54-month Follow-up Research Articles

The Norwegian Watch and Wait study: Norwait for rectal cancer. A report from a failed study-a word of caution.

The paucity of prospective data on the subject of Watch and Wait for rectal cancer prompted the implementation of Norwait, a population-based study including rectal cancer patients after neoadjuvant therapy. The aim of the study was to assess the accuracy of clinical complete response (cCR) and quantify the regrowth rates. Norwait was a prospective population-based observational study with ethical approval (2017/935) registered at clinicaltrials.com (NTC03402477). Residents of Norway with histologically proven rectal cancer located within 15cm from anal verge were eligible following completion of radiotherapy or chemoradiation at seven hospitals. cCR was the disappearance of tumour and of any ulcer with/without the appearance of whitening of prior tumour site and telangiectasia evaluated at 12weeks by digital rectal exam, and endoscopic imaging. The study aimed to include 100 cCR patients with regrowth rates as primary endpoint. The data are presented in crude form. Eighty-two patients were included in seven hospitals from 2018 to 2020 when the study was terminated. Fifty-one patients were included in six hospitals, whereas protocol violations were identified in one hospital, where thirty-one (rather than protocol-estimated 12) patients were enrolled. Amongst the 31 patients, there were only 2 with documented cCR. Of the latter 29, there were 16 with ulcer or persistent tumour, and 13 without any documentation of cCR. Of these, 23 underwent surgery with a delay up to 50weeks. At median 54-month follow-up of 31 patients, there were 77% local regrowths (n = 23), 40% metachronous metastases (n = 12) and 23% deaths (n = 7). At median 54-month follow-up of 51 cCR patients, there were 53% local regrowths (n = 27), 14% metachronous metastases (n = 7) and 4% deaths (n = 2). Norwait admonishes a word of caution reaching beyond the inconclusive results of a population-based study jeopardised by serious violation to protocol and legislation for conducting safe research.

Eye care following pre-school vision screening: Data from the Growing Up in New Zealand study.

This study aimed to determine adherence with follow-up from the New Zealand pre-school vision screening programme. The study also examined associations between pre-school vision screening outcomes and cognitive measures assessed at the 54-month follow-up in the Growing Up in New Zealand study cohort. A cross-sectional retrospective record review of pre-school vision screening outcomes and hospital ophthalmology records with linkage to Growing Up in New Zealand cohort study data. Of 176 children referred from vision screening, 21.6% did not attend a referral appointment. Of 138 children who attended a referral appointment, 21.0% did not attend one or more follow-up appointments. Ethnic differences were observed in attendance at referral appointments (attended Māori 13%, Pacific 22.5%, European/Other 64.5%; not attended Māori 26.3%, Pacific 28.9%, European/Other 44.7%; P = 0.04) and follow-up appointments (attended Māori 11.9%, Pacific 15.6%, European/Other 72.5%; not attended Māori 17.2%, Pacific 48.3%, European/Other 34.5%; P = 0.001). Vision screening outcome was significantly associated with letter naming fluency scores (P = 0.01) but not name and numbers scores (P = 0.05). Non-attendance at referral and follow-up appointments limits the efficacy of vision screening, particularly for children of Māori and Pacific ethnicity. Children referred from vision screening achieve lower scores on letter naming fluency, a key predictor of reading ability in later childhood. Equity-based improvements are required to ensure that all children referred from vision screening receive appropriate follow-up eye care.

How often are intrathyroidal parathyroid glands a cause of primary hyperparathyroidism, and how should they be managed?

The purpose of our study was to determine the frequency and management of intrathyroidal parathyroid glands in patients with primary hyperparathyroidism and evaluate whether intrathyroidal parathyroid glands were more often superior or inferior glands. A retrospective review of the prospective parathyroid database was completed to determine the number of patients with primary hyperparathyroidism and an intrathyroidal parathyroid gland. Demographic data, laboratory and localization studies, operative management, pathology, and outcome were determined for patients with an intrathyroidal parathyroid gland and were compared with patients with an extrathyroidal parathyroid gland. From 1990-2023, 808 patients were operated on for primary hyperparathyroidism; 17 (2%) patients had an intrathyroidal parathyroid gland, an adenoma in 15 (88.2%), and a hyperplastic gland in 2(11.8%). The mean age was 53 years; 16 (94%) patients were female. Mean calcium and parathyroid hormone was 12 mg/dL and 150 pg/mL, and there were no differences from the extrathyroidal parathyroid group. Ultrasound and Sestamibi imaging were valuable in identifying an intrathyroidal parathyroid gland in 10 of 13 patients and 13 of 17 patients, respectively. Local excision was performed in 9(53%) patients and lobectomy in 8 (47%) patients. Intraoperative parathyroid hormone was measured and predictive of cure in 12 patients. The location of intrathyroidal parathyroid glands was determined in 15 patients and was inferior in 11 (73%). All patients were cured. No patient developed recurrent disease after a median 54-month follow-up. Intrathyroidal parathyroid glands are the cause of primary hyperparathyroidism in 2% of patients and are most often inferior glands. Local excision was accomplished in 53% of our patients.

Management of Multiple Idiopathic Root Resorption in a Rheumatoid Arthritis Patient: A Case Report with 4-year Follow-up

Cervical root resorption is a rare destructive disease that originates from the external cervical root surface. It has a multifactorial etiology. Cervical root resorption may affect several teeth and its treatment can be complicated due to the size, location, and extension of the resorptive defect. Rheumatoid arthritis is a chronic inflammatory autoimmune disease that has systemic effects. The objective of this article was to report a rare case of multiple idiopathic cervical resorptions in a patient with rheumatoid arthritis. A 52-year-old male patient with a 20-year history of rheumatoid arthritis was diagnosed with multiple idiopathic cervical resorptions through cone-beam computed tomography (CBCT) and clinical examination. All known causes for cervical resorption were ruled out after a detailed anamnesis. This report details inflammation due to rheumatoid arthritis as a possible cause of idiopathic cervical resorption. The systemic alterations wrought by rheumatoid arthritis could be related to the etiopathogenesis of cervical root resorption. Non-surgical endodontic treatment was done for the maxillary left canine. The defect was surgically repaired using bioceramic putty. The 12-month recall revealed the good healing of the periodontal and periradicular conditions with no obvious clinical symptoms. At the 36-month recall visit, clinical and radiographic evidence of deterioration in the repair material was observed. At the 54-month follow-up, deterioration of repair material was observed with an increase in the extension of resorption in tooth 14 was detected. Reasons for this deterioration remain unclear. Ruling out all other factors for cervical root resorption, how rheumatoid arthritis contributes to cervical root resorption is still lacking/unclear. Dental care providers must be vigilant for signs of cervical root resorption in vulnerable patients with rheumatoid arthritis for early diagnosis and prompt treatment. Keywords: External root resorption, Inflammatory markers, Multiple root resorption, Rheumatoid arthritis, Resorption repair.

Transosseous Meniscus Root Repair in Pediatric Patients and Association With Durable Midterm Outcomes and High Rates of Return to Sports

Background: Injuries to the meniscus root attachments result in extrusion of the meniscus, impaired distribution of hoop stresses, and progressive degenerative articular wear. As a result of these deleterious effects, there has been increasing emphasis on repairing meniscus root injuries to restore structure and function. Purpose: To describe meniscus root tear patterns, associated injuries, and outcomes of transosseous meniscus root repair in a series of pediatric patients. Study Design: Case series; Level of evidence, 4. Methods: A single-institution retrospective review approved by the institutional review board was performed on consecutive adolescent patients aged <19 years with a meniscus posterior root tear treated with transosseous root repair over 4 years. All patients had a minimum 24-month clinical follow-up. The primary outcomes were revision meniscal surgery, and Lysholm, patient satisfaction, and Tegner activity scores. Results: A total of 20 patients (11 male and 9 female patients), with a mean age of 15.6 years (range, 13-18 years), met the inclusion criteria. There were 14 lateral meniscus root tears and 6 medial meniscus root tears. Seventeen patients (85%) had an associated ligament tear: 12 anterior cruciate ligament (ACL) tears and 5 posterior cruciate ligament tears. Two root tears occurred in isolation and both were the posterior root of the medial meniscus. The majority of meniscus root tears (n = 14 patients; 70%) were root avulsions (type 5). The mean follow-up was 42 months (range, 25-71 months). One patient underwent secondary surgery on the affected meniscus after a new injury 4 years postoperatively. Patient-reported outcomes were obtained for 16 patients (80%) at a mean 54-month follow-up. The median Lysholm score was 95 (interquartile range [IQR], 90-100). The median patient satisfaction score was 10 (IQR, 8-10). Thirteen of 16 patients (81%) reported returning to the same or higher level of sports after surgery. Conclusion: Meniscus root tears most commonly occur in pediatric patients as root avulsions of the posterior root of the lateral meniscus and in association with ACL tears. This is unique compared with the adult population, in which the medial meniscus posterior root is often injured in isolation from a radial tear adjacent to the root. In our pediatric case series, transosseous root repair resulted in successful outcomes in the majority of patients, with durable results at the midterm follow-up.

Long-term follow-up of a randomized controlled trial comparing systemic family therapy (FT-S) added to treatment as usual (TAU) with TAU alone in adolescents with anorexia nervosa.

Randomized controlled trials showed the efficacy of family therapy for anorexia nervosa during adolescence, but studies examining its long-term beneficial effect are still needed. This article presents the results of a 54-month post-randomization follow-up of a previously reported randomized controlled trial that compared two post-hospitalization outpatient treatment programs: Treatment As Usual alone versus Systemic Family Therapy added to Treatment As Usual. A consecutive series of 60 female adolescents with anorexia nervosa (DSM-IV) were randomized (30 per group). During the first 18 months, in the Treatment As Usual group, subjects received a multidisciplinary treatment. In the other group, Systemic Family Therapy sessions targeting intra-familial dynamics were added to Treatment As Usual. At 54 months, the primary outcome was defined using the Morgan and Russell global Outcome Categories (Good or Intermediate versus Poor). Secondary outcomes were the Global Outcome Assessment Schedule score, body mass index, amenorrhea, number of hospitalizations, eating disorder symptoms, psychopathological features, and family functioning. Analyses were carried out using an Intention-To-Treat with the Last Observation Carried Forward procedure. Data of 59/60 subjects were available. At 54 months, significant effects in favor of adding Systemic Family Therapy to Treatment As Usual were shown for the Global Outcome Categories (60% of Good/Intermediate versus 31% in the control group, p = .026), mean body mass index (p = .048), resumption of menses (70.0% vs. 40% p = .020), and mental state score (p = .010). Family cohesion scores were lower in the Systemic Family Therapy group (p = .040). Adding Systemic Family Therapy focusing on intra-familial dynamics to a multidimensional outpatient treatment program appeared to lead to a better long-term outcome in young women who suffered from severe anorexia nervosa during adolescence.

Valve-in-Valve and Valve-in-Ring Transcatheter Mitral Valve Implantation in Young Women Contemplating Pregnancy.

Transcatheter mitral valve implantation (TMVI) is emerging as an alternative to surgical mitral valve replacement in selected high-risk patients. Delaying definitive mechanical mitral valve replacement and the constraints of anticoagulation thanks to TMVI may be an attractive option in young women contemplating pregnancy and suffering from failure of mitral bioprosthesis or annuloplasty. The aim of the study was to evaluate the possibility, safety, and outcomes of pregnancy after TMVI in this population. From 2013 to 2019, 12 young women contemplating pregnancy underwent transseptal valve-in-valve or valve-in-ring TMVI using the Edwards SAPIEN XT/3 valves and were prospectively followed up at 1 month, 6 months, 1 year, and yearly thereafter. Mean age of the patients was 30±6 years. Bioprosthesis degeneration was observed in 7 cases and annuloplasty failure in 5. Three valve-in-ring patients required the implantation of a second valve, which led to an overall procedural success rate of 75%. One delayed left ventricular outflow tract obstruction required elective surgical mitral valve replacement. At 6 months/1 year, 83% of the patients were in New York Heart Association classes I/II. Mitral regurgitation was ≤2+ in all the cases and mean gradient was 7±2 mm Hg. Four patients could complete 6 full-term pregnancies. One symptomatic thrombosis occurred and resolved under aspirin and anticoagulation therapy. All others pregnancies were uneventful. Predelivery mean gradient was 11 mm Hg, and systolic pulmonary artery pressure was 32 mm Hg. There were 4 vaginal deliveries and 2 cesarians. Newborns were alive and healthy. At last follow-up, there was no death, and 3 patients required elective surgical mitral valve replacement at 6- to 54-month follow-up. Our study suggests that, in young women, transseptal TMVI to treat failing bioprostheses may result in good short-term outcomes that allow uneventful pregnancies. The results are less favorable in women with failed annuloplasty rings.

Less agreeable, better preserved? A PET amyloid and MRI study in a community-based cohort

The relationship between personality profiles and brain integrity in old age is still a matter of debate. We examined the association between Big Five factor and facet scores and MRI brain volume changes on a 54-month follow-up in 65 elderly controls with 3 neurocognitive assessments (baseline, 18 months, and 54 months), structural brain MRI (baseline and 54 months), brain amyloid PET during follow-up, and APOE genotyping. Personality was assessed with the Neuroticism Extraversion Openness Personality Inventory-Revised. Regression models were used to identify predictors of volume loss including time, age, sex, personality, amyloid load, presence of APOE ε4 allele, and cognitive evolution. Lower agreeableness factor scores (and 4 of its facets) were associated with lower volume loss in the hippocampus, entorhinal cortex, amygdala, mesial temporal lobe, and precuneus bilaterally. Higher openness factor scores (and 2 of its facets) were also associated with lower volume loss in the left hippocampus. Our findings persisted when adjusting for confounders in multivariable models. These data suggest that the combination of low agreeableness and high openness is an independent predictor of better preservation of brain volume in areas vulnerable to neurodegeneration.

Association of Repeated Antibiotic Exposure Up to Age 4 Years With Body Mass at Age 4.5 Years

Antibiotic exposures in early life may affect weight by altering gut microbiota, potentially increasing the likelihood of childhood obesity. To examine whether repeated antibiotic exposure by age 48 months is associated with higher body mass index (BMI) at age 54 months. This research was undertaken within a prospective cohort study in New Zealand (Growing Up in New Zealand) that recruited 6853 children antenatally during 2009 to 2010. At the 54-month follow-up, 5734 of 6156 children (93%) had their weight and height measured. Community pharmacy antibiotic dispensing data were obtained from the New Zealand Pharmaceutical Collection database for children whose parents consented to external data linkage. The analytic sample comprised singletons with 54-month weight and height measurements, community antibiotic dispensing and birth weight data, gestational age greater than 27 weeks, and no congenital anomalies. Data analysis took place from 2017 to 2018. Antibiotic exposure (yes or no), the number of dispensings, age at first exposure, and timing (age) of exposures between birth and age 48 months. World Health Organization BMI-for-age z scores; and International Obesity Task Force overweight and obesity cutoff points that pass through adult BMI values of 25 and 30. Of the 5128 singletons (2622 [51%] male; mean [SD] birth weight of 3527 [542] g), 4886 (95%) had an antibiotic prescription by age 48 months and 437 (9%) had obesity at age 54 months. Adjusted mean (SE) BMI-for-age z scores increased significantly with the number of antibiotic dispensings for 4 to 6, 7 to 9, and more than 9 dispensings (unexposed, 0.87 [0.09]; 1-3 exposures, 0.92 [0.06] [P = .57]; 4-6 exposures, 1.06 [0.06] [P = .02]; 7-9 exposures, 1.06 [0.06] [P = .02]; >9 exposures, 1.08 [0.05] [P = .01]). Additionally, receiving more than 9 dispensings was associated with greater likelihood of obesity compared with no exposure (adjusted odds ratio, 2.41; 95% CI, 1.07-5.41). Children whose exposure began in the first year of life had a higher adjusted mean (SD) BMI-for-age z score than those not exposed (1.06 [0.05] vs 0.89 [0.09]; P = .03), whereas those whose exposure commenced after the first year of life did not (1.02 [0.06] vs 0.89 [0.09]; P = .10). In this study, repeated antibiotic exposure in early childhood was associated with higher mean BMI-for-age z score and an increased likelihood of obesity. Future research could examine whether interventions such as antibiotic stewardship programs, which are designed to reduce overprescribing of antibiotics, also reduce early childhood obesity.

Metabolic Syndrome With Aortic Arterial Stiffness And First Hospitalization Or Mortality In Coronary Artery Disease Patients.

PurposeMetabolic syndrome (MetS) and aortic arterial stiffness (AS) are risk factors for future cardiovascular events. We evaluated their roles in first hospitalization or all-cause mortality prediction in coronary artery disease (CAD) patients.Patients and methodsFrom January to December 2012, 115 CAD patients were enrolled from a single center and followed up for 5.5 years. The composite endpoint included hospitalization for unstable angina, myocardial infarction, revascularization, or heart failure and all-cause mortality. Patients with carotid-femoral pulse wave velocity > 10 m/s (measured using applanation tonometry) constituted the high AS group.ResultsDuring a median 54-month follow-up, there were 43 (37.4%) and 11 (9.6%) hospitalization and mortality events, respectively. Overall, 41 (35.7%) and 70 (60.9%) patients were diagnosed with AS and MetS, respectively. CAD patients with high AS had higher diabetes and MetS percentages, were older, and had higher waist circumference and systolic blood pressure (SBP) but lower glomerular filtration rate than those with low AS. Multivariate logistic regression analysis revealed old age (P < 0.001), diabetes (P = 0.003), and high waist circumference (P = 0.044) and SBP (P = 0.007) as independent predictors of AS in CAD patients. Kaplan–Meier analysis showed that CAD patients with concurrent MetS and high AS had a higher risk for hospitalization (log rank test, P = 0.005) or developing all-cause mortality (log rank test, P = 0.002). Compared with CAD patients without MetS or AS, composite outcome development risk in those with both the conditions was 10.2-fold higher (P < 0.001); this risk was 6.54-fold higher in those with AS alone (P = 0.007).ConclusionIn CAD patients, age, diabetes, and high waist circumference and SBP are the independent predictors of AS. Additionally, CAD patients with AS with and without MetS have a high first hospitalization or all-cause mortality development risk.

Long-term Outcomes of the Effects of Home Blood Pressure Telemonitoring and Pharmacist Management on Blood Pressure Among Adults With Uncontrolled Hypertension

Hypertension is a leading cause of cardiovascular disease. The results were previously reported of a trial of home blood pressure (BP) telemonitoring and pharmacist management intervention in which the interventions stopped after 12 months. There were significantly greater reductions in systolic BP (SBP) in the intervention group than in the usual care group at 6, 12, and 18 months (-10.7, -9.7, and -6.6 mm Hg, respectively). To examine the durability of the intervention effect on BP through 54 months of follow-up and to compare BP measurements performed in the research clinic and in routine clinical care. Follow-up of a cluster randomized clinical trial among 16 primary care clinics and 450 patients with uncontrolled hypertension in a large health system from March 2009 to November 2015. A home BP telemonitoring intervention with pharmacist management or usual care. Change from baseline to 54 months in SBP and diastolic BP (DBP) measured as the mean of 3 measurements obtained at each research clinic visit. Among 450 patients, 228 (mean [SD] age, 62.0 [11.7] years; 54.8% male) were randomized to the telemonitoring intervention and 222 (mean [SD] age, 60.2 [12.2] years; 55.9% male) to usual care. Research clinic BP measurements were obtained from 326 of 450 (72.4%) study patients at the 54-month follow-up visit, including 162 (mean [SD] age, 62.0 [11.1] years; 54.9% male) randomized to the telemonitoring intervention and 164 (mean [SD] age, 60.0 [11.2] years; 57.3% male) to usual care. Routine clinical care BP measurements were obtained from 439 of 450 (97.6%) study patients at 6248 visits during the follow-up period. Based on research clinic measurements, baseline mean SBP was 148 mm Hg in both groups. In the intervention group, mean SBP at 6-, 12-, 18-, and 54-month follow-up was 126.7, 125.7, 126.9, and 130.6 mm Hg, respectively. In the usual care group, mean SBP at 6-, 12-, 18-, and 54-month follow-up was 136.9, 134.8, 133.0, and 132.6 mm Hg, respectively. The differential reduction by study group in SBP from baseline to 54 months was -2.5 mm Hg (95% CI, -6.3 to 1.2 mm Hg; P = .18). The DBP followed a similar pattern, with a differential reduction by study group from baseline to 54 months of -1.0 mm Hg (95% CI, -3.2 to 1.2 mm Hg; P = .37). The SBP and DBP results from routine clinical measurements suggested significantly lower BP in the intervention group for up to 24 months. This intensive intervention had sustained effects for up to 24 months (12 months after the intervention ended). Long-term maintenance of BP control is likely to require continued monitoring and resumption of the intervention if BP increases. ClinicalTrials.gov Identifier: NCT00781365.

Does psychedelic drug use reduce risk of suicidality? Evidence from a longitudinal community-based cohort of marginalised women in a Canadian setting

ObjectiveThis study aimed to longitudinally investigate whether ever having used a psychedelic drug can have a protective effect on incidence of suicidality among marginalised women.DesignLongitudinal community-based cohort study.SettingData were drawn...

Transarterial embolization with bleomycin for symptomatic hepatic focal nodular hyperplasia.

We aimed to evaluate the therapeutic effect and safety of transarterial embolization using bleomycin-iodinated oil and polyvinyl alcohol particles for the treatment of symptomatic hepatic focal nodular hyperplasia (FNH). This retrospective study included 23 consecutive patients with symptomatic hepatic FNH, who underwent embolization using bleomycin-iodinated oil and polyvinyl alcohol particles between January 2005 and December 2012. Patients were followed-up with radiologic and clinical evaluation. Therapeutic effects including changes in lesion size and symptomatic improvement were evaluated after the procedure. Embolization was performed for 27 lesions in 23 patients. Follow-up period ranged from three months to 89 months. The mean lesion diameters decreased significantly from 5.0±2.4 cm to 3.2±1.5 cm at 3-9 months after embolization (P < 0.001). Five lesions had complete resolution in the follow-up period. The clinical symptoms were significantly relieved in all patients. Contrast-enhanced scans at follow-up showed complete lack of residual arterial blood supply in the majority of lesions. Local recurrence was found in one treated lesion at the 54-month follow-up. There were no major complications associated with the procedure. Transarterial embolization using bleomycin-iodinated oil and polyvinyl alcohol particles for hepatic FNH is a safe and effective alternative treatment with good long-term symptomatic control and reduction in lesion size after embolization.

Non-pegylated doxorubicin plus capecitabine as first-line treatment in metastatic breast cancer

Purpose: To determine the toxicity and efficacy profile of non-pegylated doxorubicin in combination with capecitabine administered according to LipAX regimen. Materials and methods: The analysis included 5 female patients undergoing first-line treatment for metastatic breast cancer. Patients received non-pegylated doxorubicin intravenously and oral capecitabine at usual doses used for monotherapy, until disease progression or unacceptable toxicity. Results: Patients received a total of 26 complete treatment cycles according to LipAX regimen. During treatment, 15 toxicities occurred, including 7 adverse events with grade 3 severity. Only two haematological toxicities were observed, and the other 13 were of a non-haematological nature. Only one patient experienced no adverse events. Apart from symptomatic treatment, the capecitabine dose was reduced twice and the non-pegylated doxorubicin once. Positive clinical outcomes were observed in 4 patients, and disease progression was reported in the case of 1 patient in the course of the treatment. The median time to disease progression was 10.4 months, and the median overall survival was 34.2 months. During the 54-month follow-up, 4 of the patients died. The surviving patient continues treatment. Conclusions: Therapy according to the LipAX regimen was relatively well tolerated, however, since the majority of patients discontinued treatment due to adverse events, and not disease progression, an adequate reduction in the cytostatic doses should be considered. The use of the LipAX regimen may contribute to the achievement of long-term remission in some patients, a fact that encourages further studies on this form of therapy.

The Simplified Acute Physiology Score II as a Predictor of Mortality in Patients Who Underwent Extracorporeal Membrane Oxygenation for Septic Shock

The use of extracorporeal membrane oxygenation (ECMO) for patients with septic shock is controversial. The outcomes are favorable in children but heterogeneous in adults. The present study aimed to analyze the outcomes of adult patients who underwent ECMO for septic shock, and to determine the factors associated with prognosis. We respectively reviewed the medical records of patients who underwent ECMO for septic shock between January 2007 and December 2013. Patients were divided into survivor and nonsurvivor groups based on survival to hospital discharge. The patient characteristics before and during ECMO were compared between the groups. Independent risk factors for mortality were evaluated using multivariate logistic regression, receiver-operating characteristic curves, and Kaplan-Meier analysis. Twenty-eight patients were treated with venoarterial (n= 21), venovenous (n= 4), or venoarteriovenous (n= 3) mode ECMO. The overall survival rate to hospital discharge was 35.7%. The Simplified Acute Physiology Score II (SAPS II) and prealbumin were predictors of survival to hospital discharge. The optimal cutoff value for SAPS II was 80 (area under the curve 0.80, p= 0.010). Kaplan-Meier survival curves showed that the cumulative survival rate at hospital discharge and at 54-month follow-up was significantly higher among patients with SAPS II of 80 or less compared with patients with SAPS II greater than 80 (66.7% versus 12.5% and 58.3% versus 12.5%, respectively; p= 0.001). It is still difficult to conclude whether ECMO should be recommended as therapy for adult patients with septic shock. However, a SAPS II score of 80 or less may be an indicator of favorable outcomes with the use of ECMO.

Predicting Alzheimer disease from a blood-based biomarker profile: A 54-month follow-up.

We assessed a blood-based signature, which previously demonstrated high accuracy at stratifying individuals with high or low neocortical β-amyloid burden (NAB), to determine whether it could also identify individuals at risk of progression to Alzheimer disease (AD) within 54 months. We generated the blood-based signature for 585 healthy controls (HCs) and 74 participants with mild cognitive impairment (MCI) from the Australian Imaging, Biomarkers and Lifestyle Study who underwent clinical reclassification (blinded to biomarker findings) at 54-month follow-up. The individuals were split into estimated high and low NAB groups based on a cutoff of 1.5 standardized uptake value ratio. We assessed the predictive accuracy of the high and low NAB groupings based on progression to mild cognitive impairment or AD according to clinical reclassification at 54-month follow-up. Twelve percent of HCs with estimated high NAB progressed in comparison to 5% of HCs with estimated low NAB (odds ratio = 2.4). Forty percent of the participants with MCI who had estimated high NAB progressed in comparison to 5% of the participants with MCI who had estimated low NAB (odds ratio = 12.3). These ratios are in line with those reported for Pittsburgh compound B-PET results. Individuals with estimated high NAB had faster rates of memory decline than those with estimated low NAB. These findings suggest that a simple blood-based signature not only provides estimates of NAB but also predicts cognitive decline and disease progression, identifying individuals at risk of progressing toward AD at the prodromal and preclinical stages.

PLASMA CORTISOL, AMYLOID-B, AND COGNITIVE DECLINE IN PRECLINICAL ALZHEIMER’S DISEASE

Hypothalamic-pituitary-adrenal (HPA) axis dysregulation, which is typically assessed by measuring cortisol levels, is associated with cognitive dysfunction, hippocampal atrophy, and increased risk for mild cognitive impairment and Alzheimer's disease (AD). However, little is known about the role of HPA axis dysregulation in predicting cognitive decline or in moderating the effect of high levels of amyloid-β (Aβ) on cognitive decline in the preclinical phase of AD, which is often protracted, and thus offers opportunities for prevention and early intervention. Cognitively normal older adults (n=401) enrolled in the AIBL study underwent Aβ neuroimaging at a single timepoint. Plasma cortisol levels were obtained through a fasted blood draw. Comprehensive neuropsychological evaluation yielding measure of global cognition, episodic memory, executive function, language and attention were conducted at baseline and at 18-, 36-, and 54-month follow-up assessments. High plasma cortisol levels at baseline were associated with 2.2 times the risk of Aβ+. Furthermore, high levels of cortisol were associated with greater decline in global cognition generally, and were also found to increase the effect of Aβ+ on decline in global cognition, episodic memory, and attention. Specifically, compared to Aβ+ older adults with low cortisol, Aβ+ older adults with high cortisol had significantly faster decline on these measures, with Cohen's d values of 0.69 for episodic memory, 0.42 for global cognition and 0.31 for attention. These effects were independent of age, education, premorbid intelligence, APOE and BDNF genotypes, subjective memory complaints, vascular risk factors, and depression and anxiety symptoms. In cognitively normal older adults, high plasma cortisol levels are associated with greater decline in global cognition, and accelerate the effect of Aβ+ on decline in global cognition, episodic memory, and attention over at 54-month period. These results suggest that therapies targeted toward lowering plasma cortisol and Aβ levels may help mitigate cognitive decline in the preclinical phase of AD.

Proximal femoral excision with interposition myoplasty for cerebral palsy patients with painful chronic hip dislocation.

PurposeProximal femoral excision is a salvage procedure for painful chronic hip dislocation in cerebral palsy (CP) patients. The primary objective of this article is to describe our experience of an amplified interposition myoplasty, with appropriate peri-operative pain and tone management strategies, in a cohort of non-ambulatory CP patients with painful chronic hip dislocation. Our secondary objective is to present the clinical outcomes of these patients.MethodsWe describe our experience in 20 CP patients (25 procedures) at mean 54-month (range 27–169) follow-up with a surgical technique that includes an augmented interposition myoplasty and tone management. The indications for surgery were pain (21 hips), poor sitting tolerance (11) and difficulty with perineal care (8).ResultsThe mean age was 22 years (range 10–40) with 11 patients Gross Motor Function Classification Scale (GMFCS) IV and 9 patients GMFCS V. Mean length of stay was 13 days (3–35). One procedure required revision at 12 months. Mean pain score improved from 7.8 (5–10) pre-operatively to 2.8 (1–5) post-operatively (p < 0.001). Sitting tolerance improved in all patients and in 75 % (15) perineal care was easier.ConclusionsOur interposition myoplasty technique with individualised pain/tone management has good outcomes in this cohort of patients with multiple co-morbidities.Electronic supplementary materialThe online version of this article (doi:10.1007/s11832-015-0662-z) contains supplementary material, which is available to authorized users.

HIV/STI risk-reduction intervention efficacy with South African adolescents over 54 months.

Little research has tested HIV/sexually transmitted infection (STI) risk-reduction interventions' effects on early adolescents as they age into middle and late adolescence. This study tested whether intervention-induced reductions in unprotected intercourse during a 12-month period endured over a 54-month period and whether the intervention reduced the prevalence of STIs, which increase risk for HIV. Grade 6 learners (mean age = 12.4 years) participated in a 12-month trial in Eastern Cape Province, South Africa, in which 9 matched pairs of schools were randomly selected and within pairs randomized to a theory-based HIV/STI risk-reduction intervention or an attention-control intervention. They completed 42- and 54-month postintervention measures of unprotected intercourse (the primary outcome), other sexual behaviors, theoretical constructs, and, at 42- and 54-month follow-up only, biologically confirmed curable STIs (chlamydial infection, gonorrhea, and trichomoniasis) and herpes simplex virus 2. The HIV/STI risk-reduction intervention reduced unprotected intercourse averaged over the entire follow-up period (OR = 0.42, 95% CI [0.22, 0.84]), an effect not significantly reduced at 42- and 54-month follow-up compared with 3-, 6-, and 12-month follow-ups. The intervention caused positive changes on theoretical constructs averaged over the 5 follow-ups, although most effects weakened at long-term follow-up. Although the intervention's main effect on STIs was nonsignificant, an Intervention Condition × Time interaction revealed that it significantly reduced curable STIs at 42-month follow-up in adolescents who reported sexual experience. These results suggest that theory-based behavioral interventions with early adolescents can have long-lived effects in the context of a generalized severe HIV epidemic.

Trajectories of memory decline in preclinical Alzheimer's disease: results from the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing

Memory changes in preclinical Alzheimer's disease (AD) are often characterized by heterogenous trajectories. However, data regarding the nature and determinants of predominant trajectories of memory changes in preclinical AD are lacking. We analyzed data from 333 cognitively healthy older adults who participated in a multicenter prospective cohort study with baseline and 18-, 36-, and 54-month follow-up assessments. Latent growth mixture modeling revealed 3 predominant trajectories of memory change: a below average, subtly declining memory trajectory (30.9%); a below average, rapidly declining memory trajectory (3.6%); and an above average, stable memory trajectory (65.5%). Compared with the stable memory trajectory, high Αβ (relative risk ratio [RRR] = 2.1), and lower Mini-Mental State Examination (RRR = 0.6) and full-scale IQ (RRR = 0.9) scores were independently associated with the subtly declining memory trajectory; and high Αβ (RRR = 8.3), APOE ε4 carriage (RRR = 6.1), and greater subjective memory impairment (RRR = 1.2) were independently associated with the rapidly declining memory trajectory. Compared with the subtly declining memory trajectory group, APOE ε4 carriage (RRR = 8.4), and subjective memory complaints (RRR = 1.2) were associated with a rapidly declining memory trajectory. These results suggest that the preclinical phase of AD may be characterized by 2 predominant trajectories of memory decline that have common (e.g., high Αβ) and unique (e.g., APOE ε4 genotype) determinants.