Frailty Status as a Novel Risk Stratification Tool in Patients with Acute Pancreatitis.

BACKGROUND: Although frailty is a known predictor of mortality and complications across various disease states, it remains an understudied topic among patients with acute pancreatitis (AP). OBJECTIVES: Our aim was to assess the impact of frailty on outcomes in patients with AP. DESIGN: Retrospective cohort study. SETTING: Appended data was obtained from the 2016-2017 National Inpatient Sample (NIS) database. PARTICIPANTS: 574,895 adult patients with a primary discharge diagnosis of AP. MEASUREMENTS: We performed a nationwide cohort study utilizing International Classification of Diseases (ICD) diagnostic codes to identify adult patients with AP. The Hospital Frailty Risk Score (HFRS) was used to classify patients as frail or non-frail. The primary outcome was complications related to AP including all-cause mortality. Secondary outcomes were length of stay and total hospitalization costs. Multivariable logistic regression models were used to determine the association between frailty and complications. RESULTS: 574,895 patients were represented; 24.7% (141,999) characterized as frail and 75.3% (432,896) as non-frail. 26.7% of frail patients suffered composite complications related to AP versus 13.3% of non-frail patients (P < 0.001). Frail patients had more cardiovascular, pulmonary, gastrointestinal, and infectious adverse events compared to non-frail patients. Frail patients also had higher mortality rates (2.0% vs 0.1% P < 0.001), increased length of stay (6.5 days vs 3.6, P < 0.001) and total hospitalization charges ($60,136 vs $31,095, P < 0.001). On multivariable analysis, positive frailty status was associated with 2.33 times increased odds of having composite complications. CONCLUSIONS: Frailty assessments can be utilized as an adjunct to validated scoring systems to improve risk stratification and clinical management of patients with AP.

A basic dynamic transmission model of Staphylococcus aureus in the US population--ERRATUM.

doi: http://dx.doi.org/10.1017/S0950268813001106. Published online: 23 May 2013. In the above-mentioned article [1] the y axis in Figure 3a is incorrect. The correct version is given below. US pop. growth (estimated) (×108)

A basic dynamic transmission model of Staphylococcus aureus in the US population.

We present a basic mathematical model of Staphylococcus aureus transmission in the USA based on natural history of infection and nationally representative data. We employed a Susceptible-Colonized-Infected-Recovered-Susceptible compartmental modelling framework with two different phenotypes of S. aureus: methicillin-susceptible (MSSA) and methicillin-resistant (MRSA). The model is dynamic and accounts for the US population growth. For model calibration/validation, we used published 1999-2005 S. aureus infection data in conjunction with the 2001-2004 National Health and Nutrition Examination Survey colonization data. Baseline model projections illustrated how MRSA might continue to expand and gradually replace MSSA over time, in the absence of intervention, if there is strong competition for colonization. The model-based estimate of the basic reproduction number (R0) highlights the need for infection control. We illustrate the potential population-level impact of intervention with a hypothetical S. aureus vaccination component.

Risk factors associated with typhoid fever in children aged 2-16 years in Karachi, Pakistan.

We analysed the data from the control group in a typhoid vaccine trial in Karachi to assess the differences in individual-, household- and cluster-level characteristics for developing typhoid fever. The annual incidence of typhoid in children aged 2-16 years in the control arm of the vaccine trial was 151/100 000 population. After adjustment, the risk of typhoid was lower with increasing age [risk ratio (RR) 0·89, 95% confidence interval (CI) 0·83-0·95], was higher with an increase in population density (RR 1·13, 95% CI 1·05-1·21) and was lower in the households using a safe drinking-water source (RR 0·63, 95% CI 0·41-0·99). Typhoid fever affects younger children living in areas of high population density and lack of access to safe water in Pakistan. A combination of environmental and biological interventions is required to prevent the continued epidemiological and economic impact of typhoid fever in high-risk areas of Pakistan.

Vaccines for preventing typhoid fever.

BACKGROUND: Two typhoid vaccines are commercially available, Ty21a (oral) and Vi polysaccharide (parenteral), but neither is used routinely. Other vaccines, such as a new modified, conjugated Vi vaccine called Vi-rEPA, are in development. OBJECTIVES: To evaluate vaccines for preventing typhoid fever. SEARCH STRATEGY: In December 2006, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2006, Issue 3), MEDLINE, EMBASE, LILACS, and mRCT. We also searched relevant conference proceedings up to 2004 and scanned the reference lists of all included trials. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials (RCTs) comparing typhoid fever vaccines with other typhoid fever vaccines or an inactive agent (placebo or vaccine for a different disease). DATA COLLECTION AND ANALYSIS: Two authors independently applied inclusion criteria and extracted data. We computed vaccine efficacy per year of follow up and cumulative three-year efficacy, stratifying for vaccine type and dose. We calculated relative risks (RR) and efficacy (1-RR as a percentage) with 95% confidence intervals (CI). MAIN RESULTS: Of the 17 included RCTs, 10 evaluated efficacy (Ty21a: 5 trials; Vi polysaccharide: 4 trials, Vi-rEPA: 1 trial), and 11 reported on adverse events.Ty21a vaccine (3 doses). According to one trial (20,543 participants), this vaccine provided statistically significant protection in each of the first three years (one: 35%, 95% CI 8% to 54%; two: 58%, 95% CI 40% to 71%; three: 46%, 95% CI -6% to 72%), and the cumulative efficacy for 2.5 to 3 years was 48% (95% CI 34% to 58%). Four cluster-RCTs that did not adjust for clustering were not included in the meta-analyses. Compared with placebo, this vaccine was not associated with an increased rate of fever, vomiting, diarrhoea, nausea or abdominal pain, headache, or rash.Vi polysaccharide vaccine (1 dose). This vaccine provided protection in year one (68%, 95% CI 50% to 80%; 99,979 participants, 3 trials) and year two (60%, 95% CI 31% to 76%; 142,555 participants, 2 trials), but not in year three (11,384 participants, 1 trial). The three-year cumulative efficacy was 55% (95% CI 30% to 70%; 11,384 participants, 1 trial). Compared with placebo, there was no statistically significant difference in the incidence of fever or erythema, but local swelling was more common with the vaccine.Vi-rEPA vaccine (2 doses). In one trial of 12,008 participants, this vaccine provided protection in year one (94%, 95% CI 75% to 99%) and year two (87%, 95% CI 56% to 96%). Cumulative efficacy at 46 months (3.8 years) was 89% (95% CI 76% to 97%). No swelling or erythema occurred in the vaccine or placebo group; fever was more frequent in the vaccine group. AUTHORS' CONCLUSIONS: The licensed Ty21a and Vi polysaccharide vaccines are efficacious. The new and unlicensed Vi-rEPA vaccine is as efficacious and may confer longer immunity.

Optimizing typhoid fever case definitions by combining serological tests in a large population study in Hechi City, China.

Blood culture-based diagnosis can only detect a fraction of the total burden of Salmonella enterica subsp. enterica serovar Typhi. The objective of the study was to detect additional typhoid fever cases through serological tests. A total of 1732 prolonged fever episodes were evaluated using three serological tests, Widal, Tubex and Typhidot-M in a typhoid fever endemic area of southern China. A case definition which included a positive Widal test (TO>or=80 & TH>A), a positive Tubex test (>or=4) and a positive Typhidot-M test, increased the detection of cases by more than twofold from 13 to 28 cases. The case definition has a specificity of 100% and a sensitivity of 39%. Case definitions based on combinations of serological tests can detect additional typhoid fever cases with higher specificity than a single serological test. Improved case detection is essential to understand the true disease burden and can help to boost the power of intervention trials.

Introducing Vi polysaccharide typhoid fever vaccine to primary school children in North Jakarta, Indonesia, via an existent school-based vaccination platform.

OBJECTIVES: To report results on coverage, safety and logistics of a large-scale, school-based Vi polysaccharide immunization campaign in North Jakarta. METHODS: Of 443 primary schools in North Jakarta, Indonesia, 18 public schools were randomly selected for this study. Exclusion criteria were fever 37.5 degrees C or higher at the time of vaccination or a known history of hypersensitivity to any vaccine. Adverse events were monitored and recorded for 1 month after immunization. Because this was a pilot programme, resource use was tracked in detail. RESULTS: During the February 2004 vaccination campaign, 4828 students were immunized (91% of the target population); another 394 students (7%) were vaccinated during mop-up programmes. Informed consent was obtained for 98% of the target population. In all, 34 adverse events were reported, corresponding to seven events per 1000 doses injected; none was serious. The manufacturer recommended cold chain was maintained throughout the programme. CONCLUSIONS: This demonstration project in two sub-districts of North Jakarta shows that a large-scale, school-based typhoid fever Vi polysaccharide vaccination campaign is logistically feasible, safe and minimally disruptive to regular school activities, when used in the context of an existing successful immunization platform. The project had high parental acceptance. Nonetheless, policy-relevant questions still need to be answered before implementing a widespread Vi polysaccharide vaccine programme in Indonesia.

Vaccines against cholera, typhoid fever and shigellosis for developing countries.

Enteric diseases, such as cholera, typhoid fever and shigellosis, still produce a significant burden, especially among the poor in countries where these illnesses are endemic. Older-generation, parenteral, whole-cell vaccines against cholera and typhoid fever were abandoned in many countries as public health tools because of problems with insufficient protection and/or inadequate safety profiles. Modern-generation licensed vaccines are available for cholera and typhoid fever, but are not widely used by those in greatest need. A number of experimental candidates exist for all three diseases. Future research should focus on generating the evidence necessary to obtain a consensus on the deployment of existing vaccines against cholera and typhoid fever, and on clinical evaluation of pipeline vaccine candidates against all three diseases.

Cytotoxic activity of five compounds isolated from Colombian plants.

Cytotoxic effect of five known compounds, khellin, berberine, lupeol, scopolin, rapanone, obtained from Colombian plants, were determined against human tumor cell lines as an indicator of the potential anticancer activity of these compounds. Berberine and rapanone presented interesting cytotoxicity.

Cholera outbreak in southern Tanzania: risk factors and patterns of transmission.

To identify risk factors and describe the pattern of spread of the 1997 cholera epidemic in a rural area (Ifakara) in southern Tanzania, we conducted a prospective hospital-based, matched case- control study, with analysis based on the first 180 cases and 360 matched controls. Bathing in the river, long distance to water source, and eating dried fish were significantly associated with risk for cholera. Toxigenic Vibrio cholerae O1, biotype El Tor, serotype Ogawa, was isolated in samples from Ifakara's main water source and patients' stools. DNA molecular analyses showed identical patterns for all isolates.

Humoral immune responses during a malaria vaccine trial in Tanzanian infants.

The development of a malaria vaccine is a priority for improved and sustained malaria control. Optimal use of a vaccine in Africa will only be achieved if it can be delivered through the Expanded Programme of Immunization (EPI). We have completed a trial of the peptide vaccine SPf66 in Tanzanian infants, given alongside the EPI vaccines. This paper describes the humoral responses to SPf66 and the EPI vaccines. A total of 1207 infants were recruited into a two-arm, double-blind, individually randomized placebo-controlled trial of SPf66. The objectives of the trial were to determine the safety, immunogenicity and efficacy of SPf66 and to assess interactions with EPI vaccines when three doses of SPf66 were delivered alongside the EPI vaccines. Cross-sectional surveys were carried out to asses seroconversion rates to the EPI vaccines and the antibody response to SPf66 (NANP)50 and Plasmodium falciparum lysates. Seroconversion rates to EPI vaccines were high and no statistically significant differences in prevalence or titres were found between SPf66 and placebo recipients. IgG antibodies against SPf66 (NANP)50 and whole P. falciparum lysate were present in high titres in mothers of recruited children at the time of birth. Vaccination with SPf66 stimulated a good anti-SPf66 IgG response which declined to preimmunization levels by 2 years of age and which was not associated with protection against clinical malaria. The vaccine induced no IgG antibodies against (NANP)50 or P. falciparum lysates. SPf66 stimulated a humoral immune response when given to very young infants and did not interfere with seroconversion to EPI vaccines. The response to SPf66 was qualitatively different from that seen in older children, in whom SPf66 has been shown to be moderately efficacious. This difference raises concerns about the difficulties of immunizing very young infants who need to be targeted by antimalarial vaccination programs.

Evaluation of the SPf66 vaccine for malaria control when delivered through the EPI scheme in Tanzania.

BACKGROUND: Malaria control programmes need to protect young children, who bear the brunt of malaria disease and death in Africa. The development of a vaccine is a priority if improved and sustained malaria control is to be achieved. The best use of a vaccine in Africa will be achieved if it can be delivered through the expanded programme of immunization (EPI). We conducted a trial designed to evaluate the efficacy of SPf66 vaccine for malaria control when delivered through the EPI scheme in Tanzania. METHODS: The study was a two-arm, double blind, individually randomized placebo controlled trial involving 1207 infants. The primary objective of the trial was to estimate the efficacy of three doses of SPf66 given at 1, 2 and 7 months of age in preventing clinical episodes of malaria. These were documented through a health facility-based passive case detection system. RESULTS: Among 1207 randomized children, overall compliance for third dose was 91%. SPf66 was safe, immunogenic and did not interfere with the humoral immune responses to EPI vaccines. There were 294 children among SPf66 recipients and 288 among placebo recipients with at least one malaria episode, yielding a vaccine efficacy estimate of 2% (95% CI: -16, 16; P = 0.84). CONCLUSION: This has been the first trial of a malaria vaccine among very young infants. It provides information on the safety of peptide vaccines administered at this early age as well as their capacity to induce immune responses without negatively interacting with EPI vaccines. Given the modest protection previously documented in older age groups and the lack of efficacy in younger infants, this vaccine in its current alum-based formulation does not appear to have a role in malaria control in sub-Saharan Africa. The lack of efficacy found in this trial also raises concerns about potential difficulties of inducing protective immune responses against malaria through immunization in infants.

Safety in infants of SPf66, a synthetic malaria vaccine, delivered alongside the EPI.

The most likely mechanism to deliver a malaria vaccine in African countries is through the Expanded Program of Immunization (EPI). So far only SPf66, a multistage synthetic peptide, has shown any evidence of protection in Phase III field trials. In Tanzania, SPf66 reduced the risk of clinical malaria by 31% in children aged 1-5 years. In order to progress in the critical path of vaccine development and testing towards the implementation of a new vaccine in malaria control programs, we carried out a randomized double-blind placebo controlled efficacy trial of SPf66 when given alongside the EPI scheme. Monitoring of safety and reactogenicity during this trial included detailed clinical and laboratory assessments on 98 infants and assessment of adverse effects within 1 h of vaccination for all 1207 children vaccinated. Surveillance systems monitored attendances as outpatients, admissions to hospital and fatal events in the community. No serious adverse effects were detected more frequently amongst SPf66 recipients compared to placebo. This first assessment in very young infants of a synthetic vaccine provides evidence of a good safety profile.

Randomised placebo-controlled trial of iron supplementation and malaria chemoprophylaxis for prevention of severe anaemia and malaria in Tanzanian infants.

BACKGROUND: Malaria and anaemia, especially that due to iron deficiency, are two leading causes of morbidity worldwide. Little is known about the relative contribution of Plasmodium falciparum infection and iron deficiency to the aetiology of anaemia in malaria-endemic areas. We undertook a randomised comparison of different strategies for control of anaemia and malaria in infants, including an assessment of the effect of iron supplementation on malaria susceptibility. METHODS: 832 infants born at one hospital in a malaria-hyperendemic area of Tanzania between January and October, 1995, were randomly assigned to group DI, receiving daily oral iron (2 mg/kg daily) plus weekly Deltaprim (3.125 mg pyrimethamine plus 25 mg dapsone); group IP, receiving iron plus weekly placebo; group DP, receiving daily placebo plus weekly Deltaprim; or group PP. supplementation was given from 8 to 24 weeks of age, and the weekly chemoprophylaxis from 8 to 48 weeks. The frequency of severe anaemia (packed-cell volume < 25%) and malaria episodes was assessed through a combination of passive case detection and cross-sectional surveys. FINDINGS: The groups that received iron supplementation had a lower frequency of severe anaemia than those that did not receive iron (0.62 vs 0.87 cases per person-year; protective efficacy 28.8% [95% CI 6.3-45.8). Iron supplementation had no effect on the frequency of malaria (0.87 vs 1.00 cases per person-year; protective efficacy 12.8% [-12.8 to 32.5]). The groups that received malaria prophylaxis had lower frequencies of both severe anaemia (0.45 vs 1.04 episodes per person-year; protective efficacy 57.3% [43.0-67.9]) and malaria (0.53 vs 1.34 episodes per person-year; protective efficacy 60.5% [48.2-69.9]) than the groups that did not receive prophylaxis. After the end of the intervention period, children who had received malaria chemoprophylaxis had higher rates of severe anaemia and malaria than non-chemoprophylaxis groups (relative risks 2.2 [1.3-3.7] and 1.8 [1.3-2.6]). INTERPRETATION: Malaria chemoprophylaxis during the first year of life was effective in prevention of malaria and anaemia but apparently impaired the development of natural immunity. Iron supplementation was effective in preventing severe anaemia without increasing susceptibility to malaria. Our findings support iron supplementation of infants to prevent iron-deficiency anaemia, even in malaria-endemic areas.

PIP: The impact of iron supplementation and malaria chemoprophylaxis was investigated in a double-blind, placebo-controlled study involving 832 infants born in a malaria-hyperendemic area of Tanzania in 1995. Infants were randomly assigned to receive daily oral iron (2 mg/kg) and weekly Deltaprim (3-125 mg pyrimethamine plus 25 mg dapsone), daily iron plus weekly placebo, or daily and weekly placebo. Daily supplementation was provided from 8 to 24 weeks of age, while weekly chemoprophylaxis was given from 8 to 48 weeks. The 2 groups that received iron supplementation had a lower frequency of severe anemia (packed cell volume under 25%) than those who received placebo (0.62 versus 0.87 cases per person-year; protective efficacy, 28.8%), but iron supplementation did not have a significant effect on malaria incidence (0.87 versus 1.00 cases per person-year; protective efficacy, 12.8%). Infants who received malaria prophylaxis had lower frequencies of both severe anemia (0.45 versus 1.04 episodes per person-year; protective efficacy, 57.3%) and malaria (0.53 versus 1.43 episodes per person-year; protective efficacy, 60.5%) than those who received placebo. However, after the end of the intervention period, children who had received malaria prophylaxis had higher rates of severe anemia and malaria than those in the non-chemoprophylaxis groups (relative risks, 2.2 and 1.8, respectively). These findings indicate that malaria chemoprophylaxis during the first year of life can impair the development of natural immunity, while iron supplementation effectively prevents severe anemia without increasing susceptibility to malaria.