A prospective observational study of the change in regional cerebral oxygen saturation during cesarean delivery in women receiving phenylephrine prophylaxis for spinal hypotension.

BACKGROUND: Spinal hypotension causes decreased regional cerebral oxygen saturation (ScO2) in women undergoing cesarean delivery. In this study we aimed to measure the change in ScO2 using near infrared spectroscopy in women receiving a prophylactic phenylephrine infusion during cesarean delivery under spinal anesthesia. METHODS: This was a prospective, observational cohort study. Fifty-three women had ScO2 measurements at the following time points: preoperatively, in the supine position with 30° of left lateral tilt; one and five minutes after spinal anesthesia; at the time of skin incision; immediately after delivery; one minute after commencing the oxytocin infusion; at completion of surgery, and one hour after surgery. Spinal anesthesia and a prophylactic phenylephrine infusion were administered according to a standard treatment protocol. Statistical analysis used the Wilcoxon Signed Rank test with Bonferroni's correction for multiple comparisons. RESULTS: Blood pressure was maintained within 20% of baseline throughout surgery. The baseline mean (range) ScO2 was 61.5% (54.0-66.3%). It decreased significantly at all subsequent measurement points. The maximum decrease was five minutes after spinal anesthesia. Thirty-four (64.2%) of the parturients exhibited ScO2 values <20% of baseline, or a decrease to below an absolute value of 50%. There was no significant correlation between systolic blood pressure and mean ScO2. CONCLUSION: Spinal anesthesia with phenylephrine infusion during cesarean delivery is associated with a significant decrease in ScO2 levels, maximal five minutes later. Further studies are required to establish the clinical significance of this finding.

Primary care networks and team effectiveness: the case of a large-scale quality improvement disparity reduction program.

Documentation of primary care teams' involvement in disparity reduction efforts exists, yet little is known about how teams interact or perceive their effectiveness. We investigated how the social network and structural ties among primary-care-clinic team members relate to their perceived team effectiveness (TE), in a large-scale disparity reduction intervention in Israel's largest insurer and provider of services. A mixed-method design of Social Network Analysis and qualitative data collection was employed. 108 interviews with medical, nursing, and administrative teams of 26 clinics and their respective managerial units were performed and information on the organizational ties, analyzing density and centrality, collected. Pearson correlations examined association between network measures and perceived TE. Clinics with strong intra-clinic density and high clinic-subregional-management density were positively correlated with perceived TE. Clinic in-degree centrality was also positively associated with perceived TE. Qualitative analyses support these findings with teamwork emerging as a factor which can impede or facilitate teams' ability to design and implement disparity reduction interventions. The study demonstrates that in an organization-wide disparity reduction initiative, cohesive intra-network structure and close relations with mid-level management increase the likelihood that teams perceive themselves as possessing the skills and resources needed to lead and implement disparity reduction efforts. List of abbreviations Team Effectiveness (TE); Clalit Health Services (Clalit); Social Network Analysis (SNA); Quality Improvement (QI); National Health Care Collaborative (NHPC); Tampa Bay Community Cancer Network (TBCCN).

Reducing inequity in primary care clinics treating low socioeconomic Jewish and Arab populations in Israel.

Background: An organization-wide inequity-reduction quality improvement (QI) initiative was implemented in primary care clinics serving disadvantaged Arab and Jewish populations. Using the Chronic Care Model (CCM), this study investigated the types of interventions associated with success in inequity reduction. Methods: Semi-structured interviews were conducted with 80 staff members from 26 target clinics, and information about intervention types was coded by CCM and clinical domains (e.g. diabetes, hypertension and lipid control; performance of mammography tests). Relationships between type and number of interventions implemented and inequity reduction were assessed. Results: Target clinics implemented 454 different interventions, on average 17.5 interventions per clinic. Interventions focused on Decision support and Community linkages were positively correlated with improvement in the composite quality score (P < 0.05). Conversely, focusing on a specific clinical domain was not correlated with a higher quality score. Conclusions: Focusing on training team members in selected QI topics and/or tailoring interventions to meet community needs was key to the interventions' success. Such findings, especially in light of the lack of association between QI and a focus on a specific clinical domain, support other calls for adopting a systems approach to achieving wide-scale inequity reduction.

Risk factors for and impact of carbapenem-resistant Acinetobacter baumannii colonization and infection: matched case-control study.

The objective of this investigation was to identify risk factors for carbapenem-resistant Acinetobacter baumannii (CRAB) and its association with mortality. A population-based matched case-control study using the computerized database of Clalit Health Services (CHS) in the period between 2007 and 2012 was conducted. Hospitalized patients with CRAB colonization or infection were compared to hospitalized patients without evidence of A. baumannii, matched by age, ward of hospitalization, season, Charlson score, and length of hospitalization. Risk factors for CRAB isolation were searched for using multivariate analysis. Association of CRAB and other risk factors with mortality were assessed in the cohort. A total of 1190 patients with CRAB were matched to 1190 patients without CRAB. Low socioeconomic status was independently associated with CRAB isolation and CRAB bacteremia [odds ratio 2.18, 95% confidence interval (CI) 1.02-5]. Other risk factors were invasive procedures and bacteremia with other pathogens prior to CRAB isolation, and various comorbidities. Among all patients, CRAB isolation was independently associated with increased mortality (hazard ratio 2.33, 95% CI 2.08-2.6). Socioeconomic status is associated with health outcomes. Our population-based study revealed an almost doubled risk for CRAB in patients at lower socioeconomic status and an association with healthcare exposure. CRAB was associated with mortality and might become a risk indicator for complex morbidity and mortality.

Religiosity is a protective factor against self-injurious thoughts and behaviors in Jewish adolescents: findings from a nationally representative survey.

PURPOSE: Few studies have investigated the association between religiosity and self-injurious thoughts and behaviors specifically in adolescents, yielding inconsistent results. To date, no study has examined this relationship in a Jewish adolescent cohort. METHODS: Self-injurious thoughts and behaviors, as well as depression, were assessed in a nationally representative sample of Jewish adolescents (n=620) and their mothers, using the Development and Well-Being Assessment Inventory (DAWBA) structured interview. Degree of religiosity was obtained by a self-report measure. RESULTS: Using multivariate analysis, level of religiosity was inversely associated with self-injurious thoughts and behaviors (Wald χ(2)=3.95, P=0.047), decreasing the likelihood of occurrence by 55% (OR=0.45, 95% CI 0.2-0.99), after adjusting for depression and socio-demographic factors. This model (adjusted R(2)=0.164; likelihood ratio χ(2)=7.59; df=1; P<0.047) was able to correctly classify 95.6% of the patients as belonging either to the high or low risk groups. CONCLUSION: This is the first study demonstrating religiosity to have a direct independent protective effect against self-injurious thoughts and behaviors in Jewish adolescents. This finding has clinical implications regarding risk assessment and suicide prevention. Further research can potentially elucidate the complex relationship between religiosity, self-injury and suicide in this population.

A case-control study to identify predictors of 14-day mortality following carbapenem-resistant Acinetobacter baumannii bacteraemia.

Carbapenem-resistant Acinetobacter baumannii (CRAB) is an increasingly common nosocomial pathogen. We sought to identify clinical and microbiological predictors of 14-day mortality among patients with CRAB bacteraemia. This case-control study included all adult patients in one Israeli hospital with CRAB on blood culture between July 2008 and June 2011. Cases were defined as patients who died within 14 days of bacteraemia onset and controls as patients who survived over 14 days. Sequence-typing of the blaOXA-51-like gene and REP-PCR identified CRAB clone groups. Logistic regression was performed to analyze predictors of 14-day all-cause mortality. To correct for differences in treatment onset, Cox regression was used to examine the effect of receiving an active antibiotic. Eighty-three cases and 89 controls were included. Six major CRAB clone groups were identified, with 14-day mortality ranging from 17 to 66%. Independent predictors of 14-day mortality were severity of illness (OR = 1.38 for each 1-point increase in Sequential Organ Failure Assessment (SOFA) score; 95% CI, 1.21, 1.56), independence in activities of daily living (ADL) on admission (OR = 3.40; 95% CI, 1.20, 9.67, for fully dependent vs. independent), surgery before bacteraemia (OR = 0.25; 95% CI, 0.11, 0.59) and clone group (OR = 7.76; 95% CI, 2.52, 23.85, for the most virulent group vs. the reference group). In the multivariate Cox model using a propensity score to adjust for SOFA, clone, ADL and surgery, active antibiotic treatment was protective (HR = 0.30; 95% CI, 0.15, 0.60). Differences in virulence between CRAB clones may partly explain heterogeneous results in previous studies of mortality following CRAB infection.

Treatment outcome of TB/HIV positive and negative smear positive pulmonary tuberculosis patients treated using daily self-administered therapy in a Cameroonian district hospital.

BACKGROUND: In our previous study we found that half of the patients treated at the Nylon District Hospital tuberculosis (TB) treatment centre were seropositive. HIV does not only fuel the number of tuberculosis (TB) cases worldwide but it is also at least in part, responsible for the non-achievement of the 85% cure rate target. OBJECTIVE: To compare the TB treatment outcome of smear positive pulmonary tuberculosis (SPPT) patients who did an HIV test and those who refused the test as well as compare the treatment outcomes between the HIV positive and HIV negative SPPT patients from 2003 to 2005, all of whom were treated as outpatients under routine programme conditions. DESIGN: A retrospective study. SUBJECTS: Four hundred and twenty patients were registered from 2003 to 2005 as having SPPT. SETTING: The Nylon District Hospital, Cameroon. RESULTS: Thirty five point two per cent of the 386 SPPT patients also had HIV. The overall cure rate, default rate and death rate were 69%, 23.6% and 3.3% respectively. SPPT/HIV co-infected patients were significantly more likely to default from treatment (28.7% versus 16.8%, OR 1.943, 95% CI 1.150-3.285) to die in the course of treatment (7.4% versus 0.4%, OR 23.714, 95% CI 2.894-194.330) or not to be cured (58.8% versus 78.8%, OR 0.404, 95% CI 0.250-0.652) compared to SPPT/HIV negative patients. Likewise SPPT patients not tested for HIV were significantly less cured (38.2% versus 71.8%, OR 0.21, 95% CI 0.099-0.445) and defaulted most (52.9% versus 21%, OR 4.773 95% CI 2.281-9.991) compared to SPPT patients tested for HIV. CONCLUSION: SPPT patients infected with HIV or not tested for HIV in the course of TB treatment are likely to suffer from unfavorable treatment outcomes. Thus health personnel prescribing anti- TB drugs should be provided with the necessary expertise to diagnose and manage HIV so that TB/HIV co-infected patients benefit from an integrated package of care in and out of the hospital.

Using modelling to assess the risk of malarial infection during the dry season, on a local scale in an endemic area of rural Burkina Faso.

Mathematical modelling has been used to assess the level of malarial transmission, during the dry season, in Nouna province, in north-western Burkina Faso. The data used were collected, at four sites (one semi-urban and three rural), from 867 children aged 6-60 months who were randomly selected. Almost all of the children (850) completed the follow-up, which involved the active detection of malaria (i.e. febrile, smear-positive malarial infection) throughout a single dry season (December 2003-May 2004). Light traps were used to sample the local populations of Anopheles vectors, in order to estimate the daily biting rate. The mathematical model was then used to simulate the incidence of malaria, which was compared with the observed incidence. At all four study sites, new cases of malaria were observed throughout the dry season, although the level of transmission was low. The monthly incidence of malaria estimated using the mathematical model was very close to the observed incidence. The fit was sensitive to daily mosquito survival and daily human parasite clearance. In Nouna province, effective interventions to prevent malaria should not be confined to the rainy season but must continue throughout the year. The focus should be on the clearance of parasitaemias, by the use of effective drugs, and on decreasing vector survival, by the use of vector-control methods.

Is the development of falciparum malaria in the human host limited by the availability of uninfected erythrocytes?

BACKGROUND: The development and propagation of malaria parasites in their vertebrate host is a complex process in which various host and parasite factors are involved. Sometimes the evolution of parasitaemia seems to be quelled by parasite load. In order to understand the typical dynamics of evolution of parasitaemia, various mathematical models have been developed. The basic premise ingrained in most models is that the availability of uninfected red blood cells (RBC) in which the parasite develops is a limiting factor in the propagation of the parasite population. PRESENTATION OF THE HYPOTHESIS: We would like to propose that except in extreme cases of severe malaria, there is no limitation in the supply of uninfected RBC for the increase of parasite population. TESTING THE HYPOTHESIS: In this analysis we examine the biological attributes of the parasite-infected RBC such as cytoadherence and rosette formation, and the rheological properties of infected RBC, and evaluate their effects on blood flow and clogging of capillaries. We argue that there should be no restriction in the availability of uninfected RBC in patients. IMPLICATION OF THE HYPOTHESIS: There is no justification for the insertion of RBC supply as a factor in mathematical models that describe the evolution of parasitaemia in the infected host. Indeed, more recent models, that have not inserted this factor, successfully describe the evolution of parasitaemia in the infected host.

Mathematical modelling of malaria chemotherapy: combining artesunate and mefloquine.

Clinical data on the use of artesunate combined with mefloquine in a variety of treatment regimens and parasite loads in Thailand were modelled on the basis of experimentally determined pharmacokinetic data. The model assumed no pharmacodynamic interaction between artesunate and mefloquine, but that the parasites were already resistant to mefloquine. Predictions of the model accorded well with the data. In articular, in accordance with clinical observations, the model showed that monotherapy with either drug failed to cure at moderate parasitaemia, yet such patients could be treated effectively with the combination of 3 days of artesunate + mefloquine. For high levels of parasitaemia, 5 days of artesunate + mefloquine were needed. Simulations were also performed for situations of lower resistance to mefloquine and for the immune human populations found in Africa. The importance of mathematical modelling of combination therapy is borne out by this study and suggests its wider application for other drug combinations.

Pharmacokinetic-pharmacodynamic modelling of the antimalarial activity of mefloquine.

Treatment protocols for the chemotherapy of malaria are usually acquired through clinical trials. Once pharmacokinetic and pharmacodynamic information becomes available, it is possible to use mathematical modelling for testing these protocols and, possibly, for improving them. In this report the case of monotherapy by mefloquine is analysed. Published pharmacokinetic and clinical results are used to derive the essential model parameters such as kill rate, parasite growth rates, drug sensitivity and the pharmacokinetic parameters. Good agreement is obtained between clinical results and simulated parasite numbers using the derived parameters. It is demonstrated that the 2 exponential kinetics of mefloquine elimination can be reduced to an operational single exponent for pharmacodynamic modelling by educated choice of sampling times of plasma drug concentration. It is deduced that a second drug dose, at a properly chosen time-interval, results in radical cure even when resistant parasites are present and at maximal parasite growth rates such as those found in non-immune patients. Finally, a table is provided for guiding the optimal choice of dosing intervals under different values of population pharmacokinetics, drug resistance and individual immunity parameters.

Mathematical modelling of the within-host dynamics of Plasmodium falciparum.

The development of malaria due to Plasmodium falciparum is a complex, multi-stage process. It is usually characterized by an exponential growth in the number of parasite-infected erythrocytes, followed by marked oscillations in this number with a period of 48 h, which are eventually dampened. This course of events has been the subject of various mathematical models. In this paper we propose a new mathematical model for the in-host asexual erythrocytic development of P. falciparum malaria. Synchronicity of the infection is shown to be an inherent feature of infection, irrespective of the duration of merozoite release from the liver. It will, therefore, cause periodic symptoms, as known in malaria patients. We also simulate the effects of an induced host immune response and show how the level of immunity affects the development of disease. The simulations fit well with the clinical observations. We show how infection can become asynchronous and discuss the effect of desynchronization on the circulating and total parasitaemia and demonstrate that synchronized broods will show parasitaemia fluctuations.

Mathematical modelling of the chemotherapy of Plasmodium falciparum malaria with artesunate: postulation of 'dormancy', a partial cytostatic effect of the drug, and its implication for treatment regimens.

Although artesunate, one of the potent derivatives of the qinghaosu family of drugs for treating falciparum malaria, is already in use in the field, its therapeutic protocol has only been developed empirically by hit-or-miss. A pharmacokinetic-pharmacodynamic (PK-PD) model, required for creating such a protocol, is not straightforward. Artesunate presents extremely fast pharmacokinetics. As a result the stage specificity of its action must be treated explicitly. Also, use of standard PK-PD modelling fails to explain the clinical results. Our PK-PD modelling of its activity leads us to the postulation of the existence of a novel effect: a small fraction of the parasites, as a result of chemotherapeutic pressure, become cytostatic, or 'dormant'. At this stage, the parasite cycle is halted, making them unsusceptible to further dosing until wakening. This slows down the antimalarial activity of the drug, entailing either many frequent doses or an extended period of treatment and surveillance. Based on our modelling, we suggest a method for deciding on rational models of chemotherapy against falciparum malaria.

Modelling the chloroquine chemotherapy of falciparum malaria: the value of spacing a split dose.

We have attempted to provide a rational basis for improving the protocols for chemotherapy of malaria. We model the regression of parasitaemia by Plasmodium falciparum, its subsequent elimination from the body, or recrudescence, for populations of cells treated with chloroquine. Our model assumes that drug forms a complex with some receptor in the parasite and that parasites possessing this complex die at a defined rate. We take into account that chloroquine is eliminated exponentially from the body. We show how the parameters of the model can be derived from observations in the field. The model correctly predicts the effects of drug dose, degree of initial parasitaemia, rate of parasite multiplication and degree of drug resistance to chloroquine chemotherapy. The level of parasitaemia will reduce to a minimum at sufficiently high concentrations of chloroquine, but only if the parasitaemia is reduced to below that of 1 parasite per infected person will a cure of malaria be obtained. Otherwise, recrudescence will, sooner or later, occur. We show that, even for drug-resistant malaria, if 2 doses of chloroquine are given to a patient with an interval of some 10 days between them, parasites can be eliminated from the body without toxic levels of chloroquine being reached.