Utility of Repeat Sampling in Bilateral Aldosterone Suppression During Adrenal Vein Sampling for Primary Aldosteronism.

Primary aldosteronism (PA) is the most common form of secondary hypertension. Accurate subtyping of PA is essential to identify unilateral disease, as adrenalectomy improves outcomes. Subtyping PA requires adrenal vein sampling (AVS), which is technically challenging and results from AVS may not always be conclusive. We present a case of a 37-year-old man with PA whose AVS studies were inconclusive due to apparent bilateral aldosterone suppression (ABAS). As a result, our patient was misdiagnosed as having bilateral PA and medically managed until a repeat AVS showed lateralization to the right adrenal gland. ABAS is an underrecognized phenomenon that may confound the subtyping of PA. We recommend repeating AVS in such cases and discuss strategies to minimize ABAS.

Real-world prevalence of PD-L1 expression in non-small cell lung cancer: an Australia-wide multi-centre retrospective observational study.

An investigator-initiated, Australia-wide multi-centre retrospective observational study was undertaken to investigate the real-world prevalence of programmed death ligand-1 (PD-L1) expression in non-small cell lung carcinoma (NSCLC). Multiple centres around Australia performing PD-L1 immunohistochemistry (IHC) were invited to participate. Histologically confirmed NSCLC of any stage with a PD-L1 IHC test performed for persons aged ≥18 years between 1 January 2018 and 1 January 2020, and eligible for review, were identified at each centre, followed by data extraction and de-identification, after which data were submitted to a central site for collation and analysis. In total data from 6690 eligible PD-L1 IHC tests from histologically (75%) or cytologically (24%) confirmed NSCLC of any stage were reviewed from persons with a median age of 70 years, 43% of which were female. The majority (81%) of tests were performed using the PD-L1 IHC SP263 antibody with the Ventana BenchMark Ultra platform and 19% were performed using Dako PD-L1 IHC 22C3 pharmDx assay. Reported PD-L1 tumour proportion score (TPS) was ≥50% for 30% of all tests, with 62% and 38% scoring PD-L1 ≥1% and <1%, respectively. Relative prevalence of clinicopathological features with PD-L1 scores dichotomised to <50% and ≥50%, or to <1% and ≥1%, were examined. Females scored ≥1% slightly more often than males (64% vs 61%, respectively, p=0.013). However, there was no difference between sexes or age groups (<70 or ≥70 years) where PD-L1 scored ≥50%. Specimens from patients with higher stage (III/IV) scored ≥1% or ≥50% marginally more often compared to specimens from patients with lower stage (I/II) (p≤0.002). Proportions of primary and metastatic specimens did not differ where PD-L1 TPS was ≥1%, however more metastatic samples scored TPS ≥50% than primary samples (metastatic vs primary; 34% vs 27%, p<0.001). Cytology and biopsy specimens were equally reported, at 63% of specimens, to score TPS ≥1%, whereas cytology samples scored TPS ≥50% slightly more often than biopsy samples (34% vs 30%, respectively, p=0.004). Resection specimens (16% of samples tested) were reported to score TPS ≥50% or ≥1% less often than either biopsy or cytology samples (p<0.001). There was no difference in the proportion of tests with TPS ≥1% between PD-L1 IHC assays used, however the proportion of tests scored at TPS ≥50% was marginally higher for 22C3 compared to SP263 (34% vs 29%, respectively, p<0.001). These real-world Australian data are comparable to some previously published global real-world data, with some differences noted.

Knowledge exchange in crisis settings: A scoping review.

BACKGROUND: Public health practice and efforts to improve the social determinants of health operate within a climate characterised by multiple and intersecting crises. This includes the Covid-19 pandemic as well as more protracted crises such as climate change and persistent social inequalities that impact health. We sought to understand and compare how knowledge exchange (KE) processes occur across different crises, and how knowledge on improving social determinants of health can be utilised at times of crisis to reduce health inequalities and strengthen public systems. METHODS: We conducted a scoping review to understand how KE on improving social determinants of health can occur across different types of crises (e.g. environmental, pandemics, humanitarian). Relevant studies were identified through electronic searching of Medline, EMBASE, Global Health, Scopus and Web of Science databases. RESULTS: We identified 86 studies for inclusion in the review. Most studies concerned pandemic or environmental crises. Fewer studies explored KE during technical (e.g. nuclear), terror-related or humanitarian crises. This may reflect a limitation of the searches. Few studies assessed KE as part of longer-term responses to social and economic impacts of crises, with studies more likely to focus on immediate response or early recovery stages. Exchange of research evidence or data with policy or practice contextual knowledge was common but there was variation in the extent that lay (public) knowledge was included as part of KE processes. CONCLUSION: As ongoing crises continue with significant public health implications, KE processes should appropriately reflect the complexity inherent in crises and foreground health inequalities. Doing so could include the utilisation of systems or complexity-informed methods to support planning and evaluation of KE, a greater focus on KE to support action to address social determinants of health, and the inclusion of a plurality of knowledge-including lived experience-in planning and responding to crises.

The Effects of Intravenous Iron Infusion on Preoperative Hemoglobin Concentration in Iron Deficiency Anemia: Retrospective Observational Study.

BACKGROUND: An iron infusion pathway using Ferrinject (ferric carboxymaltose) was implemented at Southend University Hospital for preoperative surgical patients with iron deficiency anemia undergoing major surgery. This was based on a treatment algorithm proposed by Munting and colleagues according to the international consensus statement on perioperative management of anemia and the UK National Institute for Health and Care Excellence (NICE) guidelines. These guidelines state that intravenous iron is indicated when oral iron is poorly tolerated or ineffective, there is insufficient time to surgery, or due to a functional iron deficiency. OBJECTIVE: The objective of this study was to evaluate the change in adult hemoglobin (Hb) concentration (g/L) after Ferrinject infusion at the time of surgery. METHODS: Data were retrospectively collected on all surgical patients that received an iron infusion preoperatively for iron deficiency anemia from July 2019 to April 2020. Nonsurgical, obstetric, and pediatric patients, and those without a postinfusion Hb level measurement were excluded. Data collected included the Hb, ferritin, and transferrin levels pre and postinfusion; correct dose of intravenous iron received; and any adverse reactions noted. RESULTS: Thirty-two surgical patients with iron deficiency anemia received intravenous iron between July 2019 and April 2020 prior to surgery. The average pre and post iron infusion Hb concentration across the cohort was 97 g/L and 114 g/L, respectively (18% increase; P=.001). Two (6%) patients had a posttransfusion Hb level ≥130 g/L prior to surgery after infusion. Nine patients had both a pre and postinfusion ferritin level recorded, which showed an increase from 12 ng/mL preinfusion to 94 ng/mL postinfusion (P=.02). Twenty-three (72%) patients did not receive the full dose of intravenous iron based on their Hb level and weight. Twenty-four (75%) patients received an iron infusion >2 weeks prior to surgery and the other 8 (25%) patients received the infusion <2 weeks before their surgery. There was an average increase in Hb of 22% (21 g/L, 95% CI 13-28) and 5% (5 g/L, 95% CI 1-10), respectively, across the two groups (P=.03). There were no documented adverse reactions to intravenous iron. CONCLUSIONS: Intravenous iron is an effective intervention to improve the Hb concentration in patients with iron deficiency anemia despite the majority of patients not receiving the full dose based on their baseline Hb level and weight. Increasing the interval time between infusion and surgery was associated with a greater increase in Hb, with only a minimal increase observed if given less than 2 weeks prior to surgery.

A 'strategy of resistance'? How can a place-based empowerment programme influence local media portrayals of neighbourhoods and what are the implications for tackling health inequalities?

Place-based stigma is linked with health and social harms, but few studies have assessed what actions may reduce these. Area-based programmes are one potential strategy but may exacerbate stigma by targeting disadvantaged neighbourhoods. We reviewed newspaper coverage in two stigmatised neighbourhoods to identify whether a programme funded in these localities influenced reporting. While both areas were dominated by negative coverage, the progamme provided an impetus for some positive stories over time and enabled community activists to articulate alternative narratives about where they lived, countering negative external portrayals. The involvement of residents should be central to strategies to tackle place-based stigma.

Spatial and temporal alterations in protein structure by EGF regulate cryptic cysteine oxidation.

Stimulation of plasma membrane receptor tyrosine kinases (RTKs), such as the epidermal growth factor receptor (EGFR), locally increases the abundance of reactive oxygen species (ROS). These ROS then oxidize cysteine residues in proteins to potentiate downstream signaling. Spatial confinement of ROS is an important regulatory mechanism of redox signaling that enables the stimulation of different RTKs to oxidize distinct sets of downstream proteins. To uncover additional mechanisms that specify cysteines that are redox regulated by EGF stimulation, we performed time-resolved quantification of the EGF-dependent oxidation of 4200 cysteine sites in A431 cells. Fifty-one percent of cysteines were statistically significantly oxidized by EGF stimulation. Furthermore, EGF induced three distinct spatiotemporal patterns of cysteine oxidation in functionally organized protein networks, consistent with the spatial confinement model. Unexpectedly, protein crystal structure analysis and molecular dynamics simulations indicated widespread redox regulation of cryptic cysteine residues that are solvent exposed only upon changes in protein conformation. Phosphorylation and increased flux of nucleotide substrates served as two distinct modes by which EGF specified the cryptic cysteine residues that became solvent exposed and redox regulated. Because proteins that are structurally regulated by different RTKs or cellular perturbations are largely unique, these findings suggest that solvent exposure and redox regulation of cryptic cysteine residues contextually delineate redox signaling networks.

Long-term outcomes up to 25 years following balloon pulmonary valvuloplasty: A multicenter study.

OBJECTIVE: Evaluate long-term outcomes following balloon pulmonary valvuloplasty (BPV) for pulmonary stenosis (PS). BACKGROUND: Long-term data following BPV is limited to small, single center studies. METHODS: BPV from April 12, 1985 to January 7, 2015 from three centers were included. Outcomes studied were ≥ moderate PI by echocardiogram and residual PS ≥ 40 mm Hg. Risk factors for ≥ moderate PI, residual PS, and repeat intervention were assessed by univariate and multivariate analysis. RESULTS: Among 254 patients, mean age at BPV was 3.8 years (range 1 day-67 years), initial PS catheter gradient was 56 mm Hg (IQR 40-70), 19% had critical PS, and 9% had genetic syndromes. Mean follow-up duration was 7.5 years (maximum 25 years). Sixty-nine (29%) had ≥ moderate PI, 41 patients (17%) had residual PS > 40 mm Hg, and 31 (13%) had re-intervention. In univariate analysis, younger age, lower weight, greater initial PS gradient, greater initial RV/systemic pressure ratio, critical PS, and longer follow-up duration were associated with ≥ moderate PI. Greater initial PS gradient was associated with long-term residual PS or repeat intervention. In multivariate analysis, greater initial gradient and lower weight were independently associated with > moderate PI and greater initial PS gradient and genetic abnormality were independently associated with residual PS and repeat intervention. CONCLUSION: Smaller patients with greater initial PS were more likely to develop significant long-term PI. Patients with greater initial PS and genetic abnormalities were more likely to have residual PS or require repeat intervention following BPV.

Use of a Dacron Annular Sparing Versus Limited Transannular Patch With Nominal Pulmonary Annular Expansion in Infants With Tetralogy of Fallot.

BACKGROUND: Repair of tetralogy of Fallot (ToF) using a transannular patch can result in severe pulmonary insufficiency (PI) and subsequent right ventricular (RV) dilation. Use of a Dacron (Maquet Cardiovascular LLC, Wayne, NJ) limited transannular patch with nominal pulmonary annular expansion (LTAP) attempts to limit PI. We sought to evaluate the degree of PI and RV dilation resulting from a LTAP or annular sparing (AS) approach. METHODS: Infants less than 1 year of age undergoing ToF repair between 2000 and 2010 were divided into 2 groups: LTAP and AS RV outflow tract patch. Echocardiograms were used to determine RV dimensions and corresponding Z-values. RESULTS: From 94 infants, 48 required a LTAP and 46 required an AS patch. The preoperative pulmonary valve annulus Z-value was significantly smaller in the LTAP versus AS group (-2.7 ± 1.4 versus -0.9 ± 1.5; p < 0.001). Mean follow-up was obtained at 7.9 ± 3.4 years. Ten-year freedom from severe pulmonary insufficiency was 78.5% versus 93.2% (p = 0.3) in the LTAP and AS groups, respectively. There was no significant difference in the diameter of the RV base Z-value between groups (LTAP: 0.9 ± 0.8 versus AS: 0.0 ± 2.3; p = 0.1). Further, the freedom from reoperation at 10 years was also not significantly different between the LTAP and AS groups (95.6% versus 91.8%; p = 0.5). CONCLUSIONS: When required, a LTAP results in a similar change in RV chamber size and rate of reoperation at an intermediate-term follow-up.

Physical and mental health outcomes following housing improvements: evidence from the GoWell study.

BACKGROUND: Existing research points towards physical and mental health gains from housing improvements, but findings are inconsistent and often not statistically significant. The detailed characteristics and variability of housing improvement works are problematic and studies are often small, not experimental, with short follow-up times. METHODS: A quasi-experimental design was used to assess the impact on physical health and mental health (using SF-12v2 Physical and Mental health component summary scales) of four types of housing improvement works-central heating, 'Secured By Design' front doors, fabric works, kitchens and bathrooms-both singly and in pairwise combinations. A longitudinal sample of 1933 residents from 15 deprived communities in Glasgow, UK was constructed from surveys carried out in 2006, 2008 and 2011. Sociodemographic characteristics and changes in employment status were taken into account. RESULTS: Fabric works had positive associations with physical health (+2.09, 95% CI 0.13 to 4.04) and mental health (+1.84, 95% CI 0.04 to 3.65) in 1-2 years. Kitchens and bathrooms had a positive association with mental health in 1-2 years (+2.58, 95% CI 0.79 to 4.36). Central heating had a negative association with physical health (-2.21, 95% CI -3.74 to -0.68). New front doors had a positive association with mental health in <1 year (+5.89, 95% CI 0.65 to 11.14) and when provided alongside kitchens and bathrooms (+4.25, 95% CI 1.71 to 6.80). Gaining employment had strong associations with physical health (+7.14, 95% CI 4.72 to 9.55) as well as mental health (+5.50, 95% CI 3.27 to 7.73). CONCLUSIONS: Fabric works may provide insulation benefits and visual amenity benefits to residents. Front doors may provide important security benefits in deprived communities. Economic regeneration is important alongside property-led regeneration.

Predictors of ductus arteriosus in-stent stenosis in the hybrid approach to hypoplastic left heart syndrome.

The hybrid approach to palliation of hypoplastic left heart syndrome using pulmonary artery bands, a patent ductus arteriosus (PDA) stent, and atrial septostomy has been well described. One potential complication of hybrid stage 1 palliation is the development of neointimal formation and in-stent stenosis (ISS). This study aimed to identify predictors of ISS development. Patients who underwent hybrid stage 1 palliation between 2002 and 2010 were included in the study. The clinical information included oxygen saturation, weight, vital signs, and medications. Echocardiographic data included ventricular function, degree of tricuspid regurgitation, and velocity through the PDA stent and pulmonary artery bands. Hemodynamic data from interstage catheterizations were similarly noted. Patients who developed clinically significant ISS requiring either transcatheter intervention or early stage 2 repair were compared with those who did not. Of the 66 patients included in the study, 40 were boys (61 %). The median age at hybrid palliation was 7 days (range, 1-93 days), and the median initial weight was 3.2 kg (range, 1.4-5 kg). In 13 patients (20 %), ISS developed. The mean initial weight was significantly greater in the ISS group (3.5 ± 0.5 vs. 3.0 ± 0.6 kg) (p = 0.03). The mean oxygen saturations did not differ significantly between the no-ISS group (82.2 % ± 5.7 %) and the ISS group (81.4 % ± 2.0 %) (p = 0.31). The mean PDA velocities were higher in the ISS group (2.7 ± 0.4 m/s) and increased at a faster rate than in the no-ISS group at (2.4 ± 0.4 m/s) (p = 0.01). The degree of tricuspid regurgitation, ventricular function, and pulmonary artery band gradients shown by echocardiography were similar in the two groups. The development of ISS after hybrid stage 1 palliation can lead to interstage interventions or earlier comprehensive stage 2 repair. Patients with greater initial weight and a lower stent-to-weight ratio are more likely to develop ISS. The cause of ISS is complex, and additional investigation of its etiology currently is ongoing.

Mid-term differences in right ventricular function in patients with congenital diaphragmatic hernia compared with controls.

BACKGROUND: Patients with congenital diaphragmatic hernia (CDH) may have abnormal lung development, which may cause detrimental effects on right ventricular (RV) function. This study aimed to determine if there are persistent echocardiographic differences in RV function in patients with CDH years after repair versus control patients. METHODS: Patients who underwent repair for CDH were recruited. RV function was evaluated by strain analysis and tissue Doppler imaging (TDI). Wilcoxon's rank-sum test was used for analysis. RESULTS: Seven CDH patients and 16 control patients were studied. There was no difference in age between the CDH and control groups (6.2±1.7 years vs. 5.7±1.7 years). TDI demonstrated significantly lower values in the RV early diastolic wave (12.8±1.5 cm/s vs. 16.1±3.1 cm/s) and RV systolic wave (10.2± 0.8cm/s vs. 13.4±1.3 cm/s) when comparing the CDH group and the control group. Interventricular apical septal strain was signifi cantly lower in the CDH group than in the control group (-20.1±4.6% vs. -25.4±4.1%). There was a trend towards lower strain values in the RV mid-lateral segment in the CDH group (-30.8±9.9% versus -39.7±6.0%, P=0.06) and a lower global RV strain (-27.8±3.0% vs. -31.1±3.1%, P=0.06). CONCLUSIONS: Patients who underwent CDH repair continue to have differences in RV function years after repair. Follow-up is needed to determine how these differences impact cardiac function in adult survivors of CDH.

Histopathologic evaluation of patent ductus arteriosus stents after hybrid stage I palliation.

The aim of this study was to determine the histopathology of patent ductus arteriosus (PDA) in-stent stenosis after hybrid stage I palliation. The hybrid approach to palliation of hypoplastic left heart syndrome can be complicated by the development of in-stent stenosis of the PDA. This may obstruct retrograde aortic arch flow, decrease systemic circulation, and lead to interstage interventional procedures. Stented PDA samples removed from eight patients undergoing comprehensive stage II repair were examined by way of radiography and histochemistry (hematoxylin and eosin, Movat pentachrome, α-smooth muscle actin, and proliferating cell nuclear antigen). A retrospective chart review of the patients was also performed. PDA stents were in place in the PDA for a mean period of 169 ± 28 days in patients who had a mean age of 176 ± 30 days at the time of stent removal. Stent deployment caused chronic inflammation, caused fibrin deposition, and induced vascular smooth muscle-cell (VSMC) proliferation in the area immediately surrounding the stent struts. The neointimal region was composed largely of smooth muscle cells that appeared to be fully differentiated by the lack of PCNA staining. Neointimal thickening occurs in the PDA after stent placement for hybrid palliation of HLHS and is the result of inflammation, extracellular matrix deposition, and smooth muscle-cell proliferation in the peristrut region. This finding suggests that proliferating VSMCs in the peristrut region may provide the impetus for inward neointimal formation and therefore the manifestation of in-stent stenosis.

Predictors of retrograde aortic arch obstruction after hybrid palliation of hypoplastic left heart syndrome.

A potential complication after hybrid stage 1 palliation for hypoplastic left heart syndrome (HLHS) is retrograde aortic arch obstruction (RAAO). This can lead to increased morbidity and unplanned surgical or interventional procedures in the interstage period. This study aimed to identify potential predictors of RAAO by analyzing initial echocardiograms and angiograms before hybrid stage 1 palliation. For this study, 96 patients who underwent hybrid stage 1 palliation between July 2002 and July 2009 were reviewed, 68 of which had standard HLHS and met the inclusion criteria. The initial echocardiogram, hybrid stage 1 angiograms, and follow-up echocardiograms were reviewed. Anatomic and hemodynamic measurements were obtained by both modalities, and comparisons were made between those who developed RAAO and those who did not. Of the 68 patients, 20 (29%) had RAAO. The mean aortic root size was smaller for the patients who had RAAO (3.6 vs 4.4 mm; p = 0.036). The angiographic angle between the aortic isthmus and the patent ductus arteriosus (PDA) was significantly larger in the RAAO group (86° vs 63°; p = 0.008). The retrograde aortic arch velocities were higher in the RAAO group. Patients with RAAO have a smaller aortic root and higher retrograde velocities on initial echocardiogram. Patients with RAAO show a larger angle between the retrograde arch and PDA on angiogram. Because RAAO is an important potential complication after hybrid stage 1 palliation for HLHS, identification of predictors of RAAO may lead to improved care and outcome for patients with RAAO.

The retrograde aortic arch in the hybrid approach to hypoplastic left heart syndrome.

BACKGROUND: Before palliative stage 2 for hypoplastic left heart syndrome, the coronary and cerebral circulations are often dependent on retrograde perfusion by means of the aortic arch. Results of hybrid palliation with a focus on patients exhibiting retrograde aortic arch obstruction (RAAO) were analyzed. METHODS: From July 2002 to March 2008 66 consecutive hybrid procedures for hypoplastic left heart syndrome were performed. Patients requiring RAAO intervention based on cardiology-surgery consensus were defined as group 1 (n = 16), whereas all other hypoplastic left heart syndrome patients formed group 2 (n = 50). RESULTS: At birth there were no differences between groups in terms of demographics or cardiac function. Group 1 had more patients with aortic atresia (94% versus 58%; p = 0.01), and 69% of patients had initial echocardiographic comments regarding incipient RAAO versus 26% in group 2 (p = 0.007). The type of ductal stent, balloon versus self-expandable, did not influence the subsequent development of RAAO. Before RAAO intervention (mean age, 74 days), group 1 patients had significantly more tricuspid regurgitation. The main treatment for RAAO in group 1 was coronary stent insertion, with 3 patients having a reverse central shunt. At a mean follow-up of 611 days, group 1 had reduced survival interstage (56.3% versus 88%; p = 0.005) and overall (43.7% versus 70%; p = 0.03). CONCLUSIONS: Clinically important RAAO occurred in 24% of the hypoplastic left heart syndrome patients in this series. If RAAO is detected at birth or early interstage, a Norwood operation is now favored. Palliative interventional catheterization remains very important mid and late interstage for continuing the hybrid strategy toward comprehensive stage 2.

Comparing balloon angioplasty, stenting and surgery in the treatment of aortic coarctation.

This article summarizes the currently available data regarding the management of coarctation, comparing balloon angioplasty, surgery and transcatheter stent therapy. The vast majority of reported studies are retrospective institutional series and comparative prospective studies are scarce, making it difficult to clearly recommend a treatment strategy. Long-term data are lacking, with most studies evaluating transcatheter approaches having a median follow-up of 5 years or less. Surgical repair is recommended for most patients with duct-dependent neonatal coarctation, while stent implantation for older children and adults has been shown to have excellent short-term results. Balloon angioplasty for (native) coarctation is effective in leading to an acute gradient reduction, but has been found to have a higher incidence of recoarctation or aortic wall complications. Long-term data from prospective registries, such as the Comprehensive, Continuous, Integrated System of Care (CCISC), are required before being able to make more firm recommendations upon the most appropriate treatment algorithm.

Pediatric myocarditis: presenting clinical characteristics.

OBJECTIVE: The objective of the study was to characterize the clinical profiles of pediatric patients with acute myocarditis and dilated cardiomyopathy (DCM) before diagnosis. METHODS: A retrospective cross-sectional study was conducted to identify patients with myocarditis and DCM who presented over a 10-year span at 2 tertiary care pediatric hospitals. Patients were identified based on the International Classification of Diseases, Ninth Revision, diagnostic codes. RESULTS: A total of 693 charts were reviewed. Sixty-two patients were enrolled in the study. Twenty-four (39%) patients had a final diagnosis of myocarditis, and 38 (61%) had DCM. Of the 62 patients initially evaluated, 10 were diagnosed with myocarditis or DCM immediately, leaving 52 patients who required subsequent evaluation before a diagnosis was determined. Study patients had a mean age of 3.5 years, 47% were male, and 53% were female. Common primary complaints were shortness of breath, vomiting, poor feeding, upper respiratory infection (URI), and fever. Common examination findings were tachypnea, hepatomegaly, respiratory distress, fever, and abnormal lung examination result. Sixty-three percent had cardiomegaly on chest x-ray, and all had an abnormal electrocardiogram results. CONCLUSIONS: These data suggest children with acute myocarditis and DCM most commonly present with difficulty breathing. Myocarditis and DCM may mimic other respiratory or viral illnesses, but hepatomegaly or the finding of cardiomegaly and an abnormal electrocardiogram result may help distinguish these diagnoses from other more common pediatric illnesses.

A randomized controlled trial of sertraline for the treatment of depression in persons with traumatic brain injury.

OBJECTIVE: To examine the efficacy of sertraline in the treatment of depression after traumatic brain injury (TBI). DESIGN: Double-blind, randomized controlled trial. SETTING: Research center at a major urban medical center. PARTICIPANTS: Subjects were a referred and volunteer sample of 52 participants with TBI, a diagnosis of major depression disorder (MDD), and a score on the Hamilton Rating Scale for Depression (HAM-D) of 18 or greater. The majority of the sample was male (58%), had less than 14 years of education (73%), had incomes below $20,000 (82%), and were from minority backgrounds (75%). Approximately one third of the sample had mild brain injuries, and two thirds had moderate to severe brain injuries. The mean age was 47+/-11, and the mean time since injury was 17+/-14 years. One participant withdrew from the study because of side effects. INTERVENTION: Daily oral sertraline in doses starting at 25mg and increasing to therapeutic levels (up to 200mg) or placebo for 10 weeks. MAIN OUTCOME MEASURES: The HAM-D, the Beck Anxiety Inventory, and the Life-3 quality of life (QOL). RESULTS: No statistically significant differences were found at baseline between drug and placebo groups on baseline measures of depression (24.8+/-7.3 vs 27.7+/-7.0), anxiety (16.4+/-12.3 vs 24.0+/-14.9), or QOL (2.96+/-1.0 vs 2.9+/-0.9). The income level of those receiving placebo was significantly lower than those participants receiving medication. Analyses of covariance revealed significant changes from preintervention to posttreatment for all 3 outcome measures (P<.001) but no group effects. Random-effects modeling did not find any significant difference in patterns of scores of the outcome measures between the placebo and medication groups. CONCLUSIONS: Both groups showed improvements in mood, anxiety, and QOL, with 59% of the experimental group and 32% of the placebo group responding to the treatment, defined as a reduction of a person's HAM-D score by 50%.

A comparison of cognitive functioning in older adults with and without traumatic brain injury.

OBJECTIVE: Cognitive impairments are common sequelae of traumatic brain injury (TBI) and are often associated with the natural process of aging. Few studies have examined the effect of both age and TBI on cognitive functioning. The purpose of this study was to compare cognitive functioning between older adults who sustained a TBI to an age-matched group of individuals without a brain injury and to determine whether the presence or absence of a genetic marker apolipoprotein epsilon (APOEepsilon4 allele) accounts for additional cognitive decline in both groups examined. METHODS AND PROCEDURES: Cognitive performance was measured by 11 neuropsychological tests, in 54 adults with TBI aged 55 and older and 40 age-matched control participants. All participants were reexamined 2 to 5 years later. SETTING: Community volunteer-based sample examined at a large, urban medical center. MAIN OUTCOME MEASURE(S): California Verbal Learning Test; Wechsler Memory Scale-III (Logical Memory I & II; Visual Reproduction I & II); Grooved Pegboard; Woodcock-Johnson Test of Cognitive Ability (Visual Matching and Cross-out); Wisconsin Card Sorting Test; Trail Making Test A & B; Conners' Continuous Performance Task; Wechsler Adult Intelligence Scale-III (Vocabulary); Controlled Oral Word Association Test; and Boston Naming Test. RESULTS: Participants with TBI had lower scores on tests of attention and verbal memory than did participants with no disability. Neither group exhibited a significant decline in cognitive function over time. The presence of the APOEepsilon4 allele did not account for additional decline in cognitive function in either group. CONCLUSION(S): The findings suggest that older adults with TBI may not be at increased risk for cognitive decline over short time periods (2 to 5 years) even if they are carriers of the APOEepsilon4 allele.