency virus (HIV)-infected patients on combination active antiretroviral therapy (cART) are at increased risk of age-related complications. We hypothesized that nucleos(t)ide reverse transcriptase inhibitors (NRTI) may contribute to accelerated aging in HIV-infected individuals on cART via inhibition of telomerase activity. METHODS: Telomerase activity and telomere length (TL) were measured by quantitative polymerase chain reaction in vitro in activated peripheral blood mononuclear cells (PBMCs) cultured with NRTI and ex vivo in PBMCs from uninfected patients exposed to NRTI and from HIV-infected patients on NRTI-containing cART. RESULTS: Lamivudine, abacavir, zidovudine, emtricitabine, and tenofovir significantly inhibited telomerase activity in activated PBMCs in vitro. Tenofovir was the most potent inhibitor of telomerase activity and caused greatest shortening of TL in vitro at the therapeutic concentration of 0.3 µM. PBMCs from HIV-infected patients receiving NRTI-containing cART (n = 39) had significantly lower telomerase activity than HIV-uninfected patients (n = 47; P = .011) and HIV-infected patients receiving non-NRTI-containing cART (n = 11; P < .001). TL was significantly inversely associated with age (P = .009) and the total duration on any NRTI (P = .01). CONCLUSIONS: NRTIs and, specifically tenofovir at therapeutic concentrations, inhibit telomerase activity leading to accelerated shortening of TL in activated PBMCs. The relationship between NRTI, reduced telomerase activity, and accelerated aging requires further investigation in HIV-infected individuals on cART.

Linkages between HIV-1 specificity for CCR5 or CXCR4 and in vitro usage of alternative coreceptors during progressive HIV-1 subtype C infection.

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) subtype C (C-HIV) is spreading rapidly and is now responsible for >50% of HIV-1 infections worldwide, and >95% of infections in southern Africa and central Asia. These regions are burdened with the overwhelming majority of HIV-1 infections, yet we know very little about the pathogenesis of C-HIV. In addition to CCR5 and CXCR4, the HIV-1 envelope glycoproteins (Env) may engage a variety of alternative coreceptors for entry into transfected cells. Whilst alternative coreceptors do not appear to have a broad role in mediating the entry of HIV-1 into primary cells, characterizing patterns of alternative coreceptor usage in vitro can provide valuable insights into mechanisms of Env-coreceptor engagement that may be important for HIV-1 pathogenesis. RESULTS: Here, we characterized the ability of luciferase reporter viruses pseudotyped with HIV-1 Envs (n = 300) cloned sequentially from plasma of 21 antiretroviral therapy (ART)-naïve subjects experiencing progression from chronic to advanced C-HIV infection over an approximately 3-year period, who either exclusively maintained CCR5-using (R5) variants (n = 20 subjects) or who experienced a coreceptor switch to CXCR4-using (X4) variants (n = 1 subject), to utilize alternative coreceptors for entry. At a population level, CCR5 usage by R5 C-HIV Envs was strongly linked to usage of FPRL1, CCR3 and CCR8 as alternative coreceptors, with the linkages to FPRL1 and CCR3 usage becoming statistically more robust as infection progressed from chronic to advanced stages of disease. In contrast, acquisition of an X4 Env phenotype at advanced infection was accompanied by a dramatic loss of FPRL1 usage. Env mutagenesis studies confirmed a direct link between CCR5 and FPRL1 usage, and showed that the V3 loop crown, but not other V3 determinants of CCR5-specificity, was the principal Env determinant governing the ability of R5 C-HIV Envs from one particular subject to engage FPRL1. CONCLUSIONS: Our results suggest that, in the absence of coreceptor switching, the ability of R5 C-HIV viruses to engage certain alternative coreceptors in vitro, in particular FPRL1, may reflect an altered use of CCR5 that is selected for during progressive C-HIV infection, and which may contribute to C-HIV pathogenicity.

Hepatitis B virus exposure and vaccination in a cohort of people who inject drugs: what has been the impact of targeted free vaccination?

BACKGROUND AND AIM: Forty percent of new hepatitis B virus (HBV) infections in Australia occur in people who inject drugs (PWID); long-term infection carries the risk of serious liver disease. HBV incidence among Australian PWID has not been measured since the advent of targeted (2001) and adolescent school-based "catch-up" (1998) vaccination programs. We measured HBV incidence and prevalence in a cohort of PWID in Melbourne, Australia and examined demographic and behavioral correlates of exposure and vaccination. METHODS: Community-recruited PWID were surveyed about blood-borne virus risk behaviors and their sera tested for HBV markers approximately three-monthly over three years. Incidence was assessed using prospectively collected data. A cross-sectional design was used to examine prevalence of HBV exposure and vaccination at baseline. Poisson regression was used to identify correlates of HBV exposure and vaccination. RESULTS: At baseline, 33.1% of participants (114/344) had been vaccinated against HBV, 40.4% (139/344) had been exposed (previously or currently infected), and 26.5% (91/344) were susceptible. HBV incidence was 15.7 per 100 person-years. Independent associations with HBV exposure included female gender, South-East Asian ethnicity, drug treatment in the past three months, injecting in prison, and prior exposure to hepatitis C virus. Independent associations with vaccination included being ≤ 25 years old, reporting HBV vaccination, and never having been to prison. CONCLUSIONS: HBV infection continues at high incidence among Australian PWID despite the introduction of free vaccination programs. Innovative methods are needed to encourage PWID to complete HBV vaccination.

Comparing short versions of the AUDIT in a community-based survey of young people.

BACKGROUND: The 10-item Alcohol Use Disorders Identification Test (AUDIT-10) is commonly used to monitor harmful alcohol consumption among high-risk groups, including young people. However, time and space constraints have generated interest for shortened versions. Commonly used variations are the AUDIT-C (three questions) and the Fast Alcohol Screening Test (FAST) (four questions), but their utility in screening young people in non-clinical settings has received little attention. METHODS: We examined the performance of established and novel shortened versions of the AUDIT in relation to the full AUDIT-10 in a community-based survey of young people (16-29 years) attending a music festival in Melbourne, Australia (January 2010).Among those reporting drinking alcohol in the previous 12 months, the following statistics were systematically assessed for all possible combinations of three or four AUDIT items and established AUDIT variations: Cronbach's alpha (internal consistency), variance explained (R2) and Pearson's correlation coefficient (concurrent validity). For our purposes, novel shortened AUDIT versions considered were required to represent all three AUDIT domains and include item 9 on alcohol-related injury. RESULTS: We recruited 640 participants (68% female) reporting drinking in the previous 12 months. Median AUDIT-10 score was 10 in males and 9 in females, and 127 (20%) were classified as having at least high-level alcohol problems according to WHO classification.The FAST scored consistently high across statistical measures; it explained 85.6% of variance in AUDIT-10, correlation with AUDIT-10 was 0.92, and Cronbach's alpha was 0.66. A number of novel four-item AUDIT variations scored similarly high. Comparatively, the AUDIT-C scored substantially lower on all measures except internal consistency. CONCLUSIONS: Numerous abbreviated variations of the AUDIT may be a suitable alternative to the AUDIT-10 for classifying high-level alcohol problems in a community-based population of young Australians. Four-item AUDIT variations scored more consistently high across all evaluated statistics compared to three-item combinations. Novel AUDIT versions may be more effective than many established shortened versions as an alternative screening tool to the AUDIT-10 to measure hazardous or harmful alcohol consumption in this population.

Missed opportunities--low levels of chlamydia retesting at Australian general practices, 2008-2009.

OBJECTIVE: Chlamydia reinfection is common and increases the risk of reproductive complications. Guidelines for Australian general practitioners recommend retesting 3-12 months after a positive result but not before 6 weeks. The authors describe retesting rates among 16-29-year-old patients diagnosed as having chlamydia at 25 general practice clinics participating in the Australian Collaboration for Chlamydia Enhanced Sentinel Surveillance system. METHODS: The authors calculated annual testing and positivity rates for 16-29-year-olds attending in 2008-2009, re-attendance and retesting rates within <6 weeks, 1.5-4 months and 1.5-12 months of a positive test in 2008-2009 and positivity at retest (where results were available). Results There were 50,408 individuals (60.4% women) who attended in 2008-2009. Annually, 7.4% and 7.3% were tested for chlamydia, of whom 9.1% and 8.0% tested positive, respectively. Within 1.5-4 months of a positive test, 24.6% re-attended and were retested (19% tested positive), 31.6% re-attended and were not retested and 43.9% did not re-attend. Within 1.5-12 months, 40% re-attended and were retested (16% tested positive), 40% re-attended and were not retested and 20% did not re-attend. Of individuals re-attending in 1.5-12 months but not retested, 50% had re-attended three or more times in the period. Within 6 weeks of a positive test, 25% were retested. DISCUSSION: A high proportion of 16-29-year-olds re-attended general practices in the recommended retest periods, but retesting rates were low and multiple missed opportunities were common. The findings highlight the need for strategies such as electronic clinician prompts, patient recall systems and promotion of retesting guidelines.

Stop the drama Downunder: a social marketing campaign increases HIV/sexually transmitted infection knowledge and testing in Australian gay men.

INTRODUCTION: Since 2000, notifications of HIV and other sexually transmitted infections (STIs) have increased significantly in Australian gay men. We evaluated the impact of a social marketing campaign in 2008-2009 aimed to increase health-seeking behavior and STI testing and enhance HIV/STI knowledge in gay men. METHODS: A convenience sample of 295 gay men (18-66 years of age) was surveyed to evaluate the effectiveness of the campaign. Participants were asked about campaign awareness, HIV/STI knowledge, health-seeking behavior, and HIV/STI testing. We examined associations between recent STI testing and campaign awareness. Trends in HIV/STI monthly tests at 3 clinics with a high case load of gay men were also assessed. Logistic and Poisson regressions and χ tests were used. RESULTS: Both unaided (43%) and aided (86%) campaign awareness was high. In a multivariable logistic regression, awareness of the campaign (aided) was independently associated with having had any STI test within the past 6 months (prevalence ratio = 1.5; 95% confidence interval = 1.0-2.4. Compared with the 13 months before the campaign, clinic data showed significant increasing testing rates for HIV, syphilis, and chlamydia among HIV-negative gay men during the initial and continued campaign periods. CONCLUSION: These findings suggest that the campaign was successful in achieving its aims of increasing health-seeking behavior, STI testing, and HIV/STI knowledge among gay men in Victoria.

Measuring the accuracy of self-reported height and weight in a community-based sample of young people.

BACKGROUND: Self-reported anthropometric data are commonly used to estimate prevalence of obesity in population and community-based studies. We aim to: 1) Determine whether survey participants are able and willing to self-report height and weight; 2) Assess the accuracy of self-reported compared to measured anthropometric data in a community-based sample of young people. METHODS: Participants (16-29 years) of a behaviour survey, recruited at a Melbourne music festival (January 2011), were asked to self-report height and weight; researchers independently weighed and measured a sub-sample. Body Mass Index was calculated and overweight/obesity classified as ≥25 kg/m². Differences between measured and self-reported values were assessed using paired t-test/Wilcoxon signed ranks test. Accurate report of height and weight were defined as <2 cm and <2 kg difference between self-report and measured values, respectively. Agreement between classification of overweight/obesity by self-report and measured values was assessed using McNemar's test. RESULTS: Of 1405 survey participants, 82% of males and 72% of females self-reported their height and weight. Among 67 participants who were also independently measured, self-reported height and weight were significantly less than measured height (p=0.01) and weight (p<0.01) among females, but no differences were detected among males. Overall, 52% accurately self-reported height, 30% under-reported, and 18% over-reported; 34% accurately self-reported weight, 52% under-reported and 13% over-reported. More females (70%) than males (35%) under-reported weight (p=0.01). Prevalence of overweight/obesity was 33% based on self-report data and 39% based on measured data (p=0.16). CONCLUSIONS: Self-reported measurements may underestimate weight but accurately identified overweight/obesity in the majority of this sample of young people.

Biological determinants of immune reconstitution in HIV-infected patients receiving antiretroviral therapy: the role of interleukin 7 and interleukin 7 receptor α and microbial translocation.

BACKGROUND: Multiple host factors may influence CD4(+) T cell reconstitution in human immunodeficiency virus (HIV)-infected patients after suppressive antiretroviral therapy (ART). We hypothesized that residual immune activation and polymorphisms in the interleukin 7 (IL-7) receptor α (IL-7Rα) gene were important for immune recovery. METHODS: We examined HIV-infected patients receiving suppressive ART (n = 96) for their IL-7Rα haplotypes and measured levels of lipopolysaccharide (LPS), soluble CD14, and IL-7 in plasma samples collected before and after ART initiation. Levels of soluble IL-7Rα were measured in HIV-infected patients with IL-7Rα haplotype 2 (n = 11) and those without IL-7Rα haplotype 2 (n = 22). Multivariate analysis was used to identify variables associated with faster recovery to CD4(+) T cell counts of >500 and >200 cells/µL. RESULTS: Both LPS and soluble CD14 levels were significantly decreased with ART (P < .001, respectively) but remained elevated compared with uninfected controls. In a multivariate analysis, faster recovery to a CD4(+) T cell count of >500 cells/µL was significantly associated with higher baseline CD4(+) T cell count, younger age, lower pre-ART LPS level, higher pre-ART soluble CD14 level, lower pre-ART IL-7 level, and IL-7Rα haplotype 2 (hazard ratio, 1.50; 95% confidence interval, 1.03-2.19; P = .034). HIV-infected patients with haplotype 2 had significantly lower soluble IL-7Rα levels compared with those of patients without haplotype 2 (P < .001). CONCLUSION: Both the extent of immune depletion prior to ART and IL-7Rα haplotype 2 are important determinants of time to CD4(+) T cell recovery to counts of >500 cells/µL.

Assessment of major salivary gland size in primary Sjögren's syndrome: Comparison between clinical examination and ultrasonography.

OBJECTIVE: Parotidomegaly is a criterion of the EULAR Primary Sjögren Syndrome Disease Activity Index (ESSDAI). The cut-off value was set at 3 cm in length for the parotid gland, 2 cm for the submandibular glands. However, clinical appreciation of salivary glands size remains hazardous. The objective is to evaluate inter-observer reproducibility of parotid gland measurement by palpation, and to secondary evaluate its reliability compared to US assessment. METHODS: Outpatients with primary Sjögren Syndrome (pSS) or with a diagnostic suspicion, in a single reference centre, were included. They underwent clinical examination by two independent investigators (VDP and DC), evaluating: parotid gland swelling, parotid gland size (direct measurement with a decameter under the mandibular angle), and pain. Cohen's kappa coefficient was calculated to determine inter-observer concordance for parotid gland swelling, and intraclass correlation coefficient to determine inter-observer agreement of gland size measurement. RESULTS: Thirty-four patients (33 women, 1 man) were included. Clinical data were complete for 33 patients. Inter-observer concordance Kappa coefficient was 0.90 [0.76-1.00] for detection of parotidomegaly over 66 parotid glands. It was of 0.60 [0.42-0.73] for gland length measurement. For one observer, the median cut-off for defining parotidomegaly was 4.15 cm; for the second observer, it was of 4.92 cm. For submandibular glands palpation, no correlation was found between investigators. A significant association between clinical parotidomegaly and a larger echographic surface was found. CONCLUSION: Clinical measurement of parotidomegaly was concordant between two observers on a binary mode (presence/absence). However, concordance on direct measurement was weak. US could be a complementary examination.

Multi-modal pain assessment: are near-infrared spectroscopy, skin conductance, salivary cortisol, physiologic parameters, and Neonatal Facial Coding System interrelated during venepuncture in healthy, term neonates?

BACKGROUND: Improving pain and stress assessments in neonates remains important in preventing the short- and long-term consequences. We aimed to identify the relationships between different pain assessment parameters by simultaneously measuring changes in cortical, autonomic, hormonal, physiological, and behavioral evoked responses to venepuncture in healthy, full-term neonates. METHODS: This observational, prospective study (ancillary to the ACTISUCROSE trial) included 113 healthy, 3-day old, full-term neonates who underwent venepuncture for systematic neonatal screening, from July to October 2013, in a tertiary-level maternity ward of a university hospital. During venepuncture, we simultaneously measured the cortical single-channel near-infrared spectroscopy (NIRS) signals, foot skin conductance, salivary cortisol, physiological responses, and behavioral (Neonatal Facial Coding System [NFCS]) evoked responses. RESULTS: Regarding the NIRS analysis, the highest correlation was between the NFCS at venepuncture and the change in NIRS integrated values of total hemoglobin (r=0.41, P<0.001) or oxygenated hemoglobin (r=0.27, P<0.001). The NFCS at venepuncture was moderately positively correlated with changes in salivary cortisol (r=0.42, P<0.001) and skin conductance (r=0.29, P<0.001). Salivary cortisol and skin conductance changes were not correlated; the latter parameters were not correlated with heart rate, respiratory rate, or SpO2. CONCLUSION: During venepuncture, NFCS was mildly or moderately correlated with salivary cortisol, skin conductance, and cortical NIRS changes.