Elevation of cell-associated HIV-1 transcripts in CSF CD4+ T cells, despite effective antiretroviral therapy, is linked to brain injury.

Antiretroviral therapy (ART) can attain prolonged undetectable HIV-1 in plasma and cerebrospinal fluid (CSF), but brain injury remains prevalent in people living with HIV-1 infection (PLHIV). We investigated cell-associated (CA)-HIV-1 RNA transcripts in cells in CSF and blood, using the highly sensitive Double-R assay, together with proton Magnetic Resonance Spectroscopy (1H MRS) of major brain metabolites, in sixteen PLHIV. 14/16 CSF cell samples had quantifiable CA-HIV-1 RNA, at levels significantly higher than in their PBMCs (median 9,266 vs 185 copies /106 CD4+ T-cells; p<0.0001). In individual PLHIV, higher levels of HIV-1 transcripts in CSF cells were associated with greater brain injury in the frontal white matter (Std ß=-0.73; p=0.007) and posterior cingulate (Std ß=-0.61; p=0.03). 18-colour flow cytometry revealed that the CSF cells were 91% memory T-cells, equally CD4+ and CD8+ T-cells, but fewer B cells (0.4 %), and monocytes (3.1%). CXCR3+CD49d+integrin ß7-, CCR5+CD4+ T-cells were highly enriched in CSF, compared with PBMC (p <0.001). However, CA-HIV-1 RNA could not be detected in 10/16 preparations of highly purified monocytes from PBMC, and was extremely low in the other six. Our data show that elevated HIV-1 transcripts in CSF cells were associated with brain injury, despite suppressive ART. The cellular source is most likely memory CD4+ T cells from blood, rather than trafficking monocytes. Future research should focus on inhibitors of this transcription to reduce local production of potentially neurotoxic and inflammatory viral products.

What are the predictors of TOMM failure in clinical TBI populations? A retrospective analysis.

OBJECTIVES: To determine base rates of invalid performance on the Test of Memory Malingering (TOMM) in patients with traumatic brain injury (TBI) undertaking rehabilitation who were referred for clinical assessment, and the factors contributing to TOMM failure. METHODS: Retrospective file review of consecutive TBI referrals for neuropsychological assessment over seven years. TOMM failure was conventionally defined as performance <45/50 on Trial 2 or Retention Trial. Demographic, injury, financial compensation, occupational, and medical variables were collected. RESULTS: Four hundred and ninety one TBI cases (Median age = 40 years [IQR = 26-52], 79% male, 82% severe TBI) were identified. Overall, 48 cases (9.78%) failed the TOMM. Logistic regression analyses revealed that use of an interpreter during the assessment (adjusted odds ratio [aOR] = 8.25, 95%CI = 3.96-17.18), outpatient setting (aOR = 4.80, 95%CI = 1.87-12.31) and post-injury psychological distress (aOR = 2.77, 95%CI = 1.35-5.70) were significant multivariate predictors of TOMM failure. The TOMM failure rate for interpreter cases was 49% (21/43) in the outpatient setting vs. 7% (2/30) in the inpatient setting. By comparison, 9% (21/230) of non-interpreter outpatient cases failed the TOMM vs. 2% (4/188) of inpatient cases. CONCLUSIONS: TOMM failure very rarely occurs in clinical assessment of TBI patients in the inpatient rehabilitation setting. It is more common in the outpatient setting, particularly in non-English-speaking people requiring an interpreter. The findings reinforce the importance of routinely administering stand-alone performance validity tests in assessments of clinical TBI populations, particularly in outpatient settings, to ensure that neuropsychological test results can be interpreted with a high degree of confidence.

Reversible large-scale network disruption correlates with neurocognitive improvement in HIV-associated minor neurocognitive disorder with combined anti-retroviral therapy intensification: a prospective longitudinal resting-state functional magnetic resonance imaging study.

OBJECTIVE: HIV-associated neurocognitive disorder (HAND) affects multiple cognitive domains and currently, the neuropsychological testing is the gold standard to identify these deficits. The aim of this longitudinal 12-month pilot study is to determine the effect of intensified combination antiretroviral therapy (cART) on rs-fMRI in virally suppressed (both in CSF and blood) patients with active HAND (those who have progressive neurocognitive impairment) and correlated with neurocognitive function tests. METHODS: In this pilot study, we have evaluated sixteen patients with active HAND with viral suppression in both blood and CSF to study the effect of cART on functional connectivity. Participants underwent rs-fMRI at the baseline (time point-1 (TP-1) and 12-month visits (time point-2 (TP-2)). Connectivity in the five major networks was measured at TP-1 and TP-2 using the seed-based approach. All the participants underwent a five-domain neuropsychological battery at TP-1 and TP-2. Neurocognitive scores (NC) as well as blood and CSF markers were correlated with functional connectivity (FC). RESULTS: There was a significant increase in the FC between the two time points within the executive, salience, default mode, dorsal attention, and visual networks at voxel level threshold of p < 0.001 and cluster level threshold of p < 0.05 and corrected for false detection rate (FDR). The neurocognitive scores were positively correlated with all the networks at similar cluster and voxel level thresholds. CONCLUSIONS: These results indicate that rs-fMRI can be potentially used as one of the biomarkers for treatment efficacy in HAND.

Lack of cognitive impairment in long-term survivors of colorectal cancer.

BACKGROUND: Our longitudinal study reported cognitive impairment in 43% of people following diagnosis of localised colorectal cancer (CRC) versus 15% in healthy controls (p < 0.001) and 50% versus 13% 1-2 years later (p < 0.001). Here we evaluate cognitive function and neuroimaging in a subgroup at long-term follow-up. PATIENTS AND METHODS: Cancer-free Australian participants in the study, and controls, completed cognitive and functional assessments. Neuroimaging was optional. Blood tests included inflammatory markers, clotting factors, sex hormones and apolipoprotein E genotype. The primary endpoint was demographically and practice effect-corrected cognitive scores comparing CRC survivors with controls over time examined using a linear mixed model, adjusted for baseline performance. Secondary endpoints included cognitive impairment rate using the Global Deficit Score [GDS > 0.5], Functional Deficit Score, blood results and neuroimaging. RESULTS: The study included 25 CRC survivors (60% men, median age 72) at mean 9 years after baseline (9 received adjuvant chemotherapy) and 25 controls (44% men, median age 68) at mean 6 years after baseline. There were no significant differences in cognitive scores or proportion with cognitive impairment (16 vs. 8%) between survivors and controls and no evidence of accelerated ageing in CRC survivors. Baseline cognitive performance predicted for subsequent cognitive function. There were no differences in functional tests or blood tests between groups. In 18 participants undergoing neuroimaging, 10 CRC survivors had higher myoinositol levels than 8 controls, and lower volume in the right amygdala and caudate and left hippocampal regions. CONCLUSIONS: There was no difference in cognitive capacity and function between CRC survivors and controls 6-12 years after diagnosis. Differences in neuroimaging require confirmation in a larger sample. HIGHLIGHTS: • No evidence of long term cognitive impairment in colorectal cancer survivors compared to controls 6-12 years after diagnosis • No evidence of accelerated cognitive ageing in colorectal cancer survivors • No evidence of long-term functional impairment in colorectal cancer survivors.

Increasing utilisation of perinatal services: estimating the impact of community health worker program in Neno, Malawi.

BACKGROUND: By 2015, Malawi had not achieved Millennium Development Goal 4, reducing maternal mortality by about 35% from 675 to 439 deaths per 100,000 livebirths. Hypothesised reasons included low uptake of antenatal care (ANC), intrapartum care, and postnatal care. Involving community health workers (CHWs) in identification of pregnant women and linking them to perinatal services is a key strategy to reinforce uptake of perinatal care in Neno, Malawi. We evaluated changes in uptake after deployment of CHWs between March 2014 and June 2016. METHODS: A CHW intervention was implemented in Neno District, Malawi in a designated catchment area of about 3100 women of childbearing age. The pre-intervention period was March 2014 to February 2015, and the post-intervention period was March 2015 to June 2016. A 5-day maternal health training package was delivered to 211 paid and supervised CHWs. CHWs were deployed to identify pregnant women and escort them to perinatal care visits. A synthetic control method, in which a "counterfactual site" was created from six available control facilities in Neno District, was used to evaluate the intervention. Outcomes of interest included uptake of first-time ANC, ANC within the first trimester, four or more ANC visits, intrapartum care, and postnatal care follow-up. RESULTS: Women enrolled in ANC increased by 18% (95% Credible Interval (CrI): 8, 29%) from an average of 83 to 98 per month, the proportion of pregnant women starting ANC in the first trimester increased by 200% (95% CrI: 162, 234%) from 10 to 29% per month, the proportion of women completing four or more ANC visits increased by 37% (95% CrI: 31, 43%) from 28 to 39%, and monthly utilisation of intrapartum care increased by 20% (95% CrI: 13, 28%) from 85 to 102 women per month. There was little evidence that the CHW intervention changed utilisation of postnatal care (- 37, 95% CrI: - 224, 170%). CONCLUSIONS: In a rural district in Malawi, uptake of ANC and intrapartum care increased considerably following an intervention using CHWs to identify pregnant women and link them to care.

External causes of death after severe traumatic brain injury in a multicentre inception cohort: clinical description and risk factors.

Objective: To characterize the clinical profile of patients dying from external causes (EC) following severe traumatic brain injury (TBI). Design and Methods: Data from 2545 patients forming the NSW-BIRP inception cohort discharged from post-acute inpatient rehabilitation between 1 July 1990 and 1 October 2007 were retrospectively reviewed. Standardized mortality ratios (SMRs) were calculated for EC sub-categories. Demographic, clinical and rehabilitation service factors were compared between deaths from EC, deaths from other causes (OC), and non-deceased. Clinical profiles of EC sub-categories were analysed descriptively. Results: Overall, patients with TBI were 5.2x more likely to die from EC relative to the general population. Risk of death was elevated in all EC sub-categories examined, with the largest risks relating to other accidental threats to breathing (SMR = 33.0; 95%CI = 13.79-60.45) and falls (SMR = 14.3; 95%CI = 5.01-28.39). The EC group were younger, more likely to have pre-injury psychiatric histories, less severe injuries, greater functional independence, and die earlier than the OC group. There was considerable heterogeneity in the clinical profiles of patients dying from different EC sub-categories. Conclusions: EC constitutes one of the largest causes of mortality following TBI in patients surviving beyond the post-acute phase. Potential implications for risk modification and prevention of premature and avoidable deaths are discussed.

The impact of compensation on late mortality after traumatic brain injury: A multi-centre study.

OBJECTIVES: To determine the impact of financial compensation on long-term mortality in adults with severe traumatic brain injury (TBI). DESIGN, SETTING AND PARTICIPANTS: An inception cohort of 2545 adults consecutively discharged from three metropolitan, post-acute inpatient rehabilitation services of the NSW Brain Injury Rehabilitation Programme from 1 July 1990 to 1 October 2007. MAIN OUTCOME MEASURE: Survival status at 1 October 2009. RESULTS: Compensation data were available for 1851 (73%) participants, with 826 (45%) receiving financial compensation. Yearly standardized mortality ratios remained elevated above general population norms for six to ten years for both groups. Compensation had a protective effect on mortality risk as a univariate predictor. However, when considered in multivariate Cox regression analysis, compensation had minimal effect on mortality risk when modelled with non-modifiable demographic factors and pre-existing medical history. Conversely, compensation trended towards a protective effect when modelled with post-injury variables. CONCLUSIONS: Financial compensation had a protective effect against late mortality following rehabilitation for severe TBI through complex interactions with rehabilitation service variables but not with injury-related variables. This finding suggests that wider access to compensation (and hence rehabilitation) through recently implemented schemes (e.g., NSW Lifetime Care and Support) may further improve life expectancy for this clinical population.

Irreducible Indirect Inguinal Hernia in Premature Infant with Ectopic Uterus and Bilateral Adnexa.

Indirect inguinal hernia is one of the most common congenital anomalies in children, with a reported prevalence of 0.8-4.4%.1 About 15-20% of hernias in female infants contain ovary, and in rare cases a fallopian tube.2 However, only a few cases contain the uterus and both ovaries in the hernia sac.3 The normal anatomy is altered when an ovary is trapped in a hernia sac, and these changes make torsion more likely and increase the risk of infertility. Although an irreducible ovary is not at great risk of compression of its blood supply, in these occurrences, ovarian torsions have been reported in 2%-33%, emphasizing the importance of early surgical repair in irreducible hernias, even in asymptomatic patients.4 The presentation of an asymptomatic palpable movable mass over the labium major always suggests sliding hernia with ovary. To our knowledge, only a few reports of hernia sac containing uterus, fallopian tube, and ovary in a female patient have appeared in the literature. We suggest that sonography be performed routinely in female infants with an inguinal hernia containing a palpable movable mass. We present a rare case of premature female infant with a labial mass containing the uterus, both ovaries, and fallopian tubes.

Retroperitoneal immature teratoma.

Retroperitoneal immature teratoma is a rare tumor in the newborn infant with only a few instances reported in several case series.(1,2,3) We report a case of retroperitoneal immature teratoma presenting unusually on day one of life with severe abdominal distension and respiratory failure.

HIV-associated neurocognitive disorder in Australia: a case of a high-functioning and optimally treated cohort and implications for international neuroHIV research.

The Australian HIV-infected (HIV+) population is largely comprised of high-functioning men who have sex with men (MSM). Like other English-speaking countries, Australia mostly relies on US neuropsychological normative standards to detect and determine the prevalence of neurological disorders. Whether the US neuropsychological (NP) normative standards are appropriate in Australian HIV+ MSM has not been established. Ninety virally suppressed HIV+ and 49 HIV-uninfected (HIV-) men (respectively 86 and 85 % self-reported MSM; mean age 54 and 56 years, mean premorbid verbal IQ estimate 110 and 111) undertook standard NP testing. The raw neuropsychological data were transformed using the following: (1) US standards as uncorrected scaled scores and demographically corrected T scores (US norms); and (2) z scores (without demographic corrections) derived from Australian comparison group scaled scores (local norms). To determine HIV-associated neurocognitive disorder prevalence, we used a standard definition of impairment based upon a battery-wide summary score: the global deficit score (GDS). Impairment classification (GDS ≥ 0.5) based on the local norms was best at discriminating between the two groups (HIV- = 14.3 % vs. HIV+ = 53.3 %; p < 0.0001). This definition was significantly associated with age. Impairment classification based on the US norms yielded much lower impairment rate regardless of the HIV status (HIV- = 4.1 % vs. HIV+ = 14.7 %; p = 0.05), but was associated with historical AIDS, and not age. Both types of summary scores were associated with reduced independence in activities of daily living (p ≤ 0.03). Accurate neuropsychological classifications of high (or low) functioning individuals may need country-specific norms that correct for performance-based (e.g., reading) estimates of premorbid cognition in addition to the traditional demographic factors.

Imaging findings of successful and failed fundoplication.

Postoperative imaging findings contribute to the diagnosis of successful and failed fundoplication procedures. Gastroesophageal reflux disease, a common illness in the United States, is primarily treated medically but may require surgery if there are persistent symptoms or reflux complications despite medical treatment. Laparoscopic Nissen fundoplication has become the most used and successful surgical antireflux procedure since its introduction in 1991. Radiologists should understand the anatomy of the esophagogastric junction, antireflux and esophageal protective mechanisms, and preoperative radiologic findings that contribute to selection of the surgical technique, as well as the most commonly used antireflux operations and their indications. Barium examination and computed tomography of the thorax and abdomen play an important role in the follow-up of patients with gastric fundoplication, including evaluation of surgical effectiveness and detection and characterization of postoperative complications. Failed fundoplications are classified into six types: tight Nissen, incompetent repair, disruption of the wrap, stomach slippage above the diaphragm, slipped Nissen, and transdiaphragmatic wrap herniation. Classification is based on radiologic visualization of the obstructed esophageal lumen, recurrence of gastroesophageal reflux, integrity and location of the gastric wrap, stomach slippage, and recurrence of hiatal hernia. Imaging findings are useful in detecting complications, providing anatomic information to identify the cause of surgical failure, and selecting appropriate medical or surgical management.

The most characteristic lesions and radiologic signs of Crohn disease of the small bowel: air enteroclysis, MDCT, endoscopy, and pathology.

This pictorial essay describes the most characteristic lesions and radiologic signs of Crohn disease of the small bowel: nodular lymphoid hyperplasia, abnormal mucosal folds, villous pattern, aphthous ulcerations, linear ulcerations, cobblestone pattern, string sign, target sign, comb sign, creeping fat, sinus tracts, fistulas, and abscesses. Each description includes the definition, a correlation with the pathologic findings, an explanation of the possible physiopathologic mechanism, sample radiologic images with air enteroclysis or MDCT, the correspondence with the endoscopic findings when possible, and a list of differential diagnoses.

Screening for cancer: concepts and controversies.

Early detection of cancer is a core task in family medicine, and patients have come to expect screening tests, sometimes out of proportion to what evidence can justify. To understand the controversies surrounding screening and to provide sound advice to patients, family physicians should be familiar with the fundamental concepts of screening. Failure to account for the effects of lead-time, length-time, and overdiagnosis biases can lead to overestimation of screening benefits. For this reason, the best method for evaluating the benefit of screening tests is a randomized controlled trial showing decreased disease-specific or all-cause mortality. The number needed to screen can be used to measure the magnitude of benefit of screening tests. Accepted screening tests often require screening several hundred to more than 1,000 asymptomatic patients to prevent one death from the disease. The U.S. Preventive Services Task Force and American Academy of Family Physicians recommend screening for colorectal cancer in adults 50 to 75 years of age, and recommend against prostate-specific antigen testing to screen for prostate cancer. Annual low-dose computed tomography screening for lung cancer reduces mortality in persons 55 to 80 years of age with at least a 30-pack-year history who are otherwise healthy smokers or who have quit smoking within the past 15 years; however, it is associated with a high false-positive rate, uncertain harms from radiation exposure, and overdiagnosis. Therefore, it should be performed only in conjunction with smoking cessation interventions.

Validation of the work-ability support scale in individuals seeking to return to work after severe acquired brain injury.

PURPOSE: To assess the reliability and validity of the work-ability support scale (WSS) in a severe traumatic/acquired brain injury (TBI/ABI) population seeking to return to work (RTW). MATERIALS AND METHODS: One hundred forty-four clients were enrolled in a vocational rehabilitation (VR) intervention trial through the Brain Injury Rehabilitation Program in New South Wales, Australia. Each client's primary brain injury clinician and VR provider completed the WSS pre- and post-intervention. Validating measures assessing dysexecutive behavior, disability, participation, and work instability were completed. Several aspects of reliability and validity were evaluated. RESULTS: Internal consistency was excellent for Part A (Cronbach's αs > 0.9) but unacceptably low to questionable for Part B (αs < 0.6). Inter-rater reliability between clinicians and VR providers was generally fair to moderate for Part A (κw < 0.6) and worse for Part B (κw < 0.5), with both slightly improving at post-intervention. Strong support was found for predictive and convergent validity, but not divergent validity. Confirmatory factor analysis indicated a poor fit for Part A, whereas most Part B fit indices met criteria. CONCLUSIONS: The WSS can play a useful role in assessing return to work (RTW) potential, planning and evaluation after severe TBI/ABI. Training could improve consistency of administration among staff working across health and VR service sectors.

The work-ability support scale (WSS) has potential as a screening tool in assisting return to work (RTW) assessment, planning, and evaluation, following severe traumatic brain injury and acquired brain injury.Employment success following a RTW intervention was predicted by the initial WSS Part A total score.The low inter-rater reliability between brain injury clinicians in health settings and vocational rehabilitation providers suggests that training will be important to improve consistency in WSS administration across service sectors.

A vocational intervention that enhances return to work after severe acquired brain injury: A pragmatic trial.

BACKGROUND: Following a severe acquired brain injury, individuals often have low return to work rates. The Vocational Intervention Program (VIP), a partnership of Brain Injury Rehabilitation Program community rehabilitation centres with external vocational rehabilitation providers in New South Wales, Australia, was developed to facilitate a return to competitive employment for working-age people. OBJECTIVES: To evaluate the efficacy of the VIP partnership model, this intervention was compared to outcomes from a health-based brain injury vocational rehabilitation centre (H-VR) or community brain injury rehabilitation centres ("treatment as usual"; TAU). METHODS: A 3-arm non-randomized controlled trial was conducted among the 12 adult rehabilitation centres of the NSW Brain Injury Rehabilitation Program. The VIP arm was delivered by 6 community rehabilitation centres in partnership with 3 external private Vocational Rehabilitation providers. The H-VR arm was delivered by 1 health-based vocational rehabilitation centre and the 5 remaining centres delivered TAU. Competitive employment status ("Yes"/"No") and clinician ratings of disability and participation were collected pre- and post-intervention, and at 3-month follow-up. Multilevel models were conducted to investigate change over time by treatment arm. RESULTS: In total, 148 individuals with severe brain injury were included in the trial: n = 75 (VIP), n = 33 (H-VR) and n = 40 (TAU). Sixty-five people (of 108, 60%) completed the VR intervention. A significant arm-by-time interaction was found, with higher return to work rates from pre- to post-intervention in VIP and H-VR arms compared to TAU (P = 0.0002). Significant arm-by-time interactions also indicated improved work-related participation and independent living skills from pre- to post-intervention in VIP and H-VR compared to the TAU arm (P < 0.05). These improvements were maintained at 3-month follow-up. CONCLUSIONS: The VIP improved return to competitive employment at comparable rates to the specialist H-VR. Larger-scale adoption of the VIP model could provide significant improvements in vocational rehabilition sevices to support people in their return to work following severe brain injury. ANZCTR TRIAL REGISTRY NUMBER: ACTRN12622000769785.

Meaningful cognitive decline is uncommon in virally suppressed HIV, but sustained impairment, subtle decline and abnormal cognitive aging are not.

Background: High antiretroviral therapy (ART) coverage and viral suppression among people with HIV (PWH) in Australia provide a unique context to study individual cognitive trajectories, cognitive aging and factors associated with longitudinal cognitive function during chronic and stable HIV disease. Methods: Participants from the Predictors of Adherence to Antiretroviral Therapy study (n = 457, recruited between September 2013 and November 2015, median age = 52 years, and all with HIV RNA <50 copies mL) completed a cognitive assessment with CogState Computerized Battery (CCB) at baseline, Month-12, and Month-24. Demographics, psycho-social and socioeconomic factors, healthcare seeking behaviors, HIV disease characteristics and comorbidities were assessed. The CCB data were corrected for age, sex and practice effect and averaged into a global z-score (GZS). Cognitive impairment was defined with the global deficit score method (GDS>0.5). Meaningful cognitive change was statistically defined (decline or improvement versus stability, i.e., 90% CI, that is p < 0.05, 2-tailed) using a novel evidence-based change score: the linear mixed-effect regression (LMER)-based GZS change score. A separate LMER model with a top-down variable selection approach identified the independent effects of age and other demographic, HIV disease characteristics, socioeconomic and health-related factors on the demographically corrected GZS. The combined definitions of change and cross-sectional impairment enabled the identification of cognitive trajectories. Findings: At Month-12 and Month-24, 6% and 7% showed meaningful cognitive decline and 4% and 3% improved respectively. Only 1% showed sustained decline. Incident impairment due to subtle cognitive decline (i.e., below the threshold of meaningful cognitive decline) was 31% and 25% at Month-12 and Month-24, while 14% showed sustained impairment (i.e., cognitively impaired at all study visits). Older age (≥50 years) and time interaction was associated with lower demographically corrected GZS (ß = -0.31, p < 0.001). Having a regular relationship, excellent English proficiency, and perceived stigma (avoidance) were associated with higher GZS (all p < 0.05). Relying on government subsidy, severe depression, and lower belief in ART necessity and higher concerns were associated with lower GZS (all p < 0.05). No HIV disease characteristics had a significant effect. Interpretations: Meaningful cognitive decline was not different from normal expectation in chronic stable HIV disease. Despite this, subtle cognitive decline, sustained cognitive impairment, and greater than normative-age cognitive aging were evident. Funding: Funding for the PAART study was provided in part by unrestricted educational grants from Gilead Sciences (www.gilead.com) (Grant Number: IN-AU-264- 0131), the Balnaves Foundation (www.balnavesfoundation.com), the Victorian Department of Health and Human Services (Australia) (www.dhs.vic.gov.au/home), Western Australia Health (www.health.wa.gov.au), the ACT Ministry of Health (Australia) (www.health.act.gov.au), and in-kind support from the Queensland Department of Health (Australia) (www.health.qld.gov.au), and NHMRC Partnership grant APP1058474 (PI: Carr, Andrew).

Abnormal cognitive aging in people with HIV: evidence from data integration between two countries' cohort studies.

OBJECTIVES: Previous research has shown inconsistent results on whether cognitive aging is abnormal in people with HIV (PWH) because of low sample size, cross-sectional design, and nonstandard neuropsychological methods. To address these issues, we integrated data from two longitudinal studies: Australian HIV and Brain Ageing Research Program ( N  = 102) and CNS HIV Antiretroviral Therapy Effects Research (CHARTER) study ( N  = 924) and determined the effect of abnormal aging on neurocognitive impairment (NCI) among PWH. METHODS: Both studies used the same neuropsychological test battery. NCI was defined based on demographically corrected global deficit score (≥0.5 = impaired). Both studies also assessed comorbidities, neuropsychiatric conditions and functional status using similar tools. To determine the cross-sectional and longitudinal effects of age on the risk of NCI, a generalized linear mixed-effect model tested main and interaction effects of age group (young, <50 vs. old, ≥50) and time on NCI adjusting the effects of covariates. RESULTS: Older PWH had 83% higher chance of NCI compared with younger PWH [odds ratio (OR) = 1.83 (1.15-2.90), P  < 0.05]. Older participants also had a greater risk of increases in NCI over the follow-up [OR = 1.66 (1.05-2.64), P  < 0.05] than younger participants. Nonwhite ethnicity ( P  < 0.05), having a contributing ( P  < 0.05) or confounding ( P  < 0.001) comorbidity, greater cognitive symptoms ( P  < 0.001), and abnormal creatinine level ( P  < 0.05), plasma viral load greater than 200 copies/ml ( P  < 0.05), being from the Australian cohort ( P  < 0.05) were also associated with a higher risk of NCI. CONCLUSION: Data integration may serve as a strategy to increase sample size and study power to better assess abnormal cognitive aging effect in PWH, which was significant in the current study.

Gollop-Wolfgang Complex: Clinical and Imaging Implications.

Gollop-Wolfgang complex is defined as the presence of a distal bifid femur and tibial hemimelia with or without hand ectrodactyly. The condition commonly presents with several skeletal abnormalities and internal organ congenital defects. We hereby report a case with a classical presentation of Gollop-Wolfgang complex.

An examination of reliable change methods for measuring cognitive change with the Cogstate Computerized Battery: Research and clinical implications.

OBJECTIVE: To compare the performance of four reliable change (RC) methods with respect to measuring cognitive change on the Cogstate Computerized Battery (CCB). METHOD: We assessed cognitive change in 57 healthy, urban, well-educated males on the CCB at baseline and 6 months (Median age = 50, 65% university-educated). The study CCB version comprised seven measures covering attention, processing speed, verbal learning, and memory. Raw scores were z-score transformed using age-corrected Cogstate norms (CN) or the sample mean and standard deviation (internal standardization [IS]), and then averaged to create composite z-scores. Composite scores were entered into four RC formulae. RC was defined based on a 90% two-tailed confidence interval. Change scores were compared as continuous (z-scores) and ordinal variables (RC outcomes). RESULTS: CCB composite score reliability (rXY = .78-.79) was replicated in an age- and sex-matched Cogstate database sample of similar size. There was good overall agreement between the four RC methods (Bland-Altman Mdiff = .00; 95% limits of agreement with the mean-CN: z = ± .90; IS: z = ± .93), with each model adhering closely to the 10% rate of RC expected by chance alone (largest χ2 = .86, p = .99). Initial norming strategy (CN or IS) did not affect these outcomes. CONCLUSIONS: Norming strategy and RC method choice did not significantly impact cognitive change predictions on CCB composite scores. A series of example case data are provided to practically demonstrate the steps involved in applying the longitudinal norms generated in this study. Research in more diverse normative samples is warranted.

How all-type dementia risk factors and modifiable risk interventions may be relevant to the first-generation aging with HIV infection?

PURPOSE: The purpose of this review is to provide an overview of established risk factors for all-type dementia and results of interventions on dementia modifiable risk factors, all with relevance to aging people living with HIV (PLHIV). METHODS: Narrative literature review. RESULTS: Our review identifies a high prevalence of risk factors for dementia in the global HIV population that is entering dementia age range (60 +), in relation to both traditional and HIV-specific risk factors. This includes age (HIV-related premature aging and possibly HIV-related accelerated brain aging and cerebrovascular injury), HIV-related and non-HIV-related cardiovascular diseases burden with related-vascular brain damage, HIV-associated neurocognitive disorders, high mental health burden, low educational/socio-economic status, historical immune compromise, and persistent immune activation with consequent augmented immune senescence. Our review highlights that the results of interventions on all-type dementia modifiable factors show discrepancies between positive observational study results and inconclusive clinical trials. The main reasons for such discrepancies relate to the preventative framework that complex interventions' trials have difficulty to emulate and the suboptimal measurement of cognitive change. Multi-domain intervention trials are now advocated to concomitantly tackle complex age-related comorbid profiles. CONCLUSIONS: The burden of dementia risk in aging PLHIV is higher than that in the general population, particularly in the most vulnerable clusters. Epidemiological studies are urgently needed to provide accurate estimates. Lessons from interventions trials in all-type dementia on modifiable factors need to be carefully considered for enhancing trials' potential in aging PLHIV. A comprehensive and preventative neurogeriatric healthcare response linked with HIV communities and dementia associations should be urgently put in place.