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Background: Stimulants such as cocaine and amphetamines are well-established risk factors for acute aortic dissection. Despite the fact that marijuana is the most commonly used illicit drug in the United States, its relationship to acute aortic syndromes has not been well studied. Methods: A comprehensive retrospective review was undertaken of all consecutive patients who presented with acute Stanford type A aortic dissection from January 2017 to December 2019. Of 152 patients identified, 51 (33.6%) underwent comprehensive urine toxicology screening at clinical presentation. The characteristics and outcomes of the patients with urine results positive for tetrahydrocannabinol (THC) (n = 9, 17.6%) were compared with the 42 patients who had no evidence of recent marijuana consumption. Results: Of the 51 dissection patients who underwent broad-spectrum urine toxicology screening upon presentation, 9 (17.6%) returned positive results for THC, a proportion higher than would be expected for the general population. All THC patients were male; 3 concurrently tested positive for cocaine, and 3 others had evidence of recent amphetamine use. The THC patients were significantly younger than the non-THC patients (mean ± standard deviation age 48 ± 11.3 versus 61.4 ± 12.3 years, respectively, P = .004). A greater proportion of the THC cohort had a known diagnosis of aortic aneurysm before the dissection (44.4% versus 4.8%, P = .006). All patients underwent expeditious surgical repair. Thirty-day mortality for the entire cohort of 51 patients was 19.6% (10 deaths); for the THC group, it was 11.1% (1 death). There was no difference in the incidence of major postoperative complications between the 2 groups. Conclusion: Marijuana is the third most commonly used substance in the United States, after alcohol and tobacco. Although marijuana use is understudied, our results suggest that marijuana may be a contributing risk factor for acute type A aortic dissection, particularly in patients with other predisposing risk factors. Given the recent national trend to legalize marijuana, with the concomitant potential for exponential increases in its consumption, we suggest that the diagnosis of aortic dissection be considered earlier in any younger patient who presents with suggestive symptoms, especially if there is a history of recent marijuana use.

Background Time of day has been associated with adverse outcomes in certain surgical pathologies. Because acute type A aortic dissection typically mandates immediate repair, relatively little attention has been paid to the potential impact of the day–night timing of the operation itself. We sought to determine whether patients with acute dissection treated during typical working hours demonstrated a difference in outcomes compared with those who required surgery after hours. Methods We undertook a comprehensive review of our prospectively collected database from July 2014 to October 2018. A total of 164 consecutive patients underwent primary repair of an acute type A dissection. Based on the procedure start time, patients were divided into 2 groups: working hours (7 am to 4 pm , Monday to Friday; n = 60), and after hours (all other times, including weekends and holidays; n = 104). We propensity-matched 58 pairs of patients and analyzed perioperative data and short-term clinical outcomes. Results Thirty-day mortality for all 164 patients was 10.4% (17 deaths), which was not significantly different between the matched groups (working-hours: 8 deaths [13.8%] versus after hours: 4 deaths [6.9%]; P = .36). Perfusion, cross-clamp, and circulatory arrest times did not differ between groups, nor did the types of aortic repairs performed. Postoperative complications were also comparable, including stroke, reoperation for bleeding, and new-onset renal failure requiring dialysis. Conclusions Thirty-day mortality and major morbidity after acute type A dissection repair are independent of when the operation is performed. Expeditious surgical intervention is recommended for all primary acute type A dissection, irrespective of time of day.

Background Direct cannulation of the innominate artery for selective antegrade cerebral perfusion has been shown to be safe in elective proximal aortic reconstructions. We sought to evaluate the safety of this technique in acute aortic dissection. Methods A multi-institutional retrospective review was undertaken of patients who underwent proximal aortic reconstruction for Stanford type A dissection between 2006 and 2016. Those patients who had direct innominate artery cannulation for selective antegrade cerebral perfusion were selected for analysis. Results Seventy-five patients underwent innominate artery cannulation for ACP for Stanford Type A Dissections. Isolated replacement of the ascending aorta was performed in 36 patients (48.0%), concomitant aortic root replacement was required in 35 patients (46.7%), of whom 7 had a valve-sparing aortic root replacement, ascending aorta and arch replacement was required in 4 patients (5%). Other procedures included frozen elephant trunk (n = 11 (14.7%)), coronary artery bypass grafting (n = 20 (26.7%)), and peripheral arterial bypass (n = 4 (5.3%)). Mean hypothermic circulatory arrest time was 19 ± 13 min. Thirty-day mortality was 14.7% (n = 11). Perioperative stroke occurred in 7 patients (9.3%). Conclusions This study is the first comprehensive review of direct innominate artery cannulation through median sternotomy for selective antegrade cerebral perfusion in aortic dissection. Our experience suggests that this strategy is a safe and effective technique compared to other reported methods of cannulation and cerebral protection for delivering selective antegrade cerebral perfusion in these cases.

Purpose/Background: Clozapine clearance is influenced by sex, smoking status, ethnicity, co-prescription of inducers or inhibitors, obesity and inflammation. In 126 Beijing inpatients, we measured repeated trough steady-state serum concentrations and identified 4% (5/126) who were phenotypical poor metabolizers (PMs); none were ultrarapid metabolizers (UMs). They were defined as being 2 standard deviations beyond the means of total clozapine concentration/dose ratios stratified by sex and smoking. Using this definition, this study explores the prevalences of PMs and UMs using data from 4 already-published Asian samples. Three samples were East Asian (Beijing 2, Taipei and Seoul); one was from South India (Vallore). Findings/Results: The prevalence of phenotypical PMs ranged from 2-13%, but inflammation was not excluded. The prevalence was 7.3% (14/191) for Beijing 2, 11% (8/70) for Taipei, 13% (9/67) for Seoul, and 2% (2/101) for the Vellore sample. Five phenotypical PMs appeared to be associated with extreme obesity. Phenotypic UM prevalence ranged from 0-1.6%, but may be partly explained by lack of adherence. A Vellore phenotypic UM appeared to be associated with induction through high coffee intake. Implications/Conclusions: Around 10% of Asians may be clozapine PMs and may only need 50-150 mg/day to get therapeutic concentrations. Future studies combining gene sequencing for new alleles with repeated concentrations and careful control of confounders including inhibitors, inflammation and obesity should provide better estimations of the prevalence of phenotypic clozapine PMs across races. Clozapine UM studies require excluding potent inducers, careful supervision of compliance in inpatient settings and multiple serum concentrations.

Background The World Health Organization (WHO) has reframed health and healthcare for older people around achieving the goal of healthy ageing. The recent WHO Integrated Care for Older People (ICOPE) guidelines focus on maintaining intrinsic capacity, i.e., addressing declines in neuromusculoskeletal, vitality, sensory, cognitive, psychological, and continence domains, aiming to prevent or delay the onset of dependence. The target group with 1 or more declines in intrinsic capacity (DICs) is broad, and implementation may be challenging in less-resourced settings. We aimed to inform planning by assessing intrinsic capacity prevalence, by characterising the target group, and by validating the general approach—testing hypotheses that DIC was consistently associated with higher risks of incident dependence and death. Methods and findings We conducted population-based cohort studies (baseline, 2003–2007) in urban sites in Cuba, Dominican Republic, Puerto Rico, and Venezuela, and rural and urban sites in Peru, Mexico, India, and China. Door-knocking identified eligible participants, aged 65 years and over and normally resident in each geographically defined catchment area. Sociodemographic, behaviour and lifestyle, health, and healthcare utilisation and cost questionnaires, and physical assessments were administered to all participants, with incident dependence and mortality ascertained 3 to 5 years later (2008–2010). In 12 sites in 8 countries, 17,031 participants were surveyed at baseline. Overall mean age was 74.2 years, range of means by site 71.3–76.3 years; 62.4% were female, range 53.4%–67.3%. At baseline, only 30% retained full capacity across all domains. The proportion retaining capacity fell sharply with increasing age, and declines affecting multiple domains were more common. Poverty, morbidity (particularly dementia, depression, and stroke), and disability were concentrated among those with DIC, although only 10% were frail, and a further 9% had needs for care. Hypertension and lifestyle risk factors for chronic disease, and healthcare utilisation and costs, were more evenly distributed in the population. In total, 15,901 participants were included in the mortality cohort (2,602 deaths/53,911 person-years of follow-up), and 12,939 participants in the dependence cohort (1,896 incident cases/38,320 person-years). One or more DICs strongly and independently predicted incident dependence (pooled adjusted subhazard ratio 1.91, 95% CI 1.69–2.17) and death (pooled adjusted hazard ratio 1.66, 95% CI 1.49–1.85). Relative risks were higher for those who were frail, but were also substantially elevated for the much larger sub-groups yet to become frail. Mortality was mainly concentrated in the frail and dependent sub-groups. The main limitations were potential for DIC exposure misclassification and attrition bias. Conclusions In this study we observed a high prevalence of DICs, particularly in older age groups. Those affected had substantially increased risks of dependence and death. Most needs for care arose in those with DIC yet to become frail. Our findings provide some support for the strategy of optimising intrinsic capacity in pursuit of healthy ageing. Implementation at scale requires community-based screening and assessment, and a stepped-care intervention approach, with redefined roles for community healthcare workers and efforts to engage, train, and support them in these tasks. ICOPE might be usefully integrated into community programmes for detecting and case managing chronic diseases including hypertension and diabetes., In a population-based cohort study, Martin J. Prince and colleagues evaluate intrinsic capacity and its associations with incident dependence and mortality in Latin America, India and China., Author summary Why was this study done? As we grow older, we are affected to different degrees by declines in the working of our organs and body systems, limiting our ability to get around, be well nourished, see, hear, and think clearly, stay continent, and maintain mood and well-being. The World Health Organization has proposed a programme—Integrated Care for Older People (ICOPE)—supported by evidence that simple interventions may slow or reverse these processes, with potential to improve health and functioning and delay needs for care developing among older people. ICOPE targets low- and middle-income countries, but we do not yet know how many older people in these settings are significantly affected by early age-related decline, or whether these changes predict who will go on to deteriorate further, leading to needs for care and earlier death. What did the researchers do and find? We had already completed (between 2003 and 2007) baseline community surveys of 17,031 people aged 65 years and over living in 12 urban and rural sites in 6 Latin American countries, India, and China; we then tried to interview them again 3 to 5 years later (between 2008 and 2010) to identify who had died (in 11 sites, among 15,901 older people) and who had developed needs for care (in 10 sites, among 12,939 older people). Analysing baseline data from these studies, we found that between two-thirds and three-quarters of older people were affected by significant decline in at least 1 of the areas targeted by the ICOPE programme; this proportion was highest among the older old, who were also more likely to have problems in multiple areas. Most (nearly three-quarters) of those with significant decline at baseline had not yet gone on to become physically frail or develop needs for care; they were nevertheless 1.7 to 1.9 times more likely than those without any significant decline to develop needs for care over the follow-up period, and 1.3 to 1.4 times more likely to have died. What do these findings mean? Delivering comprehensive assessment, care planning, and community interventions to up to three-quarters of the older population would be a major challenge for poorly resourced health systems in low- and middle-income countries. Nevertheless, findings from our analyses support the World Health Organization’s strategy to promote health and well-being by targeting a broad group with early decline who do seem to be at increased risk of adverse outcomes. Future research should focus upon feasible, acceptable, and efficient methods of delivering the ICOPE programme (implementation science) and its effectiveness and cost-effectiveness in improving health and social outcomes (controlled trials). The main limitations were that health declines were measured in different ways, some of which may have been imprecise, and those who could not be followed up may have had different characteristics to those who were included in the analysis.

Juvenile crime or delinquency has been increasing at an alarming rate in recent times. In many countries, including India, the minimum age for criminal responsibility is 16 years. The present study aimed to estimate the probability of a south Indian adolescent either being or being older than the legally relevant age of 16 years using Demirjian's tooth formation stages. Orthopantomograms (OPG) of 640 south Indian adolescents (320 boys and 320 girls) aged between 12 and 20 years were retrospectively analyzed. In each OPG, Demirjian's formation stage of the mandibular left third molar was recorded and the data was subjected to statistical analysis. Descriptive and Pearsons correlation statistics were performed. The empirical probabilities were provided relative to the medico-legal question of predicting 16 years of age. The distribution of age throughout the 10th, 25th, 50th, 75th and 90th percentile follows a logical distribution pattern horizontally and vertically. Pearson's correlation statistics showed a strong positive correlation between the Demirjian's stages and age for both sexes. Therefore, it can be concluded that stage "F" can be used to predict the attainment of age equal to or older than 16 years with a probability of 93.9% for boys and 96.6% for girls.

BACKGROUND There is, as yet, no broad consensus regarding the optimal surgical approach for patients requiring reoperative mitral valve surgery. Consequently, we sought to evaluate the perioperative outcomes for patients undergoing redo mitral surgery via right mini thoracotomy as compared with traditional resternotomy. METHODS A comprehensive retrospective review of our prospectively collected database was undertaken from January 2011 to December 2017. We propensity matched 90 patients who underwent reoperative mitral valve surgery via right mini thoracotomy with a concurrent cohort of patients who had redo median sternotomy. Intraoperative data and short-term clinical outcomes were analyzed. RESULTS The 30-day mortality was 3.3% (six deaths) in the entire cohort, not significantly different between redo sternotomy and mini thoracotomy groups. Patients who had their procedure via right mini thoracotomy had reduced intensive care unit (P = .029) and overall hospital (P

Background It is recognized that healthcare workers (HCWs) are at high risk of contracting Covid-19. It is incumbent on occupational health staff to recognize potential symptoms of Covid-19 among HCWs. Aims The aims of the study were to describe the presenting symptoms of HCWs who developed Covid-19 in Ireland, and to estimate the odds of specific symptoms being associated with a positive Covid-19 polymerase chain reaction (PCR) result. Methods A retrospective chart review of all symptomatic HCWs who self-presented for Covid-19 testing in Cork from March to May 2020 was conducted. A sex-matched case–control study was carried out to compare presenting features among those who tested positive compared to those who tested negative. Univariate and multivariable-adjusted conditional logistic regression models were run using Stata 15.0 to identify the symptoms associated with positive Covid-19 swab results. Results Three hundred and six HCWs were included in the study; 102 cases and 204 controls. Common presenting features among cases were fever/chills (55%), cough (44%) and headache (35%). The symptoms which were significantly associated with a positive Covid-19 swab result were loss of taste/smell (adjusted odds ratio [aOR] 12.15, 95% confidence interval [CI] 1.36–108.79), myalgia (aOR 2.36, 95% 1.27–4.38), fatigue (aOR 2.31, 95% CI 1.12–4.74), headache (aOR 2.11, 95% CI 1.19–3.74) and fever/chills (aOR 1.88, 95% CI 1.12–3.15). Conclusions Fever, fatigue, myalgia, loss of taste/smell and headache were associated with increased odds of a Covid-19 diagnosis among symptomatic self-referred HCWs compared with those had negative swab results. Testing criteria for HCWs should reflect the broad range of possible symptoms of Covid-19.

Background: Immune checkpoint inhibitor (ICI) therapy predisposes patients to immune-related adverse events (irAEs). Data are limited regarding the incidence, management, and outcomes of one such irAE: mucositis. In this study, we evaluated the clinical characteristics, disease course, treatment, and outcomes of ICI-mediated mucositis. Methods: This was a retrospective, single-center study of patients who received ICI therapy and developed oral mucositis at The University of Texas MD Anderson Cancer Center from January 2009 to September 2019. Inclusion criteria included age ≥18 years, a diagnosis of oral mucositis and/or stomatitis based on ICD-9 and ICD-10 codes, and therapy using CTLA-4 or PD-1/L1 inhibitors alone or combined with other agents. Results: We identified 152 patients with a mean age of 60 years, 51% of whom were men. Of the sample patients, 73% had stage IV cancer, with melanoma the most common (28%). Median time from ICI initiation to mucositis was 91 days. The most common clinical presentation of mucositis was odynophagia and/or oral pain (89%), 91% developed CTCAE grade 1–2 mucositis, and 78% received anti–PD-1/L1 monotherapy. Compared with anti–PD-1/L1–based therapy, anti–CTLA-4–based therapy was more frequently associated with earlier onset of mucositis (73 vs 96 days; P=.077) and a lower rate of symptom resolution (76% vs 92%; P=.029); 24% of patients required immunosuppressive therapy, which was associated with longer symptom duration (84 vs 34 days; P=.002) and higher mucositis recurrence rate (61% vs 32%; P=.006). ICI interruption was associated with worse survival (P=.037). Mucositis recurrence, immunosuppressant use, and presence of other irAEs did not affect survival. Conclusions: For ICI-mediated mucositis, a diagnosis of exclusion has not been well recognized and is understudied. Although the clinical symptoms of mucositis are mostly mild, approximately 25% of patients require immunosuppression. Mucositis recurrence can occur in approximately 39% patients. Our results showed that ICI interruption compromises overall survival.

Background Hybrid coronary revascularization (HCR) constitutes a left internal mammary artery graft to the left anterior descending (LAD) coronary artery, coupled with percutaneous coronary intervention (PCI) for non-LAD lesions. This management strategy is not commonly offered to patients with complex multivessel disease. Our objective was to evaluate 8-year survival in patients with triple-vessel disease (TVD) treated by HCR, compared with that of concurrent matched patients managed by traditional coronary artery bypass grafting (CABG) or multivessel PCI. Methods A retrospective review was undertaken of 4805 patients with TVD who presented between January 2009 and December 2016. A cohort of 100 patients who underwent HCR were propensity-matched with patients treated by CABG or multivessel PCI. The primary endpoint was all-cause mortality at 8 years. Results Patients with TVD who underwent HCR had similar 8-year mortality (5.0%) as did those with CABG (4.0%) or multivessel PCI (9.0%). A composite endpoint of death, repeat revascularization, and new myocardial infarction, was not significantly different between patient groups (HCR 21.0% vs CABG 15.0%, P = .36; HCR 21.0% vs PCI 25.0%, P = .60). Despite a higher baseline synergy between percutaneous coronary intervention with taxus and cardiac surgery(SYNTAX) score, HCR was able to achieve a lower residual SYNTAX score than multivessel PCI (P = .001). Conclusions In select patients with TVD, long-term survival and FREEDOM from major adverse cardiovascular events after HCR are similar to that seen after traditional CABG or multivessel PCI. HCR should be considered for patients with multivessel disease, presuming a low residual SYNTAX score can be achieved.

Rationale: Toxic shock syndrome (TSS) typically is an acute onset multi-organ infection caused by TSS toxin-1 producing Staphylococcus aureus. Herein we describe a highly unusual case report. Patient concerns: A male patient self-referred to the University of Minnesota Hospital with a chronic history of S aureus infection with accompanying fever, hypotension, and nonhealing, football-sized lesion on his leg. Diagnosis: An unusual case presentation of TSS/hyperimmunoglobulin E syndrome is described. The patient had a leg wound from which TSS toxin-1 S aureus was isolated. The patient exhibited characteristic skewing of T cells to those with variable region, β-chain T cell receptor-2. Other patients have been seen with related presentations. Interventions: The following therapeutic regimen was instituted: vigorous antibacterial scrubs several times daily plus intravenous Ancef 3 days each month; intravenous infusions of immunoglobulin G infusions (28 gm) every 3 weeks; and weekly subcutaneous injections of recombinant granulocyte colony-stimulating factor. Outcome: Improvement was obvious within 3 months: no further cellulitic episodes occurred; the patient regained 95 pounds in 9 months; blanching and cyanosis of fingers disappeared within 3 months as did intractable pain although mild hypesthesias continued for 2 years; erythroderma resolved, and repeat skin biopsies performed after 2 years no longer demonstrated T cell receptor skewing. Although IgE levels have not completely returned to normal, the patient remains in excellent health. Lessons: We propose that staphylococcal TSST-1 was responsible for the serious problems suffered by this patient as suggested by the following features: rapid onset of chronic, life-threatening, disorder that began with an episode of staphylococcal sepsis; the extraordinary elevation of IgE levels in this previously non-atopic individual; the acquired severe granulocyte chemotactic defect that accompanied this hyperimmunoglobulinemia (“Job Syndrome”) with its accompanying wound-healing defect; and the striking diffuse erythroderma, including palmar erythema (“Red Man Syndrome”) with hypotension and fever that also characterizes TSS.

Background Cognitive deficits, self-reported or found following electroconvulsive therapy (ECT), and their correlates are diverse. Despite the characteristics of people receiving ECT in Asia differ widely from the west, pertinent research from Asia remains sparse. Methods We investigated the correlates of self-reported, mini-mental status examination (MMSE) defined, and autobiographical memory deficits in a cohort that received ECT in a south Indian tertiary-care setting. 76 consecutive consenting people were recruited within seven days of completing their ECT course. Memory was assessed by a subjective Likert scale, MMSE, and an autobiographical memory scale (AMS). Psychopathology was assessed by brief psychiatric rating scale, and serum cortisol levels were estimated by chemi-luminescence immunoassays. Relevant sociodemographic and clinical data were collected from the participants, and their medical records. The correlates were analysed using generalised linear models after adjusting for the effects of potential confounders. Results Self-reported, MMSE-defined, and autobiographical memory deficits were present in 27.6% (95%CI 17.6–37.7%), 42.1% (95%CI 31.0–53.2%), and 36.8% (95%CI 26.0–47.7%) of participants, respectively. Agreement between the memory deficits was poor. Age, less education, duration of illness, hypothyroidism, and past history of another ECT course were significantly associated with MMSE-defined deficits. Age, anaemia, past ECT course, and pre-ECT blood pressure were significantly associated with autobiographical memory deficits, while residual psychopathology and cortisol levels were significantly associated with self-reported memory deficits. Conclusion Self-reported, MMSE-defined, and autobiographical memory deficits are common at the completion of ECT course, and their correlates differ. All service users receiving ECT need periodic cognitive assessments evaluating multiple cognitive domains.

Clozapine is the drug of choice for treatment-resistant schizophrenia. However, its use is associated with variable clinical responses and serious adverse effects. Polymorphisms in genes encoding proteins involved in synaptic neurotransmission may account for such variability. Here, we studied independent and epistatic genetic associations of polymorphisms in DRD4 (120-bp duplication) and COMT (Val158Met) with clinical response to clozapine in people with treatment-resistant schizophrenia. We studied 93 participants who were on stable doses of clozapine for at least 12 weeks. A total score of less than or equal to 35 on the Brief Psychiatric Rating Scale was defined as a clinical response. The genetic associations were tested using logistic regression analyses. Neither polymorphism studied was found to be independently associated with response to clozapine. However, a statistically significant gene-gene interaction was observed between the polymorphisms. Participants with the COMT Val/Met or Met/Met genotype, who also had one or two DRD4 120-bp alleles (120/240 and 120/120), showed significantly better clinical response to clozapine. Our results highlight the importance of investigating gene-gene interactions, while studying the pharmacogenetics of clozapine.

The hallmark of resting EEG spectra are distinct rhythms emerging from a broadband, aperiodic background. This aperiodic neural signature accounts for most of total EEG power, although its significance and relation to functional neuroanatomy remains obscure. We hypothesized that aperiodic EEG reflects a significant metabolic expenditure and therefore might be associated with the default mode network while at rest. During eyes-open, resting-state recordings of simultaneous EEG-fMRI, we find that aperiodic and periodic components of EEG power are only minimally associated with activity in the default mode network. However, a whole-brain analysis identifies increases in aperiodic power correlated with hemodynamic activity in an auditory-salience-cerebellar network, and decreases in aperiodic power are correlated with hemodynamic activity in prefrontal regions. Desynchronization in residual alpha and beta power is associated with visual and sensorimotor hemodynamic activity, respectively. These findings suggest that resting-state EEG signals acquired in an fMRI scanner reflect a balance of top-down and bottom-up stimulus processing, even in the absence of an explicit task.

Background: Emotional distress among caregivers of people with mental illness is common, changes overtime and requires appropriate coping strategies to prevent long-term disability. Explanatory models, which underpin understanding of disease and illness, are crucial to coping. Aim: To study the association of explanatory models and distress among caregivers of people with acute psychotic illness. Method: A total of 60 consecutive patients and their primary caregivers who presented to the Department of Psychiatry, Christian Medical College, Vellore, were recruited for the study. Positive and Negative Syndrome Scale (PANSS), Short Explanatory Model Interview (SEMI) and the General Health Questionnaire-12 (GHQ-12) were used to assess severity of psychosis, explanatory models of illness and emotional distress. Standard bivariate and multivariable statistics were employed. Results: Majority of the caregivers simultaneously held multiple models of illness, which included medical and non-medical perspectives. The GHQ-12 score were significantly lower in people who held multiple explanatory models of illness when compared to the caregivers who believed single explanations. Conclusion: Explanatory models affect coping in caregivers of patients with acute psychotic presentations. There is a need to have a broad-based approach to recovery and care.

Data on blood use in proximal aortic surgery is limited. This study sought to establish quality benchmarks in the pattern of transfusion during elective aortic root replacement.The Society of Thoracic Surgeons Adult Cardiac Surgery Database was queried to identify all patients who underwent primary elective aortic root replacement between July 2014 and June 2017. Multivariable negative binomial regressions were used to determine whether perioperative transfusion was associated with demographic or procedural factors. Multivariable logistic regression analysis was performed for clinical outcomes.Of 5559 patients analyzed, 38.95% (n = 2165) received no blood products. Patients who had a valve-sparing root replacement were less likely to undergo transfusion than those who received composite roots (bioprosthetic or mechanical valves) or homografts. The 30-day mortality for all patients was 2.57% (n = 143). Transfusion was associated with an increased risk of death at 30 days (odds ratio [OR], 1.833; P = .012), more frequent reoperation for bleeding (OR, 1.766; P .001), prolonged ventilation (OR, 1.935; P.001), a longer postoperative hospital stay (OR, 1.056; P.001), and a higher incidence of new dialysis-dependent renal failure (OR, 2.088; P = .003). There was no correlation between institutional case volume and transfusion practice.Elective aortic root replacement can be performed with acceptable requirements for blood products. Composite root replacement has a greater likelihood of transfusion than does a valve-sparing procedure. Transfusion is independently associated with more complications after elective aortic root surgery, including 30-day mortality.

Background The N400 event-related potential (ERP) is triggered by meaningful stimuli that are incongruous, or unmatched, with their semantic context. Functional magnetic resonance imaging (fMRI) studies have identified brain regions activated by semantic incongruity, but their precise links to the N400 ERP are unclear. In schizophrenia (SZ), N400 amplitude reduction is thought to reflect overly broad associations in semantic networks, but the abnormalities in brain networks underlying deficient N400 remain unknown. We utilized joint independent component analysis (JICA) to link temporal patterns in ERPs to neuroanatomical patterns from fMRI and investigate relationships between N400 amplitude and neuroanatomical activation in SZ patients and healthy controls (HC). Methods SZ patients (n = 24) and HC participants (n = 25) performed a picture-word matching task, in which words were either matched (APPLE→apple) by preceding pictures, or were unmatched by semantically related (in-category; IC, APPLE→lemon) or unrelated (out of category; OC, APPLE→cow) pictures, in separate ERP and fMRI sessions. A JICA “data fusion” analysis was conducted to identify the fMRI brain regions specifically associated with the ERP N400 component. SZ and HC loading weights were compared and correlations with clinical symptoms were assessed. Results JICA identified an ERP-fMRI “fused” component that captured the N400, with loading weights that were reduced in SZ. The JICA map for the IC condition showed peaks of activation in the cingulate, precuneus, bilateral temporal poles and cerebellum, whereas the JICA map from the OC condition was linked primarily to visual cortical activation and the left temporal pole. Among SZ patients, fMRI activity from the IC condition was inversely correlated with unusual thought content. Conclusions The neural networks associated with the N400 ERP response to semantic violations depends on conceptual relatedness. These findings are consistent with a distributed network underlying neural responses to semantic incongruity including unimodal visual areas as well as integrative, transmodal areas. Unusual thoughts in SZ may reflect impaired processing in transmodal hub regions such as the precuneus, leading to overly broad semantic associations., Highlights • Hemodynamic activity linked to N400 responses is distributed across the brain. • N400 linked networks depend on conceptual relatedness. • Magnitude of the N400 ERP-fMRI fused component is reduced in schizophrenia. • N400 linked network activity inversely correlates with unusual thought content.

Summary Background The male genital examination is a common source of discomfort for the patient and medical provider. Performance of male genital examination is imperative; however, as many treatable diagnoses can be made. Undescended testicles (UDTs), hernias, testicular tumors, and urethral abnormalities are all potentially concerning findings which can be discovered on routine examination. Objective The objectives of this study are to determine the rate at which general pediatricians perform routine genitourinary (GU) examinations in the pediatric population and to determine the rate at which UDT are diagnosed or documented in the patient's history. The authors hypothesize the rate of pediatric GU examination during routine well-child visits to be in line with the previously reported rates in the adult literature. Study design Nine hundred ninety-six consecutive male well-child visits conducted by general pediatricians at the study institution were reviewed. These visits were evaluated for documentation of a detailed GU examination as well as the presence of UDT from these examinations. In addition, past medical and surgical histories were reviewed to determine if a diagnosis of UDT was noted. Results Pediatricians at the study institution documented GU examinations 99.1% of the time during male well-child visits. Only 1.1% of the cohort had a documentation of UDT at any time point. Of the 11 patients with UDT, 6 boys (54.5%) had spontaneous descent with no referral to urology, whereas 5 (45.5%) required orchidopexy. Discussion Prior reports suggest 70–75% of routine office visits include a genital examination. None of these reports reviewed the pediatric population, thus making this review novel in this respect. In addition, the results are vastly different from these prior studies as the authors demonstrated over 99% of male well-child examinations included documentation of a thorough genital examination. A limitation of the study is its retrospective nature, which creates a lack of standardization across the data set. In addition, without being physically present in the examination room, one cannot discern whether an examination is simply being documented without actual performance because of the template format of the electronic medical record (EMR). Furthermore, the study was not designed to best evaluate the true rate of UDTs; therefore, the reported rate of 1.1% cannot be accurately associated with a particular age at diagnosis. Conclusions Pediatricians do, in fact, document GU examinations on a routine basis. This finding cannot be taken with complete certainty as verification of actual examination performance is impractical. While the data demonstrated a lower than expected rate of UDT, depending upon age at diagnosis, this could indicate that although examinations are being documented, their accuracy may be diminished because of various factors at play in the healthcare system as a whole, including improper exam performance and EMR templates. Follow-up studies are required to verify these potentially changing rates of UDT and to determine if there is discordance between documentation and performance of GU examinations.

Steering demands rapid responses to heading deviations and uses optic flow to redirect self-movement toward the intended destination. We trained monkeys in a naturalistic steering paradigm and recorded dorsal medial superior temporal area (MSTd) cortical neuronal responses to the visual motion and spatial location cues in optic flow. We found that neuronal responses to the initial heading direction are dominated by the optic flow's global radial pattern cue. Responses to subsequently imposed heading deviations are dominated by the local direction of motion cue. Finally, as the monkey steers its heading back to the goal location, responses are dominated by the spatial location cue, the screen location of the flow field's center of motion. We conclude that MSTd responses are not rigidly linked to specific stimuli, but rather are transformed by the task relevance of cues that guide performance in learned, naturalistic behaviors.SIGNIFICANCE STATEMENTUnplanned heading changes trigger lifesaving steering back to a goal. Conventionally, such behaviors are thought of as cortical sensory-motor reflex arcs. We find that a more reciprocal process underlies such cycles of perception and action, rapidly transforming visual processing to suit each stage of the task. When monkeys monitor their simulated self-movement, dorsal medial superior temporal area (MSTd) neurons represent their current heading direction. When monkeys steer to recover from an unplanned change in heading direction, MSTd shifts toward representing the goal location. We hypothesize that this transformation reflects the reweighting of bottom-up visual motion signals and top-down spatial location signals, reshaping MSTd's response properties through task-dependent interactions with adjacent cortical areas.

We report a case of cerebral phaeohyphomycosis, a fungal brain infection due to a dark (dematiaceous) fungi in a 6-year-old French Guyanese boy. The child presented fever and drowsiness due to several paraventricular brain abscesses. Neurological surgeries were performed to reduce intracranial hypertension and to obtain abscess biopsies. Mycological cultures of intraoperative samples led to the diagnosis of cerebral phaeohyphomycosis due to Cladophialophora bantiana. The patient neurological status deteriorated and remained critical after several weeks of combination antifungal therapy with voriconazole 8 mg/kg/day, liposomal amphotericin B 10 mg/kg/day and flucytosine 200 mg/kg/day. A complete surgical resection was not possible because of multiple small abscesses. A multidisciplinary ethical staff decided on home medical care with palliative ventriculoperitoneal shunt, nasogastric feeding and analgesics. One year later, the patient's neurological condition had improved and cerebral lesions had regressed, while he had not received any antifungal treatment but only traditional medicines. Cerebral phaeohyphomycosis are rare diseases affecting immunocompromised but also apparently non-immunocompromised patients, as in this case. A complete surgical resection is not always possible and mortality rates are high in spite of treatments with a combination of antifungals. The diagnosis may be difficult because of these dematiaceous fungi's slowly growing and their potential pathogenicity for laboratory staff.

Background and Aims:The changes in DSM-5 diagnostic criteria for dementia (Major neurocognitive disorder (NCD)) and mild cognitive impairment (mild NCD) mandate a re-evaluation of screening instruments. This study attempted to validate screening instruments, identify optimum threshold, and describe their indices of efficacy.Method:Consecutive people above the age of 65 years attending the outpatient department of a general hospital were recruited. They were assessed using the Mini-Mental State Examination and the Vellore Screening Instruments for Dementia and were evaluated against the DSM-5 standard. Bivariate and multivariate statistics were obtained. Receiver-operating-characteristic curves were drawn, optimum thresholds obtained, sensitivity, specificity, and predictive values calculated.Results:One hundred and thirty four older people were recruited. The majority were women, married, with low levels of education, not employed, living with family, and had medical co-morbidity. A minority satisfied DSM-5 criteria for major (1.5%) and mild NCD (36.5%). The factors associated with NCD were older age, fewer years of education, and lower socio-economic status. MMSE, VSID patient, and VSID informant scores were significantly associated with NCD. The indices of efficacy for the MMSE and VSID patient version were modest for identifying Mild NCD. However, their performance in identifying major NCD was better. Nevertheless, optimal thresholds for recognition differed markedly from their originally recommended cut-offs.Conclusions:The DSM-5 standards, with new and different cognitive domains, mandate a revaluation and recalibration of existing screening instruments. Ideally, new screening instruments, which match the cognitive domains and DSM-5 standard should be developed.

Current guidelines recommend against surgical repair of subclinical varicoceles (SCVs) for infertility; several studies demonstrate mixed fertility results after SCV correction. To determine whether surgical correction of SCV improves semen parameters and/or reproductive outcomes, we performed a systematic review and meta-analysis. Seven biomedical literature databases were searched through January 2018 for studies that assessed reproductive outcomes and/or change in semen parameters in men with corrected SCV compared to either (1) uncorrected SCV or (2) corrected clinical varicocele. Estimates were pooled using random-effects meta-analysis. Data were extracted from 13 studies involving 1357 men. Overall, the risk of bias for included studies was high and without a consistent SCV definition across studies. Surgical correction of SCV was associated with a minor increase in sperm density and total motile sperm count (TMSC) compared to uncorrected SCV. This increase in semen parameters is not clinically significant, as men prior to varicocelectomy were on average normospermic nor was correction of a SCV associated with an increase in pregnancy rates when compared to men with uncorrected SCV. Comparing corrected SCV to corrected clinical varicocele, SCV correction resulted in a smaller increase in TMSC but no difference in average annual pregnancy rate. The risk of bias within and heterogeneity between studies assessing SCV correction are high, yet overall very little clinical benefit is derived from SCV correction.

We sought to evaluate midterm survival data and resource use for patients who received hybrid coronary revascularization for 2-vessel coronary disease (robotic-assisted left internal thoracic artery graft to left anterior descending coronary artery (minimally invasive direct coronary artery bypass), coupled with a stent to the circumflex or right coronary artery), compared with a concurrent cohort who had traditional coronary artery bypass grafting.A comprehensive retrospective review was undertaken of our prospectively collected database from January 2009 to December 2016. We propensity matched 207 patients who underwent hybrid coronary revascularization for double-vessel disease with patients who underwent coronary artery bypass grafting. Eight-year survival data were obtained from the National Death Index.Thirty-day mortality was 1 patient (0.5%) in each of the hybrid coronary revascularization and coronary artery bypass grafting groups. Eight-year survival for the hybrid coronary revascularization group was 187 of 207 patients (90.3%) compared with 182 of 207 patients (87.9%) for the coronary artery bypass grafting cohort. End-stage renal disease independently predicted late mortality in all patients (overall hazard ratio, 5.60, P .001; hybrid coronary revascularization hazard ratio, 5.58, P = .002; coronary artery bypass grafting hazard ratio, 4.59, P = .006). Female patients who underwent hybrid coronary revascularization had a higher incidence of late death (hazard ratio, 2.47, P = .05). Length of stay and perioperative transfusion requirements were lower in the hybrid coronary revascularization group (P .0001).Hybrid coronary revascularization for double-vessel coronary disease is associated with similar short-term outcomes and intermediate-term survival as traditional coronary artery bypass grafting. Hybrid coronary revascularization is associated with lower transfusion requirements and a shorter length of stay than coronary artery bypass grafting.

OBJECTIVEAlthough various predictors of postoperative outcome have been previously identified in patients with Chiari malformation Type I (CMI) with syringomyelia, there is no known algorithm for predicting a multifactorial outcome measure in this widely studied disorder. Using one of the largest preoperative variable arrays used so far in CMI research, the authors attempted to generate a formula for predicting postoperative outcome.METHODSData from the clinical records of 82 symptomatic adult patients with CMI and altered hindbrain CSF flow who were managed with foramen magnum decompression, C-1 laminectomy, and duraplasty over an 8-year period were collected and analyzed. Various preoperative clinical and radiological variables in the 57 patients who formed the study cohort were assessed in a bivariate analysis to determine their ability to predict clinical outcome (as measured on the Chicago Chiari Outcome Scale [CCOS]) and the resolution of syrinx at the last follow-up. The variables that were significant in the bivariate analysis were further analyzed in a multiple linear regression analysis. Different regression models were tested, and the model with the best prediction of CCOS was identified and internally validated in a subcohort of 25 patients.RESULTSThere was no correlation between CCOS score and syrinx resolution (p = 0.24) at a mean ± SD follow-up of 40.29 ± 10.36 months. Multiple linear regression analysis revealed that the presence of gait instability, obex position, and the M-line–fourth ventricle vertex (FVV) distance correlated with CCOS score, while the presence of motor deficits was associated with poor syrinx resolution (p ≤ 0.05). The algorithm generated from the regression model demonstrated good diagnostic accuracy (area under curve 0.81), with a score of more than 128 points demonstrating 100% specificity for clinical improvement (CCOS score of 11 or greater). The model had excellent reliability (κ = 0.85) and was validated with fair accuracy in the validation cohort (area under the curve 0.75).CONCLUSIONSThe presence of gait imbalance and motor deficits independently predict worse clinical and radiological outcomes, respectively, after decompressive surgery for CMI with altered hindbrain CSF flow. Caudal displacement of the obex and a shorter M-line–FVV distance correlated with good CCOS scores, indicating that patients with a greater degree of hindbrain pathology respond better to surgery. The proposed points-based algorithm has good predictive value for postoperative multifactorial outcome in these patients.

Object T2-weighted intramedullary increased signal intensity (ISI) on MRI in patients with cervical spondylotic myelopathy (CSM) appears to represent a wide spectrum of pathological changes that determine reversibility of cord damage. Although sharp T2-weighted ISI on preoperative imaging may correlate with poorer surgical outcomes, there are limited data on how these changes progress following surgery. In this study, the authors characterized pre-and postoperative ISI changes in patients undergoing surgery for CSM and studied their postoperative evolution in an attempt to quantify their clinical significance. Methods The preoperative and postoperative MR images obtained in 56 patients who underwent oblique cervical corpectomy for CSM were reviewed, and the ISI was classified into 4 subtypes based on margins and intensity: Type 0 (none), Type 1 (“fuzzy”), Type 2 (“sharp”), and Type 3 (“mixed”). The locations of the ISI were further classified as focal if they represented single discrete lesions, multifocal if there were multiple lesions with intervening normal cord, and multisegmental if the lesions were continuous over more than 1 segment. The maximum craniocaudal length of the ISI was measured on each midsagittal MR image. The Nurick grade and Japanese Orthopaedic Association (JOA) score were used to assess clinical status. The mean duration of follow-up was 28 months. Results T2-weighted ISI changes were noted preoperatively in 54 patients (96%). Most preoperative ISI changes were Type 1 (41%) or Type 3 (34%), with a significant trend toward Type 2 (71%) changes at follow-up. Multi-segmental and Type 3 lesions tended to regress significantly after surgery (p = 0.000), reducing to Type 2 changes at follow-up. Clinical outcomes did not correlate with ISI subtype; however, there was a statistically significant trend toward improvement in postoperative Nurick Grade in patients with a > 50% regression in ISI size. In addition, patients with more than 18 months of follow-up showed significant regression in ISI size compared with patients imaged earlier. On logistic regression analysis, preoperative Nurick grade and duration of follow-up were the only significant predictors of postoperative improvement in functional status (OR 4.136, p = 0.003, 95% CI 1.623–10.539 and OR 6.402, p = 0.033, 95% CI 1.165–35.176, respectively). Conclusions There is a distinct group of patients with multisegmental Type 3 intramedullary changes who show remarkable radiological regression after surgery but demonstrate a residual sharp focal ISI at follow-up. A regression of the ISI by > 50% predicts better functional outcomes. Patients with a good preoperative functional status remain the most likely to show improvement, and the improvement continues to occur even at remote follow-up. The clinical relevance of the quality of the T2-weighted ISI changes in patients with CSM remains uncertain; however, postoperative regression of the ISI change is possibly a more important correlate of patient outcome than the quality of the ISI change alone.

Background There have been few cross-national studies of the prevalence of the frailty phenotype conducted among low or middle income countries. We aimed to study the variation in prevalence and correlates of frailty in rural and urban sites in Latin America, India, and China. Methods Cross-sectional population-based catchment area surveys conducted in 8 urban and 4 rural catchment areas in 8 countries; Cuba, Dominican Republic, Puerto Rico, Venezuela, Peru, Mexico, China, and India. We assessed weight loss, exhaustion, slow walking speed, and low energy consumption, but not hand grip strength. Therefore, frailty phenotype was defined on 2 or more of 4 of the usual 5 criteria. Results We surveyed 17,031 adults aged 65 years and over. Overall frailty prevalence was 15.2% (95% confidence inteval 14.6%–15.7%). Prevalence was low in rural (5.4%) and urban China (9.1%) and varied between 12.6% and 21.5% in other sites. A similar pattern of variation was apparent after direct standardization for age and sex. Cross-site variation in prevalence of frailty indicators varied across the 4 indicators. Controlling for age, sex, and education, frailty was positively associated with older age, female sex, lower socioeconomic status, physical impairments, stroke, depression, dementia, disability and dependence, and high healthcare costs. Discussion There was substantial variation in the prevalence of frailty and its indicators across sites in Latin America, India, and China. Culture and other contextual factors may impact significantly on the assessment of frailty using questionnaire and physical performance-based measures, and achieving cross-cultural measurement invariance remains a challenge. Conclusions A consistent pattern of correlates was identified, suggesting that in all sites, the frailty screen could identify older adults with multiple physical, mental, and cognitive morbidities, disability and needs for care, compounded by socioeconomic disadvantage and catastrophic healthcare spending.

Summary Objective Sickle retinopathy is a severe complication of sickle cell disease than can lead to blindness. We aim to describe the epidemiology of sickle retinopathy in homozygous sickle cell (SS) African patients and to analyze its association with non-ophthalmologic disease complications of sickle cell anemia. Methods We conducted a nested study within the CADRE cohort in Cameroon. Eighty-four consecutive SS outpatients, aged 10 years and older, with no visual symptoms, underwent an ophthalmologic examination. Mean age was 23 ± 10 years. Clinical and biological features were compared between patients with and without sickle retinopathy. We compared the prevalence of the clinical complications and main biological characteristics in patients with and without sickle retinopathy using a univariate logistic regression . The same analysis was used to compare the patients with non-proliferative sickle retinopathy to those with proliferative sickle retinopathy. Statistical analyses were done using the R software (version 3.1.2). Results Fifty-two patients (62%) displayed sickle retinopathy, among them 23 (27%) had a non-proliferative sickle retinopathy, and 29 (35%) had proliferative sickle retinopathy. Patients with proliferative sickle cell retinopathy had a mean age of 28 ± 11 years. Sickle retinopathy was associated with higher hemoglobin level (P = 0.047) and fewer leg ulcers ( P = 0.018). Proliferative SR was associated with increasing age (P = 0.008) and male sex (P = 0.025) independently of the hemoglobin level. Conclusions Sickle retinopathy is particularly frequent in sub-Saharan sickle cell SS patients, which advocates for early systematic screening.

Background: Techniques for aortic surgery continue to evolve. A real-world snapshot of patients undergoing elective surgery for aneurysm in the modern era is helpful to assist in deciding the appropriate timing for intervention. We herein describe our experience with 100 consecutive patients who underwent primary elective surgery for aneurysm of the proximal thoracic aorta over a two-year period at a single institution. Methods: The majority of our patients were male, mean age 61.19 ± 13.33 years. Two patients had Marfan syndrome. Twenty-eight patients had bicuspid aortic valve. Thirty-four patients underwent aortic root replacement utilizing a composite valve/graft conduit; 23 had valve-sparing root replacements. The ascending aorta was replaced in 89 patients; 80 (89.9%) of these included a period of circulatory arrest at moderate hypothermia utilizing unilateral selective antegrade cerebral perfusion. Results: Thirty-day mortality was zero. Perioperative stroke occurred in 2 patients, both of whom completely recovered prior to discharge. No patients required re-exploration for bleeding. One patient developed a sternal wound infection. Fifteen patients required readmission to hospital within thirty days of discharge. Conclusion: Elective surgery for aneurysm of the proximal aorta is safe, reproducible, and is associated with outcomes that are superior to those seen in an acute aortic syndrome. It may be appropriate to offer surgery to younger patients with proximal aortic aneurysms at smaller diameters, even if their aortic dimensions do not yet meet traditional guidelines for surgical intervention.

Objective: This study attempted to examine psychological morbidity among co-residents of older people living in Vellore, Tamil Nadu, India. Method: This cross-sectional study evaluated psychological morbidity among co-residents using the Self-Reporting Questionnaire and psychiatric morbidity among older people using the 10/66 Dementia Research Group’s population-based studies protocol. Socio-demographic data were also collected. Logistic regression was used for multivariate analysis. Results: Of 807 residents evaluated, 73 (9.0%) had significant psychological morbidity. Such morbidity was associated with being older, female, poorer, illiterate, currently employed and being a spouse of the older person. A diagnosis of depression, neuropsychiatric symptoms and greater disability in older people were also associated with psychological morbidity among co-residents. Conclusion: Co-residents living with older people have significant psychological morbidity, which needs to be recognised and treated.

Objectives Urine microscopy is a common test performed in emergency departments (EDs). Urine specimens can easily become contaminated by different factors, including the collection method. The midstream clean-catch (MSCC) collection technique is commonly used to reduce urine contamination. The urine culture contamination rate from specimens collected in our ED is 30%. We developed an instructional application (app) to show ED patients how to provide a MSCC urine sample. We hypothesized that ED patients who viewed our instructional app would have significantly lower urine contamination rates compared to patients who did not. Methods We prospectively enrolled 257 subjects with a urinalysis and/or urine culture test ordered in the ED and asked them to watch our MSCC instructional app. After prospective enrollment was complete, we retrospectively matched each enrolled subject to an ED patient who did not watch the instructional app. Controls were matched to cases based on gender, type of urine specimen provided, ED visit date and shift. Urinalysis and urine culture contamination results were compared between the matched pairs using McNemar's test. Results The overall urine culture contamination rate of the 514 subjects was 38%. The majority of the matched pairs had a urinalysis (63%) or urinalysis plus urine culture (35%) test done. There were no significant differences in our urine contamination rates between the matched pairs overall or when stratified by gender, by prior knowledge of the clean catch process or by type of urine specimen. Conclusion We did not see a lower contamination rate for patients who viewed our instructional app compared to patients who did not. It is possible that MSCC is not effective for decreasing urine specimen contamination.

Polymeric microspheres (MSs) have received attention for their potential to improve the delivery of drugs with poor oral bioavailability. Although MSs can be absorbed into the absorptive epithelium of the small intestine, little is known about the physiologic mechanisms that are responsible for their cellular trafficking. In these experiments, nonbiodegradable polystyrene MSs (diameter range: 500 nm to 5 µm) were delivered locally to the jejunum or ileum or by oral administration to young male rats. Following administration, MSs were taken up rapidly (≤5 min) by the small intestine and were detected by transmission electron microscopy and confocal laser scanning microscopy. Gel permeation chromatography confirmed that polymer was present in all tissue samples, including the brain. These results confirm that MSs (diameter range: 500 nm to 5 µm) were absorbed by the small intestine and distributed throughout the rat. After delivering MSs to the jejunum or ileum, high concentrations of polystyrene were detected in the liver, kidneys, and lungs. The pharmacologic inhibitors chlorpromazine, phorbol 12-myristate 13-acetate, and cytochalasin D caused a reduction in the total number of MSs absorbed in the jejunum and ileum, demonstrating that nonphagocytic processes (including endocytosis) direct the uptake of MSs in the small intestine. These results challenge the convention that phagocytic cells such as the microfold cells solely facilitate MS absorption in the small intestine.

Plecanatide, an analogue of uroguanylin, activates the guanylate cyclase C (GC-C) receptor found on the GI mucosal epithelial cells, leading to secretion of fluid, facilitating bowel movements. Plecanatide is being investigated as a potential treatment for constipating GI disorders. The aim of this investigation was to assess the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of single doses of plecanatide in healthy volunteers.A total of 72 healthy volunteers at a single site were randomized in 9 cohorts to receive oral plecanatide or placebo from 0.1 to 48.6 mg. Plasma PK samples were collected pre-dose and post-dose. PD assessments included time to first stool, stool frequency, and stool consistency using the Bristol Stool Form Scale. All adverse events were documented.Plecanatide was safe and well-tolerated at all dose levels. A total of 17 of 71 subjects (23.9%) reported 25 treatment-emergent adverse events (TEAEs) during the study. The number of TEAEs reported by subjects who received plecanatide or placebo was comparable (24.5 vs. 22.2%, respectively). There were no dose-related increases in TEAEs or any SAEs reported. No measurable systemic absorption of oral plecanatide was observed at any of the oral doses studied, utilizing an assay sensitive down to 1 ng/mL.Plecanatide, an oral GC-C agonist, acting locally within the GI tract without measurable systemic exposure, was safe and well-tolerated in single doses up to 48.6 mg. The study was not powered for statistical analyses, but trends in PD parameters supported continued clinical development.

AB PURPOSE: To test the reliability of Timed Up and Go Tests (TUGTs) in cardiac rehabilitation (CR) and compare TUGTs to the 6-Minute Walk Test (6MWT) for outcome measurement. METHODS: Sixty-one of 154 consecutive community-based CR patients were prospectively recruited. Subjects undertook repeated TUGTs and 6MWTs at the start of CR (start-CR), postdischarge from CR (post-CR), and 6 months postdischarge from CR (6 months post-CR). The main outcome measurements were TUGT time (TUGTT) and 6MWT distance (6MWD). RESULTS: Mean (SD) TUGTT1 and TUGTT2 at the 3 assessments were 6.29 (1.30) and 5.94 (1.20); 5.81 (1.22) and 5.53 (1.09); and 5.39 (1.60) and 5.01 (1.28) seconds, respectively. A reduction in TUGTT occurred between each outcome point (P

To determine whether motion preservation following oblique cervical corpectomy (OCC) for cervical spondylotic myelopathy (CSM) persists with serial follow-up. We included 28 patients with preoperative and at least two serial follow-up neutral and dynamic cervical spine radiographs who underwent OCC for CSM. Patients with an ossified posterior longitudinal ligament (OPLL) were excluded. Changes in sagittal curvature, segmental and whole spine range of motion (ROM) were measured. Nathan’s system graded anterior osteophyte formation. Neurological function was measured by Nurick’s grade and modified Japanese Orthopedic Association (JOA) scores. The majority (23 patients) had a single or 2-level corpectomy. The average duration of follow-up was 45 months. The Nurick’s grade and the JOA scores showed statistically significant improvements after surgery (p

There is a dearth of recent data on the relationship between nutritional status and intellectual development among children in India. To determine whether such a relationship exists, we studied children in a rural area of Tamil Nadu.We stratified villages in Kaniyambadi block, Tamil Nadu, and recruited consecutive children who satisfied the study criteria. We assessed nutritional status by measuring height and weight and recording chronological age, and calculated indices weight-for-age, height-for-age, weight-forheight and their Z scores. We assessed intellectual development using the Indian adaptation of the Vineland Social Maturity Scale. We used a case-control framework to determine the relationship and logistic regression to adjust for common confounders.We recruited 114 children between the ages of 12 and 72 months. Z score means (weight-for-age -1.36; height-for-age -1.42; weight-for-height -0.78) were much less than 0 and indicate undernutrition. Z score standard deviations (weight-for-age 1.04; height-for-age 1.18; weightfor- height 1.06) were within the WHO recommended range for good quality of nutrition data suggesting reduced measurement errors and incorrect reporting of age. The frequency distributions of population Z scores suggest high undernutrition, wasting and medium stunting. A tenth of the population (9.6%) had values to suggest borderline/below average intelligence (social quotient89). Lower height-forage, height-for-age Z score and weight-for-height Z score were significantly associated with a lower social quotient. These relationships remained statistically significant after adjusting for sex and socioeconomic status using logistic regression.Chronic undernutrition, wasting and stunting and their association with lower intellectual development demand an urgent re-assessment of national food policies and programmes.

Background: Little is known of the epidemiology of diabetes among older people in low and middle income countries. We aimed to study and compare prevalence, social patterning, correlates, detection, treatment and control of diabetes among older people in Latin America, India, China and Nigeria. Methods: Cross-sectional surveys in 13 catchment area sites in nine countries. Diagnosed diabetes was assessed in all sites through self-reported diagnosis. Undiagnosed diabetes was assessed in seven Latin American sites through fasting blood samples (glucose > = 7mmol/L). Results: Total diabetes prevalence in catchment sites in Cuba (prevalence 24.2%, SMR 116), Puerto Rico (43.4%, 197), and urban (27.0%, 125), and rural Mexico (23.7%, 111) already exceeds that in the USA, while that in Venezuela (20.9%, 100) is similar. Diagnosed diabetes prevalence varied very widely, between low prevalences in sites in rural China (0.9%), rural India (6.6%) and Nigeria (6.0%). and 32.1% in Puerto Rico, explained mainly by access to health services. Treatment coverage varied substantially between sites. Diabetes control (40 to 61% of those diagnosed) was modest in the Latin American sites where this was studied. Diabetes was independently associated with less education, but more assets. Hypertension, central obesity and hypertriglyceridaemia, but not hypercholesterolaemia were consistently associated with total diabetes. Conclusions: Diabetes prevalence is already high in most sites. Identifying undiagnosed cases is essential to quantify population burden, particularly in least developed settings where diagnosis is uncommon. Metabolic risk factors and associated lifestyles may play an important part in aetiology, but this requires confirmation with longitudinal data. Given the high prevalence among older people, more population research is indicated to quantify the impact of diabetes, and to monitor the effect of prevention and health system strengthening on prevalence, treatment and control.

OBJECTIVE: Although depression among older people is an important public health problem worldwide, systematic studies evaluating its prevalence and determinants in low and middle income countries (LMICs) are sparse. The biopsychosocial model of depression and prevailing socioeconomic hardships for older people in LMICs have provided the impetus to determine the prevalence of geriatric depression; to study its associations with health, social, and economic variables; and to investigate socioeconomic inequalities in depression prevalence in LMICs.METHODS: The authors accessed the World Health Organization Study on Global AGEing and Adult Health Wave 1 data that studied nationally representative samples from six large LMICs (N = 14,877). A computerized algorithm derived depression diagnoses. The authors assessed hypothesized associations using survey multivariate logistic regression models for each LMIC and pooled their risk estimates by meta-analyses and investigated related socioeconomic inequalities using concentration indices.RESULTS: Cross-national prevalence of geriatric depression was 4.7% (95% CI: 1.9%-11.9%). Female gender, illiteracy, poverty, indebtedness, past informal-sector occupation, bereavement, angina, and stroke had significant positive associations, whereas pension support and health insurance showed significant negative associations with geriatric depression. Pro-poor inequality of geriatric depression were documented in five LMICs.CONCLUSIONS: Socioeconomic factors and related inequalities may predispose, precipitate, or perpetuate depression amongolder people in LMICs. Relative absence of health safety net places socioeconomically disadvantaged older people in LMICs at risk. The need for population-based public health interventions and policies to prevent and to manage geriatric depression effectively in LMICs cannot be overemphasized.

There are limited contemporary data on the presentation, management, and outcomes of acute coronary syndrome (ACS) admissions in India. We aimed to develop a prospective registry to address treatment and health systems gaps in the management of ACSs in Kerala, India.We prospectively collected data on 25 748 consecutive ACS admissions from 2007 to 2009 in 125 hospitals in Kerala. We evaluated data on presentation, management, and in-hospital mortality and major adverse cardiovascular events (MACE). We created random-effects multivariate regression models to evaluate predictors of outcomes while accounting for confounders. Mean (SD) age at presentation was 60 (12) years and did not differ among ACS types [ST-segment myocardial infarction (STEMI) = 37%; non-STEMI = 31%; unstable angina = 32%]. In-hospital anti-platelet use was high (90%). Thrombolytics were used in 41% of STEMI, 19% of non-STEMI, and 11% of unstable angina admissions. Percutaneous coronary intervention rates were marginally higher in STEMI admissions. Discharge medication rates were variable and generally suboptimal (80%). In-hospital mortality and MACE rates were highest for STEMI (8.2 and 10.3%, respectively). After adjustment, STEMI diagnosis (vs. unstable angina) [odds ratio (OR) (95% confidence interval = 4.06 (2.36, 7.00)], symptom-to-door time6 h [OR = 2.29 (1.73, 3.02)], and inappropriate use of thrombolysis [OR = 1.33 (0.92, 1.91)] were associated with higher risk of in-hospital mortality and door-to-needle time30 min [OR = 0.44 (0.27, 0.72)] was associated with lower mortality. Similar trends were seen for risk of MACE.These data represent the largest ACS registry in India and demonstrate opportunities for improving ACS care.

Objectives In a multi-site population-based study in several middle-income countries, we aimed to investigate relative contributions of care arrangements and characteristics of carers and care recipients to strain among carers of people with dementia. Based on previous research, hypotheses focused on carer sex, care inputs, behavioural and psychological symptoms (BPSD) and socioeconomic status, together with potential buffering effects of informal support and employing paid carers. Methods In population-based catchment area surveys in 11 sites in Latin America, India and China, we analysed data collected from people with dementia and care needs, and their carers. Carer strain was assessed with the Zarit Burden Interview. Results With 673 care recipient/carer dyads interviewed (99% of those eligible), mean Zarit Burden Interview scores ranged between 17.1 and 27.9 by site. Women carers reported more strain than men. The most substantial correlates of carer strain were primary stressors BPSD, dementia severity, needs for care and time spent caring. Socioeconomic status was not associated with carer strain. Those cutting back on work experienced higher strain. There was tentative evidence for a protective effect of having additional informal or paid support. Conclusions Our findings underline the global impact of caring for a person with dementia and support the need for scaling up carer support, education and training. That giving up work to care was prevalent and associated with substantial increased strain emphasizes the economic impact of caring on the household. Carer benefits, disability benefits for people with dementia and respite care should all be considered. Copyright © 2012 John Wiley & Sons, Ltd.

To analyze whether an association exists between keratometric and pachymetric changes in the cornea, and whether it can be used to create pachymetric cutoff criteria secondary to keratometric criteria.In this cross-sectional study, 1000 candidates presenting to the refractive surgery services of a tertiary care hospital underwent bilateral Orbscan IIz (Bausch and Lomb) assessment along with other ophthalmic evaluation.Stepwise regression analysis-based models showed that simulated keratometry (simK) astigmatism was significantly predicted by the minimum corneal thickness (MCT) and difference between central and MCT (δCT), mean SimK by the MCT and δCT, and maximum keratometry in the central 10-mm zone by the MCT and δCT (P0.001). The mean MCT values were 542.5 ± 39.6, 539.9 ± 39.2, 524.2 ± 49.5, and 449.3 ± 73.7 μm for flatter normal (44 D), steeper normal (≥ 44 D), keratoconus suspect and keratoconic eyes, respectively (P0.001). The mean differences between central corneal thickness and MCT (δCT) were 12.2 ± 7.1 μm, 12.4 ± 7.4 μm, 14.4 ± 8.9 μm and 23.2 ± 10.1 μm for the flatter normal, steeper normal, keratoconus suspect, and keratoconic eyes, respectively (P0.001). Mean and 2SD cutoff were used to suggest that a cornea having MCT461 μm or δCT27 μm has only a 2.5% chance of being normal and not a keratoconus suspect or worse.Pachymetric diagnostic cutoffs can be used as adjuncts to the existing topographic criteria to screen keratoconus suspect and keratoconic eyes.

OBJECTIVES: To estimate the prevalence, social patterning, treatment and control of hypertension among older people in the 10/66 Dementia Research Group developing country sites. METHODS: Cross-sectional surveys of SBP, hypertension, and hypertension awareness, treatment and control among 17?014 people aged 65 years and over in eight urban and four rural sites in Latin America, India and China. RESULTS: Hypertension prevalence was higher in urban (range 52.6-79.8%) than rural sites (range 42.6-56.9%), and lower in men than women [pooled prevalence ratio 0.89, 95% confidence interval (CI) 0.85-0.93]. Educational attainment was positively associated with hypertension in rural and least-developed sites. Age-standardized morbidity ratios, compared to USA (100), were higher in urban sites in Cuba (105), Dominican Republic (109), and Venezuela (107), similar in Puerto Rico (105), urban Mexico (99) and urban India (101), and lower in urban (75) and rural (61) Peru, rural Mexico (81), urban (91) and rural (84) China and rural India (65). In most Latin American centres, and urban China just over one-third of those with hypertension were controlled (BP?140/90). Control was poor in rural China (2%), urban India (12%) and rural India (9%). The proportion controlled, not compositional factors (age, sex, education and obesity), explained most of the between-site variation in SBP. CONCLUSION: Uncontrolled hypertension is common among older people in developing countries, and may rise further during the demographic and health transitions. It is a major determinant of population SBP level. Strengthening primary care to improve hypertension management is necessary for primary prevention.

To evaluate the visual acuity and quality-related satisfaction of patients implanted with a refractive design multifocal intraocular lens (IOL), and evaluate the factors predicting it including angle kappa.Dr Agarwal's Eye Hospital and Eye Research Centre, Chennai.In this prospective trial, 50 eyes of 44 consecutive patients were included. All patients underwent phacoemulsification with multifocal IOL implantation (Rezoom IOL, Abbott Medical Optics). The preoperative and postoperative assessment included slit lamp biomicroscopy, uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA) and kappa angle assessment. At 1 year, 37 patients (43 eyes), who finished follow-up, were asked to rate their symptoms on a graded questionnaire (0-5 for five queries).The decimal scores for UCVA and BCVA were 0.38±0.21 and 0.47±0.17 (preoperative), and 0.75±0.22 and 0.99±0.11 (postoperative), respectively. Symptom scores were haloes 0.98±1.7, glare 0.69±1.48, blurred distance 1.0±1.7, intermediate 1.34±1.6, near 1.06±1.8. On regression analysis haloes depended on angle kappa and distance UCVA (R (2)=0.26, P=0.029), and glare on angle kappa (R (2)=0.26, P=0.033). Poor satisfactions with distance, intermediate, and near vision were linked with distance UCVA (R (2)=0.17, P=2.3 × 10(-4)), distance UCVA (R (2)=0.1, P=0.04), and near UCVA (R (2)=0.12, P=0.03), respectively. The strongest predictor, however, for overall visual discomfort was distance UCVA (R (2)=0.1, P=0.04).Our study suggests that there may be a role of misalignment between the visual and pupillary axis (angle kappa) in the occurrence of photic phenomenon after refractive multifocal IOL implantation.

BackgroundTranscultural studies have found lack of insight to be an almost invariable feature of acute and chronic schizophrenia, but its influence on prognosis is unclear.AimsTo investigate the relationship between insight, psychopathology and outcome of first-episode schizophrenia in Vellore, India.MethodPatients with a DSM–IV diagnosis of schizophrenia (η = 131) were assessed prospectively at baseline and at 6-month and 12-month follow-up. Demographic and clinical measures included insight, psychopathology, duration of untreated psychosis (DUP) and social functioning. Linear and logistic regression was used to measure predictors of outcome.ResultsFollow-up data were available for 115 patients at 1 year. All achieved remission, half of them with and half without residual symptoms. Changes in psychopathology and insight during the first 6 months and DUP strongly predicted outcome (relapse or functional impairment), controlling for baseline measures.ConclusionsOutcome of schizophrenia in this setting is driven by early symptomatic improvement and is relatively favourable, in line with other studies from low- and middle-income countries. Early improvement in insight might be a useful clinical guide to future outcome. Reduction of DUP should be a target for intervention.

To evaluate the post-operative outcome of fibrin glue-assisted posterior chamber intraocular lens (IOL) implantation in eyes with deficient capsular support after 1 year. Eyes operated with fibrin glue-assisted posterior chamber IOL implantation from December 2007 to May 2008 were included. The post-operative best spectacle-corrected visual acuity (BCVA), uncorrected visual acuity (UCVA), intraocular pressure (IOP), central macular thickness, and specular count were evaluated. IOL position and centration at 1 year was determined. The 1-year post-operative complications were analysed. A total of 53 eyes of 53 patients were analysed. There was significant improvement in UCVA (P=0.000) and BCVA (P=0.000). There was no significant change (P=0.447) in IOP from the pre-operative value. The early post-operative complication was decentration (5.6%). The late complication was pigment dispersion (3.7%) and healed macular oedema (7.5%). No vision threatening complications such as retinal break, retinal detachment, or endophthalmitis were seen. The percentage (%) loss of endothelial cells was 5.23±3.4% at 1-year follow-up. No pseudophakodonesis was seen in the follow-up visits. Results obtained at 1 year after fibrin glue-assisted posterior chamber IOL implantation showed a good visual outcome with minimal complications in eyes with deficient capsular support.

BackgroundThe relative contributions of psychosocial stress and psychiatric morbidity to suicide are a subject of debate.AimsTo determine major risk factors for suicide in rural south India.MethodWe used a matched case–control design and psychological autopsy to assess 100 consecutive suicides and 100 living controls matched for age, gender and neighbourhood.ResultsThirty-seven (37%) of those who died by suicide had a DSM–III–R psychiatric diagnosis. Alcohol dependence (16%) and adjustment disorders (15%) were the most common categories. The prevalence rates for schizophrenia, major depressive episode and dysthymia were 2% each. Ongoing stress and chronic pain heightened the risk of suicide. Living alone and a break in a steady relationship within the past year were also significantly associated with suicide.ConclusionsPsychosocial stress and social isolation, rather than psychiatric morbidity, are risk factors for suicide in rural south India.

Purpose Delirium is common but underdiagnosed in critical care units, which results in increased morbidity and mortality. This study aimed to evaluate the reliability and validity of diagnosing delirium with the Memorial Delirium Assessment Scale (MDAS) in India. Materials and Methods One hundred twenty consecutive patients admitted to medical and cardiac intensive care units of a tertiary care hospital, who were neither mute nor intubated, participated in this study. A trained junior resident screened for delirium using MDAS. A consultant psychiatrist established the reference diagnosis of delirium in accordance with International Classification of Diseases, 10th Revision diagnostic criteria for research. Results Interrater agreement and test-retest reliability of MDAS were 0.92 (95% confidence interval, 0.81-0.96) and 0.93 (95% confidence interval, 0.83-0.97), respectively. The MDAS had good internal consistency, with Cronbach α of .89 and Guttman split-half coefficient of 0.71. Factor analysis revealed a 2-factor structure, namely, cognitive disturbances and behavioral abnormalities. A receiver operating characteristic curve obtained the optimal threshold for screening as MDAS total score of at least 10. The sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 95.45%, 75%, and 100%, respectively. Conclusions Our findings suggest that training junior residents to use a brief screening instrument to diagnose delirium is a reliable and valid option in resource-poor critical care settings.

Cisplatin (cis-diaminedichloroplatinum-II) is a widely used antineoplastic agent in the treatment of a variety of cancers. The aim of the present study was to investigate the testicular toxicity of cisplatin in mice at human therapeutic dose-levels, and to investigate any protective effects of concomitantly administered l-ascorbic acid (i.p.; 10 mg/kg). Adult male BALB/C mice (13-15-week-old) were treated (i.p.) with two cycles of 5 days each of cisplatin with 17 days of recovery period between cycles, as follows: Group I (G-I) - water (N = 10); Group II (G-II) -L-ascorbic acid (N = 6); Group III (G-III) - 1mg/kg (N = 6); Group IV (G-IV) - 1 mg/kg + L-ascorbic acid (N = 6); Group V (G-V) - 2.5 mg/kg (N = 6); and Group VI (G-VI) - 2.5 mg/kg + L-ascorbic acid (N = 8). All animals were sacrificed on third day after the last treatment. The testis weight was decreased in a dose-dependent pattern (G-III - 44% and G-V - 54% against G-I), but l-ascorbic acid (10 mg/kg) recovered the lost weight in G-VI up to 32% against G-V (p0.05). Seminiferous tubular pathology was indicated by vacuoles, epithelial gaps, epithelial sloughing, delayed spermiation, malorientation of spermatids, germ cell degeneration, phagocytosis of spermatids, multinucleated germ cell formation and atrophy. Structurally abnormal tubules (G-III - 33%; G-V - 100%) were induced, and protective effects were seen in G-IV (77%) and G-VI (25%; p0.05). The tubular diameter was decreased in G-III-VI, but recovery was seen only in G-IV. The epithelial height was decreased in G-III, G-V and G-VI and the recovery was seen only in G-VI. The sperm count was decreased up to 53% and 71% against control in G-III and G-V, respectively, and recovery up to 47% and 61% was observed in G-IV and G-VI, respectively. The sperm motility was decreased up to 56% and 63% against control in G-III and G-V, respectively, and recovery was only marginal in G-IV and G-VI (p0.05). Total sperm abnormalities were increased in G-III-V (274%, 156% and 232%, respectively, p0.05) and l-ascorbic acid protected the effect in G-VI up to 156% (p0.05). In conclusion, at human therapeutic dose-levels, cisplatin induces testicular damage and spermato-toxicity. l-Ascorbic acid only partially nullifies the gonadotoxic effects of cisplatin.

Aim: The study aimed to examine the perceptions of illness in self and among others in patients with bipolar disorder in remission. The effect of a structured educational programme on the perceptions of illness was also tested. Method: We examined the perceptions of illness in self and in others (using a vignette) among patients with bipolar disorder in remission attending the Department of Psychiatry, Christian Medical College, Vellore, India. We also examined the effect of a structured educational programme on explanatory models in a randomized controlled trial. Explanatory models were assessed using the Tamil version of the Short Explanatory Model Interview. Results: Eighty two subjects were recruited for the trial; half of them received structured education while the other half received treatment as usual. There was agreement between perceptions related to the individual’s own illness and their opinion of illness in others as assessed using a vignette at baseline and at follow-up. There were no significant differences in explanatory models between patients who received education and those who did not. Conclusions: The results of this study show that during periods of remission, patients can clearly see the relationship between their own illness and that described in others, suggesting that insight is state dependent and may be related to psychopathology with good recovery of insight during periods of remission. These findings also argue for the fact that the current multi-dimensional models of insight which focus on biomedical explanations and treatments are not culturally sensitive. The assessment of insight demands universal conventions with comparison to the local cultural standards rather than universal defi nitions and yardsticks which employ Western and biomedical perspectives.

Background: Follicular streamers are residual fibrovascular tracts representing the impermanent lower third of the hair follicle below the bulge region. Streamers are generally not counted in transverse alopecia samples as they may represent catagen/telogen (CT) follicles and vellus-like (VL) follicles, or be mistaken as follicular scars. Design: We evaluated 22 non-scarring alopecia cases, including alopecia areata (AA) and androgenetic alopecia (AGA), and 22 scarring alopecia cases, including follicular degeneration syndrome (FDS)/central centrifugal cicatricial alopecia and other scarring alopecia (OSA) disorders. We counted terminal follicular streamers found at a deep dermal level (L2) and followed them into a mid-dermal level at the central follicular unit (FU) to determine their precise derivation. Results: We found streamers in 8/9 AA, 11/13 AGA, 6/12 FDS and 3/10 OSA cases. We counted a total of 74 streamers at L2, including 61 in non-scarring alopecia cases (p < 0.001). At the more superficial FU level, 72% of streamers corresponded to CT follicles, 25% to VL follicles and 3% to follicular scars. Conclusions: Follicular streamers are found predominantly in non-scarring alopecia cases. Streamers found at deep dermal or subcutaneous levels should be followed and identified at the FU level in order to obtain accurate follicular counts and follicular ratios needed for non-scarring alopecia diagnosis.