The pathophysiologic process of Alzheimer's disease (AD) begins years before the diagnosis of clinical dementia. This concept of preclinical AD has arisen from the observation of AD pathologic findings such as senile plaques and neurofibrillary tangles in the brains of people who at the time of death had normal cognitive function. Recent advances in biomarker studies now provide the ability to detect the pathologic changes of AD, which are antecedent to symptoms of the illness, in cognitively normal individuals. Functional and structural brain alterations that begin with amyloid-beta accumulation already show the patterns of abnormality seen in individuals with dementia due to AD. The presence of preclinical AD provides a critical opportunity for potential interventions with disease-modifying therapy. This review focuses on the studies of antecedent biomarkers for preclinical AD.
Aging ; Alzheimer Disease ; Biomarkers ; Brain ; Dementia ; Neurofibrillary Tangles ; Plaque, Amyloid

OBJECTIVE: Myelography has been shown to highlight foraminal and lateral recess stenosis more readily than computed tomography (CT) or magnetic resonance imaging (MRI). It also has the advantage of providing dynamic assessment of stenosis in the loaded spine. The advent of weight-bearing MRI may go some way towards improving assessment of the loaded spine and is less invasive, however availability remains limited. This study evaluates the potential role of myelography and its impact upon surgical decision making. METHODS: Of 270 patients undergoing myelography during 2006–2009, a period representing peak utilisation of this imaging modality in our unit, we identified 21 patients with degenerative scoliosis who fulfilled our inclusion criteria. An operative plan was formulated by our senior author based initially on interpretation of an MRI scan. Subsequent myelogram and CT myelogram investigations were scrutinised, with any additional abnormalities noted and whether these impacted upon the operative plan. RESULTS: From our 21 patients, 18 (85.7%) had myelographic findings not identified on MRI. Of note, in 4 patients, supine CT myelography yielded additional information when compared to supine MRI in the same patients. The management of 7 patients (33%) changed as a result of myelographic investigation. There were no complications of myelography of the total 270 analysed. CONCLUSION: MRI scan alone understates the degree of central and lateral recess stenosis. In addition to the additional stenosis displayed by dynamic myelography in the loaded spine, we have also shown that static myelography and CT myelography are also invaluable tools with regards to surgical planning in these patients.
Congenital Abnormalities ; Constriction, Pathologic ; Decision Making ; Humans ; Magnetic Resonance Imaging ; Myelography* ; Scoliosis* ; Spine ; Weight-Bearing

Background: /Aim: Endoscopic retrograde cholangiopancreatography (ERCP) training requires varying degrees of staff assistance regarding operation of the fluoroscopy machine via a foot pedal. Efficiency is important to acquire during this training due to radiation risks. In this study, we evaluate the effect of controlling endoscopy and fluoroscopy unit on duct cannulation rates (CRs) and total fluoroscopy time (FT) for fellows in training. Methods: 204 patients undergoing ERCP were randomized to one of two groups: 1) “Endoscopist Driven” group in which the endoscopist controlled the foot pedal for fluoroscopy, and 2) “Assistant Driven” group in which attending or fellow controlled the foot pedal while the other team member controlled the endoscope. Various measures including selective duct CR and total FT were recorded. Results: There was no significant difference in mean procedure duration between the two groups (32 minutes vs. 33 minutes, p=0.70). There was also no statistically significant difference in CR (83.7% vs. 77.4%, p=0.25) or FT (3.27 minutes vs. 3.54 minutes, p=0.48). Conclusions ERCP is a technically challenging procedure which requires extensive supervision. This study demonstrates that CR and FT are not affected by who controls the fluoroscopy.

PURPOSE: Body mass index (BMI) is often used to predict surgical difficulty in patients receiving total knee arthroplasty (TKA); however, BMI neglects variation in the central versus peripheral distribution of adipose tissue. We sought to examine whether anthropometric factors, rather than BMI alone, may serve as a more effective indication of surgical difficulty in TKA. MATERIALS AND METHODS: We prospectively enrolled 67 patients undergoing primary TKA. Correlation coefficients were used to evaluate the associations of tourniquet time, a surrogate of surgical difficulty, with BMI, pre- and intraoperative anthropometric measurements, and radiographic knee alignment. Similarly, Knee Injury and Osteoarthritis Outcome Score (KOOS) was compared to BMI. RESULTS: Tourniquet time was significantly associated with preoperative inferior knee circumference (p=0.025) and ankle circumference (p=0.003) as well as the intraoperative depth of incision at the quadriceps (p=0.014). BMI was not significantly associated with tourniquet time or any of the radiographic parameters or KOOS scores. CONCLUSIONS: Inferior knee circumference, ankle circumference, and depth of incision at the quadriceps (measures of peripheral obesity) are likely better predictors of surgical difficulty than BMI. Further study of alternative surgical indicators should investigate patients that may be deterred from TKA for high BMI, despite relatively low peripheral obesity.
Adipose Tissue ; Ankle ; Anthropometry ; Arthroplasty ; Arthroplasty, Replacement, Knee ; Body Mass Index ; Humans ; Knee ; Knee Injuries ; Obesity ; Osteoarthritis ; Prospective Studies ; Tourniquets

In recent years, there have been increased efforts to reduce the high maternal mortality ratio (MMR) in Papua New Guinea. This retrospective study conducted at Modilon Hospital in Papua New Guinea documented maternal and perinatal mortality over the 6 years from 2009 to 2014. In-hospital maternal mortality, though still high, significantly declined by over 50% from 24/2598 (924 per 100,000) in 2009 to 12/3217 (373 per 100,000) in 2014 (p <0.001) while stillbirth rates and early neonatal death rates remained unchanged. There is a need for an approach with interventions aimed at reducing both maternal and perinatal mortality. While monitoring and auditing of maternal deaths should be possible throughout the entire country, in settings where there is limited capacity to monitor population-based perinatal and neonatal mortality, an emphasis on improved data quality as part of hospital-and health centre-based surveillance can provide important information.

Background:Missed clinic appointments negatively impact clinic patient flow and health outcomes of people living with HIV (PLHIV).PLHIV likelihood of missing clinic appointments is associated with direct and indirect expenditures made while accessing HIV care.The objective of this study was to examine the relationship between out-of-pocket (OOP) health expenditures and the likelihood of missing appointments.Method:Totally 618 PLHIV older than 18 years attending two HIV care and treatment centres (CTC) in Northern Tanzania were enrolled in the study.Clinic attendance and clinical characteristics were abstracted from medical records.Information on OOP health expenditures,demographics,and socio-economic factors were self-reported by the participants.We used a hurdle model.The first part of the hurdle model assessed the marginal effect of a one Tanzanian Shillings (TZS) increase in OOP health expenditure on the probability of having a missed appointment and the second part assessed the probability of having missed appointments for those who had missed an appointment over the study period.Results:Among these 618 participants,242 (39％) had at least one missed clinic appointment in the past year.OOP expenditure was not significantly associated with the number of missed clinic appointments.The median amount of OOP paid was 5100 TZS per visit,about 7％ of the median monthly income.Participants who were separated from their partners (adjusted odds ratio[AOR]=1.83,95％ confidence interval[CI]:1.11-8.03) and those aged above 50 years (AOR =2.85,95％ CI:1.01-8.03) were significantly associated with missing an appointment.For those who had at least one missed appointment over the study period,the probability of missing a clinic appointment was significantly associated with seeking care in a public CTC (P =0.49,95％ CI:0.88-0.09) and aged between ＞ 25-35 years (P =0.90,95％ CI:0.11-1.69).Conclusion:Interventions focused on improving compliance to clinic appointments should target public CTCs,PLHIV aged between ＞ 25-35 years,above 50 years of age and those who are separated from their partners.

Objective: Brainstem segmentation has been useful in identifying potential imaging biomarkers for diagnosis and progression in atypical parkinsonian syndromes (APS). However, the majority of work has been performed using manual segmentation, which is time consuming for large cohorts. Methods: We investigated brainstem involvement in APS using an automated method. We measured the volume of the medulla, pons, superior cerebellar peduncle (SCP) and midbrain from T1-weighted MRIs in 67 patients and 42 controls. Diagnoses were corticobasal syndrome (CBS, n = 14), multiple system atrophy (MSA, n = 16: 8 with parkinsonian syndrome, MSA-P; 8 with cerebellar syndrome, MSA-C), progressive supranuclear palsy with a Richardson’s syndrome (PSP-RS, n = 12), variant PSP (n = 18), and APS not otherwise specified (APS-NOS, n = 7). Results: All brainstem regions were smaller in MSA-C (19–42% volume difference, p < 0.0005) and in both PSP groups (18–33%, p < 0.0005) than in controls. MSA-P showed lower volumes in all regions except the SCP (15–26%, p < 0.0005). The most affected region in MSA-C and MSA-P was the pons (42% and 26%, respectively), while the most affected regions in both the PSP-RS and variant PSP groups were the SCP (33% and 23%, respectively) and midbrain (26% and 24%, respectively). The brainstem was less affected in CBS, but nonetheless, the pons (14%, p < 0.0005), midbrain (14%, p < 0.0005) and medulla (10%, p = 0.001) were significantly smaller in CBS than in controls. The brainstem was unaffected in APS-NOS. Conclusion Automated methods can accurately quantify the involvement of brainstem structures in APS. This will be important in future trials with large patient numbers where manual segmentation is unfeasible.

Purpose: Prostate cancer (PCa) screening can lead to potential over-diagnosis/over-treatment of indolent cancers. There is a need to optimize practices to better risk-stratify patients. We examined initial longitudinal outcomes of mid-life men with an elevated baseline prostate-specific antigen (PSA) following initiation of a novel screening program within a system-wide network. Materials and Methods: We assessed our primary care network patients ages 40 to 49 years with a PSA measured following implementation of an electronic health record screening algorithm from 2/2/2017–2/21/2018. The multidisciplinary algorithm was developed taking factors including age, race, family history, and PSA into consideration to provide a personalized approach to urology referral to be used with shared decision-making. Outcomes of men with PSA ≥1.5 ng/mL were evaluated through 7/2021. Statistical analyses identified factors associated with PCa detection. Clinically significant PCa (csPCa) was defined as Gleason Grade Group (GGG) ≥2 or GGG1 with PSA ≥10 ng/mL. Results: The study cohort contained 564 patients, with 330 (58.5%) referred to urology for elevated PSA. Forty-nine (8.7%) underwent biopsy; of these, 20 (40.8%) returned with PCa. Eleven (2.0% of total cohort and 55% of PCa diagnoses) had csPCa. Early referral timing (odds ratio [OR], 4.58) and higher PSA (OR, 1.07) were significantly associated with PCa at biopsy on multivariable analysis (both p<0.05), while other risk factors were not. Referred patients had higher mean PSAs (2.97 vs. 1.98, p=0.001). Conclusions Preliminary outcomes following implementation of a multidisciplinary screening algorithm identified PCa in a small, important percentage of men in their forties. These results provide insight into baseline PSA measurement to provide early risk stratification and detection of csPCa in patients with otherwise extended life expectancy. Further follow-up is needed to possibly determine the prognostic significance of such mid-life screening and optimize primary care physician-urologist coordination.