Test–retest repeatability of [18F]Flortaucipir PET in Alzheimer’s disease and cognitively normal individuals

The aim of this study was to investigate the test–retest (TRT) repeatability of various parametric quantification methods for [¹⁸F]Flortaucipir positron emission tomography (PET). We included eight subjects with dementia or mild cognitive impairment due to Alzheimer’s disease and six cognitively normal subjects. All underwent two 130-min dynamic [¹⁸F]Flortaucipir PET scans within 3 ± 1 weeks. Data were analyzed using reference region models receptor parametric mapping (RPM), simplified reference tissue method 2 (SRTM2) and reference logan (RLogan), as well as standardized uptake value ratios (SUVr, time intervals 40–60, 80–100 and 110–130 min post-injection) with cerebellar gray matter as reference region. We obtained distribution volume ratio or SUVr, first for all brain regions and then in three tau-specific regions-of-interest (ROIs). TRT repeatability (%) was defined as |retest–test|/(average (test + retest)) × 100. For all methods and across ROIs, TRT repeatability ranged from (median (IQR)) 0.84% (0.68–2.15) to 6.84% (2.99–11.50). TRT repeatability was good for all reference methods used, although semi-quantitative models (i.e. SUVr) performed marginally worse than quantitative models, for instance TRT repeatability of RPM: 1.98% (0.78–3.58) vs. SUVr_80–100: 3.05% (1.28–5.52), p < 0.001. Furthermore, for SUVr_80–100 and SUVr_110–130, with higher average SUVr, more variation was observed. In conclusion, while TRT repeatability was good for all models used, quantitative methods performed slightly better than semi-quantitative methods.     

Risk Factors and Hospitalization Costs of Dementia Patients: Examining Race and Gender Variations

Aims:

To examine the variation in risk factors and hospitalization costs among four elderly dementia cohorts by race and gender.

Materials and Methods:

The 2008 Tennessee Hospital Discharged database was examined. The prevalence, risk factors and cost of inpatient care of dementia were examined for individuals aged 65 years and above, across the four race gender cohorts - white males (WM), black males (BM), white females (WF), and black females (BF).

Results:

3.6% of patients hospitalized in 2008 had dementia. Dementia was higher among females than males, and higher among blacks than whites. Further, BF had higher prevalence of dementia than WF; similarly, BM had a higher prevalence of dementia than WM. Overall, six risk factors were associated with dementia for the entire sample including HTN, DM, CKD, CHF, COPD, and stroke. These risk factors varied slightly in predicting dementia by race and gender. Hospital costs were 14% higher among dementia patients compared to non-dementia patients.

Conclusions:

There exist significant race and gender disparities in prevalence of dementia. A greater degree of co-morbidity, increased duration of hospital stay, and more frequent hospitalizations, may result in a higher cost of inpatient dementia care. Aggressive management of risk factors may subsequently reduce stroke and cost of dementia care, especially in the black population. Race and gender dependent milestones for management of these risk factors should be considered.     

Urinary C-peptide creatinine ratio to detect absolute insulin deficiency in type 2 diabetes

BackgroundNational Institute for Health and Clinical Excellence guidelines (CG87) recommend neutral protamine hagedorn (NPH) insulin for the provision of basal insulin in type 2 diabetes, but use of analogue insulin is as much as 40%. Where residual endogenous insulin secretory capacity is present there is no evidence that analogue insulins provide any additional benefit over human insulins, and they come at an expensive premium. Anecdotally, however, there is a reluctance to switch people back to NPH insulin, partly because of a perceived risk of pancreatic failure and potential ketosis. Urinary C-peptide creatinine ratio (UCPCR) has been validated as a method for evaluating residual endogenous insulin secretion in type 1 and type 2 diabetes, with a UCPCR of no more than 0·2 nmol/mmol suggestive of absolute insulin deficiency. We aimed to evaluate the prevalence of true insulin deficiency among patients with type 2 diabetes with UCPCR, and confirm findings with the gold standard mixed meal tolerance test (MMTT).Methods191 insulin-treated patients with a clinical diagnosis of type 2 diabetes (diagnosed at or after age 45 years and who did not start insulin within the first year of diagnosis) collected a 2-h post-prandial urine sample for UCPCR measurement. Nine patients from two subgroups (UCPCR ≤0·2 nmol/mmol and UCPCR >0·2) completed a standard MMTT.Findings11 (5·8%) of 191 patients had two consistent UCPCRs of less than or equal to 0·2 nmol/mmol. Nine were able to do the MMTT, of whom five were confirmed to have absolute insulin deficiency (stimulated serum c-peptide <0·2 nmol/L). Three of these five patients were glutamic acid decarboxylase antibody-negative. Nine of nine patients with UCPCR of more than 0·2 nmol/L had confirmed endogenous insulin secretion in their MMTT. Those with insulin deficiency had a shorter time to starting insulin (median 2·5 years [IQR 1·5–3·0] vs 6·0 [3·0–10·75], p=0·005) and lower body-mass index (25 kg/m² vs 29, p=0·04) but no other significant differences in clinical characteristics.InterpretationWe have demonstrated a very low prevalence of true pancreatic failure in this population of insulin-treated patients with type 2 diabetes. This requires further exploration by comparison of a population being treated with NPH insulin with one on analogue insulin, and then determining whether UCPCR could act as a clinical decision support tool to safely switch from analogue insulin to NPH insulin.FundingNational Institute for Health Research.     

A radioreceptor assay for quantitating plasma factor VIII/von Willebrand's protein

A sensitive and precise radioreceptor assay for determining plasma levels of human factor VIII/von Willebrand's factor (FVIII/vWF) has been developed by taking advantage of the FVIII/vWF receptor sites on human platelets. Paraformaldehyde-fixed platelets, which were processed and then stored, retained FVIII/vWF binding activity and therefore could be used as a convenient source of receptors. The human plasma samples to be tested were initially filtered on 4% agarose columns to concentrate the FVIII/vWF protein in the void volume and to remove the factor(s) that interferes with the assay. The percent recovery of FVIII/vWF in the pooled eluent was measured by the recovery of added trace 125I-FVIII/vWF. The coefficients of intra- and interassay variation were 6% and 10%, respectively. The plasma FVIII/vWF concentrations determined by the assay for pooled normal plasma, hemophilia A plasma, and plasmas from two patients with von Willebrand's disease were 16.3 +/- 0.5, 52.6 +/- 1.5, 6.8 +/- 0.8, and 3.2 +/- 0.2 microgram/ml, respectively. The range of plasma FVIII/vWF concentrations varied between 8.3 microgram/ml and 24.9 microgram/ml for 10 normal adults. The plasma FVIII/vWF concentrations determined by the radioreceptor assay correlated well with levels measured by the ristocetin-induced platelet aggregation method, thus demonstrating the functional relevancy of the radioreceptor assay for plasma FVIII/vWF.     

Molecular characterization of human factor XSan Antonio

Enzymatic amplification technique was used to isolate all eight exons and sequences around the splice junctions, putative promoter, and polyadenylation sites of human factor X DNA from a patient with factor X deficiency. Two genetic changes in factor X have been observed in this patient. The patient is most likely a compound heterozygote since there is only 14% activity associated with factor X. A point mutation that resulted in the substitution of cysteine (TGC) for arginine (CGC) at amino acid 366 was found in exon VIII of one allele of the factor X gene. This mutation, which occurs in the catalytic domain, can affect the formation of a disulfide bridge and thus could result in a reduction in factor X activity. Sequencing all the regions revealed a second mutation: a deletion of one nucleotide (TCCT to TCT) in exon VII that would cause a frame shift at amino acid 272 followed by termination. We have also shown that the point mutation in exon VIII creates an ApaL1 restriction site and destroys the HinP1 site. Enzymatic DNA amplification followed by restriction digestion provides a quick, reliable, and sensitive method for carrier detection and antenatal diagnosis in affected kindreds. This is the first characterization of factor X deficiency at the molecular level. We propose to name this mutation Factor XSan Antonio.     

Efficacy and Safety of Terbinafine Hydrochloride 1% Cream vs. Sertaconazole Nitrate 2% Cream in Tinea Corporis and Tinea Cruris: A Comparative Therapeutic Trial

Context:

To the best of our knowledge, till date no study comparing the efficacy and safety of terbinafine hydrochloride 1% cream and sertaconazole nitrate 2% cream has been done in localized tinea corporis and tinea cruris.

Aims:

This clinical trial was carried out to study and compare the efficacy of topical terbinafine hydrochloride 1% cream and sertaconazole nitrate 2% cream in localized tinea corporis and tinea cruris and to know the adverse effects of these antifungal creams.

Settings and Design:

In this prospective, single blind, randomized control trial with two arms, patient were randomized into two groups Group A (treatment with terbinafine cream) and Group B (treatment with sertaconazole cream). A total of 38 patients were enrolled for the study, 20 patients in group A and 18 patients in group B. But five patients of group A and three patients of group B were lost for follow-ups. Therefore sample size was of 30 patients with 15 patients in group A and group B each.

Materials and Methods:

Patients in group A and B were treated with twice daily topical 1% terbinafine hydrochloride and 2% sertaconazole nitrate cream respectively for a total duration of three weeks. Clinical improvement in signs and symptoms of each clinical parameter, namely itching, erythema, papules, pustules, vesicles, and scaling were graded weekly and clinical cure was assessed. KOH mount and culture was done weekly up to 3 weeks to access mycological cure. Fungal culture was done on Sabouraud''s dextrose agar with chloramphenicol and cycloheximide.

Statistical Analysis Used:

Statistical analysis was done using students paired and unpaired t-tests from the data obtained.

Results:

Comparison between Group A and Group B for complete cure (clinical and mycological) showed that at the end of 3 weeks both terbinafine and sertaconazole groups had 100% complete cure. When the two groups were compared for complete cure, at the end of 1^st and 2^nd week, statistically non-significant results were observed (P = 0.461 and P = 0.679 respectively). However, at the end of 2^nd week, complete cure rate for terbinafine was 80% as compared to 73.35% for sertaconazole with no statistical significance. In both Group A and Group B, clinically significant local side effects like erythema, swelling, stinging sensation, or increased itching were not noticed. A majority of our patients in both the group showed Trichophyton rubrum followed by Trichophyton mentagrophytes growth on culture. In Group A, 11 patients showed growth of T. rubrum, 2 patients showed growth of T. mentagrophytes, and 1 patient had only KOH test positive. In Group B, 10 patients revealed growth of T. rubrum, followed by growth of T. mentagrophytes in 3 and Microsporum canis in 2 patients. The therapeutic response is more or less same in infection with different species.

Conclusions:

The newer fungistatic drug sertaconazole nitrate 2% cream was as effective as terbinafine hydrochloride 1% cream which is one of the fungicidal drugs, though terbinafine hydrochloride 1% cream has higher rates of complete cure at the end of 2 weeks as compared to sertaconazole nitrate 2% cream. Both the drugs showed good tolerability with no adverse effects.     

Effect of Community-based Behavior Change Communication on Delivery and Newborn Health Care Practices in a Resettlement Colony of Delhi

Background:

Neonatal morbidity and mortality in India continue to be high. Among other reasons, newborn care practices are major contributors for such high rates.

Objective:

To assess the effect of behavior change communication (BCC) package among pregnant women regarding neonatal care.

Materials and Methods:

Semistructured and pretested schedule was used to interview 200 multigravidas on various aspects of neonatal care. Based on the preliminary data, BCC package was designed and implemented in intervention block in the community. Follow-up was done to find out change in their behavior.

Statistical Analysis:

Data were analyzed using Epi info and Fischer exact test and chi-square test were applied in the baseline data. A P value of less than 0.05 was considered significant. Effect of the BCC package is given in terms of relative risk.

Results:

BCC package increased 1.76 times higher number of deliveries conducted by trained dais in intervention group. There was significant improvement in using sterile cord tie (P = 0.01), applied nothing to the cord (P < 0.0001) and giving bath to their baby within 6 h of birth (P = 0.02) in intervention group as compared to nonintervention group. Significant difference was found between the two groups with regard to breastfeeding practices of baby. Harmful practices were reduced in the intervention group. Significant improvement was found in intervention group as compared to nonintervention group with regard to knowledge of danger signals, physiological variants, management of breastfeeding-related problems, and awareness of skin-to-skin technique for the management of hypothermic baby.

Conclusion:

Inadequate knowledge and adverse practices regarding neonatal care among mothers in study areas were found. BCC package had favorable impact on behavior of mothers for neonatal care in intervention group.     

Bronchial artery embolization: monitoring with somatosensory evoked potentials. Work in progress

Surgery remains the treatment of choice for massive and recurrent hemoptysis. In some instances, however, immediate surgical intervention is contraindicated. In these situations, bronchial artery embolization (BAE) has proved to be a successful definitive treatment for non-surgical candidates and a palliative therapy in patients requiring hemodynamic stabilization prior to surgery. The most serious complication of BAE is spinal cord ischemia. This relates directly to the potential anastomotic connections between the bronchial circulation and the anterior spinal artery. Somatosensory evoked potentials (SSEPs) have been used in the past to monitor spinal cord ischemia during procedures that threaten the vascularity of the spinal cord. The authors report two cases in which SSEPs were employed to monitor spinal cord ischemia during bronchial artery embolization.