Cerebral Phospho-Tau Acts Synergistically with Soluble Aß42 Leading to Mild Cognitive Impairment in AAV-AD Rats.

BACKGROUND: Alzheimer's disease (AD) is a continuum of events beginning with an increase in brain soluble Aß42 followed by the appearance of hyperphosphorylated tau (P-tau, asymptomatic stage). Mild Cognitive Impairment (MCI) then appears (prodromal stage). However, the individual contribution of these two soluble proteins in the onset of the first cognitive symptoms remains unclear. OBJECTIVES: We sought to understand the specific impact of p-tau on the development of MCI in the AAV-AD rat model, a model of late-onset Alzheimer's disease (LOAD) predementia. METHODS: We specifically reduced the phosphorylation level of tau while leaving Aß42 levels unchanged using a DYRK1A protein kinase inhibitor, Leucettine L41, in an adeno-associated virus-based Alzheimer's disease (AAV-AD) rat model. Leucettine L41 was administered by intraperitoneal injection at 20 mg/kg per day in AAV-AD rats from 9 (late asymptomatic phase) to 10 (prodromal phase) months of age. RESULTS: Decreased soluble forms of P-tau induced by chronic administration of Leucettine L41 did not change soluble Aß42 levels but prevented MCI onset in 10-month-old AAV-AD rats. CONCLUSIONS: The present study argues that P-tau is required to induce the development of MCI. Consistent with our previous findings that soluble Aß42 is also required for MCI onset, the data obtained in the AAV-AD rat model confirm that the transition from the asymptomatic to the prodromal stage may be caused by the combined presence of both soluble brain forms of Aß42 and p-tau, suggesting that the development of MCI may be the consequence of their synergistic action.

Efficacy of early use of remdesivir: a systematic review of subgroup analysis.

OBJECTIVE: A possible benefit has been suggested for early treatment of severe coronavirus disease 2019 (COVID-19) with remdesivir. The efficacy of this drug is controversial and could significantly influence the efficiency in healthcare systems. The objective is the methodological interpretation of subgroup analyzes according to starting of remdesivir treatment with respect to symptom onset of COVID-19. METHODS: A search in Pubmed® database was performed. Randomized clinical trials (RCTs) with subgroup analysis regarding early and late use of remdesivir were selected. All endpoints were assessed using two methodologies. First methodology considered statistical interaction, pre-specification, biological plausibility, and consistency of results. Second methodology was a validated tool with preliminary questions to discard subset analysis without relevant minimum conditions, and a checklist with recommendations for applicability. RESULTS: A total of 54 results were found and five RCTs were selected. According first methodology, consistent heterogeneity was only found in time to clinical improvement and better clinical status score at day 15 for patients with severe COVID-19 and <7 days of symptoms. About second methodology, these results about early use of remdesivir may be applied to clinical practice with caution. CONCLUSIONS: We developed a systematic search and application of an established methodology for interpretation of subgroup analysis about early use of remdesivir. Results in severe COVID-19 suggested that early use of remdesivir provides a greater benefit in <7 days of symptoms for time to clinical improvement and better clinical status score at day 15. Future studies could use 7-day cut-off of symptoms to evaluate remdesivir.

Management of anticoagulation in pregnant women with venous thromboembolism: An international survey of clinical practice.

INTRODUCTION: Venous thromboembolism (VTE) is an important cause of maternal morbidity and mortality. During pregnancy, VTE is treated with low-molecular-weight-heparin (LMWH). Studies assessing the optimal duration and peripartum management of therapeutic anticoagulation are lacking. This survey aimed to assess clinician practices for the management of anticoagulation in pregnant women with acute VTE. METHODS: An electronic survey consisting of clinical scenarios addressing anticoagulation management for VTE in pregnancy was created. The target sample was clinicians likely to be involved in the management of pregnant women with acute VTE. The survey completion rate and proportion of individuals selecting a response were determined. RESULTS: 96 respondents completed the survey including general internists (56.3%), hematologists (21.9%), and obstetricians (6.3%). In the management of a VTE in first or second trimester, most respondents preferred therapeutic LMWH until 6 weeks postpartum. In the first and second trimester, 48.0% and 37.5% of respondents, respectively, opted to reduce the dose of anticoagulation after 3 or 6 months. 29.2% of physicians opted for bridging with intravenous heparin around delivery when treating a VTE in the third trimester. 73.0% perceived an increased risk of clinically relevant non-major bleeding associated with the use of therapeutic anticoagulation in the peripartum and postpartum periods. CONCLUSIONS: The survey highlights a wide variability of practice in the management of therapeutic anticoagulation in pregnancy. Larger scale studies with relevant clinical outcomes including thrombosis and bleeding risks are needed to inform clinical practice.

Organizing pneumonia.

Organizing pneumonia is a nonspecific pathologic pattern of response to lung damage. It can be idiopathic, or it can occur secondary to various medical processes, most commonly infections, connective tissue disease, and pharmacological toxicity. Although there is no strict definition of the pattern of organising pneumonia as in other idiopathic interstitial pneumonias, the characteristic pattern of this disease could be considered to include patchy consolidations and ground-glass opacities in the peribronchial and subpleural areas of both lungs. Moreover, studies of the course of the disease show that these lesions respond to treatment with corticoids, migrate with or without treatment, and tend to recur when treatment is decreased or withdrawn. Other manifestations of organising pneumonia include nodules of different sizes and shapes, solitary masses, nodules with the reverse halo sign, a perilobular pattern, and parenchymal bands.

Hemorrhagic complicationes after percutaneous nephrolithotomy: The importance of an early endovascular management.

INTRODUCTION AND OBJECTIVES: Hemorrhage due to arteriovenous fistula (AVF) or pseudoaneurysm (PA) is a rare complication after percutaneous nephrolithotomy (PCNL). The objective of this study is to evaluate hemorrhagic complications (HC) after PCNL and the results of their endovascular treatment. MATERIALS AND METHODS: Between May 2009 and December 2019, 1335 PCNL were performed in our center for kidney stone disease. We analyzed the incidence of early and late HC, their management, the need for subsequent embolization, as well as clinical and analytical data of these patients. RESULTS: A total of 59 (4.4%) patients presented HC. Bleeding was managed with arteriography and selective embolization (ASE). Perirenal hematoma was seen in 38 patients (64%). Regarding angiographic findings, there were 32 (54%) PA, 8 (14%) AVF, 4 (7%) extravasations due to vascular laceration and 15 (25%) PA combined with AVF. In one case, 3 procedures were required to control the bleeding. In 30 patients (51%) blood transfusions were not necessary, while in 29 (49%), a mean of 1.3 units were transfused. Median follow-up was 24 ±â€¯21 months. Mean time interval between PCNL and ASE was 7.3 ±â€¯4.9 days. A total of 24 (41%) patients were readmitted after discharge due to late HC requiring ASE. Delay between readmission and ASE was 4.8 ±â€¯4.6 h in average. CONCLUSION: Early and late HC after PCNL can be severe. Rapid identification and treatment with ASE is an effective and minimally invasive and avoids multiple blood transfusions which in many cases constitute an insufficient treatment.

Hemorrhagic complicationes after percutaneous nephrolithotomy: The importance of an early endovascular management. / Complicaciones hemorrágicas de la nefrolitotomía percutánea: valor del tratamiento endovascular precoz.

INTRODUCTION AND OBJECTIVES: Hemorrhage due to arteriovenous fistula (AVF) or pseudoaneurysm (PA) is a rare complication after percutaneous nephrolithotomy (PCNL). The objective of this study is to evaluate hemorrhagic complications (HC) after PCNL and the results of their endovascular treatment. MATERIALS AND METHODS: Between May 2009 and December 2019, 1335 PCNL were performed in our center for kidney stone disease. We analyzed the incidence of early and late HC, their management, the need for subsequent embolization, as well as clinical and analytical data of these patients. RESULTS: A total of 59 (4.4%) patients presented HC. Bleeding was managed with arteriography and selective embolization (ASE). Perirenal hematoma was seen in 38 patients (64%). Regarding angiographic findings, there were 32 (54%) PA, 8 (14%) AVF, 4 (7%) extravasations due to vascular laceration and 15 (25%) PA combined with AVF. In one case, 3 procedures were required to control the bleeding. In 30 patients (51%) blood transfusions were not necessary, while in 29 (49%), a mean of 1.3 units were transfused. Median follow-up was 24±21 months. Mean time interval between PCNL and ASE was 7.3±4.9 days. A total of 24 (41%) patients were readmitted after discharge due to late HC requiring ASE. Delay between readmission and ASE was 4.8±4.6hours in average. CONCLUSION: Early and late HC after PCNL can be severe. Rapid identification and treatment with ASE is an effective and minimally invasive and avoids multiple blood transfusions which in many cases constitute an insufficient treatment.

Posterior pelvic tilt evolution in patients undergoing total hip arthroplasty. A minimum 5-years follow-up clinico-radiological study. / Evolución de la inclinación pélvica a lo largo del tiempo en pacientes intervenidos de prótesis total de cadera. Estudio clínico-radiológico con un seguimiento mínimo de cinco años.

BACKGROUND AND OBJECTIVE: Pelvic tilt influences the relative position between total hip arthroplasty (THA) components. Changes in lumbar spine over time may affect clinical and radiological outcomes of THA during follow-up. We assessed the evolution of pelvic tilt and cup position after THA for a minimum follow-up of five years and the possible appearance of complications. MATERIAL AND METHODS: This retrospective study includes 48 patients operated between 2008 and 2012. Clinical data, complication and radiological analysis included sacro-femoral-pubic and acetabular abduction angles on the anteroposterior pelvic view; and cup anteversion angle on the lateral cross-table hip view according to Woo and Morrey. All assessments were done pre-operatively and at 6 weeks, one, two and five years post-operatively. RESULTS: Mean sacro-femoral-pubic decreased from 60.6∘ preoperatively to 58.8∘ at five years (p > .05), more in females (from 63.3 to 59.3) than males (58.7 to 58.3). Acetabular abduction increased from 47.3 at six-week postoperatively to 48.2 at five years (p > .05) and acetabular anteversion varied from 24.3∘ to 36.1∘ (p < .04). There were four dislocations: one late recurrent dislocation which required cup revision. CONCLUSION: Despite the sacro-femoral-pubic angle tendency to decrease and anteversion tendency to increase after five years, larger studies with longer follow-up are needed to confirm the potential increasing in long term complications.

Safety considerations during prescription of non-steroidal anti-inflammatory drugs (NSAIDs), through a review of systematic reviews.

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs worldwide. This makes it necessary to carry out a comprehensive synthesis of the available evidence on the safe and adequate prescription of NSAIDs in patients with cardiovascular disease, chronic kidney disease, hypertension, heart failure or liver cirrhosis and in general population. For this, a review of systematic reviews was carried out. Data extraction and analysis were performed independently by two reviewers and a narrative synthesis of the results was carried out. The use of NSAIDs is associated with a significantly higher probability of hepatotoxicity and kidney damage, as well as increased risk of exacerbation of heart failure. Taking into account the increased cardiovascular, liver and kidney risk, the prescription of NSAIDs should be carried out with caution, considering the treatment duration and the patient's situation. For this reason, patients should be informed about their possible health consequences as well as ensuring adequate monitoring of them.

Association between xerostomia, oral and general health, and obesity in adults. A cross-sectional pilot study.

BACKGROUND: The objective of this study was to analyse the association between oral and general health variables and obesity indicators with the sensation of dry mouth or xerostomia as evaluated on the Xerostomia Inventory (XI). MATERIAL AND METHODS: A total of 354 randomly selected subjects participated in this cross-sectional pilot study and completed an anonymous questionnaire. Anthropometric, clinical, and xerostomic variables were evaluated. Kruskal-Wallis, ANOVA and Bonferroni test were used for multiple comparisons. ROC curves and multinomial logistic regression were used to determine the (OR) risk of xerostomia. RESULTS: A total of 30.7 % of respondents reported xerostomia based on XI. The dry mouth question, the XI taken as a "gold standard", showed a diagnostic sensitivity of 70.37 %, and a specificity of 83.27 % (AUC=0.768, p<0.001). Logistical regression showed the highest xerostomia OR was associated to patients with bad self-perceived health, 6.31 (CI 95% 2.89-13.80, p<0.001). In the model adjusted for tooth mobility, bone or respiratory diseases, and the consumption of anxiolytics and antidepressants, the OR was 3.46 (CI 95% 1.47-8.18, p=0.005). CONCLUSIONS: a high prevalence of xerostomia was found in this cross-sectional pilot study, which was significantly more frequent in women, and increased with age. Xerostomia was associated to several systemic diseases, psychological conditions, and oral functional disorders such as tooth mobility. These preliminary results can serve as the basis for developing guidelines for the application of innovative measures designed to improve the quality of life of individuals with xerostomia.

Assessing the viability of recovered phosphorus from eutrophicated aquatic ecosystems as a liquid fertilizer.

One of the most important worldwide environmental challenges is the alteration of the biogeochemical cycle of phosphorus (P). P is globally exported from terrestrial to aquatic ecosystems, causing the eutrophication of the receiving waters. In this context, magnetic microparticles (MPs) have been recently proposed for trapping P in natural eutrophicated ecosystems, as well as in treated wastewaters. The main advantage of using MPs is that both P and MPs can be recovered from the treated water. Thus, the working hypothesis of the present study is that P can be desorbed from P-loaded MPs and recovered P can be later used as a fertilizer. To test this hypothesis, the best working conditions for desorbing P from P-loaded MPs were identified; then, an experiment with different plant nutrient solutions (neutralized solutions containing recovered P and an unfertilized control) was carried out with three different plant species: Ocimum basilicum L., Cucumis sativus L. and Cucumis melo L. Finally, germination, height, root and shoot biomass and P concentration in root and shoot were compared among treatments. Our results show that the best conditions for P desorption from P-loaded MPs occurred when using 0.1 M NH4OH and using H3PO4 for neutralizing pH. The greenhouse fertirrigation pot experiment showed that the neutralized solution containing desorbed P from P-loaded MPs can be used as a liquid fertilizer, since its combination with macro and microelements significantly increased plant height, growth rate, shoot and root biomass and shoot and root P concentration. As a result, MPs can be proposed to be used for counteracting the widespread and coupled problems of the exhaustion of the P reserves and the eutrophication of aquatic ecosystems.

Ceftaroline fosamil: clinical experience after 23-month prescription in a tertiary hospital.

OBJECTIVE: To determine the indications, success rate and adverse effects of ceftaroline fosamil treatment in a tertiary hospital. METHODS: In total, 84 cases from February 2018 to December 2019 were retrospectively analysed. No exclusion criteria were applied. RESULTS: Eighty-four patients, with a median age of 70 years, of which, 6.7% (56) were male, were treated with ceftaroline fosamil for a median of 14 days. Most indications were off-label, including 29 endocarditis (34.5%), 14 bacteraemia (16.6%), 5 Central nervous system (CNS) infections (6%) and 19 osteoarticular infections (22.6%). Staphylococcus aureus was the most frequently isolated microorganism, including 28 methicillin-sensitive S. aureus (MSSA; 33.3%) and 14 methicillin-resistant S. aureus (MRSA; 16.7%), followed by coagulase-negative Staphylococcus (23, 27.4%). The main reason for ceftaroline fosamil prescription was the failure of previous treatment (41.7% of cases). Treatment was successful in 60/84 patients (71.4%) and failed clinically or microbiologically in 14 (16.7%). Eight patients died for a reason not related to the infection and two were found to have a non-infectious condition. Twenty-two of thirty-five (62.8%) patients prescribed ceftaroline because of failure of previous treatment improved, including eight endocarditis and seven bacteraemia. Adverse effects were reported in five patients (5.9%) including neutropenia, thrombocytopenia, transaminases elevation and creatinine elevation; all except one were mild and all resolved after discontinuation of treatment. CONCLUSIONS: Ceftaroline fosamil is a well-tolerated cephalosporine, effective against multi- resistant gram-positive and many gram-negative microorganisms. Our experience suggests that it is effective as a rescue or first-line therapy in other indications than those currently approved.

The impact of pre-eclampsia definitions on the identification of adverse outcome risk in hypertensive pregnancy - analyses from the CHIPS trial (Control of Hypertension in Pregnancy Study).

OBJECTIVE: To examine the association between pre-eclampsia definition and pregnancy outcome. DESIGN: Secondary analysis of Control of Hypertension in Pregnancy Study (CHIPS) trial data. SETTING: International multicentre randomised controlled trial (RCT). POPULATION: In all, 987 women with non-severe non-proteinuric pregnancy hypertension. METHODS: We evaluated the association between pre-eclampsia definitions and adverse pregnancy outcomes, stratified by hypertension type and blood pressure control. MAIN OUTCOME MEASURES: Main CHIPS trial outcomes: primary (perinatal loss or high-level neonatal care for >48 hours), secondary (serious maternal complications), birthweight <10th centile, severe maternal hypertension, delivery at <34 or <37 weeks, and maternal hospitalisation before birth. RESULTS: Of 979/987 women with informative data, 280 (28.6%) progressed to pre-eclampsia defined restrictively by new proteinuria, and 471 (48.1%) to pre-eclampsia defined broadly as proteinuria or one/more maternal symptoms, signs or abnormal laboratory tests. The broad (versus restrictive) definition had significantly higher sensitivities (range 62-79% versus 36-50%), lower specificities (range 53-65% versus 72-82%), and similar or higher diagnostic odds ratios and 'true-positive' to 'false-positive' ratios. Stratified analyses showed similar results. Addition of available fetoplacental manifestations (stillbirth or birthweight <10th centile) to the broad pre-eclampsia definition improved sensitivity (74-87%). CONCLUSIONS: A broad (versus restrictive) pre-eclampsia definition better identifies women who develop adverse pregnancy outcomes. These findings should be replicated in a prospective study within routine healthcare to ensure that the anticipated increase in surveillance and intervention in a larger number of women with pre-eclampsia is associated with improved outcomes, reasonable costs and congruence with women's values. TWEETABLE ABSTRACT: A broad (versus restrictive) pre-eclampsia definition better identifies the risk of adverse pregnancy outcomes.

Mortality as a competition risk factor in the survival analysis of the results of the type of fixation of the total hip prosthesis in octogenarian patients. / Mortalidad como factor de riesgo de competencia en el análisis de supervivencia de los resultados del tipo de fijación de la prótesis total de cadera en pacientes octogenarios.

INTRODUCTION: Total hip replacement (THR) is challenging in octogenarians due to associated comorbidities and controversy regarding fixation type. We ask whether cemented THR is superior to uncemented THR in patients above the age of 80 years. MATERIAL AND METHODS: A total of 382 patients (441 hips) aged 80 years or older who underwent THR between 2004 and 2015 were analysed. A cemented THR was implanted in 196 hips (group 1), an uncemented THR with a grit-blasted stem in 121 (group 2), or with a porous-coated stem in 124 (group 3). Patients in group 1 had a higher mean age, more comorbidities and osteoporotic bone. Survival analysis was calculated using cumulative incidence function to account for the competing risk of death. RESULTS: Medical complications rate was similar. There were 3post-operative fractures: one in group 2 and 2in group 3. Competing risk analysis showed that the cumulative incidence of revision for any cause was 2.3 in group 1, 6.0 in group 2 and 4.1 in group 3 at 10years, and the cumulative incidence of revision for aseptic loosening was 1.2 in group 1, 3.7 in group 2 and 0 in group 3 at the same period. CONCLUSIONS: THR presents an acceptable number of adverse events for octogenarian patients. Despite uncemented fixation was satisfactory, the higher peri-prosthetic fracture rate worsens results in this group.

Outcome of a hemispherical porous-coated acetabular component with a proximally hydroxyapatite-coated anatomical femoral component: an update at 23 to 26 years' follow-up

AIMS: We previously reported the long-term results of the cementless Duraloc-Profile total hip arthroplasty (THA) system in a 12- to 15-year follow-up study. In this paper, we provide an update on the clinical and radiological results of a previously reported cohort of patients at 23 to 26 years´ follow-up. PATIENTS AND METHODS: Of the 99 original patients (111 hips), 73 patients (82 hips) with a mean age of 56.8 years (21 to 70) were available for clinical and radiological study at a minimum follow-up of 23 years. There were 40 female patients (44 hips) and 33 male patients (38 hips). RESULTS: All acetabular and femoral components were well fixed and showed signs of bone ingrowth. Nine acetabular components were revised due to wear-osteolysis-related problems and four due to late dislocation. The probability of not having component revision at 25 years was 83.2% (95% confidence interval (CI) 74.5 to 91.8; number at risk 41). Acetabular osteolysis was observed in ten hips. The mean femoral head penetration was 1.52 mm (sd 0.8) at 15 years and 1.92 mm (sd 1.2) at 25 years. Receiver operating characteristic (ROC) analysis revealed that mean femoral penetration with a value of 0.11 mm/year or more was associated with the appearance of osteolysis. The 25-year Kaplan-Meier survival with different endpoints was 89.9% for acetabular osteolysis (95% CI 83.3 to 96.5), 92.1% for proximal femoral osteolysis (95% CI 86.1 to 98.2), and 75.5% for femoral osteopenia (95% CI 66.5 to 84.5). CONCLUSION: The Duraloc-Profile THA system showed excellent long-term bone fixation. Nevertheless, monitoring is recommended in order to detect wear and late dislocations in this population that was relatively young at the time of surgery. Cite this article: Bone Joint J 2019;101-B:378-385.

Estimation of the maximal lactate steady state in postmenopausal women.

This study aimed to estimate the maximal lactate steady-state velocity (vMLSS) from non-invasive bloodless variables and/or blood lactate-related thresholds (BLRTs) measured during an Incremental submaximal Shuttle Test (IST), and to determine whether the addition of a Constant Velocity Test (CVT) could improve the estimation. Seventy-five postmenopausal women conducted an IST to determine several BLRTs and bloodless variables, and two to seven CVTs to determine vMLSS. Determined BLRTs were conventionally used lactate threshold (LT) measured either visually (vLT+0.1mM) or mathematically (vLEmin), and 0.5, 1 and 1.5 mmol·L-1 above LT, along with fixed BLRTs. The best single predictor of vMLSS (7.1 ± 1.0 km·h-1) was vLEmin+1.5mM (R2 = 0.80, P < 0.001; SEE = 0.46 km·h-1). The combination of BLRTs and bloodless variables improved the estimation of vMLSS (R2 = 0.85, P < 0.001; SEE = 0.38 km·h-1). The addition of a CVT still improved the prediction of vMLSS up to 89.2%, with lower SEE (0.32 km·h-1). This study suggests that vLEmin-related thresholds obtained from a single submaximal IST are accurate estimates of vMLSS in postmenopausal women, and thus the time-consuming procedure of vMLSS testing could be avoided. Performing an additional CVT is encouraged because it improves the prediction of vMLSS.

Point-of-Care Assessment of Folate Status in Women of Reproductive Age Using a Fluorescence Lateral Flow Assay.

Folate is an essential vitamin to the development of a fetus in early pregnancy. Maternal folate supplementation around the time of conception has been shown to decrease the risk of neural tube defects (NTDs), a class of serious birth defects. The closure of the neural tube before the 28th day after conception necessitates that the folate intake must take place before most women know that they are pregnant. Therefore, screening women of reproductive age for folate status would allow for an improved understanding of the need for supplementation in women who could become pregnant as well as the effectiveness of current supplementation and fortification recommendations. Current folate assessment is limited to labbased assays which require expensive equipment, trained personnel, and are time-intensive. Our point-of-care diagnostic test quantifies levels of folate in human serum with the use of a lateral flow assay and a portable imaging device. We have designed an assay which uses fluorescent particles, folate binding protein, and antibodies to measure serum folate. This test could be used in resource-limited settings, where access to laboratory infrastructure is limited and where knowledge of folate status in women of reproductive age is lacking. By increasing our understanding of folate status around the world, we can improve implementation of folic acid supplementation and fortification and therefore reduce the risk of NTDs.

Beer effects on postprandial digestive symptoms and gastroesophagic physiology.

BACKGROUND: Beer has been related to gastroesophageal reflux (GER) and dyspepsia, based on its alcohol and gas content. The aim of this study is to evaluate the association between moderate consumption of traditional and alcohol-free beer and upper digestive symptoms, gastric accommodation and GER. METHODS: Healthy adults without frequent gastrointestinal symptoms and GER disease were included. The intervention involved administration of traditional beer to 10 subjects (substudy 1) and alcohol-free beer to 20 (substudy 2); control intervention entailed administration of water. Study duration was 2 weeks (control/intervention). Postprandial gastric accommodation was assessed through the maximum tolerated volume during a nutrient drink test after the ingestion of water (day 1) and beer (day 8), in which symptoms of dyspepsia were evaluated every 5 minutes. An impedance-pH monitoring assessed 24 hours and post-NDT GER (days 1 and 8). Symptoms were evaluated daily during the study. The defined variables were compared between visits and weeks using a nonparametric test for paired data. KEY RESULTS: Dyspepsia symptoms showed a progressive increase during the NDT for both interventions in the 2 substudies, though no significant differences were detected in the MTV analysis. No differences were detected in the sum of weekly symptoms. The analysis of impedance-pH monitoring did not show any differences between intervention and control visits for both interventions. CONCLUSIONS AND INFERENCES: Moderate consumption of traditional and alcohol-free beer does not increase dyspeptic symptoms or GER in healthy subjects, whether in a controlled-intake or real-life situation. Neither gastric accommodation nor reflux episodes are modified in this context.

A Quantitative Point-of-Need Assay for the Assessment of Vitamin D3 Deficiency.

Vitamin D is necessary for the healthy growth and development of bone and muscle. Vitamin D deficiency, which is present in 42% of the US population, is often undiagnosed as symptoms may not manifest for several years and long-term deficiency has been linked to osteoporosis, diabetes and cancer. Currently the majority of vitamin D testing is performed in large-scale commercial laboratories which have high operational costs and long times-to-result. Development of a low-cost point-of-need assay could be transformative to deficiency analysis in limited-resource settings. The best biomarker of vitamin D status, 25hydroxyvitamin D3 (25(OH)D3), however, is particularly challenging to measure in such a format due to complexities involved in sample preparation, including the need to separate the marker from its binding protein. Here we present a rapid diagnostic test for the accurate, quantitative assessment of 25(OH)D3 in finger-stick blood. The assay is accompanied by a smartphone-assisted portable imaging device that can autonomously perform the necessary image processing. To achieve accurate quantification of 25(OH)D3, we also demonstrate a novel elution buffer that separates 25(OH)D3 from its binding protein in situ, eliminating the need for sample preparation. In human trials, the accuracy of our platform is 90.5%.

The evolution of an uncemented acetabular component in alumina-on-alumina total hip arthroplasty has improved clinical outcome: a prospective, comparative five- to 15-year follow-up study.

AIMS: To determine the effect of a change in design of a cementless ceramic acetabular component in fixation and clinical outcome after total hip arthroplasty PATIENTS AND METHODS: We compared 342 hips (302 patients) operated between 1999 and 2005 with a relatively smooth hydroxyapatite coated acetabular component (group 1), and 337 hips (310 patients) operated between 2006 and 2011 using a similar acetabular component with a macrotexture on the entire outer surface of the component (group 2). The mean age of the patients was 53.5 (14 to 70) in group 1 and 53.0 (15 to 70) in group 2. The mean follow-up was 12.7 years (10 to 17) for group 1 and 7.2 years (4 to 10) for group 2. RESULTS: No hips were revised due to complications related to bearing fracture or to stem loosening. A total of 15 acetabular components were revised for aseptic loosening in group 1 and two in group 2. The survival rate for acetabular component aseptic loosening at eight years was 96.8% (95% confidence interval (CI) 94.8 to 98.7) for group 1 and 99.2% (95% CI 98.0 to 100) for group 2. The risk for aseptic loosening of the acetabular component was higher in group 1 (p = 0.04, Hazard Ratio (HR) 4.99), dysplastic acetabula (p = 0.01, HR 4.12), components outside Lewinnek´s zone (p < 0.001, HR 6.13) and in those with a hip rotation centre distance greater than 5 mm (p = 0.005, HR 4.09). CONCLUSION: Alumina ceramic-on-ceramic THA is an excellent option for young patients. Although newer components appeared to improve fixation, acetabular reconstruction is essential to obtain a satisfactory outcome. Cite this article: Bone Joint J 2017;99-B:749-58.