Showing papers by "Public Health Research Institute published in 2012"

Immune-Correlates Analysis of an HIV-1 Vaccine Efficacy Trial

Abstract: Background In the RV144 trial, the estimated efficacy of a vaccine regimen against human immunodeficiency virus type 1 (HIV-1) was 31.2%. We performed a case–control analysis to identify antibody and cellular immune correlates of infection risk. Methods In pilot studies conducted with RV144 blood samples, 17 antibody or cellular assays met prespecified criteria, of which 6 were chosen for primary analysis to determine the roles of T-cell, IgG antibody, and IgA antibody responses in the modulation of infection risk. Assays were performed on samples from 41 vaccinees who became infected and 205 uninfected vaccinees, obtained 2 weeks after final immunization, to evaluate whether immune-response variables predicted HIV-1 infection through 42 months of follow-up. Results Of six primary variables, two correlated significantly with infection risk: the binding of IgG antibodies to variable regions 1 and 2 (V1V2) of HIV-1 envelope proteins (Env) correlated inversely with the rate of HIV-1 infection (estimated odds...

Advanced practice physiotherapy in patients with musculoskeletal disorders: a systematic review

Abstract: The convergence of rising health care costs and physician shortages have made health care transformation a priority in many countries resulting in the emergence of new models of care that often involve the extension of the scope of practice for allied health professionals. Physiotherapists in advanced practice/extended scope roles have emerged as key providers in such new models, especially in settings providing services to patients with musculoskeletal disorders. However, evidence of the systematic evaluation of advance physiotherapy practice (APP) models of care is scarce. A systematic review was done to update the evaluation of physiotherapists in APP roles in the management of patients with musculoskeletal disorders. Structured literature search was conducted in 3 databases (Medline, Cinahl and Embase) for articles published between 1980 and 2011. Included studies needed to present original quantitative data that addressed the impact or the effect of APP care. A total of 16 studies met all inclusion criteria and were included. Pairs of raters used four structured quality appraisal methodological tools depending on design of studies to analyse included studies. Included studies varied in designs and objectives and could be categorized in four areas: diagnostic agreement or accuracy compared to medical providers, treatment effectiveness, economic efficiency or patient satisfaction. There was a wide range in the quality of studies (from 25% to 93%), with only 43% of papers reaching or exceeding a score of 70% on the methodological quality rating scales. Their findings are however consistent and suggest that APP care may be as (or more) beneficial than usual care by physicians for patients with musculoskeletal disorders, in terms of diagnostic accuracy, treatment effectiveness, use of healthcare resources, economic costs and patient satisfaction. The emerging evidence suggests that physiotherapists in APP roles provide equal or better usual care in comparison to physicians in terms of diagnostic accuracy, treatment effectiveness, use of healthcare resources, economic costs and patient satisfaction. There is a need for more methodologically sound studies to evaluate the effectiveness APP care.

Evolution of Heterogeneity (I2) Estimates and Their 95% Confidence Intervals in Large Meta-Analyses

Abstract: Background Assessment of heterogeneity is essential in systematic reviews and meta-analyses of clinical trials. The most commonly used heterogeneity measure, I2, provides an estimate of the proportion of variability in a meta-analysis that is explained by differences between the included trials rather than by sampling error. Recent studies have raised concerns about the reliability of I2 estimates, due to their dependence on the precision of included trials and time-dependent biases. Authors have also advocated use of 95% confidence intervals (CIs) to express the uncertainty associated with I2 estimates. However, no previous studies have explored how many trials and events are required to ensure stable and reliable I2 estimates, or how 95% CIs perform as evidence accumulates. Methodology/Principal Findings To assess the stability and reliability of I2 estimates and their 95% CIs, in relation to the cumulative number of trials and events in meta-analysis, we looked at 16 large Cochrane meta-analyses - each including a sufficient number of trials and events to reliably estimate I2 - and monitored the I2 estimates and their 95% CIs for each year of publication. In 10 of the 16 meta-analyses, the I2 estimates fluctuated more than 40% over time. The median number of events and trials required before the cumulative I2 estimates stayed within +/−20% of the final I2 estimate was 467 and 11. No major fluctuations were observed after 500 events and 14 trials. The 95% confidence intervals provided good coverage over time. Conclusions/Significance I2 estimates need to be interpreted with caution when the meta-analysis only includes a limited number of events or trials. Confidence intervals for I2 estimates provide good coverage as evidence accumulates, and are thus valuable for reflecting the uncertainty associated with estimating I2.

Guidelines for Reporting Novel mecA Gene Homologues

Abstract: Methicillin-resistant staphylococci are disseminated all over the world and are frequent causes of health care- and community-associated infections. Methicillin-resistant strains typically carry the acquired mecA gene that encodes a low-affinity penicillin-binding protein (PBP), designated PBP2a or

Neuronal mRNAs travel singly into dendrites.

Abstract: RNA transport granules deliver translationally repressed mRNAs to synaptic sites in dendrites, where synaptic activity promotes their localized translation. Although the identity of many proteins that make up the neuronal granules is known, the stoichiometry of their core component, the mRNA, is poorly understood. By imaging nine different dendritically localized mRNA species with single-molecule sensitivity and subdiffraction-limit resolution in cultured hippocampal neurons, we show that two molecules of the same or different mRNA species do not assemble in common structures. Even mRNA species with a common dendritic localization element, the sequence that is believed to mediate the incorporation of these mRNAs into common complexes, do not colocalize. These results suggest that mRNA molecules traffic to the distal reaches of dendrites singly and independently of others, a model that permits a finer control of mRNA content within a synapse for synaptic plasticity.

The role of gap junction channels during physiologic and pathologic conditions of the human central nervous system

Abstract: Gap junctions (GJs) are expressed in most cell types of the nervous system, including neuronal stem cells, neurons, astrocytes, oligodendrocytes, cells of the blood brain barrier (endothelial cells and astrocytes) and under inflammatory conditions in microglia/macrophages. GJs connect cells by the docking of two hemichannels, one from each cell with each hemichannel being formed by 6 proteins named connexins (Cx). Unapposed hemichannels (uHC) also can be open on the surface of the cells allowing the release of different intracellular factors to the extracellular space. GJs provide a mechanism of cell-to-cell communication between adjacent cells that enables the direct exchange of intracellular messengers, such as calcium, nucleotides, IP3, and diverse metabolites, as well as electrical signals that ultimately coordinate tissue homeostasis, proliferation, differentiation, metabolism, cell survival and death. Despite their essential functions in physiological conditions, relatively little is known about the role of GJs and uHC in human diseases, especially within the nervous system. The focus of this review is to summarize recent findings related to the role of GJs and uHC in physiologic and pathologic conditions of the central nervous system.

Characterization of Nasal and Blood Culture Isolates of Methicillin-Resistant Staphylococcus aureus from Patients in United States Hospitals

Abstract: A total of 299 nares and 194 blood isolates of methicillin-resistant Staphylococcus aureus (MRSA), each recovered from a unique patient, were collected from 23 U.S. hospitals from May 2009 to March 2010. All isolates underwent spa and staphylococcal cassette chromosome mec element (SCCmec) typing and antimicrobial susceptibility testing; a subset of 84 isolates was typed by pulsed-field gel electrophoresis (PFGE) using SmaI. Seventy-six spa types were observed among the isolates. Overall, for nasal isolates, spa type t002-SCCmec type II (USA100) was the most common strain type (37% of isolates), while among blood isolates, spa type t008-SCCmec type IV (USA300) was the most common (39%). However, the proportion of all USA100 and USA300 isolates varied by United States census region. Nasal isolates were more resistant to tobramycin and clindamycin than blood isolates (55.9% and 48.8% of isolates versus 36.6% and 39.7%, respectively; for both, P < 0.05). The USA300 isolates were largely resistant to fluoroquinolones. High-level mupirocin resistance was low among all spa types (<5%). SCCmec types III and VIII, which are rare in the United States, were observed along with several unusual PFGE types, including CMRSA9, EMRSA15, and the PFGE profile associated with sequence type 239 (ST239) isolates. Typing data from this convenience sample suggest that in U.S. hospitalized patients, USA100 isolates of multiple spa types, while still common in the nares, have been replaced by USA300 isolates as the predominant MRSA strain type in positive blood cultures.

Differential In Vivo Activities of Anidulafungin, Caspofungin, and Micafungin against Candida glabrata Isolates with and without FKS Resistance Mutations

Abstract: We recently observed that the micafungin MICs for some Candida glabrata fks hot spot mutant isolates are less elevated than those for the other echinocandins, suggesting that the efficacy of micafungin may be differentially dependent on such mutations. Three clinical C. glabrata isolates with or without (S3) fks hot spot mutations R83 (Fks2p-S663F) and RR24 (Fks1p-S629P) and low, medium, and high echinocandin MICs, respectively, were evaluated to assess the in vivo efficacy in an immunocompetent mouse model using three doses of each echinocandin. Drug concentrations were determined in plasma and kidneys by high-performance liquid chromatography (HPLC). A pharmacokinetic-pharmacodynamic mathematical model was used to define the area under the concentration-time curve (AUC) that produced half- and near-maximal activity. Micafungin was equally efficacious against the S3 and R83 isolates. The estimates for the AUCs of each echinocandin that induced half-maximal effect (E(50)s) were 194.2 and 53.99 mg · h/liter, respectively. In contrast, the maximum effect (E(max)) for caspofungin was higher against S3 than R83, but the estimates for E(50) were similar (187.1 and 203.5 mg · h/liter, respectively). Anidulafungin failed to induce a ≥1-log reduction for any of the isolates (AUC range, 139 to 557 mg · h/liter). None of the echinocandins were efficacious in mice challenged with the RR24 isolate despite lower virulence (reduced maximal growth, prolonged lag phase, and lower kidney burden). The AUC associated with half-maximal effect was higher than the average human exposure for all drug-dose-bug combinations except micafungin and the R83 isolate. In conclusion, differences in micafungin MICs are associated with differential antifungal activities in the animal model. This study may have implications for clinical practice and echinocandin breakpoint determination, and further studies are warranted.

Pyrethroid Pesticide Exposure and Risk of Childhood Acute Lymphocytic Leukemia in Shanghai

Abstract: Significant amounts of pyrethroid pesticides are used throughout China. Previous studies have suggested that exposure to pesticides may increase the risk of childhood cancer; however, few studies have focused on pyrethroid metabolites. We investigated five nonspecific metabolites of pyrethroid pesticides found in children’s urine and examined the correlation with childhood leukemia. We conducted a hospital-based case-control study of childhood acute lymphocytic leukemia (ALL) in Shanghai between 2010 and 2011. The study included 176 children aged 0–14 years and 180 controls matched for age and sex. Compared with those in the lowest quartiles of total and individual metabolites, the highest quartiles were associated with an approximate 2-fold increased risk of ALL [total metabolites: odds ratio (OR) = 2.75, 95% confidence interval (CI), 1.43–5.29; cis-DCCA: OR = 2.21, 95% CI, 1.16–4.19; trans-DCCA: OR = 2.33, 95% CI, 1.23–4.41; and 3-PBA: OR = 1.84, 95% CI, 1.00–3.38], and most of the positive trends were ...

Evidence-based cognitive rehabilitation after acquired brain injury: A systematic review of content of treatment

Abstract: We reviewed all randomised trials on cognitive rehabilitation in order to determine the effective elements in terms of patients' and treatment characteristics, treatment goals and outcome. A total of 95 random controlled trials were included from January 1980 until August 2010 studying 4068 patients in total. Most studies had been conducted on language (n = 25), visuospatial functioning (n = 24), and memory (n = 14). Stroke patients were the commonest subjects (57%; overall mean age = 52.2, SD = 15.0 years). Of the interventions 39% were offered more than 12 months after onset and 23% were offered within two months of onset. The mean (SD) number of hours of treatment actually delivered was 4.1 (3.6) per week; treatment was mostly offered individually. No papers gave specific information on the expertise or competences of the staff involved. With 95 RCTs there is a large body of evidence to support the efficacy of cognitive rehabilitation, and the current study can serve as a database for clinicians and re...

Purinergic Receptors Are Required for HIV-1 Infection of Primary Human Macrophages

Abstract: Macrophages play a significant role in HIV infection, viral rebound, and the development of AIDS. However, the function of host proteins in viral replication is incompletely characterized in macrophages. Purinergic receptors P2X and P2Y are major components of the macrophage immune response to pathogens, inflammation, and cellular damage. We demonstrate that these receptors are necessary for HIV infection of primary human macrophages. Inhibition of purinergic receptors results in a significant reduction in HIV replication in macrophages. This inhibition is independent of viral strain and is dose dependent. We also identify that P2X(1), P2X(7), and P2Y(1) receptors are involved in viral replication. We show that P2X(1), but not P2X(7) or P2Y(1), is necessary for HIV entry into macrophages. We demonstrate that interaction of the HIV surface protein gp120 with macrophages stimulates an increase in ATP release. Thus, we propose that HIV's binding to macrophages triggers a local release of ATP that stimulates purinergic receptors and facilitates HIV entry and subsequent stages of viral replication. Our data implicate a novel role for a family of host proteins in HIV replication in macrophages and suggest new therapeutic targets to reduce the devastating consequences of HIV infection and AIDS.

Diagnostic Accuracy of Point-of-Care Fecal Calprotectin and Immunochemical Occult Blood Tests for Diagnosis of Organic Bowel Disease in Primary Care: The Cost-Effectiveness of a Decision Rule for Abdominal Complaints in Primary Care (CEDAR) Study

Abstract: BACKGROUND: Fecal biomarker tests that differentiate between organic bowel disease (OBD) and non-OBD in primary care patients with persistent lower-abdomen complaints could reduce the number of unnecessary referrals for endoscopy. We quantified the accuracy of fecal calprotectin and immunochemical occult blood (iFOBT) point-of-care (POC) tests and a calprotectin ELISA in primary care patients with suspected OBD. METHODS: We performed biomarker tests on fecal samples from 386 patients with lower-abdomen complaints suggestive for OBD. Endoscopic and histological diagnosis served as reference. RESULTS: OBD was diagnosed in 99 patients (prevalence 25.9%); 19 had adenocarcinoma, 53 adenoma, and 27 inflammatory bowel disease. Sensitivity for OBD was 0.64 (95% CI 0.54–0.72) for calprotectin POC, 0.56 (0.46–0.66) for iFOBT POC, and 0.74 (0.65–0.82) for calprotectin ELISA; specificities were 0.53 (0.48–0.59), 0.83 (0.78–0.87), and 0.47 (0.41–0.53), respectively. Negative predictive values (NPVs) were 0.81 (0.74–0.86), 0.85 (0.80–0.88), and 0.84 (0.78–0.89); positive predictive values (PPVs) varied from 0.32 (0.26–0.39) and 0.33 (0.27–0.39) (calprotectin tests) to 0.53 (0.44–0.63) (iFOBT POC). Combining the 2 POC tests improved sensitivity [0.79 (0.69–0.86)] and NPV [0.87 (0.81–0.91)] but lowered specificity [0.49 (0.44–0.55)] and PPV [0.35 (0.29–0.42)]. When adenomas ≤1 cm were considered non-OBD, the NPV of all tests improved to >0.90 [combined POC tests, 0.97 (0.93–0.99)]. CONCLUSIONS: Diagnostic accuracy of the tests alone or combined was insufficient when all adenomas were considered OBD. When only adenomas >1 cm were considered OBD, all tests could rule out OBD to a reasonable extent, particularly the combined POC tests. The tests were less useful for inclusion of OBD.

Nicotine vaccines to assist with smoking cessation: current status of research.

Abstract: Tobacco smoking causes cardiovascular, respiratory and malignant disease, and stopping smoking is among the key medical interventions to lower the worldwide burden of these disorders. However, the addictive properties of cigarette smoking, including nicotine inhalation, render most quit attempts unsuccessful. Recommended therapies, including combinations of counselling and medication, produce long-term continuous abstinence rates of no more than 30%. Thus, more effective treatment options are needed. An intriguing novel therapeutic concept is vaccination against nicotine. The basic principle of this approach is that, after entering the systemic circulation, a substantial proportion of nicotine can be bound by antibodies. Once bound to antibodies, nicotine is no longer able to cross the blood-brain barrier. As a consequence, the rewarding effects of nicotine are diminished, and relapse to smoking is less likely to occur. Animal studies indicate that antibodies profoundly change the pharmacokinetics of the drug and can interfere with nicotine self-administration and impact on the severity of withdrawal symptoms. To date, five phase I/II clinical trials using vaccines against nicotine have been published. Results have been disappointing in that an increase in quit rates was only observed in small groups of smokers displaying particularly high antibody titres. The failure of encouraging preclinical data to completely translate to clinical studies may be partially explained by shortcomings of animal models of addiction and an incomplete understanding of the complex physiological and behavioural processes contributing to tobacco addiction. This review summarizes the current status of research and suggests some directions for the future development of vaccines against nicotine. Ideally, these vaccines could one day become part of a multifaceted approach to treating tobacco addiction that includes counselling and pharmacotherapy.

Systematic review of efficacy and safety of buprenorphine versus fentanyl or morphine in patients with chronic moderate to severe pain.

Abstract: To systematically assess efficacy and safety of buprenorphine patch versus fentanyl patch in patients with chronic moderate to severe pain.Fifteen databases were searched up to December 2010. Rando...

Lipidomic discovery of deoxysiderophores reveals a revised mycobactin biosynthesis pathway in Mycobacterium tuberculosis

Abstract: To measure molecular changes underlying pathogen adaptation, we generated a searchable dataset of more than 12,000 mass spectrometry events, corresponding to lipids and small molecules that constitute a lipidome for Mycobacterium tuberculosis. Iron is essential for M. tuberculosis survival, and the organism imports this metal using mycobactin and carboxymycobactin siderophores. Detection of an unexpected siderophore variant and deletions of genes for iron scavenging has led to a revised mycobactin biosynthesis model. An organism-wide search of the M. tuberculosis database for hypothetical compounds predicted by this model led to the discovery of two families of previously unknown lipids, designated monodeoxymycobactins and monodeoxycarboxymycobactins. These molecules suggest a revised biosynthetic model that alters the substrates and order of action of enzymes through the mycobactin biosynthetic pathway. We tested this model genetically by solving M. tuberculosis lipidomes after deletion of the iron-dependent regulator (ideR), mycobactin synthase B (mbtB), or mycobactin synthase G (mbtG). These studies show that deoxymycobactins are actively regulated during iron starvation, and also define essential roles of MbtG in converting deoxymycobactins to mycobactin and in promoting M. tuberculosis growth. Thus, lipidomics is an efficient discovery tool that informs genetic relationships, leading to a revised general model for the biosynthesis of these virulence-conferring siderophores.

Spo0A∼P Imposes a Temporal Gate for the Bimodal Expression of Competence in Bacillus subtilis

Abstract: ComK transcriptionally controls competence for the uptake of transforming DNA in Bacillus subtilis. Only 10%–20% of the cells in a clonal population are randomly selected for competence. Because ComK activates its own promoter, cells exceeding a threshold amount of ComK trigger a positive feedback loop, transitioning to the competence ON state. The transition rate increases to a maximum during the approach to stationary phase and then decreases, with most cells remaining OFF. The average basal rate of comK transcription increases transiently, defining a window of opportunity for transitions and accounting for the heterogeneity of competent populations. We show that as the concentration of the response regulator Spo0A∼P increases during the entry to stationary phase it first induces comK promoter activity and then represses it by direct binding. Spo0A∼P activates by antagonizing the repressor, Rok. This amplifies an inherent increase in basal level comK promoter activity that takes place during the approach to stationary phase and is a general feature of core promoters, serving to couple the probability of competence transitions to growth rate. Competence transitions are thus regulated by growth rate and temporally controlled by the complex mechanisms that govern the formation of Spo0A∼P. On the level of individual cells, the fate-determining noise for competence is intrinsic to the comK promoter. This overall mechanism has been stochastically simulated and shown to be plausible. Thus, a deterministic mechanism modulates an inherently stochastic process.

Epidemiologic Features of Vulvovaginal Candidiasis among Reproductive-Age Women in India

Abstract: Background. Vulvovaginal candidiasis is characterized by curd-like vaginal discharge and itching, and is associated with considerable health and economic costs. Materials and Methods. We examined the incidence, prevalence, and risk factors for vulvovaginal candidiasis among a cohort of 898 women in south India. Participants completed three study visits over six months, comprised of a structured interview and a pelvic examination. Results. The positive predictive values for diagnosis of vulvovaginal candidiasis using individual signs or symptoms were low (<19%). We did not find strong evidence for associations between sociodemographic characteristics and the prevalence of vulvovaginal candidiasis. Women clinically diagnosed with bacterial vaginosis had a higher prevalence of vulvovaginal candidiasis (Prevalence 12%, 95% CI 8.2, 15.8) compared to women assessed to be negative for bacterial vaginosis (Prevalence 6.5%, 95% 5.3, 7.6); however, differences in the prevalence of vulvovaginal candidiasis were not observed by the presence or absence of laboratory-confirmed bacterial vaginosis. Conclusions .F or correct diagnosis of vulvovaginal candidiasis, laboratory confirmation of infection with Candida is necessary as well as assessment of whether the discharge has been caused by bacterial vaginosis. Studies are needed of women infected with Candida yeast species to determine the risk factors for yeast’s overgrowth.

The role of self‐efficacy, recovery self‐efficacy, and preparatory planning in predicting short‐term smoking relapse

Abstract: Objectives. This study aims to identify the role of self-efficacy, recovery self-efficacy, and preparatory planning with regard to short-term smoking relapse. We also assessed whether the importance of these variables differed for smokers quitting individually and without help (self-quitters) and smokers quitting with the help of a smoking cessation course (group quitters). Design. A longitudinal quasi-experimental study with follow-ups at 1 and 3 months after the quit attempt was conducted in order to assess the role of baseline self-efficacy, recovery self-efficacy, and preparatory planning on short-term relapse. Methods. The recruitment included adult daily smokers (N= 121), quitting in a smoking cessation course (N= 57) and self-quitters (N= 64). Respondents received internet-based questionnaires 2 weeks before quitting (baseline) and 1 and 3 months after the quit attempt. Predictors of relapse were analysed using logistic regression analyses. Results. Relapse at 1 and 3 months after the quit attempt was predicted by low levels of baseline self-efficacy. Simple slope analyses revealed that less preparatory planning significantly predicted relapse at 1 month after the quit attempt among group quitters, but not among self-quitters. Recovery self-efficacy was only predictive of relapse after 1 month when self-efficacy was excluded from the analyses. Moreover, among group quitters, the results indicated a borderline significant curved relation between recovery self-efficacy and relapse after 1 month. Conclusions. Our results suggest that more research is needed on the role of preparatory planning and recovery self-efficacy. Moreover, we recommend incorporating self-efficacy increasing techniques in relapse-prevention interventions.

Proteome-Scale Antibody Responses and Outcome of Mycobacterium tuberculosis Infection in Nonhuman Primates and in Tuberculosis Patients

Abstract: Background.Biomarkers of progression from latent Mycobacterium tuberculosis infection to active tuberculosis are needed. We assessed correlations between infection outcome and antibody responses in macaques and humans by high-throughput, proteome-scale serological studies. Methods.Mycobacterium tuberculosis proteome microarrays were probed with serial sera from macaques representing various infection outcomes and with single-point human sera from tuberculosis suspects. Fluorescence intensity data were analyzed by calculating Z scores and associated P values. Temporal changes in macaque antibody responses were analyzed by polynomial regression. Correlations between human responses and sputum bacillary burden were assessed by quantile and hurdle regression. Results.Macaque outcome groups exhibited distinct antibody profiles: early, transient responses in latent infection and stable antibody increase in active and reactivation disease. In humans, antibody levels and reactive protein numbers increased with bacillary burden. Responses to a subset of 10 proteins were more tightly associated with disease state than reactivity to the broader reactive proteome. Conclusions.Integration of macaque and human data reveals dynamic properties of antibody responses in relation to outcome and leads to actionable findings for translational research. These include the potential of antibody responses to detect acute infection and preclinical tuberculosis and to identify serodiagnostic proteins for the spectrum of bacillary burden in tuberculosis.

Are marginalized women being left behind? A population-based study of institutional deliveries in Karnataka, India

Abstract: While India has made significant progress in reducing maternal mortality, attaining further declines will require increased skilled birth attendance and institutional delivery among marginalized and difficult to reach populations. A population-based survey was carried out among 16 randomly selected rural villages in rural Mysore District in Karnataka, India between August and September 2008. All households in selected villages were enumerated and women with children 6 years of age or younger underwent an interviewer-administered questionnaire on antenatal care and institutional delivery. Institutional deliveries in rural areas of Mysore District increased from 51% to 70% between 2002 and 2008. While increasing numbers of women were accessing antenatal care and delivering in hospitals, large disparities were found in uptake of these services among different castes. Mothers belonging to general castes were almost twice as likely to have an institutional birth as compared to scheduled castes and tribes. Mothers belonging to other backward caste or general castes had 1.8 times higher odds (95% CI: 1.21, 2.89) of having an institutional delivery as compared to scheduled castes and tribes. In multivariable analysis, which adjusted for inter- and intra-village variance, Below Poverty Line status, caste, and receiving antenatal care were all associated with institutional delivery. The results of the study suggest that while the Indian Government has made significant progress in increasing antenatal care and institutional deliveries among rural populations, further success in lowering maternal mortality will likely hinge on the success of NRHM programs focused on serving marginalized groups. Health interventions which target SC/ST may also have to address both perceived and actual stigma and discrimination, in addition to providing needed services. Strategies for overcoming these barriers may include sensitization of healthcare workers, targeted health education and outreach, and culturally appropriate community-level interventions. Addressing the needs of these communities will be critical to achieving Millennium Development Goal Five by 2015.

Pakistani Pharmacy Students' Perception about Complementary and Alternative Medicine

Abstract: Objectives. To assess Pakistani pharmacy students’ perceptions of complementary and alternative medicine (CAM), the frequency with which they use CAM, and barriers to use of CAM. Method. A CAM health belief questionnaire was administered to 595 students enrolled in a 5-year doctor of pharmacy program (PharmD) in Pakistan. Results. Attitudes of students towards CAM were positive. Lack of evidence supporting CAM practices was considered to be the major barrier toward more students using CAM. A majority of students (79%) agreed that clinical care should integrate conventional medicine and CAM practices. Many CAM-based therapies, such as dietary supplements, massage, herbal medicines, and homoeopathic medicines were used by the students. Significant gender differences in attitude were observed, with male students having more conservative attitudes toward CAM use. A high percentage of students desired more training in CAM. Conclusions. Pakistani students exhibited positive attitudes about the value of CAM and most felt that CAM should be included in the PharmD curriculum.

Active Case Finding and Prevention of Tuberculosis Among a Cohort of Contacts Exposed to Infectious Tuberculosis Cases in New York City

Abstract: Background Tuberculosis contact investigation identifies individuals who may be recently infected with tuberculosis and are thus at increased risk for disease. Contacts with latent tuberculosis infection (LTBI) are offered chemoprophylaxis to prevent active disease; however, the effectiveness of this intervention is unclear as treatment completion is generally low. Methods A retrospective cohort study of 30 561 contacts identified during investigation of 5182 cases of tuberculosis diagnosed in New York City, 1997-2003, was performed. We searched the NYC tuberculosis registry to identify contacts developing active tuberculosis within 4 years of follow-up. We estimated the following: number of contacts undergoing evaluation (ie, tuberculin skin test and/or chest radiograph) per prevalent case diagnosed; number of contacts with LTBI that need to be treated with standard chemoprophylaxis to prevent 1 active case. Results Of 30 561 contacts, 27 293 (89%) were evaluated and 268 prevalent cases were diagnosed (102 contacts evaluated per prevalent case diagnosed, 95% confidence interval [CI], 90-115). LTBI was diagnosed in 7597 contacts, including 6001 (79%) who initiated chemoprophylaxis, 3642 (61%) who later completed treatment, and 2359 (39%) who did not complete treatment. During 4 years of follow-up, active tuberculosis was diagnosed in 46 contacts with LTBI, including 22 of 6001 (0.4%) who initiated chemoprophylaxis and 24 of 1596 (1.5%) who did not initiate treatment. The absolute risk reduction afforded by chemoprophylaxis initiation was 1.1% (95% CI, .6%-1.9%), leading to an estimated 88 contacts treated to prevent 1 tuberculosis case (95% CI, 53-164). Conclusions Contact investigation facilitates active case finding and tuberculosis prevention, even when completion rates of chemoprophylaxis are suboptimal.

Epidemiology and echinocandin susceptibility of Candida parapsilosis sensu lato species isolated from bloodstream infections at a Spanish university hospital

Abstract: Objectives: The aims of this work were to study the epidemiological profiles, differences in echinocandin susceptibilities and clinical relevance of the Candida parapsilosis sensu lato species isolated from proven fungaemia cases at La Fe University Hospital of Valencia (Spain) from 1995 to 2007. Results: The prevalence of these species was: C. parapsilosis sensu stricto, 74.4%; Candida orthopsilosis, 23.54%; and Candida metapsilosis, 2.05%. The incidence of the species complex as agents of fungaemia remained stationary until 2005 and doubled in 2006. The incidence of C. orthopsilosis showed an increasing trend during the study period, while C. parapsilosis sensu stricto incidence diminished. Also, an important epidemiological change was observed starting in 2004, when 86.5% of the C. parapsilosis sensu lato strains were found in adult patients, while before that year only 13.5% of the isolates were found in this population. Conclusions: Echinocandin drug susceptibility testing using the CLSI M27-A3 document showed a wide range of MIC values (0.015–4 mg/L), with micafungin being the most potent in vitro inhibitor followed by anidulafungin and caspofungin (MIC geometric mean of 0.68, 0.74 and 0.87 mg/L, respectively). C. metapsilosis was the most susceptible species of the complex to anidulafungin and micafungin in vitro (MIC50 for anidulafungin and micafungin: 0.06 mg/L), while there were no differences between C. parapsilosis sensu lato species when caspofungin MIC50s were compared (MIC50 1.00 mg/L). Differences in caspofungin in vitro susceptibility were observed between the different clinical service departments of La Fe Hospital.

Genotype MTBDRplus for Direct Detection of Mycobacterium tuberculosis and Drug Resistance in Strains from Gold Miners in South Africa

Abstract: GenoType MTBDRplus is a molecular assay for detection of Mycobacterium tuberculosis and drug resistance. Assay performance as applied directly to consecutive unselected sputum samples has not been established. The objective of this study was to determine the accuracy of the MTBDRplus test for direct detection of M. tuberculosis (in sputum) and for drug resistance in consecutively submitted sputum samples. In this cross-sectional study in South Africa, one sputum specimen from each person suspected of having pulmonary tuberculosis was tested by smear microscopy, direct MTBDRplus, and Mycobacterial Growth Indicator Tube (MGIT) culture with MGIT drug susceptibility testing. MGIT results were the reference standard. We tested 2,510 sputum samples, and 529 (21.1%) were positive for M. tuberculosis by MGIT. Direct MTBDRplus identified M. tuberculosis in 256 of 529 specimens (sensitivity, 48.4%; 95% confidence interval [CI], 44.1, 52.7). The sensitivity of MTBDRplus for M. tuberculosis detection by sputum smear status was as follows: smear negative, 13.7% (95% CI, 9.8, 18.4); smear scanty, 46.2% (95% CI, 19.2, 74.9); smear 1+, 69.1% (95% CI, 55.2, 80.9); smear 2+, 86.3% (95% CI, 73.7, 94.3); smear 3+, 89.8% (95% CI, 83.7, 94.2). Direct MTBDRplus testing was negative for 1,594/1,612 sputum samples that were culture negative for M. tuberculosis (specificity, 98.9%; 95% CI, 98.2, 99.3). For specimens positive for M. tuberculosis by MTBDRplus, this assay's sensitivity and specificity for rifampin resistance were 85.7% (95% CI, 57.2, 98.2) and 96.6% (95% CI, 93.2, 98.6) and for isoniazid resistance they were 62.1% (95% CI, 42.3, 79.3) and 97.9% (95% CI, 94.8, 99.4). For sputum testing, the sensitivity of MTBDRplus is directly related to the specimen's bacillary burden. Our results support recommendations that the MTBDRplus test not be used for direct testing of smear-negative or paucibacillary sputum samples.