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Costs of hospital care for hypertension in an insured population without an outpatient medicines benefit: an observational study in the Philippines
<p>Abstract</p> <p>Background</p> <p>Hypertension is the number one attributable risk factor for death throughout the world and a major contributor to morbidity, mortality, and increasing health care expenditures in the Philippines. Lack of access to outpatient antihypertensive medicines leads to avoidable disease progression and costly inpatient admissions. We estimated the cost to the Philippine Health Insurance Corporation (PhilHealth), which generally does not cover outpatient medicines, for inpatient care for hypertension and its sequelae.</p> <p>Methods</p> <p>Using PhilHealth inpatient claims for discharges between July 1, 2002 and December 31, 2005, we describe costs to PhilHealth for hospitalizations classified by primary discharge diagnoses into hospitalizations for hypertension; hypertensive heart and/or renal disease; other definite; and other possible consequences of untreated hypertension and assess disease trajectory for patients with more than one admission.</p> <p>Results</p> <p>PhilHealth reimbursed US $56 million for 444,628 hospitalizations for hypertension-related diagnoses incurred by 360,016 patients during 3.5 years; 42% of admissions were for essential or secondary hypertension; 19% for hypertensive heart or renal disease; and 39% for other consequences of untreated hypertension. Among 60,659 patients admitted during the first 18 months of the study with a diagnosis of essential or secondary hypertension, 9% were hospitalized again for treatment of sequelae; older individuals (vs. =< 40 years old), men, dependents (vs. members), and those who were employed (vs. in the private membership category) were more likely to be hospitalized again; as were those whose first admission during the study period was for consequences of hypertension (vs. essential or secondary hypertension).</p> <p>Conclusion</p> <p>Inpatient care for hypertension and its sequelae is expensive. Since many hospitalizations may be avoided with antihypertensive pharmacologic therapy, an outpatient medicines benefit may be one cost-effective policy option for PhilHealth.</p
Cerebrospinal Fluid Cortisol Mediates Brain-Derived Neurotrophic Factor Relationships to Mortality after Severe TBI: A Prospective Cohort Study
Distinct regulatory signaling mechanisms exist between cortisol and brain derived neurotrophic factor (BDNF) that may influence secondary injury cascades associated with traumatic brain injury (TBI) and predict outcome. We investigated concurrent CSF BDNF and cortisol relationships in 117 patients sampled days 0â6 after severe TBI while accounting for BDNF genetics and age. We also determined associations between CSF BDNF and cortisol with 6-month mortality. BDNF variants, rs6265 and rs7124442, were used to create a gene risk score (GRS) in reference to previously published hypothesized risk for mortality in âyounger patientsâ (<48 years) and hypothesized BDNF production/secretion capacity with these variants. Group based trajectory analysis (TRAJ) was used to create two cortisol groups (high and low trajectories). A Bayesian estimation approach informed the mediation models. Results show CSF BDNF predicted patient cortisol TRAJ group (P = 0.001). Also, GRS moderated BDNF associations with cortisol TRAJ group. Additionally, cortisol TRAJ predicted 6-month mortality (P = 0.001). In a mediation analysis, BDNF predicted mortality, with cortisol acting as the mediator (P = 0.011), yielding a mediation percentage of 29.92%. Mediation effects increased to 45.45% among younger patients. A BDNF*GRS interaction predicted mortality in younger patients (P = 0.004). Thus, we conclude 6-month mortality after severe TBI can be predicted through a mediation model with CSF cortisol and BDNF, suggesting a regulatory role for cortisol with BDNF's contribution to TBI pathophysiology and mortality, particularly among younger individuals with severe TBI. Based on the literature, cortisol modulated BDNF effects on mortality after TBI may be related to known hormone and neurotrophin relationships to neurological injury severity and autonomic nervous system imbalance
Mycophenolic acid versus azathioprine as primary immunosuppression for kidney transplant recipients
Background Modern immunosuppressive regimens after kidney transplantation usually use a combination of two or three agents of different classes to prevent rejection and maintain graft function. Most frequently, calcineurinâinhibitors (CNI) are combined with corticosteroids and a proliferationâinhibitor, either azathioprine (AZA) or mycophenolic acid (MPA). MPA has largely replaced AZA as a first line agent in primary immunosuppression, as MPA is believed to be of stronger immunosuppressive potency than AZA. However, treatment with MPA is more costly, which calls for a comprehensive assessment of the comparative effects of the two drugs. Objectives This review of randomised controlled trials (RCTs) aimed to look at the benefits and harms of MPA versus AZA in primary immunosuppressive regimens after kidney transplantation. Both agents were compared regarding their efficacy for maintaining graft and patient survival, prevention of acute rejection, maintaining graft function, and their safety, including infections, malignancies and other adverse events. Furthermore, we investigated potential effect modifiers, such as transplantation era and the concomitant immunosuppressive regimen in detail. Search methods We searched Cochrane Kidney and Transplant's Specialised Register (to 21 September 2015) through contact with the Trials' Search Coâordinator using search terms relevant to this review. Selection criteria All RCTs about MPA versus AZA in primary immunosuppression after kidney transplantation were included, without restriction on language or publication type. Data collection and analysis Two authors independently determined study eligibility, assessed risk of bias and extracted data from each study. Statistical analyses were performed using the randomâeffects model and the results were expressed as risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes with 95% confidence intervals (CI). Main results We included 23 studies (94 reports) that involved 3301 participants. All studies tested mycophenolate mofetil (MMF), an MPA, and 22 studies reported at least one outcome relevant for this review. Assessment of methodological quality indicated that important information on factors used to judge susceptibility for bias was infrequently and inconsistently reported. MMF treatment reduced the risk for graft loss including death (RR 0.82, 95% CI 0.67 to 1.0) and for deathâcensored graft loss (RR 0.78, 95% CI 0.62 to 0.99, P < 0.05). No statistically significant difference for MMF versus AZA treatment was found for allâcause mortality (16 studies, 2987 participants: RR 0.95, 95% CI 0.70 to 1.29). The risk for any acute rejection (22 studies, 3301 participants: RR 0.65, 95% CI 0.57 to 0.73, P < 0.01), biopsyâproven acute rejection (12 studies, 2696 participants: RR 0.59, 95% CI 0.52 to 0.68) and antibodyâtreated acute rejection (15 studies, 2914 participants: RR 0.48, 95% CI 0.36 to 0.65, P < 0.01) were reduced in MMF treated patients. Metaâregression analyses suggested that the magnitude of risk reduction of acute rejection may be dependent on the control rate (relative risk reduction (RRR) 0.34, 95% CI 0.10 to 1.09, P = 0.08), AZA dose (RRR 1.01, 95% CI 1.00 to 1.01, P = 0.10) and the use of cyclosporin A microâemulsion (RRR 1.27, 95% CI 0.98 to 1.65, P = 0.07). Pooled analyses failed to show a significant and meaningful difference between MMF and AZA in kidney function measures. Data on malignancies and infections were sparse, except for cytomegalovirus (CMV) infections. The risk for CMV viraemia/syndrome (13 studies, 2880 participants: RR 1.06, 95% CI 0.85 to 1.32) was not statistically significantly different between MMF and AZA treated patients, whereas the likelihood of tissueâinvasive CMV disease was greater with MMF therapy (7 studies, 1510 participants: RR 1.70, 95% CI 1.10 to 2.61). Adverse event profiles varied: gastrointestinal symptoms were more likely in MMF treated patients and thrombocytopenia and elevated liver enzymes were more common in AZA treatment. Authors' conclusions MMF was superior to AZA for improvement of graft survival and prevention of acute rejection after kidney transplantation. These benefits must be weighed against potential harms such as tissueâinvasive CMV disease. However, assessment of the evidence on safety outcomes was limited due to rare events in the observation periods of the studies (e.g. malignancies) and inconsistent reporting and definitions (e.g. infections, adverse events). Thus, balancing benefits and harms of the two drugs remains a major task of the transplant physician to decide which agent the individual patient should be started on
Francisella tularensis subsp. novicida isolated from a human in Arizona
<p>Abstract</p> <p>Background</p> <p><it>Francisella tularensis </it>is the etiologic agent of tularemia and is classified as a select agent by the Centers for Disease Control and Prevention. Currently four known subspecies of <it>F. tularensis </it>that differ in virulence and geographical distribution are recognized:<it>tularensis </it>(type A), <it>holarctica </it>(type B), <it>mediasiatica</it>, and <it>novicida</it>. Because of the Select Agent status and differences in virulence and geographical location, the molecular analysis of any clinical case of tularemia is of particular interest. We analyzed an unusual <it>Francisella </it>clinical isolate from a human infection in Arizona using multiple DNA-based approaches.</p> <p>Findings</p> <p>We report that the isolate is <it>F. tularensis </it>subsp. <it>novicida</it>, a subspecies that is rarely isolated.</p> <p>Conclusion</p> <p>The rarity of this <it>novicida </it>subspecies in clinical settings makes each case study important for our understanding of its role in disease and its genetic relationship with other <it>F. tularensis </it>subspecies.</p
Acute Trauma Factor Associations With Suicidality Across the First 5 Years After Traumatic Brain Injury
AbstractObjectiveTo determine whether severity of head and extracranial injuries (ECI) is associated with suicidal ideation (SI) or suicide attempt (SA) after traumatic brain injury (TBI).DesignFactors associated with SI and SA were assessed in this inception cohort study using data collected 1, 2, and 5 years post-TBI from the National Trauma Data Bank and Traumatic Brain Injury Model Systems (TBIMS) databases.SettingLevel I trauma centers, inpatient rehabilitation centers, and the community.ParticipantsParticipants with TBI from 15 TBIMS Centers with linked National Trauma Data Bank trauma data (N=3575).InterventionsNot applicable.Main Outcome MeasuresSI was measured via the Patient Health Questionnaire 9 (question 9). SA in the last year was assessed via interview. ECI was measured by the Injury Severity Scale (nonhead) and categorized as none, mild, moderate, or severe.ResultsThere were 293 (8.2%) participants who had SI without SA and 109 (3.0%) who had SA at least once in the first 5 years postinjury. Random effects logit modeling showed a higher likelihood of SI when ECI was severe (odds ratio=2.73; 95% confidence interval, 1.55â4.82; P=.001). Drug use at time of injury was also associated with SI (odds ratio=1.69; 95% confidence interval, 1.11â2.86; P=.015). Severity of ECI was not associated with SA.ConclusionsSevere ECI carried a nearly 3-fold increase in the odds of SI after TBI, but it was not related to SA. Head injury severity and less severe ECI were not associated with SI or SA. These findings warrant additional work to identify factors associated with severe ECI that make individuals more susceptible to SI after TBI
Neuroproteomics and Systems Biology Approach to Identify Temporal Biomarker Changes Post Experimental Traumatic Brain Injury in Rats
Traumatic brain injury (TBI) represents a critical health problem of which diagnosis, management, and treatment remain challenging. TBI is a contributing factor in approximately one-third of all injury-related deaths in the United States. The Centers for Disease Control and Prevention estimate that 1.7 million people suffer a TBI in the United States annually. Efforts continue to focus on elucidating the complex molecular mechanisms underlying TBI pathophysiology and defining sensitive and specific biomarkers that can aid in improving patient management and care. Recently, the area of neuroproteomics-systems biology is proving to be a prominent tool in biomarker discovery for central nervous system injury and other neurological diseases. In this work, we employed the controlled cortical impact (CCI) model of experimental TBI in rat model to assess the temporal-global proteome changes after acute (1âday) and for the first time, subacute (7âdays), post-injury time frame using the established cation-anion exchange chromatography-1D SDS gel electrophoresis LC-MS/MS platform for protein separation combined with discrete systems biology analyses to identify temporal biomarker changes related to this rat TBI model. Rather than focusing on any one individual molecular entity, we use
Post-Traumatic Epilepsy Associations with Mental Health Outcomes in the First Two Years after Moderate to Severe TBI: A TBI Model Systems Analysis
Purpose
Research suggests that there are reciprocal relationships between mental health (MH) disorders and epilepsy risk. However, MH relationships to post-traumatic epilepsy (PTE) have not been explored. Thus, the objective of this study was to assess associations between PTE and frequency of depression and/or anxiety in a cohort of individuals with moderate-to-severe TBI who received acute inpatient rehabilitation.
Methods
Multivariate regression models were developed using a recent (2010â2012) cohort (n = 867 unique participants) from the TBI Model Systems (TBIMS) National Database, a time frame during which self-reported seizures, depression [Patient Health Questionnaire (PHQ)-9], and anxiety [Generalized Anxiety Disorder (GAD-7)] follow-up measures were concurrently collected at year-1 and year-2 after injury.
Results
PTE did not significantly contribute to depression status in either the year-1 or year-2 cohort, nor did it contribute significantly to anxiety status in the year-1 cohort, after controlling for other known depression and anxiety predictors. However, those with PTE in year-2 had 3.34 times the odds (p = .002) of having clinically significant anxiety, even after accounting for other relevant predictors. In this model, participants who self-identified as Black were also more likely to report clinical symptoms of anxiety than those who identified as White. PTE was the only significant predictor of comorbid depression and anxiety at year-2 (Odds Ratio 2.71; p = 0.049).
Conclusions
Our data suggest that PTE is associated with MH outcomes 2 years after TBI, findings whose significance may reflect reciprocal, biological, psychological, and/or experiential factors contributing to and resulting from both PTE and MH status post-TBI. Future work should consider temporal and reciprocal relationships between PTE and MH as well as if/how treatment of each condition influences biosusceptibility to the other condition
Incidence and risk factors of posttraumatic seizures following traumatic brain injury: A Traumatic Brain Injury Model Systems Study
Objective
Determine incidence of posttraumatic seizure (PTS) following traumatic brain injury (TBI) among individuals with moderate-to-severe TBI requiring rehabilitation and surviving at least 5 years.
Methods
Using the prospective TBI Model Systems National Database, we calculated PTS incidence during acute hospitalization, and at years 1, 2, and 5 postinjury in a continuously followed cohort enrolled from 1989 to 2000 (n = 795). Incidence rates were stratified by risk factors, and adjusted relative risk (RR) was calculated. Late PTS associations with immediate (7 day) versus no seizure prior to discharge from acute hospitalization was also examined.
Results
PTS incidence during acute hospitalization was highest immediately (<24 h) post-TBI (8.9%). New onset PTS incidence was greatest between discharge from inpatient rehabilitation and year 1 (9.2%). Late PTS cumulative incidence from injury to year 1 was 11.9%, and reached 20.5% by year 5. Immediate/early PTS RR (2.04) was increased for those undergoing surgical evacuation procedures. Late PTS RR was significantly greater for individuals who self-identified as a race other than black/white (year 1 RR = 2.22), and for black individuals (year 5 RR = 3.02) versus white individuals. Late PTS was greater for individuals with subarachnoid hemorrhage (year 1 RR = 2.06) and individuals age 23â32 (year 5 RR = 2.43) and 33â44 (year 5 RR = 3.02). Late PTS RR years 1 and 5 was significantly higher for those undergoing surgical evacuation procedures (RR: 3.05 and 2.72, respectively).
Significance
In this prospective, longitudinal, observational study, PTS incidence was similar to that in studies published previously. Individuals with immediate/late seizures during acute hospitalization have increased late PTS risk. Race, intracranial pathologies, and neurosurgical procedures also influenced PTS RR. Further studies are needed to examine the impact of seizure prophylaxis in high-risk subgroups and to delineate contributors to race/age associations on long-term seizure outcomes
Towards hydrogen energy: progress on catalysts for water splitting
This article reviews some of the recent work by fellows and associates of the Australian Research Council Centre of Excellence for Electromaterials Science (ACES) at Monash University and the University of Wollongong, as well as their collaborators, in the field of water oxidation and reduction catalysts. This work is focussed on the production of hydrogen for a hydrogen-based energy technology. Topics include: (1) the role and apparent relevance of the cubane-like structure of the Photosystem II Water Oxidation Complex (PSII-WOC) in non-biological homogeneous and heterogeneous water oxidation catalysts, (2) light-activated conducting polymer catalysts for both water oxidation and reduction, and (3) porphyrin-based light harvesters and catalysts
Prognostic models for predicting posttraumatic seizures during acute hospitalization, and at 1 and 2 years following traumatic brain injury
Objective
Posttraumatic seizures (PTS) are well-recognized acute and chronic complications of traumatic brain injury (TBI). Risk factors have been identified, but considerable variability in who develops PTS remains. Existing PTS prognostic models are not widely adopted for clinical use and do not reflect current trends in injury, diagnosis, or care. We aimed to develop and internally validate preliminary prognostic regression models to predict PTS during acute care hospitalization, and at year 1 and year 2 postinjury.
Methods
Prognostic models predicting PTS during acute care hospitalization and year 1 and year 2 post-injury were developed using a recent (2011â2014) cohort from the TBI Model Systems National Database. Potential PTS predictors were selected based on previous literature and biologic plausibility. Bivariable logistic regression identified variables with a p-value < 0.20 that were used to fit initial prognostic models. Multivariable logistic regression modeling with backward-stepwise elimination was used to determine reduced prognostic models and to internally validate using 1,000 bootstrap samples. Fit statistics were calculated, correcting for overfitting (optimism).
Results
The prognostic models identified sex, craniotomy, contusion load, and pre-injury limitation in learning/remembering/concentrating as significant PTS predictors during acute hospitalization. Significant predictors of PTS at year 1 were subdural hematoma (SDH), contusion load, craniotomy, craniectomy, seizure during acute hospitalization, duration of posttraumatic amnesia, preinjury mental health treatment/psychiatric hospitalization, and preinjury incarceration. Year 2 significant predictors were similar to those of year 1: SDH, intraparenchymal fragment, craniotomy, craniectomy, seizure during acute hospitalization, and preinjury incarceration. Corrected concordance (C) statistics were 0.599, 0.747, and 0.716 for acute hospitalization, year 1, and year 2 models, respectively.
Significance
The prognostic model for PTS during acute hospitalization did not discriminate well. Year 1 and year 2 models showed fair to good predictive validity for PTS. Cranial surgery, although medically necessary, requires ongoing research regarding potential benefits of increased monitoring for signs of epileptogenesis, PTS prophylaxis, and/or rehabilitation/social support. Future studies should externally validate models and determine clinical utility
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