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Background: Relapse (the re-emergence of depressive symptoms after some level of improvement but preceding recovery) and recurrence (onset of a new depressive episode after recovery) are common in depression, lead to worse outcomes and quality of life for patients and exert a high economic cost on society. Outcomes can be predicted by using multivariable prognostic models, which use information about several predictors to produce an individualised risk estimate. The ability to accurately predict relapse or recurrence while patients are well (in remission) would allow the identification of high-risk individuals and may improve overall treatment outcomes for patients by enabling more efficient allocation of interventions to prevent relapse and recurrence., Objectives: To summarise the predictive performance of prognostic models developed to predict the risk of relapse, recurrence, sustained remission or recovery in adults with major depressive disorder who meet criteria for remission or recovery., Search Methods: We searched the Cochrane Library (current issue); Ovid MEDLINE (1946 onwards); Ovid Embase (1980 onwards); Ovid PsycINFO (1806 onwards); and Web of Science (1900 onwards) up to May 2020. We also searched sources of grey literature, screened the reference lists of included studies and performed a forward citation search. There were no restrictions applied to the searches by date, language or publication status ., Selection Criteria: We included development and external validation (testing model performance in data separate from the development data) studies of any multivariable prognostic models (including two or more predictors) to predict relapse, recurrence, sustained remission, or recovery in adults (aged 18 years and over) with remitted depression, in any clinical setting. We included all study designs and accepted all definitions of relapse, recurrence and other related outcomes. We did not specify a comparator prognostic model., Data Collection and Analysis: Two review authors independently screened references; extracted data (using a template based on the CHecklist for critical Appraisal and data extraction for systematic Reviews of prediction Modelling Studies (CHARMS)); and assessed risks of bias of included studies (using the Prediction model Risk Of Bias ASsessment Tool (PROBAST)). We referred any disagreements to a third independent review author. Where we found sufficient (10 or more) external validation studies of an individual model, we planned to perform a meta-analysis of its predictive performance, specifically with respect to its calibration (how well the predicted probabilities match the observed proportions of individuals that experience the outcome) and discrimination (the ability of the model to differentiate between those with and without the outcome). Recommendations could not be qualified using the GRADE system, as guidance is not yet available for prognostic model reviews., Main Results: We identified 11 eligible prognostic model studies (10 unique prognostic models). Seven were model development studies; three were model development and external validation studies; and one was an external validation-only study. Multiple estimates of performance measures were not available for any of the models and, meta-analysis was therefore not possible. Ten out of the 11 included studies were assessed as being at high overall risk of bias. Common weaknesses included insufficient sample size, inappropriate handling of missing data and lack of information about discrimination and calibration. One paper (Klein 2018) was at low overall risk of bias and presented a prognostic model including the following predictors: number of previous depressive episodes, residual depressive symptoms and severity of the last depressive episode. The external predictive performance of this model was poor (C-statistic 0.59; calibration slope 0.56; confidence intervals not reported). None of the identified studies examined the clinical utility (net benefit) of the developed model., Authors' Conclusions: Of the 10 prognostic models identified (across 11 studies), only four underwent external validation. Most of the studies (n = 10) were assessed as being at high overall risk of bias, and the one study that was at low risk of bias presented a model with poor predictive performance. There is a need for improved prognostic research in this clinical area, with future studies conforming to current best practice recommendations for prognostic model development/validation and reporting findings in line with the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement., (Copyright © 2021 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Direct laryngoscopy is the method currently used for tracheal intubation in children. It occasionally offers unexpectedly poor laryngeal views. Indirect laryngoscopy involves visualizing the vocal cords by means other than obtaining a direct sight, with the potential to improve outcomes. We reviewed the current available literature and performed a meta-analysis to compare direct versus indirect laryngoscopy, or videolaryngoscopy, with regards to efficacy and adverse effects., Objectives: To assess the efficacy of indirect laryngoscopy, or videolaryngoscopy, versus direct laryngoscopy for intubation of children with regards to intubation time, number of attempts at intubation, and adverse haemodynamic responses to endotracheal intubation. We also assessed other adverse responses to intubation, such as trauma to oral, pharyngeal, and laryngeal structures, and we assessed vocal cord view scores., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), and trial registers (www.clinicaltrials.gov and www.controlledtrials) in November 2015. We reran the search in January 2017. We added new studies of potential interest to a list of 'Studies awaiting classification' and will incorporate them into formal review findings during the review update. We performed reference checking and citation searching and contacted the authors of unpublished data to ask for more information. We applied no language restrictions., Selection Criteria: We included only randomized controlled trials. Participants were children aged 28 days to 18 years. Investigators performed intubations using any type of indirect laryngoscopes, or videolaryngoscopes, versus direct laryngoscopes., Data Collection and Analysis: We used Cochrane standard methodological procedures. Two review authors independently reviewed titles, extracted data, and assessed risk of bias., Main Results: We included 12 studies (803 children) in this review and meta-analysis. We identified three studies that are awaiting classification and two ongoing studies.Trial results show that a longer intubation time was required when indirect laryngoscopy, or videolaryngoscopy, was used instead of direct laryngoscopy (12 trials; n = 798; mean difference (MD) 5.49 seconds, 95% confidence interval (CI) 1.37 to 9.60; I 2 = 90%; very low-quality evidence). Researchers found no significant differences between direct and indirect laryngoscopy on assessment of success of the first attempt at intubation (11 trials; n = 749; risk ratio (RR) 0.96, 95% CI 0.91 to 1.02; I 2 = 67%; low-quality evidence) and observed that unsuccessful intubation (five trials; n = 263) was significantly increased in the indirect laryngoscopy, or videolaryngoscopy, group (RR 4.93, 95% CI 1.33 to 18.31; I 2 = 0%; low-quality evidence). Five studies reported the effect of intubation on oxygen saturation (n = 272; very low-quality evidence). Five children had desaturation during intubation: one from the direct laryngoscopy group and four from the indirect laryngoscopy, or videolaryngoscopy, group.Two studies (n = 100) reported other haemodynamic responses to intubation (very low-quality evidence). One study reported a significant increase in heart rate five minutes after intubation in the indirect laryngoscopy group (P = 0.007); the other study found that the heart rate change in the direct laryngoscopy group was significantly less than the heart rate change in the indirect laryngoscopy, or videolaryngoscopy, group (P < 0.001). A total of five studies (n = 244; very low-quality evidence) looked at evidence of trauma resulting from intubation. Investigators reported that only two children from the direct laryngoscopy group had trauma compared with no children in the indirect laryngoscopy, or videolaryngoscopy, group.Use of indirect laryngoscopy, or videolaryngoscopy, improved the percentage of glottic opening (five trials; n = 256). Studies noted no significant difference in Cormack and Lehane score (C&L) grade 1 (three trials; n = 190; RR 1.06, 95% CI 0.93 to 1.21; I 2 = 59%)., Authors' Conclusions: Evidence suggests that indirect laryngoscopy, or videolaryngoscopy, leads to prolonged intubation time with an increased rate of intubation failure when compared with direct laryngoscopy (very low-quality evidence due to imprecision, inconsistency, and study limitations). Review authors had difficulty reaching conclusions on adverse haemodynamic responses and other adverse effects of intubation, as only a few children were reported to have these outcomes. Use of indirect laryngoscopy, or videolaryngoscopy, might lead to improved vocal cord view, but marked heterogeneity between studies made it difficult for review authors to reach conclusions on this outcome.

Background: Nausea and vomiting remain a problem for children undergoing treatment for malignancies despite new antiemetic therapies. Optimising antiemetic regimens could improve quality of life by reducing nausea, vomiting, and associated clinical problems. This is an update of the original systematic review., Objectives: To assess the effectiveness and adverse events of pharmacological interventions in controlling anticipatory, acute, and delayed nausea and vomiting in children and young people (aged less than 18 years) about to receive or receiving chemotherapy., Search Methods: Searches included the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, LILACS, PsycINFO, conference proceedings of the American Society of Clinical Oncology, International Society of Paediatric Oncology, Multinational Association of Supportive Care in Cancer, and ISI Science and Technology Proceedings Index from incept to December 16, 2014, and trial registries from their earliest records to December 2014. We examined references of systematic reviews and contacted trialists for information on further studies. We also screened the reference lists of included studies., Selection Criteria: Two review authors independently screened abstracts in order to identify randomised controlled trials (RCTs) that compared a pharmacological antiemetic, cannabinoid, or benzodiazepine with placebo or any alternative active intervention in children and young people (less than 18 years) with a diagnosis of cancer who were to receive chemotherapy., Data Collection and Analysis: Two review authors independently extracted outcome and quality data from each RCT. When appropriate, we undertook meta-analysis., Main Results: We included 34 studies that examined a range of different antiemetics, used different doses and comparators, and reported a variety of outcomes. The quality and quantity of included studies limited the exploration of heterogeneity to narrative approaches only.The majority of quantitative data related to the complete control of acute vomiting (27 studies). Adverse events were reported in 29 studies and nausea outcomes in 16 studies.Two studies assessed the addition of dexamethasone to 5-HT3 antagonists for complete control of vomiting (pooled risk ratio (RR) 2.03; 95% confidence interval (CI) 1.35 to 3.04). Three studies compared granisetron 20 mcg/kg with 40 mcg/kg for complete control of vomiting (pooled RR 0.93; 95% CI 0.80 to 1.07). Three studies compared granisetron with ondansetron for complete control of acute nausea (pooled RR 1.05; 95% CI 0.94 to 1.17; 2 studies), acute vomiting (pooled RR 2.26; 95% CI 2.04 to 2.51; 3 studies), delayed nausea (pooled RR 1.13; 95% CI 0.93 to 1.38; 2 studies), and delayed vomiting (pooled RR 1.13; 95% CI 0.98 to 1.29; 2 studies). No other pooled analyses were possible.Narrative synthesis suggests that 5-HT3 antagonists are more effective than older antiemetic agents, even when these agents are combined with a steroid. Cannabinoids are probably effective but produce frequent side effects., Authors' Conclusions: Our overall knowledge of the most effective antiemetics to prevent chemotherapy-induced nausea and vomiting in childhood is incomplete. Future research should be undertaken in consultation with children, young people, and families that have experienced chemotherapy and should make use of validated, age-appropriate measures. This review suggests that 5-HT3 antagonists are effective in patients who are to receive emetogenic chemotherapy, with granisetron or palonosetron possibly better than ondansetron. Adding dexamethasone improves control of vomiting, although the risk-benefit profile of adjunctive steroid remains uncertain.

Background: It is well documented that malnutrition is a common complication of paediatric malignancy and its treatment. Malnutrition can often be a consequence of cancer itself or a result of chemotherapy. Nutritional support aims to reverse malnutrition seen at diagnosis, prevent malnutrition associated with treatment and promote weight gain and growth. The most effective and safe forms of nutritional support in children and young people with cancer are not known., Objectives: To determine the effects of any form of parenteral (PN) or enteral (EN) nutritional support, excluding vitamin supplementation and micronutrient supplementation, in children and young people with cancer undergoing chemotherapy and to determine the effect of the nutritional content of PN and EN. This is an update of a previous Cochrane review., Search Methods: We searched the following databases for the initial review: CENTRAL (The Cochrane Library, Issue 2, 2009), MEDLINE (1950 to 2006), EMBASE (1974 to 2006), CINAHL (1982 to 2006), the National Research Register (2007) and Dissertations & Theses (2007). Experts in the field were also contacted for information on relevant trials. For this update, we searched the same electronic databases from 2006 to September 2013. We also scrutinised the reference lists of included articles to identify additional trials., Selection Criteria: Randomised or quasi-randomised controlled trials comparing any form of nutritional support with another, or control, in children or young people with cancer undergoing chemotherapy., Data Collection and Analysis: Two authors independently selected trials. At least two authors independently assessed quality and extracted data. We contacted trialists for missing information., Main Results: The current review included the eight trials from the initial review and six new trials which randomised 595 participants (< 21 years of age) with leukaemias or solid tumours undergoing chemotherapy. The trials were all of low quality with the exception of two of the trials looking at glutamine supplementation. One small trial found that compared to EN, PN significantly increased weight (mean difference (MD) 4.12, 95% CI 1.91 to 6.33), serum albumin levels (MD 0.70, 95% CI 0.14 to 1.26), calorie intake (MD 22.00, 95% CI 5.12 to 38.88) and protein intake (MD 0.80, 95% CI 0.45 to 1.15). One trial comparing peripheral PN and EN with central PN found that mean daily weight gain (MD -27.00, 95% CI -43.32 to -10.68) and energy intake (MD -15.00, 95% CI -26.81 to -3.19) were significantly less for the peripheral PN and EN group, whereas mean change in serum albumin was significantly greater for that group (MD 0.47, 95% CI 0.13 to 0.81, P = 0.008). Another trial with few participants found an increase in mean energy intake (% recommended daily amount) in children fed an energy dense feed compared to a standard calorie feed (MD +28%, 95% CI 17% to 39%). Three studies looked at glutamine supplementation. The evidence suggesting that glutamine reduces severity of mucositis was not statistically significant in two studies (RR 0.64, 95% CI 0.19 to 2.2 and RR 0.85, 95% CI 0.66 to 1.1) and differences in reduction of infection rates were also not significant in two studies (RR 1.0, 95% CI 0.72 to 1.4 and RR 0.98, 95% CI 0.63 to 1.51). Only one study compared olive oil based PN to standard lipid containing PN. Despite similar calorie contents in both feeds, the standard lipid formula lead to greater weight gain (MD -0.34 z-scores, 95% CI -0.68 to 0.00). A single study compared standard EN with fructooligosaccharide containing EN. There was no difference in weight gain between groups (mean difference -0.12, 95% CI -0.57 to 0.33), with adverse effects (nausea) occurring equally between the groups (RR 0.92, 95% CI 0.48 to 1.74)., Authors' Conclusions: There is limited evidence from individual trials to suggest that PN is more effective than EN in well-nourished children and young people with cancer undergoing chemotherapy. The evidence for other methods of nutritional support remains unclear. Limited evidence suggests an energy dense feed increases mean daily energy intake and has a positive effect on weight gain. Evidence suggesting glutamine supplementation reduces incidence and severity of mucositis, infection rates and length of hospital stay is not statistically significant. Further research, incorporating larger sample sizes and rigorous methodology utilising valid and reliable outcome measures, is essential.

An attenuated line of Leishmania infantum (the H-line), developed through exposure to gentamicin, has been shown to protect dogs against canine visceral leishmaniasis. A specific diagnostic test to differentiate dogs vaccinated with the attenuated line from dogs infected with L. infantum wild-type (L. infantum WT) could be a valuable tool in evaluating the effectiveness of canine vaccination. In this study, 28 healthy dogs were allocated into four groups. In Group I and Group II (eight dogs per group), dogs were immunized subcutaneously (s.c.) with L. infantum H-line, and the dogs of Group II challenged s.c. with L. infantum WT, at 2 months post-immunization. In Group III, eight animals were challenged s.c. with L. infantum WT, and four dogs of Group IV were injected s.c. with PBS. We found that sera from vaccinated dogs recognize a 21 kDa antigen of promastigotes of L. infantum H-line but not of L. infantum WT, whereas sera from unvaccinated dogs challenged with L. infantum WT, recognized a 21 kDa antigen of promastigotes of L. infantum WT but not of L. infantum H-line. Sera from dogs challenged with L. infantum WT with prior vaccination with L. infantum H-line, recognized a 21 kDa antigen of both L. infantum WT and L. infantum H-line. These results suggest that the Western blot analysis of antibodies against 21 kDa antigens of L. infantum H-line and WT may be a useful technique for distinguishing between dogs vaccinated with L. infantum H-line and dogs naturally infected with L. infantum WT., (© 2014 John Wiley & Sons Ltd.)

Objective: Many adult survivors of childhood cancer receive care in paediatric departments, despite national policy to transition their care to adult services. When long-term follow-up care for survivors of childhood cancer in our region moved from a paediatric to an adult environment in 2009, we prospectively assessed the impact of this change on patient satisfaction., Methods: Questionnaire data were collected in paediatric and adult clinical environments regarding the level of satisfaction with care and potential mediators: quality of life, psychological health and social difficulties. Predictors of satisfaction and optimum longitudinal risk-based care were described using path analysis and compared with previously described models., Results: There was no significant difference in satisfaction between the paediatric and adult settings. Short waiting times and increased understanding of the purpose of follow-up were significantly associated with increased satisfaction. Those with a higher perception of health problems and those that were older were more likely to not attend all of their clinic appointments., Conclusions: Within our service, transition to adult care did not impact significantly upon patient satisfaction. Shorter waits and knowing why participants were attending the clinic increased satisfaction. Joint working between adult and paediatric cancer professionals enabled adult survivors of childhood cancer to receive highly satisfactory care in adult services., (Copyright © 2013 John Wiley & Sons, Ltd.)

Although exercise is an important component of heart failure management, optimal regimens, particularly in heart failure with preserved ejection fraction (HFPEF), are uncertain. Tai chi (TC) is a mind-body exercise that may have potential benefits but has not been studied in this population. The authors randomized 16 patients with HFPEF to either 12 weeks TC or aerobic exercise. Assessments included peak oxygen uptake, 6-minute walk, quality of life, echocardiography, mood, and self-efficacy at baseline and at 12 weeks. Cardiorespiratory measures during exercise were obtained to characterize training intensities. Baseline characteristics were as follows: age 66±12 years, E/A ratio 1.3±0.7, and E/e' ratio 15.9±4.8. Overall, adherence was excellent (89% attendance). Change in peak oxygen uptake was similar between groups after 12 weeks, but 6-minute walk distance increased more after TC (69±46 m vs 10±31 m, P=.02). While both groups had improved Minnesota Living With Heart Failure scores and self-efficacy, Profile of Mood States (POMS)-Depression scores improved more with TC (-1.7±2.8 vs 1.6±3, P=.05). Cardiorespiratory assessment during TC showed lower oxygen uptake (4.3 mL/kg/min vs 9.4 mL/kg/min, P<.01), respiratory rate, and heart rate. TC is feasible and safe in HFPEF. Therepeutic endpoints appear similar with TC relative to aerobic exercise despite a lower aerobic training workload., (© 2012 Wiley Periodicals, Inc.)

Objectives: To assess the prevalence of complementary and alternative medicine (CAM) use by U.S. adults reporting neuropsychiatric symptoms and whether this prevalence changes based on the number of symptoms reported. Additional objectives include identifying patterns of CAM use, reasons for use, and disclosure of use with conventional providers in U.S. adults with neuropsychiatric symptoms., Design: Secondary database analysis of a prospective survey., Participants: A total of 23,393 U.S. adults from the 2007 National Health Interview Survey., Methods: We compared CAM use between adults with and without neuropsychiatric symptoms. Symptoms included self-reported anxiety, depression, insomnia, headaches, memory deficits, attention deficits, and excessive sleepiness. CAM use was defined as use of mind-body therapies (eg, meditation), biological therapies (eg, herbs), or manipulation therapies (eg, massage) or alternative medical systems (eg, Ayurveda). Statistical analysis included bivariable comparisons and multivariable logistical regression analyses., Main Outcome Measures: The prevalence of CAM use among adults with neuropsychiatric symptoms within the previous 12 months and the comparison of CAM use between those with and without neuropsychiatric symptoms., Results: Adults with neuropsychiatric symptoms had a greater prevalence of CAM use compared with adults who did not have neuropsychiatric symptoms (43.8% versus 29.7%, P < .001); this prevalence increased with an increasing number of symptoms (trend, P < .001). Differences in the likelihood of CAM use as determined by the number of symptoms persisted after we adjusted for covariates. Twenty percent of patients used CAM because standard treatments were either too expensive or ineffective, and 25% used CAM because it was recommended by a conventional provider. Adults with at least one neuropsychiatric symptom were more likely to disclose the use of CAM to a conventional provider (47.9% versus 39.0%, P < .001)., Conclusion: More than 40% of adults with neuropsychiatric symptoms commonly observed in many diagnoses use CAM; an increasing number of symptoms was associated with an increased likelihood of CAM use., (Copyright © 2013 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.)

Cerebral malaria is a major pathological complication of Plasmodium falciparum infection in humans. Epidemiological observations have suggested that the clinical evolution of P. falciparum infections may be influenced by the concurrent presence of another Plasmodium species. Infection of susceptible mouse strains with P. berghei ANKA (PbA) provides an experimental model of cerebral malaria which has been extensively used to identify different components of the immune system involved in cerebral malaria. This model has also been employed to investigate the influence of experimental mixed-Plasmodium-species infections on the expression of cerebral malaria; PbA-induced cerebral malaria is completely inhibited by the simultaneous presence of P. yoelii yoelii 17 X clone 1.1 parasites, and accumulation of CD8(+) T cells in the brain vasculature is abolished. We investigated whether brain levels of CD8(+) -T-cell-chemoattractant chemokines CCL3, CCL4 and CCL5 are reduced in these protected coinfected mice compared with PbA-infected mice. Coinfected mice were found to exhibit significantly reduced levels of all three chemokines on day 6 post-infection. This finding may contribute to the abolition of the accumulation of CD8(+) T cells in the brain vasculature and the prevention of the development of cerebral malaria in coinfected mice., (© 2011 Blackwell Publishing Ltd.)

Objective: Our objective was to determine patterns, reasons for, and correlates of complementary and alternative medicine (CAM) use by US adults with migraines/severe headaches., Background: While many patients with chronic conditions use CAM, little is known about CAM use by adults with migraines/severe headaches., Methods: We compared CAM use between adults with and without self-reported migraines/severe headaches using the 2007 National Health Interview Survey (n=23,393), a national cross-sectional survey., Results: Adults with migraines/severe headaches used CAM more frequently than those without (49.5% vs 33.9%, P< .0001); differences persisted after adjustment (adjusted odds ratio=1.29, 95% confidence interval [1.15, 1.45]). Mind-body therapies (eg, deep breathing exercises, meditation, yoga) were used most commonly. More than 50% of adults with migraines/severe headaches reporting CAM use had not discussed it with their health care provider. Nonetheless, those with migraines/severe headaches used CAM more often than those without because of provider recommendation and because conventional treatments were perceived as ineffective or too costly. Correlates of CAM use among adults with migraines/severe headaches included anxiety, joint or low back pain, alcohol use, higher education, and living in the western USA. Only 4.5% of adults with migraines/severe headaches reported using CAM to specifically treat their migraines/severe headaches., Conclusions: CAM is used more often among adults with migraines/severe headaches than those without. However, few report using CAM to specifically treat migraines/severe headaches. Mind-body therapies are used most frequently. Further research is needed to understand the effectiveness and mechanisms of CAM treatments in adults with migraines/severe headaches., (© 2011 American Headache Society.)

Background: Nausea and vomiting are still a problem for children undergoing treatment for malignancies despite new antiemetic therapies. Optimising antiemetic regimens could improve quality of life by reducing nausea, vomiting and associated clinical problems., Objectives: To assess the effectiveness and adverse events of pharmacological interventions in controlling anticipatory, acute and delayed nausea and vomiting in children and young people (aged < 18 years) about to receive/receiving chemotherapy., Search Strategy: Searches included CENTRAL, MEDLINE, EMBASE and LILACS, trial registries from their earliest records to February 2008, and ASCO, MASCC and SIOP conference proceedings from 2001 to 2007. We examined references of systematic reviews and contacted trialists for information on further studies., Selection Criteria: Two authors independently screened abstracts to identify randomised controlled trials (RCTs) that compared a pharmacological antiemetic, cannabinoid or benzodiazepine with placebo or any alternative active intervention in children and young people (< 18 years) with a diagnosis of cancer who were to receive chemotherapy., Data Collection and Analysis: Two authors independently extracted outcome and quality data from each RCT. When appropriate, we undertook meta-analysis., Main Results: We included 28 studies which examined a range of different antiemetics, used different doses and comparators, and reported a variety of outcomes. The quality and quantity of included studies limited the exploration of heterogeneity to narrative approaches only.The majority of quantitative data related to the complete control of acute vomiting (22 studies). Adverse events were reported in 24 studies and nausea outcomes in 10 studies.The addition of dexamethasone to 5-HT(3) antagonists was assessed in two studies for complete control of vomiting (pooled relative risk (RR) 2.03; 95% CI 1.35 to 3.04). Three studies compared granisetron 20 mcg/kg with 40 mcg/kg for complete control of vomiting (pooled RR 0.93; 95% CI 0.80 to 1.07). No other pooled analyses were possible.Narrative synthesis suggests 5-HT(3) antagonists are more effective than older antiemetic agents even when combined with a steroid. Cannabinoids are probably effective but produce frequent side effects., Authors' Conclusions: Our overall knowledge of the most effective antiemetics to prevent chemotherapy-induced nausea and vomiting in childhood is incomplete. Future research should be undertaken in consultation with children, young people and families that have experienced chemotherapy and should make use of validated, age-appropriate measures. This review suggests that 5-HT(3) antagonists with dexamethasone added are effective in patients who are to receive highly emetogenic chemotherapy although the risk-benefit profile of additional steroid remains uncertain.

A comparison of Plasmodium chabaudi AS infection in BALB/c and BALB/c IgM-deficient mice demonstrated a protective role for IgM during infection. IgM-/- mice, unlike microMT mice, display competent B cell humoral immune responses. Increased susceptibility of IgM-/- mice was demonstrated by increased mortality, an advanced ascending infection and higher peak parasitaemia, as well as enhanced anaemia and weight loss compared with wild-type mice. The recrudescent parasitaemias were also higher in the IgM-/- mice. Early specific IgM production in P. chabaudi-infected wild-type mice was followed by IgG1 and IgG2a production, while IgG1 and IgG2a production in IgM-/- mice was preceded by specific IgD production. No protective role for natural IgM against P. chabaudi AS infection was detected as passive transfer of naïve WT serum into IgM-/- mice did not alter the disease outcome or reduce parasite numbers. Passive transfer of WT antiserum, containing predominantly specific IgM, into IgM-/- mice delayed the ascending parasitaemia and reduced mortality. Similarly, coating parasitized red blood cells with WT antiserum, but not IgM-/- antisera, prior to infection also slightly delayed the ascending acute parasitaemia. Specific IgM therefore plays an important role in the limitation of parasite replication during asexual erythrocytic P. chabaudi AS infection.

Background: The Gail model is validated to estimate breast carcinoma risk. The authors assessed the association of Gail risk scores with screening and cancer risk perception., Methods: Using the 2000 National Health Interview Survey, the authors studied women ages 41-70 without a cancer history. Gail scores > or = 1.66% defined increased risk. The authors used logistic regression to assess associations between breast carcinoma risk and previous and recent (< or = 1 year) mammography and clinical breast examination (CBE)., Results: Of 6410 women, 15.7% had increased risk. High-risk women more frequently reported previous mammograms (94% vs. 85%; P < 0.0001), previous CBE (93% vs. 88%; P < 0.0001), recent mammograms (70% vs. 54%; P < 0.0001), recent CBE (71% vs. 61%; P < 0.0001), and high cancer risk perception (20% vs. 9%; P < 0.0001). However, 30% of high-risk women had not received a recent mammogram. After adjustment for sociodemographic factors, access to care factors, and cancer risk perception, high-risk women remained more likely to have received recent mammography (adjusted odds ratio [OR], 1.45, 95% confidence interval [95% CI], 1.19-1.77), recent CBE (OR, 1.32; 95% CI, 1.08-1.61]), and previous mammography than average-risk women. The authors observed an interaction between risk and age, with women ages 41-49 years more frequently reporting previous mammography (OR, 4.79; 95% CI, 1.55-4.81) than average-risk, same-age women. For women age > or = 50 years, the odds of previous mammography were similar regardless of risk., Conclusions: In a nationally representative sample, 15.7% of women had increased breast carcinoma risk using the Gail model. High-risk women perceived higher cancer risk and more often received screening. However, nearly one in three high-risk women did not receive recent screening and most of these women did not perceive increased risk., (Copyright 2004 American Cancer Society.)

An attenuated line of Leishmania mexicana (the L. mexicana H-line) has been established by culturing in vitro under gentamicin pressure. BALB/c mice infected with the L. mexicana H-line developed a CD4(+)Th1-like response, indicated by the cytokine profile of their splenocytes stimulated by L. mexicana wild-type (WT) promastigotes. This profile is sustained after these mice are challenged with L. mexicana WT. Control mice infected with L. mexicana WT alone developed a CD4(+)Th2-like cytokine profile. In mice immunized with L. mexicana H-line and then challenged with WT-line, were eliminated when immunizing H-line parasites persisted in the skin and draining popliteal lymph nodes (PLNs). In experiments in which mice were inoculated with attenuated and WT parasites at the same time, either at the same site or on separate sides of the mouse, growth of the WT parasites was significantly contained and controlled, indicating a possible therapeutic role for the attenuated parasites.

Protective immune mechanisms to the asexual erythrocytic stages of the malaria parasite Plasmodium chabaudi AS strain include antibody-independent mechanisms. Nitric oxide (NO) is produced during the infection and indirect evidence suggests that it can contribute to the antiparasitic mechanisms. We examined the effect of an NO producer, S-nitroso-acetyl-penicillamine (SNAP), on the growth and survival in vitro of P. chabaudi AS, P. berghei and P. falciparum. Growth of the parasites was monitored by the uptake of tritiated hypoxanthine and, in the case of P. falciparum, by morphological examination in stained blood smears. DL-penicillamine and sodium nitrite, as controls, had no inhibitory activity at the concentrations used. The results showed that at SNAP concentrations of approximately 182 microM and above NO was cytotoxic to P. falciparum but, at lower concentrations, there was a cytostatic effect and some parasites resumed growth and division after NO production had ceased. Rings were less susceptible to NO effects than later stages in the asexual cycle. The antimalarial activity of NO from SNAP also extended to the rodent parasites but, under the experimental conditions used, they were less sensitive than the human species. In the cultures of P. chabaudi, increasing the numbers of noninfected erythrocytes present did not diminish the antimalarial activity of SNAP, suggesting that here at least haemoglobin was not scavenging NO significantly.

P. chabaudi AS strain in laboratory mice provides an accessible and useful model for investigating antigenic variation in malaria parasites. Evidence that P. chabaudi AS undergoes antigenic variation is summarized. A live indirect fluorescent test (IFAT) detects a variable antigen on the surface of schizont-infected erythrocytes. Five different variable antigen types (VATS) (detected using the live IFAT) are described from a cloned mosquito transmitted parent population. Even during the rising primary parasitaemia VATS switch at high and variable rates (1.2-1.6%). Work towards cloning genes coding for the variable antigen is briefly summarized. Acquired immunity to blood-stage P. chabaudi AS is initially mediated through Th1 CD4+ T cells and after the primary parasitaemia there is a switch to Th2 CD4+ T cells. Acquired immune effector mechanisms are discussed in the context of antigenic variation by the parasite.

We have shown previously that at the time of peak primary parasitaemia of P. chabaudi infection in NIH mice, significant levels of nitric oxide are produced, detectable as nitrate in the serum, and that these contribute to the protective immune response to infection. Here, we demonstrate that following reinfection, mice show a markedly diminished ability to produce nitrate. However, if mice are treated with L-NG-monomethyl arginine specifically to block nitric oxide metabolism during the primary infection, and are then reinfected, production of nitrate is restored to levels approaching those attained at peak primary parasitaemia. These experiments, together with others we have reported, indicate that whereas nitric oxide appears to play a significant role in control of the primary parasitaemia of P. chabaudi infection, it performs no such function during subsequent patent parasitaemias. Furthermore, they suggest that factors as yet unknown may regulate nitric oxide activity during malaria infection, such that under normal circumstances its production comes under strict control. This is exemplified by the observation that after the burst of nitric oxide activity that coincides with peak primary parasitaemia, there follows a prolonged period of immunological tolerance during which nitrate levels remain low even at secondary challenge infection. This tolerized state is lifted only several months after initial infection, when the nitric oxide activity at reinfection appears to correlate with the size of the parasite challenge and the presence of a patent parasitaemia. The implications of these findings for protective immunity to malaria, malarial immunosuppression, and immunoregulation in general, are discussed.

Splenic T-lymphocyte lines were established in vitro from Plasmodium chabaudi-infected NIH mice on days 16 and 20 of a primary infection, and from mice after two or three infections. Each line responded specifically to stimulation with a lysed soluble extract of P. chabaudi-infected erythrocytes (pRBC), and displayed a CD4+ (L3T4+) surface phenotype. Both the day 16 and 20 cell lines, when stimulated in vitro, secreted interleukin-2 (IL-2) and gamma-interferon (IFN-gamma), indicative of their belonging to the T helper 1 (Th1) CD4+ subset. In contrast, both lines derived from reinfected mice secreted interleukin-4 (IL-4) and provided helper activity in antibody production to P. chabaudi in vitro, and thereby had the characteristics of Th2 cells. All four T-cell lines provided significant protection to naïve mice infected with P. chabaudi. In immunocompromised mice, the day 16 T-cell line was as protective as in naïve mice whereas the cell line from mice infected twice required the additional transfer of mature naïve splenic B cells to provide protection comparable to that seen in the immunocompetent naïve recipients. The results establish that protective immunity to P. chabaudi may be associated with the induction of CD4+ T cells of either the Th1 or Th2 subset which confer protection against this malaria parasite by mechanisms independent of, and dependent upon, B-cell involvement, respectively.

Previous results, using a passive transfer assay, have shown that recrudescences of Plasmodium chabaudi chabaudi AS strain are antigenically different from the infecting parental population and also that the recrudescence appears to be a mix of antigenic types. This present study examines further these recrudescent populations using an indirect fluorescent antibody test on live, schizont-infected red blood cells. This analysis shows that ten clones derived from a recrudescence are all antigenically different from the parent population and that some are different from each other. The use of this method to examine the antigenic types of recrudescent clones after transmission through mosquitoes also demonstrates a resulting change in antigenicity. Such results showing a link between mosquito transmission and varying antigenicity may have important implications in terms of immunity and vaccine development.

Considers a preventive intervention effort designed to modify the characteristics and regularities of the school environment so as to enhance the expectations conveyed to high risk students. Employing this case effort (Weinstein et al., 1991) as a base, several issues are highlighted that deserve greater attention in the design, implementation, assessment, and reporting of other preventively-focused social interventions. These issues include: (1) the degree of program implementation fidelity, (2) the impact a lack of attainment of program fidelity may have on arriving at erroneous evaluation conclusions about social programs, (3) the ways in which the theory and basic research employed in the program rationale is appropriate to and reflected in the program as designed, (4) issues of program potency and dosage, (5) the ways in which quantitative and qualitative evaluation data can enhance each other, and (6) the import of evaluability assessments of programs prior to moving to outcome evaluations. In addressing these issues, the importance of developmentally- and ecologically-informed program formulations is underscored. Finally, the critical role that program reports such as the Weinstein paper, with its careful discussion of both the process of implementation and outcome assessments, can play in the development of more effective prevention program implementation efforts is highlighted.

Previous studies have shown that the recrudescence parasitaemias seen in mice infected with Plasmodium chabaudi AS strain are antigenically different from the infecting parent population. Antigenic differences between recrudescent and parent populations were demonstrated in a passive transfer assay. In the present study, using the same assay system, it has been shown that in some mice, variant parasites (i.e. different from the parent population) can be detected at a time when the primary parasitaemia is still patent but in remission. This is the first report in Plasmodium of variant parasites being detected during the course of a patent primary parasitaemic episode of an infection initiated with a cloned line.

The antibody response to sheep red blood cells (SRBC) has been measured in C57Bl mice infected with the intra-erythrocytic piroplasm Babesia microti. The primary antibody response is severely reduced or abolished when antigen is administered at the time of maximum parasitaemia. The secondary antibody response of infected mice, which had been primed with SRBC, is reduced but retains the characteristics of a secondary response. Mice injected with SRBC at maximum parasitaemia failed to become primed to that antigen: these mice gave a primary antibody response to a second injection of SRBC given after the infection had become sub-patent. B. microti, therefore, can completely prevent the induction of memory, but only partially inhibit the expression of memory.

Nineteen of 22 recrudescent populations of Plasmodium chabaudi AS strain were found to be significantly less sensitive to the protective activity of pools of immune serum, than the parent population from which they were derived. The immune sera were collected from donor mice which had been infected with the parent population and had just reduced the patent primary parasitaemia to subpatent levels. Clones prepared from the parent population (which had previously been cloned) and recrudescent variant populations were tested for their sensitivity to the immune sera. It was found that all the clones from the parent population were sensitive to the immune sera but some were more sensitive than others and that a recrudescent variant population could include both sensitive and insensitive parasites. Two insensitive clones of the recrudescent population were found to be different from each other.

Observations of a patient with botulism requiring mechanical ventilatory support for 59 days and hospitalization for approximately 3 months are reported. During the time of greatest muscular paralysis, urinary urea nitrogen excretion exceeded 20 g per day. This degree of azoturia was thought to be due to obligate loss of lean body tissue secondary to paralysis and not to stress or starvation related demands. A contributing factor to the magnitude of azoturia was the presence of a large premorbid body frame and muscle mass. The nutritional goal was not to achieve nitrogen balance but to maintain visceral protein stores. As the patient improved neurologically, the azoturia decreased allowing a positive nitrogen balance with a rebuilding of skeletal muscle.