Nocturnal swallowing augments arousal intensity and arousal tachycardia.

Cortical arousal from sleep is associated with autonomic activation and acute increases in heart rate. Arousals vary considerably in their frequency, intensity/duration, and physiological effects. Sleep and arousability impact health acutely (daytime cognitive function) and long-term (cardiovascular outcomes). Yet factors that modify the arousal intensity and autonomic activity remain enigmatic. In this study of healthy human adults, we examined whether reflex airway defense mechanisms, specifically swallowing or glottic adduction, influenced cardiac autonomic activity and cortical arousal from sleep. We found, in all subjects, that swallows trigger rapid, robust, and patterned tachycardia conserved across wake, sleep, and arousal states. Tachycardia onset was temporally matched to glottic adduction-the first phase of swallow motor program. Multiple swallows increase the magnitude of tachycardia via temporal summation, and blood pressure increases as a function of the degree of tachycardia. During sleep, swallows were overwhelmingly associated with arousal. Critically, swallows were causally linked to the intense, prolonged cortical arousals and marked tachycardia. Arousal duration and tachycardia increased in parallel as a function of swallow incidence. Our findings suggest that cortical feedback and tachycardia are integrated responses of the swallow motor program. Our work highlights the functional influence of episodic, involuntary airway defense reflexes on sleep and vigilance and cardiovascular function in healthy individuals.

Healthcare Workers Beliefs about COVID-19; a Longitudinal, Mixed Methods Analysis.

The psychological impact of COVID-19 on Health Care Workers (HCWs) has been widely reported. Few studies have sought to examine HCWs personal models of COVID-19 utilising an established theoretical framework. We undertook a mixed methods study of beliefs about COVID-19 held by HCWs in the Mid-West and South of Ireland during the first and third waves of COVID-19. Template analysis was undertaken on the free text responses of 408 HCWs about their perceptions of the Cause of COVID-19 as assessed by the Brief Illness Perception Questionnaire (B-IPQ). Responses were re-examined in the same cohort for stability at 3 months follow-up (n = 100). This analytic template was subsequently examined in a new cohort (n = 253) of HCWs in the third wave. Female HCWs perceived greater emotional impact of COVID-19 than men (t = -4.31, df405, p < 0.01). Differences between occupational groups were evident in relation to Timeline (F4,401 = 3.47, p < 0.01), Treatment Control (F4,401 = 5.64, p < 0.001) and Concerns about COVID-19 (F4,401 = 3.68, p < 0.01). Administration staff believed that treatment would be significantly more helpful and that COVID-19 would last a shorter amount of time than medical/nursing staff and HSCP. However, administration staff were significantly more concerned than HSCP about COVID-19. Template analysis on 1059 responses to the Cause items of the B-IPQ identified ten higher order categories of perceived Cause of COVID-19. The top two Causes identified at both Waves were 'individual behavioural factors' and 'overseas travel'. This study has progressed our understanding of the models HCWs hold about COVID-19 over time, and has highlighted the utility of the template analysis approach in analysing free-text questionnaire data. We suggest that group and individual occupational identities of HCWs may be of importance in shaping HCWs responses to working through COVID-19.

Reduced peripheral activity leading to hepato-preferential action of basal insulin peglispro compared with insulin glargine in patients with type 1 diabetes.

AIMS: Basal insulin peglispro (BIL), a novel PEGylated basal insulin with a large hydrodynamic size, has a delayed absorption and reduced clearance that prolongs the duration of action. The current study compared the effects of BIL and insulin glargine (GL) on endogenous glucose production (EGP), glucose disposal rate (GDR) and lipolysis in patients with type 1 diabetes. MATERIALS AND METHODS: This was a randomized, open-label, four-period, crossover study. Patients received intravenous infusions of BIL and GL, each at two dose levels selected for partial and maximal suppression of EGP, during an 8 to 10 h euglycemic clamp procedure with d-[3-3 H] glucose. RESULTS: Following correction for equivalent human insulin concentrations (EHIC), low-dose GL infusion resulted in similar EGP at the end of the clamp compared to low-dose BIL infusion (GL/BIL ratio of 1.03) but a higher GDR (GL/BIL ratio of 2.42), indicating similar hepatic activity but attenuated peripheral activity of BIL. Consistent with this, the EHIC-corrected GDR/EGP at the end of the clamp was 1.72-fold greater for GL than BIL following low-dose administration. At the lower dose of BIL and GL (concentrations in the therapeutic range), BIL produced less suppression of lipolysis compared with GL as indicated by free fatty acid and glycerol levels at the end of the clamp. CONCLUSIONS: Compared with GL, BIL restored the hepato-peripheral insulin action gradient seen in normal physiology via its peripherally restricted action on target tissues related to carbohydrate and lipid metabolism.

Diagnostic accuracy of non-radiologist performed ultrasound for abdominal aortic aneurysm: systematic review and meta-analysis.

BACKGROUND: Ultrasonography is increasingly used by clinicians to identify abdominal aortic aneurysms (AAA). We performed a systematic review and meta-analysis comparing the accuracy of non-radiologist performed ultrasound (NRPUS) for AAA disease to the 'gold standard' of radiologist performed aortic imaging (RPI), intra-operative findings or postmortem findings. METHODS: Cochrane Library, MEDLINE, EMBASE, SCOPUS-V.4, trial registries, conference proceedings, and article reference lists were searched to identify studies comparing NRPUS with RPI as the reference standard. Data abstracted from eligible studies was used to generate 2 × 2 contingency tables allowing calculation of pooled sensitivity and specificity values. RESULTS: 11 studies (944 patients) evaluated NRPUS for AAA detection. NRPUS had a pooled sensitivity of 0.975 [95% confidence interval (CI), 0.942-0.992] for AAA detection and a pooled specificity of 0.989 (95% CI, 0.979-0.995). CONCLUSIONS: Non-radiologist performed ultrasound achieves acceptable sensitivity and specificity for both detection and measurement of AAA. There was no evidence of significant heterogeneity with respect to pooled sensitivity or specificity.

Prescreened Whole O Blood Group Walking Blood Bank Capabilities for Nontraditional Maritime Medical Receiving Platforms: A Case Series.

BACKGROUND: Tactical Combat Casualty Care (TCCC) guidelines recognize low-titer group O whole blood (LTOWB) as the resuscitative fluid of choice for combat wounded. Utilization of prescreened LTOWB in a walking blood bank (WBB) format has been well described by the Ranger O low-titer blood (ROLO) and the United States Marine Corps Valkyrie programs, but it has not been applied to the maritime setting. METHODS: We describe three WBB experiences of an expeditionary resuscitative surgical system (ERSS) team, attached to three nontraditional maritime medical receiving platforms, over 6 months. RESULTS: Significant variations were identified in the number of screened eligible donors, the number of LTOWB donors, and the timely arrival at WBB activation sites between the platforms. Overall, 95% and 84% of the screened eligible group O blood donors on the Arleigh Burke Class Destroyer (DDG) and Nimitz Class Aircraft Carrier (CVN), respectively, were determined to be LTOWB. However, only 37% of the eligible screened group O blood donors aboard the Harper's Ferry Class Dock Landing Ship (LSD) were found to be LTOWB. Of the eligible donors, 66% did not complete screening, with 52% citing a correctable reason for nonparticipation. CONCLUSION: LTOWB attained through WBBs may be the only practical resuscitative fluid on maritime platforms without inherent blood product storage capabilities to perform remote damage control resuscitation. Future efforts should focus on optimizing WBBs through capability development, education, and training efforts.

Society for Surgery of the Alimentary Tract State-of-the-Art Session 2022: Frailty in Surgery.

Given the exponentially aging population and rising life expectancy in the United States, surgeons are facing a challenging frail population who may require surgery but may not qualify based on their general fitness. There is an urgent need for greater awareness of the importance of frailty measurement and the implementation of universal assessment of frail patients into clinical practice. Pairing risk stratification with stringent protocols for prehabilitation and minimally invasive surgery and appropriate enhanced recovery protocols could optimize and condition frail patients before, during, and immediately after surgery to mitigate postoperative complications and consequences on patient function and quality of life. In this paper, highlights from the 2022 Society for Surgery of the Alimentary Tract State-of-the-Art Session on frailty in surgery are presented. This work aims to improve the understanding of the impact of frailty on patients and the methods used to augment the outcomes for frail patients during their surgical experience.

Reducing no-show visits and disparities in access: The impact of telemedicine.

BACKGROUND: No-show visits have serious consequences for patients, providers, and healthcare systems as they lead to delays in care, increased costs, and reduced access to services. Telemedicine has emerged as a promising alternative to in-person visits by reducing travel barriers, but risks exacerbating the digital divide. The aim of this study was to assess the impact of telemedicine (video and phone) at a tertiary care academic center on no-show visits compared to in-person visits. METHODS: A retrospective cohort analysis of all weekday clinic visits among in-state adult patients at a single tertiary care center in the southeast from January 2020 to April 2023 was performed. Rates of no-show visits for patients who were seen via phone and video were compared with those who were seen in-person. Demographic and clinical characteristics of these groups were also compared, including age, sex, race/ethnicity, socioeconomic status, and visit type. The primary outcome was the rate of no-show visits for each visit type. RESULTS: Our analysis included 3,105,382 scheduled appointments, of which 81.2% were in-person, 13.4% via video, and 5.4% via phone calls. Compared to in-person visits, phone calls and video visits reduced the odds of no-show visits by 50% (aOR 0.5, CI 0.49-0.51) and 15% (aOR 0.85, CI 0.84-0.86), respectively. Older patients, Black patients, patients furthest from clinic, and patients from counties with the greatest degree of vulnerability and disparities in digital access were more likely to use phone visits. No-shows were more common among non-white, male, and younger patients from counties with lower socioeconomic status. CONCLUSION: Telemedicine effectively reduced no-show visits. However, limiting telemedicine to video-based visits only exacerbated disparities in access. Phone calls allow historically underserved patients from lower socioeconomic backgrounds to access healthcare and should be included within the definition of telemedicine.

Inhibition of protein kinase A activity depresses phrenic drive and glycinergic signalling, but not rhythmogenesis in anaesthetized rat.

The cAMP-protein kinase A (PKA) pathway plays a critical role in regulating neuronal activity. Yet, how PKA signalling shapes the population activity of neurons that regulate respiratory rhythm and motor patterns in vivo is poorly defined. We determined the respiratory effects of focally inhibiting endogenous PKA activity in defined classes of respiratory neurons in the ventrolateral medulla and spinal cord by microinjection of the membrane-permeable PKA inhibitor Rp-adenosine 3',5'-cyclic monophosphothioate (Rp-cAMPS) in urethane-anaesthetized adult Sprague Dawley rats. Phrenic nerve activity, end-tidal CO2 and arterial pressure were recorded. Rp-cAMPS in the preBötzinger complex (preBötC) caused powerful, dose-dependent depression of phrenic burst amplitude and inspiratory period. Rp-cAMPS powerfully depressed burst amplitude in the phrenic premotor nucleus, but had no effect at the phrenic motor nucleus, suggesting a lack of persistent PKA activity here. Surprisingly, inhibition of PKA activity in the preBötC increased phrenic burst frequency, whereas in the Bötzinger complex phrenic frequency decreased. Pretreating the preBötC with strychnine, but not bicuculline, blocked the Rp-cAMPS-evoked increase in frequency, but not the depression of phrenic burst amplitude. We conclude that endogenous PKA activity in excitatory inspiratory preBötzinger neurons and phrenic premotor neurons, but not motor neurons, regulates network inspiratory drive currents that underpin the intensity of phrenic nerve discharge. We show that inhibition of PKA activity reduces tonic glycinergic transmission that normally restrains the frequency of rhythmic respiratory activity. Finally, we suggest that the maintenance of the respiratory rhythm in vivo is not dependent on endogenous cAMP-PKA signalling.

Improving patient care--the first year in a dedicated surgical assessment unit.

A surgical assessment unit (SAU) was established in October 2009 at the Mid-Western Regional Hospital. We assessed this servic in its initial year and compared it to Emergency Department (ED) services. We audited SAU and ED databases and theatre logbooks from November 2009 to October 2010. 1949 patients were referred to the SAU and 857 patients were admitted (44%). Only 44 SAU patients (6%) waited more than 6 hours for a bed compared to 828 patients (68%) admitted through the ED. SAU patients who required emergency surgery had a shorter waiting time before theatre (37 (18.6%) vs 9(6%) waited less than 6 hours, p < 0.05). To summarise, we found that almost 2,000 patients who would otherwise have presented to the ED were referred to the SAU. Waiting times for admission and theatre were significantly shorter. Further resource allocation could expand the service and improve it further, by diverting more patients from the ED.

Effects of intensive insulin therapy alone and in combination with pioglitazone on body weight, composition, distribution and liver fat content in patients with type 2 diabetes.

AIM: To evaluate the effects of intensive insulin therapy alone and with added pioglitazone on body weight, fat distribution, lean body mass (LBM) and liver fat in type 2 diabetic patients. METHODS: Twenty-five insulin-treated, obese patients with type 2 diabetes were randomized to addition of pioglitazone 45 mg (n = 12) or placebo (n = 13) and treated intensively for 12-16 weeks. Dual-energy X-ray absorptiometry/abdominal computed tomography scans were performed before/after treatment. LBM, visceral/subcutaneous adipose tissue (VAT/SAT) and liver/spleen (L/S) attenuation ratios were measured pre-/posttreatment (a ratio <1 represents fatty liver). RESULTS: Intensive insulin alone and insulin + pioglitazone significantly improved glycaemic control (7.8 ± 0.3 to 7.2 ± 0.3% and 7.6 ± 0.3 to 7.1 ± 0.4%, respectively). Body weight gain was greater with insulin + pioglitazone (4.9 ± 4.5 kg) versus insulin therapy alone (1.7 ± 0.7 kg). SAT increased significantly with pioglitazone + insulin therapy (393.9 ± 48.5 to 443.2 ± 56.7 cm(2) , p < 0.01) compared to a non-significant increase with insulin therapy alone (412.9 ± 42.5 to 420.8 ± 43.8 cm(2) ). VAT decreased non-significantly in both groups (240.3 ± 41.7 to 223.8 ± 38.1 cm(2) with insulin + pioglitazone and 266.6 ± 27.4 to 250.5 ± 22.2 cm(2) with insulin therapy). LBM increased significantly by 1.92 ± 0.74 kg with insulin + pioglitazone treatment. The L/S attenuation ratio in the placebo + insulin group decreased from 1.08 ± 0.1 to 1.04 ± 0.1 (p = ns) and increased from 1.00 ± 0.1 to 1.08 ± 0.05 (p = 0.06) in the pioglitazone + insulin group. CONCLUSIONS: Intensification of insulin therapy in type 2 diabetic patients causes modest weight gain and no change in body fat distribution, LBM or liver fat. In contrast, the addition of pioglitazone, at equivalent glycaemia, increases weight gain, fat mass and SAT; increases LBM and tends to decrease liver fat. These changes in fat distribution may contribute to the beneficial effects of pioglitazone, despite greater weight gain.

Wall shear stresses remain elevated in mature arteriovenous fistulas: a case study.

Maintaining vascular access (VA) patency continues to be the greatest challenge for dialysis patients. VA dysfunction, primarily due to venous neointimal hyperplasia development and stenotic lesion formation, is mainly attributed to complex hemodynamics within the arteriovenous fistula (AVF). The effect of VA creation and the subsequent geometrical remodeling on the hemodynamics and shear forces within a mature patient-specific AVF is investigated. A 3D reconstructed geometry of a healthy vein and a fully mature patient-specific AVF was developed from a series of 2D magnetic resonance image scans. A previously validated thresholding technique for region segmentation and lumen cross section contour creation was conducted in MIMICS 10.01, allowing for the creation of a 3D reconstructed geometry. The healthy vein and AVF computational models were built, subdivided, and meshed in GAMBIT 2.3. The computational fluid dynamic (CFD) code FLUENT 6.3.2 (Fluent Inc., Lebanon, NH) was employed as the finite volume solver to determine the hemodynamics and shear forces within the healthy vein and patient-specific AVF. Geometrical alterations were evaluated and a CFD analysis was conducted. Substantial geometrical remodeling was observed, following VA creation with an increase in cross-sectional area, out of plane curvature (maximum angle of curvature in AVF=30 deg), and angle of blood flow entry. The mean flow velocity entering the vein of the AVF is dramatically increased. These factors result in complex three-dimensional hemodynamics within VA junction (VAJ) and efferent vein of the AVF. Complex flow patterns were observed and the maximum and mean wall shear stress (WSS) magnitudes are significantly elevated. Flow reversal was found within the VAJ and efferent vein. Extensive geometrical remodeling during AVF maturation does not restore physiological hemodynamics to the VAJ and venous conduit of the AVF, and high WSS and WSS gradients, and flow reversal persist. It is theorized that the vessel remodelling and the continued non-physiological hemodynamics within the AVF compound to result in stenotic lesion development.

Developmental and tissue-specific expression of nuclear proteins that bind the regulatory element of the major histocompatibility complex class I gene.

Expression of MHC class I genes varies according to developmental stage and type of tissues. To study the basis of class I gene regulation in tissues in vivo, we examined binding of nuclear proteins to the conserved cis sequence of the murine H-2 gene, class I regulatory element (CRE), which contains two independent factor-binding sites, region I and region II. In gel mobility shift analyses we found that extracts from adult tissues that express class I genes, such as spleen and liver, had binding activity to region I. In contrast, extracts from brain, which does not express class I genes, did not show region I binding activity. In addition, fetal tissues that express class I gene at very low levels, also did not reveal region I binding activity. Binding activity to region I became detectable during the neonatal period when class I gene expression sharply increases. Most of these tissues showed binding activity to region II, irrespective of class I gene expression. Although region II contained a sequence similar to the AP-1 recognition site, AP-1 was not responsible for the region II binding activity detected in this work. These results illustrate a correlation between region I binding activity and developmental and tissue-specific expression of MHC class I genes. The CRE exerts an enhancer-like activity in cultured fibroblasts. We evaluated the significance of each factor binding to CRE. Single 2-bp mutations were introduced into the CRE by site-directed mutagenesis and the ability of each mutant to elicit the enhancer activity was tested in transient CAT assays. A mutation that eliminated region I protein binding greatly impaired enhancer activity. A mutation that eliminated region II binding also caused a lesser but measurable effect. We conclude that region I and region II are both capable of enhancing transcription of the class I gene. These results indicate that in vivo regulation of MHC class I gene expression is mediated by binding of trans-acting factors to the CRE.

Effects of intensive insulin therapy alone and with added pioglitazone on renal salt/water balance and fluid compartment shifts in type 2 diabetes.

OBJECTIVE: To evaluate the effects of intensive insulin therapy alone or with added pioglitazone on renal salt/water balance and body fluid compartment shifts in type 2 diabetes. METHODS: A total of 25 insulin-treated, obese patients with type 2 diabetes were randomized to pioglitazone 45 mg (n = 12) or placebo (n = 13) and treated intensively for 12-16 weeks to achieve equivalent glycaemic control. We measured total body water (TBW) and extracellular/intracellular fluid by bioimpedance analysis; plasma/RBC volume with I(131)albumin; sodium handling by fractional excretion of sodium/lithium (FeNa/FeLi) and other renal/hormonal parameters. RESULTS: Intensification of insulin therapy and the addition of pioglitazone significantly improved glycaemia (HbA1C 7.8-7.2% and 7.6-7.1%) and increased body weight (1.7 and 4.9 kg) respectively. TBW increased 1.7 l with insulin alone (65% intracellular) and 1.6 l with added pioglitazone (75% extracellular) (p = 0.06 and 0.09 respectively). Plasma volume increased 0.2 +/- 0.1 l with insulin alone (p = 0.05) and 0.4 +/- 0.1 l with added pioglitazone (p < 0.05). Extravascular, extracellular (interstitial) fluid increased significantly and more with added pioglitazone (0.8 +/- 0.2 l, p < 0.01) than with insulin alone (0.4 +/- 0.2 l, p = ns). At steady-state, FeLi (marker of proximal-tubular sodium delivery to the distal nephron) increased significantly with added pioglitazone (12.4 +/- 1.3 to 18.0 +/- 3.2%) vs. no significant change with insulin alone (15.4 +/- 1.2 to 14.5 +/- 2.3%). There were no significant changes in the other parameters. CONCLUSION: In intensively insulin-treated obese type 2 diabetic patients, at equivalent glycaemic control, the addition of pioglitazone causes greater weight gain, but a similar increase in body water that is mainly extracellular and interstitial compared with intracellular increase with insulin therapy alone. Pioglitazone also increases the filtered load of sodium reabsorbed at the distal nephron with no net change in FeNa.

The use of laboratory sand, soil and crushed-glass filter columns for polishing domestic-strength synthetic wastewater that has undergone secondary treatment.

The aim of this study was to examine the performance of intermittently loaded, 150 mm-diameter stratified filter columns of 2 depths (0.65 and 0.375 m) comprising different media--sand, crushed glass and soil--in polishing the effluent from a laboratory horizontal flow biofilm reactor (HFBR) treating synthetic domestic-strength wastewater. The HFBR has been successfully used to remove organic carbon and ammonium-nitrogen (NH4-N) from domestic wastewater. In this treatment method, wastewater is allowed to flow over and back along a stack of polyvinyl chloride (PVC) sheets. Biofilms on the sheets reduce organic carbon, suspended matter, and nutrients in the wastewater, but to achieve the quality of a septic tank system, additional treatment is required. In all filters, at a hydraulic loading rate of 100 L m(-2) d(-1), 40-65% of chemical oxygen demand (COD) and practically 100% of total suspended solids (TSS) were removed, nitrification was complete, and bacterial numbers were reduced by over 80%, with best removals achieved in the soil filters (93%). Soil polishing filters with the depth of 0.65 m performed best in terms of organic carbon, total nitrogen (Tot-N) and bacterial removal. Data from this preliminary study are useful in the design of treatment systems to polish secondary wastewaters with similar water quality characteristics.

Removal of the membrane-anchoring domain of epidermal growth factor leads to intracrine signaling and disruption of mammary epithelial cell organization.

Autocrine EGF-receptor (EGFR) ligands are normally made as membrane-anchored precursors that are proteolytically processed to yield mature, soluble peptides. To explore the function of the membrane-anchoring domain of EGF, we expressed artificial EGF genes either with or without this structure in human mammary epithelial cells (HMEC). These cells require activation of the EGFR for cell proliferation. We found that HMEC expressing high levels of membrane- anchored EGF grew at a maximal rate that was not increased by exogenous EGF, but could be inhibited by anti-EGFR antibodies. In contrast, when cells expressed EGF lacking the membrane-anchoring domain (sEGF), their proliferation rate, growth at clonal densities, and receptor substrate phosphorylation were not affected by anti-EGFR antibodies. The sEGF was found to be colocalized with the EGFR within small cytoplasmic vesicles. It thus appears that removal of the membrane-anchoring domain converts autocrine to intracrine signaling. Significantly, sEGF inhibited the organization of HMEC on Matrigel, suggesting that spatial restriction of EGF access to its receptor is necessary for organization. Our results indicate that an important role of the membrane-anchoring domain of EGFR ligands is to restrict the cellular compartments in which the receptor is activated.

Cytotoxic antibody in normal human serums reactive with tumor cells from acute lymphocytic leukemia.

Serums showing complement-dependent cytotoxic reactions to acute lymphocytic leukemia cells were detected in three normal unimmunized subjects. These serums were reactive with tumor cells from 514 (514 tested) acute lymphocytic leukemia patients, and three (12 tested) patients with acute myelocytic leukemia; they did not react with tumor cells from patients with acute monocytic leukemia (two tested), with chronic lymphocytic leukemia (two tested) or with leukolymphosarcoma (two tested); nor did they react with normal lymphocytes from 52 different donors. These reactive serums appear to recognize antigens primarily associated with acute lymphocytic leukemia.

Structure of a protein photocycle intermediate by millisecond time-resolved crystallography.

The blue-light photoreceptor photoactive yellow protein (PYP) undergoes a self-contained light cycle. The atomic structure of the bleached signaling intermediate in the light cycle of PYP was determined by millisecond time-resolved, multiwavelength Laue crystallography and simultaneous optical spectroscopy. Light-induced trans-to-cis isomerization of the 4-hydroxycinnamyl chromophore and coupled protein rearrangements produce a new set of active-site hydrogen bonds. An arginine gateway opens, allowing solvent exposure and protonation of the chromophore's phenolic oxygen. Resulting changes in shape, hydrogen bonding, and electrostatic potential at the protein surface form a likely basis for signal transduction. The structural results suggest a general framework for the interpretation of protein photocycles.

Emotional outcomes in clinically isolated syndrome and early phase multiple sclerosis: a systematic review and meta-analysis.

OBJECTIVE: To study depression, anxiety, suicide risk, and emotional health-related quality of life (HRQoL) in people with clinically isolated syndrome (CIS) and in early phase multiple sclerosis (MS). METHODS: A systematic literature review was conducted with inclusion criteria of observational studies on outcomes of depression, anxiety, suicide risk, and emotional HRQoL in CIS and within five years since diagnosis of MS. Studies were screened using the Preferred Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines, and study quality was determined for included studies. Meta-analysis and meta-regression were performed if applicable. RESULTS: Fifty-one studies were included in the systematic review. In early phase MS, meta-analyses of the Hospital Anxiety Depression Scale (HADS) indicated prevalence levels of 17% (95% confidence interval (CI): 9 to 25%; p < .001) for depressive and 35% (95% CI: 28 to 41%; p < .001) for anxiety symptoms. Meta-regression analyses revealed an increase in mean HADS-D and HADS-A associated with larger sample size, and higher HADS-D mean with increased study quality. Similar depressive and anxiety symptoms were observed in CIS, and increased suicide risk and low emotional HRQoL was associated with depressive symptoms in early phase MS. The methodological quality of the studies was considered fair. CONCLUSIONS: Findings suggest that mild-to-moderate symptoms of depression and anxiety might be prevalent in CIS and in early phase MS. Future research on both clinical populations are needed, especially longitudinal monitoring of emotional outcomes.

A novel DXA-based hip failure index captures hip fragility independent of BMD.

Capability of a novel dual-energy X-ray absorptiometry (DXA)-based hip failure index (HiFI) to discriminate between hip fracture cases and controls was evaluated. Given the constraints of planar DXA, the femoral neck was assumed a foam-filled ( approximately trabecular bone), thin-walled ( approximately cortical bone) sandwich structure, while HiFI estimated the critical force sufficient to buckle the wall of such a structure. Proximal femur DXA data from 1379 women aged 65yr and older, 268 with prior hip fracture were used. Comparison between standard areal bone mineral density (BMD), femur strength index (FSI), and HiFI was based on areas under receiver operatoring characteristic curves (AUC). The mean femoral neck BMD (SD) was 0.689 (0.109) g/cm(2) among the cases and 0.768 (0.119) g/cm(2) among the controls; the mean FSI 1.33 (0.36) and 1.54 (0.41), and the mean HiFI -0.28 (0.14) and -0.18 (0.15), respectively; all intergroup differences were highly significant (p<0.001). The intergroup difference for HiFI remained significant (p<0.002) after adjusting for age and BMD or FSI. The AUCs were 0.696 (95% confidence interval [CI]: 0.661-0.730) for BMD, 0.665 (0.630-0.700) for FSI, and 0.701 (0.666-0.736) for HiFI. In conclusion, HiFI may capture structural traits that account for femoral neck fragility independently of BMD or FSI. Obviously, the use of actual geometric and structural information from three-dimensional imaging of the femoral neck would help diminish the crude assumptions of the present DXA approach and reveal the true potential of the HiFI approach to gauge hip fragility and identify at-risk individuals for hip fractures.