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Sitagliptin, a DPP-4 inhibitor was used as an incretin enhancer in clinical practice first. In clinical trials, sitagliptin showed effective control of blood glucose level in type 2 diabetes and 100 mg once daily with metformin was similar to sulfonylurea (glipizide) with metformin in lowering HbA1c. Mostly in practice, stable blood glucose levels were maintained after change of sulfonylurea to sitagliptin in type 2 diabetes treatment. However, in some cases, there were abrupt severe hyperglycemia and uncontrolled blood glucose level after drug change to sitagliptin. Several mechanism could be considered for reduced response to DPP-4 inhibitor in some type 2 diabetes patients. Firstly, significantly reduced secretion of glucagon-like peptide 1 (GLP-1) more than expected in diabetes or functional defect of GLP-1 activity could be the mechanism of loss of GLP-1 effect irrespective of DPP-4. Secondly, mutation or functional defect of DPP-4 enzyme could not be inhibited by DPP-4 inhibitor. Thirdly, GLP-1 receptor mutation or other defect in β-cell responsiveness to GLP-1 leads to reduction of response to DPP-4 inhibitor. The purpose of this study is to confirm the mechanism of reduced response to DPP-4 inhibitor in some patients with type 2 diabetes and evaluate appropriate patients to treat with DPP-4 inhibitor

Although post-traumatic stress disorder and depression have been identified as the two most common consequences of intimate partner violence, research has generally not differentiated the effects of different types of intimate partner violence on victim's mental health. With intimate partner violence treated as a single phenomenon rather than having different types, abused women are unlikely to receive the most appropriate interventions. Johnson's typology of control has been used increasingly to classify intimate partner violence based on physical assault and controlling behavior. Two distinct types of the violence, Intimate Terrorism and Situational Couple Violence, have received much attention. The two differ not only in the cause and trajectory of the violence but also in the effects including mental health outcomes. Although control is a critical factor in distinguishing intimate terrorism from situational couple violence, there is no consensus on what constitutes high or low control in physically violent intimate relationships. Partly, this may be due to the sole reliance on quantitative measures to determine the levels of control. By understanding the context in which control tactics are used, qualitatively different phenomena between violent relationships with high control and those with low control may be more apparent. Thus, there is a need to collect both quantitative and qualitative data on the use of controlling behaviors. It has also been hypothesized that intimate terrorism and situational couple violence have different mental health outcomes but few studies have examined this empirically and none has studied women's experiences of the negative psychological consequences as victims of these two types of violence. The purpose of this study is to extend the extant work on the typology of intimate partner violence (IPV) by employing mixed methods to collect quantitative and qualitative data.

Biologic-naïve rheumatoid arthritis (RA) patients who fulfilled the 2010 criteria of the American College of Rheumatology (ACR) for RA were enrolled. All patient were randomized to a 6-month treatment with either oral DXM [dextromethorphan hydrobromide; Detosiv Slow Release® (60mg per tablet, Lotus Pharmaceutical Company, Taipei, Taiwan) with T1/2 = 7.75h, Tmax = 4.83h, Cmax = 14.6 ng mL-1 and mean residual time = 5.86 h, 120mg per day with once daily dose taken after breakfast] or placebo pills with the same appearance as DXM tablets. The randomization was performed by the pharmacy of the Taichung Veterans General Hospital. Non-study medications were not changed during the course of study. Twenty-four patients received add-one DXM therapy and the other 24 patients received traditional DMARDs alone in stable dose. Disease activity was assessed by the 28-joint disease activity score (DAS28) before starting add-on DXM therapy (as a baseline) and at the end of 6 months of therapy with or without add-on DXM. Patients were categorized as good, moderate or poor responders based on the amount of change in the DAS28 and the level of DAS28 reached. Good responders were defined as patients who had a decrease in DAS28 from baseline (∆DAS28)＞1.2 and a DAS28≦3.2 at evaluation time; moderate responders had either ∆DAS28＞1.2 and a DAS28>3.2 or ∆DAS28 of 0.6-1.2 and a DAS28≦5.1 at evaluation time; and poor responders were those who had either ∆DAS28＜0.6 or a DAS28>5.1 at evaluation time. Rheumatoid arthritis were randomized to a 6-month treatment of oral dextromethorphan hydrobromide or placebo as an add-on therapy to traditional disease-modifying anti-rheumatic drugs (DMARDs). Disease activity were assessed.

Specific Aim 1. To define and characterize the etiologic agents of community acquired bacteremic syndromes in young Nigerian children Hypothesis 1a: the role of vaccine-preventable infections such as those caused by the Pneumococcus, Hib in the etiology of CABS is currently underestimated due to widespread use of non-prescription antibiotics. Hypothesis 1b: Salmonella species are the leading cause of persistent febrile illness (fever > 2 weeks) in young Nigerian children. Specific Aim 2. To determine the role of respiratory viruses in promoting the severity of bacteremic and radio-logic pneumonia Hypothesis 2: Influenza viruses promote the severity of bacteremic pneumonia Specific Aim 3. To determine acute host inflammatory response profiles in CABS associated with respiratory distress Hypothesis 3a: Bacteremia induces a pattern of host inflammatory profile that is distinct from those induced by malaria or respiratory viral infections. Hypothesis 3b: Clinical presentation and outcome (death, survival or prolonged hospitalization) is associated with pro-inflammatory and anti-inflammatory cytokine and chemokine dissonance. The global burden of childhood deaths is largely borne by developing countries. Of the estimated 10 million deaths that occur in children aged less than 5 years, over 90% of these occur in developing countries and more than half of these in sub Saharan Africa. Causes of these deaths have been largely classified based on syndrome presentation, such as pneumonia, malaria, diarrhea, meningitis and septicemia and only recently have attempts been made to define the etiologic pathogens that are responsible for these deaths, an important step to implementing primary prevention. In sub Saharan Africa, malaria has for a long time been perceived as the leading cause of childhood deaths but recent studies from Kenya suggest that more deaths are in fact caused by bacteremia. However, disease burden varies by region and disease burden perceptions also vary, particularly in malaria endemic regions where clinical presentation of acute malaria, pneumonia and sepsis are often indistinguishable. The situation is compounded further in regions where malaria is present all-year round where children who are bacteremic may also have malaria parasitemia and healthy children may have asymptomatic parasitemia. These complex and overlapping features present a challenge for efficient clinical management and implementation of appropriate preventive measures. In most developing countries, due to lack of local data, clinical management recommendations are often obtained from the World Health Organization for common conditions based on the integrated management of childhood illness approach 3. In such settings, diagnosis is based on a limited number of clinical syndromes. However, because seriously ill children often meet criteria for several clinical syndromes, each of which could be caused by several viral or bacterial pathogens, treatment is empiric and management approach is non-specific. A key component of clinical management in malaria endemic areas with high incidence of invasive bacterial disease is the initiation of antibiotic treatment and anti-malarials. While this approach provides an easy scheme, because it is not pathogen-specific there is a significant risk of promoting long-term antibiotic resistance due to over prescription of antibiotics and paradoxically, there is also the risk of increased mortality and morbidity due to inappropriate medication. An etiology-based management approach would be more effective and also provide data to explore primary preventive measures such as immunization. Causes of bacteremia vary from reports in several sub-Saharan countries with high under-five childhood mortality. These include studies from Malawi and the Central African Republic where Non-typhoidal Salmonella (NTS) predominate and some reports from Nigeria where staphylococcus aureus has been the leading cause of bacteremia in young children. There are only a few studies from Nigeria, the most populated country in sub-Saharan Africa, and these studies have not identified S. pneumoniae nor Hib as an important pathogen in the etiology of community acquired bacteremic illness or invasive bacterial disease in young children. The disparity in prevalence of different bacterial pathogens across countries is likely due to the different study entry criteria, age groups, bacterial culture methods and the prevalence of antibiotic exposure in the population. A high rate of antibiotic use is likely to select for resistant bacterial strains in such populations. It is notable that of all the studies that identified S. pneumoniae as a leading cause of bacteremia were studies that utilized the automated Bactec culture system. Thus to determine the true burden of vaccine-preventable bacterial disease in such a setting would warrant the use of culture-based and molecular microbiology techniques that would overcome the problem of poor sensitivity secondary to partially treated infections. Of the childhood illnesses commonly associated with bacteremia, pneumonia is the leading cause of death, with Streptococcus pneumonia making a significant contribution to these deaths in reports from the Gambia but limited data from the West African sub region. Thus this study will focus on providing further understanding of the etiologic agents of bacteremia and pneumonia. Determination of the cause of pneumonia remains a challenge, since bacterial blood culture, the current "gold standard" is useful only when when pneumonia is associated with bacteremia and is positive only in about 10-15% of cases. The vast majority of pneumonias are not associated with bacteremia and to ascertain cause in these cases warrants the use of lung aspirates, a very specific but invasive procedure used only in research settings. When a clinical diagnosis of pneumonia is made using the WHO guideline, which is very sensitive but poorly specific, only a fraction of these have any radio-logic abnormality and a variable smaller fraction still, have a confluent alveolar density that culminates in a lobar consolidation. When the lung consolidation is readily assessable to the chest wall, the more sensitive and specific approach for the etiologic diagnosis is the use of a percutaneous lung aspirate which is considered invasive and only used in research settings. This approach improved etiologic diagnosis from 18% with the use of blood culture alone to 52%. Since this procedure is invasive and reserved for only selected cases, the causes of most non-bacteremic pneumonia remains poorly defined. At the population level, another approach for determining the burden of disease-attributable to an etiologic agent in a population is the use of an efficacious vaccine. For example, in The Gambia, the pneumococcal conjugate vaccine efficacy trial was associated with 37% reduction in radio-logic pneumonia and 16% reduction in all-cause childhood mortality; an important testament to the under-estimation of the true disease burden attributable to the pneumococcus and the poor sensitivity of the current diagnostic methods for the detection of invasive pneumococcal disease in young children. While the development and application of these new generation vaccines are a major advancement with a huge potential for saving several thousands of lives, they also provide a sensitive tool for probing the burden of vaccine-attributable preventable disease in a population but are very expensive. The determination of the causes of pneumonia in childhood presents a further challenge as other agents such as viruses have often been identified from respiratory secretions but their role in the patho-genesis of severe pneumonia in developing countries is less well defined. Understanding the host immune responses to infection is critical to providing insight into treatment modalities, since these responses and not necessarily the pathogen, determine outcome. This observation is further supported by the observation that prompt diagnosis and initiation of antibiotic treatment does not always avert death as recently reported from a study from the Gambia, where delayed mortality was reported within 28 days of hospital discharge after appropriate in-patient care at a hospital. The reason for these delayed deaths is unknown but prolonged immunologic dissonance (imbalance between pro-inflammatory and anti-inflammatory cytokines) is a likely contributing factor. This deserves further investigation since if these delayed deaths are due to immunologic dissonance, these deaths may be averted with the use of steroids or other immunomodulators, in addition to antibiotics. Characterization of host inflammatory responses among children with community acquired pneumonia may facilitate understanding of host inflammatory response, provide a prognostic tool for clinicians or identify potential therapeutic targets. Children presenting with an acute febrile illness, with respiratory distress in a malaria endemic region may have severe malaria, bacteremia, sepsis and/or pneumonia. A number of studies have explored acute inflammatory markers such as C-reactive protein and procalcitonin but have reported significant overlap in serum concentration of these proteins in both conditions to justify a diagnostic use for in such settings. While the clinical presentation with respiratory distress in pneumonia and malaria may be similar, understanding the molecular basis for this clinical sign could provide valuable information for diagnosis and treatment. In summary, community acquired bacteremic syndromes in malaria endemic regions of Africa presents a diagnostic conundrum for physicians and pose an important clinical management dilemma that warrants further evaluation. This study proposes to take advantage of new molecular and genomic technology in addressing this challenge with the ultimate goal of defining the etiologic agents of community acquired bacteremic syndromes in Nigerian children and generating information on host inflammatory responses that would be useful in developing primary and secondary preventative measures. To define the etiologic agents of community acquired bacteremic syndromes (defined as septicemia, bacteremia, pneumonia and/or meningitis) in a malaria endemic setting.

Advances in critical care have led to improved survival among those admitted to intensive care units (ICUs). However, survival is lower among those who develop ICU delirium, and the quality of life among survivors may be affected by post-ICU long-term cognitive impairment (CI) that lasts months to years. Long-term CI has been studied predominantly following cardiopulmonary bypass. In the much larger group of medical and general surgical ICU patients, the extent of this problem and its relationship to health-related quality of life is poorly characterized. Evidence from 6 pilot cohorts (including our own) totaling ~300 patients suggests that an astonishing 30% to 80% of ICU survivors experience long-term CI functionally equivalent to mild/moderate dementia although it may not be progressive (and thus will be referred to as long-term CI). Interestingly, this cognitive impairment arises independent of severity of illness, and older patients appear particularly prone. Our work and the work of others have shown that delirium is a major independent risk factor for impaired cognitive function at hospital discharge and increased mortality at 6 months. While it is not clear whether delirium itself is injurious to the brain or is simply a marker of brain injury, it is clear that the onset of delirium in the ICU should not be considered innocuous; rather, it may be a determinant of long-term CI and health-related quality of life. Having spent the last 8 years studying delirium and drug exposure during acute phases of critical illness and long-term CI after hospitalization, the investigators are thoroughly prepared to continue the next phases of investigation in VA (Department of Veterans Affairs) patients, many of whom are older and disproportionately at risk for adverse outcomes following ICU care. This will be the first large cohort study to define the epidemiology of and identify modifiable risk factors for long-term CI and functional deficits of ICU survivors. We will measure the independent contribution of risk factors such as delirium and exposure to sedative and analgesic medications to the incidence of long-term CI, controlling for established risk factors (e.g., age, pre-existing CI, and apoE genotype). Defining the contributions of these risk factors will make it possible to develop preventive and/or treatment strategies to reduce the incidence, severity and/or duration of long-term CI and improve functional recovery of patients with acute critical illness.

Despite extensive research, the etiology of most preterm births remains unknown. There are significant fetal consequences associated with preterm birth, which include necrotizing enterocolitis, fetal respiratory distress and intra-ventricular hemorrhage. Perinatal mortality is about 44%, 11% and 5% when deliveries occur between 25-28 weeks, 29-32 weeks and 33-34 weeks, respectively. While for many years, it was assumed that the cause of the high morbidity associated with prematurity was the birth of a neonate with a restricted adaptive capacity, it has also been suggested that part of the high perinatal morbidity was the consequence of adverse processes affecting the fetus in utero, rather than of prematurity per se. Intra-amniotic inflammation present in utero early in gestation may trigger the cascade of events leading to preterm birth (i.e. rupture of membranes, cervical ripening, uterine contractions) and provide an intrauterine milieu which is unfavorable or even harmful to the fetus. Most living organisms have developed well-integrated, antioxidant defenses to scavenge free radicals and control their intracellular concentration. A loss of balance between free radicals and antioxidants (the redox balance) is one mechanism of cell injury in diseases associated with inflammation. N-acetylcysteine is an approved anti-oxidant medication drug used during pregnancy for treatment of mothers with acetaminophen (Tylenol) toxicity. N-acetylcysteine has been safely administered during pregnancy in over 100 women who overdosed with Tylenol and to preterm and healthy term newborns for other purposes. It is a goal of our trial to prevent free radical formation by administering N-acetylcysteine and to further study whether the outcome of preterm deliveries will improve compared to a control group which will not receive placebo infusion The aim of the study is to determine if N-acetylcysteine (a potent free radical scavenger) prevents the occurrence of adverse neonatal outcomes in preterm deliveries complicated by infection associated with preterm labor or preterm premature rupture of membranes (PPROM). The working hypothesis is that in pregnancies complicated by intra-amniotic infection or inflammation, N-acetylcysteine protects the fetus by preventing the development, or decreasing the intensity and/or progression of the fetal inflammatory syndrome.

Although a number of mechanisms for cramps in liver disease have been postulated and have been targeted by medical therapies, a clear picture of the causal events has not emerged. Several agents as vitamin E, human albumin, zinc, taurine, eperisone hydrochloride and branched-chain amino acids have shown some benefit in small uncontrolled studies, although large randomized controlled trials are lacking. - Cyclobenzaprine, is a muscle relaxer medication used to relieve skeletal muscle spasms. It is one of the best-studied drug for this application.

The purpose of the study is to show a decrease in broad-spectrum antibiotics with a non-inferiority in 90-day mortality. Hospitals with a pre-intervention protocol adherence of >70% are excluded from the primary analysis. Primary analysis will be done with a mixed effects model with a random effects for clusters and time. Crude outcomes and outcomes adjusted for potential confounders will be reported. Primary analysis will be tested one-sided for a decrease in mortality. Secondary analysis to test two-sided for mortality will be performed. The purpose of this study is to determine the effect of a multifaceted antibiotic stewardship intervention on protocol adherence of moderate-severe community-acquired pneumonia.

This study will evaluate the time-course of the antiproteinuric effect of renin inhibition with Aliskiren in patients with Type 2 diabetes suffering from incipient and/or established nephropathy.

Endotracheal intubation of the morbidly obese is often performed awake. Fiberoptic bronchoscope assisted endotracheal intubation, a commonly utilized technique for securing an airway while a patient is awake, has many limitations. The video laryngoscope is a device that is similar to a conventional laryngoscope but uses a video system to visualize the larynx. Because of its low cost, ease of use, and usefulness in the presence of edema or bleeding that may obstruct the airway, video assisted laryngoscopy has been shown to be useful for awake endotracheal intubations. However, a direct comparison of the fiberoptic bronchoscope with video assisted laryngoscopy has not been performed for awake endotracheal intubations in of obese patients. Patients undergoing laparoscopic gastric bypas andrecquiring awake intubations will be randomized for either fiberoptic bronchoscope or video assisted laryngoscopy. The investigators primary outcome will be the time required for successful intubation.