Phylogenetic exploration of nosocomial transmission chains of 2009 influenza A/H1N1 among children admitted at Red Cross War Memorial Children's Hospital, Cape Town, South Africa in 2011

Traditional modes of investigating influenza nosocomial transmission have entailed a combination of confirmatory molecular diagnostic testing and epidemiological investigation. Common hospital-acquired infections like influenza require a discerning ability to distinguish between viral isolates to accurately identify patient transmission chains. We assessed whether influenza hemagglutinin sequence phylogenies can be used to enrich epidemiological data when investigating the extent of nosocomial transmission over a four-month period within a paediatric Hospital in Cape Town South Africa. Possible transmission chains/channels were initially determined through basic patient admission data combined with Maximum likelihood and time-scaled Bayesian phylogenetic analyses. These analyses suggested that most instances of potential hospital-acquired infections resulted from multiple introductions of Influenza A into the hospital, which included instances where virus hemagglutinin sequences were identical between different patients. Furthermore, a general inability to establish epidemiological transmission linkage of patients/viral isolates implied that identified isolates could have originated from asymptomatic hospital patients, visitors or hospital staff. In contrast, a traditional epidemiological investigation that used no viral phylogenetic analyses, based on patient co-admission into specific wards during a particular time-frame, suggested that multiple hospital acquired infection instances may have stemmed from a limited number of identifiable index viral isolates/patients. This traditional epidemiological analysis by itself could incorrectly suggest linkage between unrelated cases, underestimate the number of unique infections and may overlook the possible diffuse nature of hospital transmission, which was suggested by sequencing data to be caused by multiple unique introductions of influenza A isolates into individual hospital wards. We have demonstrated a functional role for viral sequence data in nosocomial transmission investigation through its ability to enrich traditional, non-molecular observational epidemiological investigation by teasing out possible transmission pathways and working toward more accurately enumerating the number of possible transmission events

Results of phase 3 of the CATIE schizophrenia trial

Objective—The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study examined the comparative effectiveness of antipsychotic treatments for individuals with chronic schizophrenia. Patients who had discontinued antipsychotic treatment in phases 1 and 2 were eligible for phase 3, in which they selected one of nine antipsychotic regimens with the help of their study doctor. We describe the characteristics of the patients who selected each treatment option and their outcomes. Method—Two hundred and seventy patients entered phase 3. The open-label treatment options were monotherapy with oral aripiprazole, clozapine, olanzapine, perphenazine, quetiapine, risperidone, ziprasidone, long-acting injectable fluphenazine decanoate, or a combination of any two of these treatments. Results—Few patients selected fluphenazine decanoate (n=9) or perphenazine (n=4). Similar numbers selected each of the other options (range 33–41). Of the seven common choices, those who selected clozapine and combination antipsychotic treatment were the most symptomatic, and those who selected aripiprazole and ziprasidone had the highest body mass index. Symptoms improved for all groups, although the improvements were modest for the groups starting with relatively mild levels of symptoms. Side effect profiles of the medications varied considerably but medication discontinuations due to intolerability were rare (7% overall). Conclusions—Patients and their doctors made treatment selections based on clinical factors, including severity of symptoms, response to prior treatments, and physical health status. Fluphenazine decanoate was rarely used among those with evidence of treatment non-adherence and clozapine was underutilized for those with poor previous response. Combination antipsychotic treatment warrants further study

Deaths from acute abdominal conditions and geographical access to surgical care in India: a nationally representative spatial analysis

Background Few population-based studies quantify mortality from surgical conditions and relate mortality to access to surgical care in low-income and middle-income countries. Methods We linked deaths from acute abdominal conditions within a nationally representative, population-based mortality survey of 1·1 million households in India to nationally representative facility data. We calculated total and age-standardised death rates for acute abdominal conditions. Using 4064 postal codes, we undertook a spatial clustering analysis to compare geographical access to well-resourced government district hospitals (24 h surgical and anaesthesia services, blood bank, critical care beds, basic laboratory, and radiology) in high-mortality or low-mortality clusters from acute abdominal conditions. Findings 923 (1·1%) of 86 806 study deaths at ages 0–69 years were identifi ed as deaths from acute abdominal conditions, corresponding to 72 000 deaths nationally in 2010 in India. Most deaths occurred at home (71%) and in rural areas (87%). Compared with 567 low-mortality geographical clusters, the 393 high-mortality clusters had a nine times higher age-standardised acute abdominal mortality rate and signifi cantly greater distance to a well-resourced hospital. The odds ratio (OR) of being a high-mortality cluster was 4·4 (99% CI 3·2–6·0) for living 50 km or more from well-resourced district hospitals (rising to an OR of 16·1 [95% CI 7·9–32·8] for >100 km). No such relation was seen for deaths from non-acute surgical conditions (ie, oral, breast, and uterine cancer). Interpretation Improvements in human and physical resources at existing government hospitals are needed to reduce deaths from acute abdominal conditions in India. Full access to well-resourced hospitals within 50 km by all of India’s population could have avoided about 50 000 deaths from acute abdominal conditions, and probably more from other emergency surgical conditions

Factors Associated with Physician Agreement on Verbal Autopsy of over 11500 Injury Deaths in India

Worldwide, injuries account for 9.8% of all deaths. The majority of these deaths occur in low- and middle-income countries where vital registration systems are often inadequate. Verbal autopsy (VA) is a tool used to ascertain cause of death in such settings. Validation studies for VA using hospital diagnosed causes of death as comparisons have shown that injury deaths can be reliably diagnosed by VA. However, no study has assessed the factors that may affect physicians' abilities to code specific causes of injury death using VA.This study used data from over 11 500 verbal autopsies of injury deaths from the Million Death Study (MDS) in which 6.3 million people in India were monitored from 2001–2003 for vital events. Deaths that occurred in the MDS were coded by two independent physicians. This study focused on whether physician agreement on the classification of injury deaths was affected by characteristics of the deceased and respondent. Agreement was analyzed using three primary methods: 1) kappa statistic; 2) sensitivity and specificity analysis using the final VA diagnosed category of injury death as gold standard; and 3) multivariate logistic regression using a conceptual hierarchical model. The overall agreement for all injury deaths was 77.9% with a kappa of 0.74 (99% CI 0.74–0.75). Deaths in the injury categories of “transport”, “falls”, “drowning” and “other unintentional injury” occurring outside the home were associated with greater physician agreement than those occurring at home. In contrast, self-inflicted injury deaths that occurred outside the home were associated with lower physician agreement.With few exceptions, most characteristics of the deceased and the respondent did not influence physician agreement on the classification of injury deaths. Physician training and continued adaptation of the VA tool should focus on the reasons these factors influenced physician agreement

Inflammatory Markers in Schizophrenia: Comparing Antipsychotic Effects in Phase 1 of the CATIE Schizophrenia Trial

C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin are systemic inflammatory markers (IM) that positively correlate with cardiovascular (CV) risk. Despite the known CV effects of atypical antipsychotics, there is limited prospective data on IM changes during treatment

Impact of antipsychotic treatment on nonfasting triglycerides in the CATIE Schizophrenia Trial phase 1

Recent literature documents a stronger association between nonfasting triglycerides (TG) and cardiovascular risk compared to fasting TG. Given concerns over antipsychotic effects on serum TG, this analysis explored changes in nonfasting TG in phase 1 of the CATIE Schizophrenia Trial

Change in metabolic syndrome parameters with antipsychotic treatment in the CATIE Schizophrenia Trial: Prospective data from phase 1

The metabolic syndrome (MS) is associated with increased risk for diabetes mellitus and coronary heart disease, and is highly prevalent among schizophrenia patients. Given concerns over antipsychotic metabolic effects, this analysis explored MS status and outcomes in phase 1 of the CATIE Schizophrenia Trial

Mould Routine Identification in the Clinical Laboratory by Matrix-Assisted Laser Desorption Ionization Time-Of-Flight Mass Spectrometry

BACKGROUND: MALDI-TOF MS recently emerged as a valuable identification tool for bacteria and yeasts and revolutionized the daily clinical laboratory routine. But it has not been established for routine mould identification. This study aimed to validate a standardized procedure for MALDI-TOF MS-based mould identification in clinical laboratory. MATERIALS AND METHODS: First, pre-extraction and extraction procedures were optimized. With this standardized procedure, a 143 mould strains reference spectra library was built. Then, the mould isolates cultured from sequential clinical samples were prospectively subjected to this MALDI-TOF MS based-identification assay. MALDI-TOF MS-based identification was considered correct if it was concordant with the phenotypic identification; otherwise, the gold standard was DNA sequence comparison-based identification. RESULTS: The optimized procedure comprised a culture on sabouraud-gentamicin-chloramphenicol agar followed by a chemical extraction of the fungal colonies with formic acid and acetonitril. The identification was done using a reference database built with references from at least four culture replicates. For five months, 197 clinical isolates were analyzed; 20 were excluded because they were not identified at the species level. MALDI-TOF MS-based approach correctly identified 87% (154/177) of the isolates analyzed in a routine clinical laboratory activity. It failed in 12% (21/177), whose species were not represented in the reference library. MALDI-TOF MS-based identification was correct in 154 out of the remaining 156 isolates. One Beauveria bassiana was not identified and one Rhizopus oryzae was misidentified as Mucor circinelloides. CONCLUSIONS: This work's seminal finding is that a standardized procedure can also be used for MALDI-TOF MS-based identification of a wide array of clinically relevant mould species. It thus makes it possible to identify moulds in the routine clinical laboratory setting and opens new avenues for the development of an integrated MALDI-TOF MS-based solution for the identification of any clinically relevant microorganism

Tiny Medicine: Nanomaterial-Based Biosensors

Tiny medicine refers to the development of small easy to use devices that can help in the early diagnosis and treatment of disease. Early diagnosis is the key to successfully treating many diseases. Nanomaterial-based biosensors utilize the unique properties of biological and physical nanomaterials to recognize a target molecule and effect transduction of an electronic signal. In general, the advantages of nanomaterial-based biosensors are fast response, small size, high sensitivity, and portability compared to existing large electrodes and sensors. Systems integration is the core technology that enables tiny medicine. Integration of nanomaterials, microfluidics, automatic samplers, and transduction devices on a single chip provides many advantages for point of care devices such as biosensors. Biosensors are also being used as new analytical tools to study medicine. Thus this paper reviews how nanomaterials can be used to build biosensors and how these biosensors can help now and in the future to detect disease and monitor therapies

Effectiveness of Antipsychotic Drugs in Patients with Chronic Schizophrenia

BACKGROUND The relative effectiveness of second-generation (atypical) antipsychotic drugs as compared with that of older agents has been incompletely addressed, though newer agents are currently used far more commonly. We compared a first-generation antipsychotic, perphenazine, with several newer drugs in a double-blind study. METHODS A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and randomly assigned to receive olanzapine (7.5 to 30 mg per day), perphenazine (8 to 32 mg per day), quetiapine (200 to 800 mg per day), or risperidone (1.5 to 6.0 mg per day) for up to 18 months. Ziprasidone (40 to 160 mg per day) was included after its approval by the Food and Drug Administration. The primary aim was to delineate differences in the overall effectiveness of these five treatments. RESULTS Overall, 74 percent of patients discontinued the study medication before 18 months (1061 of the 1432 patients who received at least one dose): 64 percent of those assigned to olanzapine, 75 percent of those assigned to perphenazine, 82 percent of those assigned to quetiapine, 74 percent of those assigned to risperidone, and 79 percent of those assigned to ziprasidone. The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine (P<0.001) or risperidone (P=0.002) group, but not in the perphenazine (P=0.021) or ziprasidone (P=0.028) group. The times to discontinuation because of intolerable side effects were similar among the groups, but the rates differed (P=0.04); olanzapine was associated with more discontinuation for weight gain or metabolic effects, and perphenazine was associated with more discontinuation for extrapyramidal effects. CONCLUSIONS The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons. Olanzapine was the most effective in terms of the rates of discontinuation, and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine, risperidone, and ziprasidone. Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism