Trimester-specific diagnostic accuracy of ultrasound for detection of placenta accreta spectrum: systematic review and meta-analysis.

OBJECTIVE: To assess the diagnostic accuracy of ultrasound for detecting placenta accreta spectrum (PAS) during the first trimester of pregnancy and compare it with the accuracy of second- and third-trimester ultrasound examination in pregnancies at risk for PAS. METHODS: PubMed, EMBASE and Web of Science databases were searched to identify relevant studies published from inception until 10 March 2023. Inclusion criteria were cohort, case-control or cross-sectional studies that evaluated the accuracy of ultrasound examination performed at < 14 weeks of gestation (first trimester) or ≥ 14 weeks of gestation (second/third trimester) for the diagnosis of PAS in pregnancies with clinical risk factors. The primary outcome was the diagnostic accuracy of sonography in detecting PAS in the first trimester, compared with the accuracy of ultrasound examination in the second and third trimesters. The secondary outcome was the diagnostic accuracy of each sonographic marker individually across the trimesters of pregnancy. The reference standard was PAS confirmed at pathological or surgical examination. The potential of ultrasound and different ultrasound signs to detect PAS was assessed by computing summary estimates of sensitivity, specificity, diagnostic odds ratio and positive and negative likelihood ratios. RESULTS: A total of 37 studies, including 5764 pregnancies at risk of PAS, with 1348 cases of confirmed PAS, were included in our analysis. The meta-analysis demonstrated that ultrasound had a sensitivity of 86% (95% CI, 78-92%) and specificity of 63% (95% CI, 55-70%) during the first trimester, and a sensitivity of 88% (95% CI, 84-91%) and specificity of 92% (95% CI, 85-96%) during the second/third trimester. Regarding sonographic markers examined in the first trimester, lower uterine hypervascularity exhibited the highest sensitivity (97% (95% CI, 19-100%)), and uterovesical interface irregularity demonstrated the highest specificity (99% (95% CI, 96-100%)). In the second/third trimester, loss of clear zone had the highest sensitivity (80% (95% CI, 72-86%)), and uterovesical interface irregularity exhibited the highest specificity (99% (95% CI, 97-100%)). CONCLUSIONS: First-trimester ultrasound examination has similar accuracy to second- and third-trimester ultrasound examinations for the diagnosis of PAS. Routine first-trimester ultrasound screening for patients at high risk of PAS may improve detection rates and allow earlier referral to tertiary care centers for pregnancy management. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Heavy clinical and economic burden of osteoporotic fracture among elderly female Medicare beneficiaries.

We comprehensively described elderly Medicare women with an outpatient visit in 2011 and fracture within 2 years before. These women were at very high risk for subsequent fracture and high healthcare utilization and cost, especially those with vertebral or multiple fractures. However, rates of fracture prevention treatments were low. INTRODUCTION: Postmenopausal women with osteoporosis are stratified to high and very-high fracture risk categories, and this categorization drives algorithms for osteoporosis management in osteoporosis treatment guidelines. This study comprehensively describes a very-high-risk cohort. METHODS: This retrospective cohort study used the Medicare 20% database; elderly women with an outpatient visit in 2011 and fracture within 2 years before the visit were included. Outcomes included fracture risk, all-cause and fracture-related healthcare resource utilization and cost, and osteoporosis medication use in the 5 years after the visit. RESULTS: Overall, 43,193 patients were included. The 5-year probability was 0.36 for major fracture and 0.11 and 0.17 for hip fracture and vertebral fracture, respectively, much higher than the guidelines' 10-year probability thresholds for very-high-risk (0.3 for major fracture, 0.045 for hip fracture). Rates of hospitalizations, emergency department visits or observation stays, and skilled nursing facility stays in year 1 were 53.7, 57.0, and 18.8 per 100 patient-years, respectively, decreasing slightly in subsequent years. Mean healthcare cost was $23,700 in year 1, decreasing to $18,500 in year 5. About 29.1% of patients received osteoporosis medications in year 1, decreasing to 16.9% by year 5. Rates for all outcomes, especially fractures, were much higher among vertebral and multiple fracture cohorts. CONCLUSION: Elderly women with a fracture within last 2 years were at very-high-risk for subsequent fracture and high healthcare utilization and cost, especially those with vertebral or multiple fractures. However, rates of fracture prevention treatments were low. More effort is needed to identify and treat patients at very-high-risk for fracture.

The Effects of a Perindopril-Based Regimen in Relation to Statin Use on the Outcomes of Patients with Vascular Disease: a Combined Analysis of the ADVANCE, EUROPA, and PROGRESS Trials.

PURPOSE: To study the effects of a perindopril-based regimen on cardiovascular (CV) outcomes in patients with vascular disease in relation to background statin therapy. METHODS: A pooled analysis of the randomized ADVANCE, EUROPA, and PROGRESS trials was performed to evaluate CV outcomes in 29,463 patients with vascular disease treated with perindopril-based regimens versus placebo. The primary endpoint was a composite of CV mortality, nonfatal myocardial infarction, and stroke. Multivariable Cox regression analyses were performed to assess the effects of a perindopril-based regimen versus placebo in relation to statin use. RESULTS: At randomization, 39.5% of the overall combined study population used statins. After a mean follow-up of 4.0 years (SD 1.0), the cumulative event-free survival was highest in the statin/perindopril group and lowest in the no statin/placebo group (91.2% vs. 85.6%, respectively, log-rank p < 0.001). In statin users (adjusted hazard ratio [aHR] 0.87, 95% confidence interval [CI] 0.77-0.98) and non-statin users (aHR 0.80, 95% CI 0.74-0.87), a perindopril-based regimen was associated with a significantly lower risk of the primary endpoint when compared to placebo. The additional treatment effect appeared numerically greater in non-statin users, but the observed difference was statistically nonsignificant. CONCLUSION: Our data suggest that the treatment benefits of a perindopril-based regimen in patients with vascular disease are independent of statin use.

Longitudinal evaluation of motor function in patients who underwent prenatal or postnatal neural tube defect repair.

OBJECTIVE: To compare the evolution of motor function from mid-gestation to 12 months of age between prenatally and postnatally repaired cases of open neural tube defect (ONTD). METHODS: This was a retrospective cohort study of all fetuses that underwent prenatal (fetoscopic or open hysterotomy) or postnatal ONTD repair at a single institution between November 2011 and December 2018. The anatomical level of the lesion was defined as the upper bony spinal defect at initial magnetic resonance imaging assessment. Prenatal motor function of the lower extremities was evaluated by ultrasound according to the metameric level of the neurological lesion, based on the methodology of Carreras et al. Fetal motor function was assessed at referral, at 6 weeks after surgery in prenatally repaired cases or 6 weeks after referral in postnatally repaired cases (6-week follow-up) and at the last scan before delivery. In addition, motor function was assessed by a detailed neurological examination at birth and 12 months of age. First sacral (S1) neurological level of the lesion was considered as intact motor function. For statistical comparisons, we attributed numerical scores to each neurological level and motor function was expressed as median (range) neurological level. Motor function (as numerical score) and the proportion of cases with intact motor function and with motor function two or more levels better than expected based on the anatomical level of the lesion were compared between the prenatal- and postnatal-repair groups. Fetal motor function was compared to the anatomical level of the lesion at referral and a better motor function was defined when it was two or more levels better than the anatomical level of the lesion. To assess the evolution of motor function, we compared motor function at referral with that at each follow-up assessment using paired t-tests. RESULTS: We included 127 patients with ONTD, of whom 93 underwent prenatal (51 fetoscopic and 42 open hysterotomy) and 34 postnatal repair. At the time of referral, cases in the prenatal- and postnatal-repair groups presented with a similar anatomical level of lesion (L3 (T9-S1) vs L3 (T7-S1); P = 0.52), similar motor function (S1 (L1-S1) vs S1 (L1-S1); P = 0.52) and a similar proportion of cases with intact motor function (81% vs 79%; P = 0.88) and with motor function two or more levels better than expected based on the anatomical level of the lesion (62% vs 74%; P = 0.24). When compared with prenatally repaired cases, postnatally repaired cases showed worse motor function at birth (S1 (L1-S1) vs L4 (L1-S1); P < 0.01) and at 12 months of age (S1 (L1-S1) vs L4 (L1-S1); P < 0.01). In the prenatal-repair group, motor function remained stable from the time of referral to 12 months of age (P = 0.26). Furthermore, the proportion of patients with intact motor function at referral (81% (75/93)) was similar to that at the 6-week follow-up (74% (64/87)), at the last scan before birth (74% (42/57)), at birth (68% (63/93)) and at 12 months of age (67% (39/58)) in the prenatal-repair group. In the postnatal-repair group, worse motor function, starting from the third trimester to 12 months of age, was observed. The proportion of patients with intact motor function at referral (79% (27/34)) was similar to that at 6-week follow-up (80% (12/15); P = 0.92), but was lower at the last assessment before birth (25% (2/8); P < 0.01), at birth (24% (8/34); P < 0.01) and at 12 months of age (28% (7/25); P < 0.01). Similar findings were noted when assessing the evolution of the proportion of cases with motor function two or more levels better than expected based on the anatomical level of the lesion in each group. CONCLUSIONS: Infants with ONTD that underwent postnatal repair had worse motor function at birth and at 12 months of age than at mid-gestation and when compared with infants that underwent prenatal ONTD repair. Prenatal motor function assessment by ultrasound is an adequate tool to identify those infants who should have a good clinical motor function after delivery. Information obtained by fetal motor function assessment can have an important role for patient counseling and case selection for surgery. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

The phenotypical implications of immune dysregulation in fragile X syndrome.

BACKGROUND AND PURPOSE: Immune system dysfunction and inflammatory dysregulation have been shown in several animal models of fragile X syndrome (FXS). However, the phenotypical implications of this dysregulation have not been systematically evaluated in a large patient cohort. METHODS: Five thousand seven hundred thirty-six FXS patients from a nationwide health insurance database were identified and compared to 573 600 age- and sex-matched controls. The phenome-wide association studies codes of FXS patients and those without FXS were compared and the false discovery rate was controlled at 0.05 using the Benjamini-Hochberg procedure. RESULTS: In addition to the commonly reported comorbidities of FXS, an over-representation of infectious diseases, including otitis media, cellulitis and abscess of fingers or toes, viral enteritis, candidiasis and pneumonia, was discovered. In addition, there was an under-representation of autoimmune disorders in FXS patients. CONCLUSIONS: Our systematic comorbidity analyses identified immunologically-based phenotypes associated with FXS. Our findings align with previous observations of compromised immunity and phagocytic defects in animal models of FXS. These results suggest the importance of immune-related pathways in FXS patients and their relevance to the FMR1 gene.

Elective delivery at 34 weeks vs routine obstetric care in fetal gastroschisis: randomized controlled trial.

OBJECTIVE: To evaluate whether elective preterm delivery (ED) at 34 weeks is of postnatal benefit to infants with isolated gastroschisis compared with routine obstetric care (RC). METHODS: Between May 2013 and September 2015, all women with a sonographic diagnosis of fetal gastroschisis referred to a single tertiary center, before 34 weeks' gestation, were invited to participate in this study. Eligible patients were randomized to ED (induction of labor at 34 weeks) or RC (spontaneous labor or delivery by 37-38 weeks, based on standard obstetric indications). The primary outcome measure was length of time on total parenteral nutrition (TPN). Secondary outcomes were time to closure of gastroschisis and length of stay in hospital. Outcome variables were compared using appropriate statistical methods. Analysis was based on intention-to-treat. RESULTS: Twenty-five women were assessed for eligibility, of whom 21 (84%; 95% CI, 63.9-95.5%) agreed to participate in the study; of these, 10 were randomized to ED and 11 to RC. The trial was stopped at the first planned interim analysis due to patient safety concerns and for futility; thus, only 21 of the expected 86 patients (24.4%; 95% CI, 15.8-34.9%) were enrolled. Median gestational age at delivery was 34.3 (range, 34-36) weeks in the ED group and 36.7 (range, 27-38) weeks in the RC group. One patient in the ED group delivered at 36 weeks following unsuccessful induction at 34 weeks. Neonates of women who underwent ED, compared to those in the RC group, showed no difference in the median number of days on TPN (54 (range, 17-248) vs 21 (range, 9-465) days; P = 0.08), number of days to closure of gastroschisis (7 (range, 0-15) vs 5 (range, 0-8) days; P = 0.28) and length of stay in hospital (70.5 (range, 22-137) vs 31 (range, 19-186) days; P = 0.15). However, neonates in the ED group were significantly more likely to experience late-onset sepsis compared with those in the RC group (40% (95% CI, 12.2-73.8%) vs 0%; P = 0.03). CONCLUSION: This study demonstrates no benefit of ED of fetuses with gastroschisis when postnatal gastroschisis management is similar to that used in routine care. Rather, the data suggest that ED is detrimental to infants with gastroschisis. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Parto inducido a las 34 semanas versus atención obstétrica rutinaria en la gastrosquisis fetal: ensayo controlado aleatorizado OBJETIVO: Evaluar si el parto pretérmino inducido (PI) a las 34 semanas es beneficioso para los recién nacidos con gastrosquisis aislada en comparación con la atención obstétrica rutinaria (AR). MÉTODOS: Entre mayo de 2013 y septiembre de 2015, se invitó a participar en este estudio a todas las mujeres con diagnóstico ecográfico de gastrosquisis fetal remitidas a un mismo centro terciario, antes de las 34 semanas de gestación. Las pacientes elegibles fueron asignadas al azar al PI (inducción del parto a las 34 semanas) o a la AR (parto espontáneo a las 37-38 semanas, en función de los indicios obstétricos estándar). La medida de resultado primaria fue la duración de la nutrición parenteral total (NPT). Las medidas de resultado secundarias fueron el tiempo hasta el cierre de la gastrosquisis y la duración de la estancia hospitalaria. Las variables de resultado se compararon mediante métodos estadísticos apropiados. El análisis se basó en la intención de tratar. RESULTADOS: Se evaluó la elegibilidad de 25 mujeres, de las cuales 21 (84%; IC 95%, 63,9-95,5%) aceptaron participar en el estudio; de ellas, 10 fueron asignadas al azar al PI y 11 a la AR. El ensayo se detuvo después del primer análisis provisional planificado debido a preocupaciones sobre la seguridad de las pacientes y por su intrascendencia; por lo tanto, sólo se reclutaron 21 de las 86 pacientes esperadas (24,4%; IC 95%, 15,8-34,9%). La mediana de la edad gestacional en el momento del parto fue de 34,3 (rango: 34-36) semanas en el grupo de PI y 36,7 (rango: 27-38) semanas en el grupo de AR. Una paciente del grupo de PI tuvo un parto a las 36 semanas, después de una inducción infructuosa a las 34 semanas. Los neonatos de las mujeres que se sometieron a PI, comparados con los del grupo de AR, no mostraron diferencias en la mediana del número de días de NPT (54 (rango: 17-248) vs 21 (rango: 9-465) días; P=0,08), número de días hasta el cierre de la gastrosquisis (7 (rango: 0-15) vs 5 (rango: 0-8) días; P=0,28) y duración de la estancia hospitalaria (70,5 (rango: 22-137) vs 31 (rango: 19-186) días; P=0,15). Sin embargo, la probabilidad de experimentar sepsis de inicio tardío fue mayor en los neonatos del grupo de PI en comparación el grupo de AR (40% (IC 95%, 12,2-73,8%) vs 0%; P=0,03). CONCLUSIÓN: Este estudio demuestra que el PI no presenta ningún beneficio para los fetos con gastrosquisis cuando el tratamiento de la gastrosquisis postnatal es similar al utilizado en la atención rutinaria. Más bien, los datos sugieren que el PI es perjudicial para los lactantes con gastrosquisis.

Placental growth factor blunts uterine artery responses to angiotensin II.

OBJECTIVE: Changes in maternal serum concentration of placental growth factor (PlGF) and vascular response to intravascular infusion of Angiotensin II (Ang II) follow a bell-shaped curve pattern during gestation. This study evaluates the effects of PlGF and soluble vascular endothelial growth factor receptor-1 (sFlt-1) on responses of human uterine arteries (UA) to Ang II. DESIGN: Experimental. SETTING: Baylor College of Medicine and Texas Children's Hospital-Pavilion for Women. SAMPLE: Uterine arteries samples (n = 14) were obtained from normotensive women undergoing caesarean hysterectomy at ≥32 weeks. METHODS: Uterine arteries rings were incubated with (1) Krebs solution; (2) PlGF at 1.45, 14.5, and 500 pg/ml; (3) sFlt-1 at 2 ng/ml; and (4) a combination of sFlt-1, and PlGF. Dose-contraction responses to Ang II were determined in UA rings incubated in the above-mentioned conditions. Responses were also measured in presence of L-NAME or inhibitors of endothelium-derived hyperpolarising factor: apamine and charybdotoxin. The t-test was used for comparisons. MAIN OUTCOME MEASURE: Changes in vascular reactivity of UA rings. RESULTS: PlGF blunted (P = 0.03) and sFlt-1 increased (P <0.01) the UA maximum responses to Ang II. A combination of sFlt-1 and PlGF blunted UA responses to Ang II (P < 0.05). l-NAME, apamine, and charybdotoxin reversed the relaxation effects of PlGF on UA responses to Ang II (P < 0.05). CONCLUSIONS: PlGF contributes to the blunted vascular response to Angiotensin II during normotensive pregnancies and sFlt-1 appears to attenuate this effect. PlGF and sFlt-1 may contribute to the regulation of vascular tone during pregnancy by altering the vascular response to Angiotensin II. FUNDING: Baylor College of Medicine. TWEETABLE ABSTRACT: Placental growth factor and soluble vascular endothelial growth factor receptor-1 modulate the uterine artery response to Angiotensin II in normotensive pregnant women.

Evaluation of a phased pneumococcal conjugate vaccine introduction in Mongolia using enhanced pneumonia surveillance and community carriage surveys: a study protocol for a prospective observational study and lessons learned.

BACKGROUND: Streptococcus pneumoniae causes substantial morbidity and mortality among children. The introduction of pneumococcal conjugate vaccines (PCV) has the potential to dramatically reduce disease burden. As with any vaccine, it is important to evaluate PCV impact, to help guide decision-making and resource-allocation. Measuring PCV impact can be complex, particularly to measure impact on one of the most common and significant diseases caused by the pneumococcus, namely pneumonia. Here we outline the protocol developed to evaluate the impact of 13-valent PCV (PCV13) on childhood pneumonia in Mongolia, and a number of lessons learned in implementing the evaluation that may be helpful to other countries seeking to undertake pneumonia surveillance. METHODS: From 2016 PCV13 was introduced in a phased manner into the routine immunisation programme with some catch-up by the Government of Mongolia. We designed an evaluation to measure vaccine impact in children aged 2-59 months with hospitalised radiological pneumonia as a primary outcome, with secondary objectives to measure impact on clinically-defined pneumonia, nasopharyngeal carriage of S. pneumoniae among pneumonia patients and in the community, and severe respiratory infection associated with RSV and/or influenza. We enhanced an existing hospital-based pneumonia surveillance system by incorporating additional study components (nasopharyngeal swabbing using standard methods, C-reactive protein, risk factor assessment) and strengthening clinical practices, such as radiology as well as monitoring and training. We conducted cross-sectional community carriage surveys to provide data on impact on carriage among healthy children. DISCUSSION: Establishing a robust surveillance system is an important component of monitoring the impact of PCV within a country. The enhanced surveillance system in Mongolia will facilitate assessment of PCV13 impact on pneumonia, with radiological confirmed disease as the primary outcome. Key lessons arising from this evaluation have included the importance of establishing a core group of in-country staff to be responsible for surveillance activities and to work closely with this team; to be aware of external factors that could potentially influence disease burden estimates; to be flexible in data collection processes to respond to changing circumstances and lastly to ensure a consistent application of the pneumonia surveillance case definition throughout the study period.

Psychosis as a risk factor for suicidal thoughts and behaviors: a meta-analysis of longitudinal studies.

BACKGROUND: Research has long noted higher prevalence rates of suicidal thoughts and behaviors among individuals with psychotic symptoms. Major theories have proposed several explanations to account for this association. Given the differences in the literature regarding the operationalization of psychosis and sample characteristics, a quantitative review is needed to determine to what extent and how psychosis confers risk for suicidality. METHODS: We searched PsycInfo, PubMed, and GoogleScholar for studies published before 1 January 2016. To be included in the analysis, studies must have used at least one psychosis-related factor to longitudinally predict suicide ideation, attempt, or death. The initial search yielded 2541 studies. Fifty studies were retained for analysis, yielding 128 statistical tests. RESULTS: Suicide death was the most commonly studied outcome (43.0%), followed by attempt (39.1%) and ideation (18.0%). The median follow-up length was 7.5 years. Overall, psychosis significantly conferred risk across three outcomes, with weighted mean ORs of 1.70 (1.39-2.08) for ideation, 1.36 (1.25-1.48) for attempt, and 1.40 (1.14-1.72) for death. Detailed analyses indicated that positive symptoms consistently conferred risk across outcomes; negative symptoms were not significantly associated with ideation, and were protective against death. Some small moderator effects were detected for sample characteristics. CONCLUSIONS: Psychosis is a significant risk factor for suicide ideation, attempt, and death. The finding that positive symptoms increased suicide risk and negative symptoms seemed to decrease risk sheds light on the potential mechanisms for the association between psychosis and suicidality. We note several limitations of the literature and offer suggestions for future directions.

Pregnancy after endometrial ablation: a systematic review.

BACKGROUND: Pregnancies have been reported after endometrial ablation but there is little data regarding subsequent pregnancy outcomes. OBJECTIVE: To review systematically the available evidence regarding pregnancy outcomes after endometrial ablation, in order to equip physicians effectively to counsel women considering endometrial ablation. SEARCH STRATEGY: MEDLINE, Embase, Cochrane, and ClinicalTrials.gov were searched through January 2017. SELECTION CRITERIA: Published and unpublished literature in any language describing pregnancy after endometrial ablation or resection was eligible. DATA COLLECTION AND ANALYSIS: Data about preconception characteristics and pregnancy outcomes were extracted and analysed according to study design of source and pregnancy viability. MAIN RESULTS: We identified 274 pregnancies from 99 sources; 78 sources were case reports. Women aged 26-50 years (mean 37.5 ± 5 years) conceived a median of 1.5 years after ablation (range: 3 weeks prior to 13 years after). When reported, 80-90% had not used contraception. In all, 85% of pregnancies from trial/observational studies ended in termination, miscarriage or ectopic pregnancy. Pregnancies that continued (case report and non-case report sources) had high rates of preterm delivery, caesarean delivery, caesarean hysterectomy, and morbidly adherent placenta. Case reports also frequently described preterm premature rupture of membranes, intrauterine growth restriction, intrauterine fetal demise, uterine rupture, and neonatal demise. CONCLUSIONS: An unexpectedly high rate of pregnancy complications is reported in the available literature (which may reflect publication bias) and high-quality evidence is lacking. However, based on the existing evidence, women undergoing endometrial ablation should be informed that subsequent pregnancy may have serious complications and should be counselled to use reliable contraception after the procedure. TWEETABLE ABSTRACT: Systematic review - pregnancies reported after endometrial ablation have an increased risk of adverse outcomes.

The Blood Donation Ambivalence Survey: measuring conflicting attitudes about giving blood.

OBJECTIVES: This study was designed to develop and conduct initial validation testing for a novel measure of ambivalence about donating blood. BACKGROUND: Previous studies of living organ, bone marrow and stem cell donors have identified donation-related ambivalence as a predictor of decisions about donation and post-donation outcomes. Ambivalence about blood donation has not received the same attention. METHODS: In Study 1, a sample of young adults (N = 396) were administered test items of ambivalence, and exploratory (EFA) and confirmatory factor analyses (CFA) were performed to identify the Blood Donation Ambivalence Survey. In Study 2, a separate sample of young adults (N = 241) completed the Blood Donation Ambivalence Survey in addition to questionnaires assessing known predictors of blood donation. RESULTS: Exploratory and confirmatory factor analyses indicated a two-factor structure reflecting commitment to donating blood and indecision about giving blood. The commitment subscale was positively related to known predictors of increased donation behaviour (e.g. donation intention, self-efficacy), whereas the indecision subscale was positively related to known predictors of decreased donation behaviour (e.g. donation anxiety, negative affect). Furthermore, a history of blood donation was associated with greater commitment and less indecision. CONCLUSIONS: The present findings provide strong initial support for the reliability and validity of a novel measure of blood donor ambivalence.

The Treatment Effect of an ACE-Inhibitor Based Regimen with Perindopril in Relation to Beta-Blocker use in 29,463 Patients with Vascular Disease: a Combined Analysis of Individual Data of ADVANCE, EUROPA and PROGRESS Trials.

INTRODUCTION: In everyday practice, angiotensin converting enzyme inhibitors and beta-blockers are cornerstone treatments in patients with (cardio-)vascular disease. Clear data that evaluate the effects of the combination of these agents on morbidity and mortality are lacking. METHODS: In this retrospective pooled analysis of three large perindopril outcome trials (ADVANCE, EUROPA, PROGRESS), clinical outcomes were evaluated in 29,463 patients with vascular disease. Multivariate Cox regression analyses were performed in patients randomized to a perindopril-based regimen or placebo (treatment effect), and data were stratified according to background beta-blocker treatment. The primary endpoint was a composite of cardiovascular mortality, non-fatal myocardial infarction, and stroke. RESULTS: The cumulative incidence of the primary endpoint over mean follow-up of 4.0 years (Sd 1.0) was significantly lower in the beta-blocker/perindopril group (9.6%; 545/5700 patients) as compared to beta-blocker/placebo (11.8%; 676/5718 patients) (p < 0.01). Adding perindopril to existing beta-blocker treatment reduced the relative risk of the primary endpoint by 20% (hazard ratio (HR) 0.80; 95% confidence interval (CI) 0.71-0.90), non-fatal myocardial infarction by 23% (HR 0.77; 95% CI 0.65-0.91), and all-cause mortality by 22% (HR 0.78; 95% CI 0.68-0.88) as compared to placebo. Significant treatment benefit was not observed for stroke (HR 0.93; 95% CI 0.75-1.15). Significance was maintained for the primary endpoint and cardiovascular endpoints when data were further stratified by baseline hypertension. However, the mortality benefit was only observed in patients with hypertension with background beta-blocker use. CONCLUSIONS: These data suggest that the beneficial cardioprotective effects of perindopril treatment are additive to the background beta-blockers use.

Perceptions of success of a local UK public health collaborative†.

Summary: Successful public health initiatives require multi-sector collaboration. AVONet was a UK collaborative developed to provide evidence-based strategies for active ageing. This study explored the success of AVONet in the achievement of its objectives as perceived by all partners. A convergent parallel mixed-methods design was employed, utilizing a quantitative survey and qualitative semi-structured interviews. Data collection was undertaken in September 2010, 18 months after establishing the collaborative and 6 months after funding had ceased. AVONet partners (n = 24) completed a 27-item survey. A sub-sample of four academics and four practitioners participated in semi-structured interviews. Quantitative and qualitative comparisons were made between academics' and practitioners' perceptions of success, potential for sustainability and satisfaction with structure and relationships. Participants perceived the AVONet collaborative positively. Significant between-group (academic v practitioner) differences in survey responses were observed for success (U = 19.5; p = 0.003) and structure (U = 125.5; p = 0.001). Strong positive correlations were observed between success and structure and balance between information transfer and exchange (r = 0.756; p < 0.001). Interviews confirmed positive perceptions and perceived importance of the collaborative and highlighted the need for further integration and tangible outcomes for practitioners. Suggestions to enhance sustainability were provided, such as smaller working groups and local council-led governance. Perceived success in building a multi-sectoral collaborative can be achieved during a 10-month period, despite differing needs of contributors. For collaboratives developed as a result of external funding aimed primarily at facilitating research, involvement of practitioners at an early stage may help set more comprehensive goals, supportive communication strategies, and increase potential for sustainability.

An exploration of barriers and facilitators to older adults' participation in higher impact physical activity and bone health: a qualitative study.

SUMMARY: This qualitative study explored the acceptability of high-impact physical activity for increasing bone strength in later life. Thematic analysis established the barriers and facilitators to this physical activity. They prioritised joint over skeletal health, of which they had little concept. Interventions need to clearly communicate the rationale and benefits. INTRODUCTION: The aim of this study was to explore the acceptability of doing high-impact physical activity in later life. METHODS: This qualitative study was embedded within a large-scale observational study and was designed to address specific objectives and feed into a subsequent intervention. Five focus groups with physically active men and women (over 50 years) were used to develop an interview topic guide to explore the acceptability of high-impact physical activity in older men and women (over 65 years) in South West England. A total of 28 semi-structured interviews with 31 participants were then conducted and transcripts analysed thematically. RESULTS: Three main barriers emerged: conceptualising bone, damage to joints and falling/safety concerns. Two main facilitators were also identified: the need to understand clear tangible benefits and incorporation of activity into everyday habits. Older adults were interested how high-impact physical activity would help to maintain their mobility, independence or social relationships. Some participants wanted tangible feedback from accelerometers, health care professionals and/or bone scans in order to develop a more intimate knowledge of their bone health. CONCLUSIONS: Interventions incorporating high-impact physical activity for older adults need to communicate how this activity can impact more broadly on health and lives; that physical activity will be safe, beneficial and not damaging to their joints will need to be clearly conveyed. Ways in which high-impact physical activity can be habitualised into everyday activities, be fun and interactive may help facilitate longer term adoption.

Self-injurious thoughts and behaviors as risk factors for future suicide ideation, attempts, and death: a meta-analysis of longitudinal studies.

BACKGROUND: A history of self-injurious thoughts and behaviors (SITBs) is consistently cited as one of the strongest predictors of future suicidal behavior. However, stark discrepancies in the literature raise questions about the true magnitude of these associations. The objective of this study is to examine the magnitude and clinical utility of the associations between SITBs and subsequent suicide ideation, attempts, and death. METHOD: We searched PubMed, PsycInfo, and Google Scholar for papers published through December 2014. Inclusion required that studies include at least one longitudinal analysis predicting suicide ideation, attempts, or death using any SITB variable. We identified 2179 longitudinal studies; 172 met inclusion criteria. RESULTS: The most common outcome was suicide attempt (47.80%), followed by death (40.50%) and ideation (11.60%). Median follow-up was 52 months (mean = 82.52, s.d. = 102.29). Overall prediction was weak, with weighted mean odds ratios (ORs) of 2.07 [95% confidence interval (CI) 1.76-2.43] for ideation, 2.14 (95% CI 2.00-2.30) for attempts, and 1.54 (95% CI 1.39-1.71) for death. Adjusting for publication bias further reduced estimates. Diagnostic accuracy analyses indicated acceptable specificity (86-87%) and poor sensitivity (10-26%), with areas under the curve marginally above chance (0.60-0.62). Most risk factors generated OR estimates of <2.0 and no risk factor exceeded 4.5. Effects were consistent regardless of sample severity, sample age groups, or follow-up length. CONCLUSIONS: Prior SITBs confer risk for later suicidal thoughts and behaviors. However, they only provide a marginal improvement in diagnostic accuracy above chance. Addressing gaps in study design, assessment, and underlying mechanisms may prove useful in improving prediction and prevention of suicidal thoughts and behaviors.

Improvement of dyskinesias with L-dopa infusion in advanced Parkinson's disease.

OBJECTIVES: We wanted to investigate whether continuous intrajejunal levodopa-carbidopa intestinal gel (LCIG) therapy has an antidyskinetic effect in patients with Parkinson's disease (PD) and troublesome dyskinesias. We also sought to examine the effect of LCIG therapy on motor function and health-related quality of life (HRQoL). MATERIALS AND METHODS: This open-label pilot study used a single group pre-post design with follow-up at 6 months. Nine patients with PD who reported to spend at least 3 h per day in on with troublesome dyskinesia were included. The patients were examined at baseline using clinical and self-assessment measures and then switched from peroral/transdermal pharmacotherapy to LCIG therapy. Data collection was repeated 6 months after the pharmaceutical intervention. Nonparametric statistical methods were used for data analyses. RESULTS: The mean time spent in on with troublesome dyskinesia per day after 6 months of LCIG therapy decreased by 47% (P < 0.05). This observation was paralleled by a 112% increase in mean time spent in on without troublesome dyskinesia (P < 0.01). Patient self-assessment of dyskinesia intensity on the visual analog scale displayed a 90% reduction of mean dyskinesia intensity (P < 0.01) and patients also exhibited less dyskinesia during standardized levodopa tests. Furthermore, we noted improvements in motor function and HRQoL. CONCLUSIONS: In this pilot study, we found indications that LCIG therapy has a substantial antidyskinetic effect and could be an alternative also for PD patients with dyskinesias as a major symptom. However, further studies with blinded evaluation and larger numbers of patients are warranted to confirm the findings.

Experimental Transmission of Bighorn Sheep Sinus Tumors to Bighorn Sheep (Ovis canadensis canadensis) and Domestic Sheep.

Bighorn sheep sinus tumors are a recently described disease affecting the paranasal sinuses of Rocky Mountain bighorn sheep (Ovis canadensis canadensis). Several features of this disease suggest an infectious cause, although a specific etiologic agent has not been identified. To test the hypothesis that bighorn sheep sinus tumors are caused by an infectious agent, we inoculated 4 bighorn sheep lambs and 4 domestic sheep lambs intranasally with a cell-free filtrate derived from a naturally occurring bighorn sheep sinus tumor; we held 1 individual of each species as a control. Within 18 months after inoculation, all 4 inoculated domestic sheep (100%) and 1 of the 4 inoculated bighorn sheep (25%) developed tumors within the ethmoid sinuses or nasal conchae, with features similar to naturally occurring bighorn sheep sinus tumors. Neither of the uninoculated sheep developed tumors. Histologically, the experimentally transmitted tumors were composed of stellate to spindle cells embedded within a myxoid matrix, with marked bone production. Tumor cells stained positively with vimentin, S100, alpha smooth muscle actin, and osteocalcin, suggesting origin from a multipotent mesenchymal cell. A periosteal origin for these tumors is suspected. Immunohistochemical staining for the envelope protein of JSRV (with cross-reactivity to ENTV) was equivocal, and PCR assays specific for these agents were negative.

Lipid-lowering treatment patterns in patients with new cardiovascular events - estimates from population-based register data in Sweden.

OBJECTIVES: The aim of this study was to assess treatment patterns of lipid-lowering therapy (LLT) in patients with hyperlipidaemia or prior cardiovascular (CV) events who experience new CV events. METHODS: A retrospective population-based cohort study was conducted using Swedish medical records and registers. Patients were included in the study based on a prescription of LLT or CV event history and followed up for up to 7 years for identification of new CV events and assessment of LLT treatment patterns. Patients were stratified into three cohorts based on CV risk level. All outcomes were assessed during the year following index (the date of first new CV event). Adherence was defined as medication possession ratio (MPR) > 0.80. Persistence was defined as no gaps > 60 days in supply of drug used at index. RESULTS: Of patients with major cardiovascular disease (CVD) history (n = 6881), 49% were not on LLT at index. Corresponding data for CV risk equivalent and low/unknown CV risk patients were 37% (n = 3226) and 38% (n = 2497) respectively. MPR for patients on LLT at index was similar across cohorts (0.74-0.75). The proportions of adherent (60-63%) and persistent patients (56-57%) were also similar across cohorts. Dose escalation from dose at index was seen within all cohorts and 2-3% of patients switched to a different LLT after index while 5-6% of patients augmented treatment by adding another LLT. CONCLUSIONS: Almost 50% of patients with major CVD history were not on any LLT, indicating a potential therapeutic gap. Medication adherence and persistence among patients on LLT were suboptimal.

Ultrananocrystalline diamond-CMOS device integration route for high acuity retinal prostheses.

High density electrodes are a new frontier for biomedical implants. Increasing the density and the number of electrodes used for the stimulation of retinal ganglion cells is one possible strategy for enhancing the quality of vision experienced by patients using retinal prostheses. The present work presents an integration strategy for a diamond based, high density, stimulating electrode array with a purpose built application specific integrated circuit (ASIC). The strategy is centered on flip-chip bonding of indium bumps to create high count and density vertical interconnects between the stimulator ASIC and an array of diamond neural stimulating electrodes. The use of polydimethylsiloxane (PDMS) housing prevents cross-contamination of the biocompatible diamond electrode with non-biocompatible materials, such as indium, used in the microfabrication process. Micro-imprint lithography allowed edge-to-edge micro-scale pattering of the indium bumps on non-coplanar substrates that have a form factor that can conform to body organs and thus are ideally suited for biomedical applications. Furthermore, micro-imprint lithography ensures the compatibility of lithography with the silicon ASIC and aluminum contact pads. Although this work focuses on 256 stimulating diamond electrode arrays with a pitch of 150 µm, the use of indium bump bonding technology and vertical interconnects facilitates implants with tens of thousands electrodes with a pitch as low as 10 µm, thus ensuring validity of the strategy for future high acuity retinal prostheses, and bionic implants in general.