Modelling the Epidemiological Impact of Intermittent Preventive Treatment against Malaria in Infants

BACKGROUND: Trials of intermittent preventive treatment against malaria in infants (IPTi) using sulphadoxine-pyrimethamine (SP) have shown a positive, albeit variable, protective efficacy against clinical malaria episodes. The impact of IPTi in different epidemiological settings and over time is unknown and predictions are hampered by the lack of knowledge about how IPTi works. We investigated mechanisms proposed for the action of IPTi and made predictions of the likely impact on morbidity and mortality. METHODS/PRINCIPAL FINDINGS: We used a comprehensive, individual-based, stochastic model of malaria epidemiology to simulate recently published trials of IPTi using SP with site-specific characteristics as inputs. This baseline model was then modified to represent hypotheses concerning the duration of action of SP, the temporal pattern of fevers caused by individual infections, potential benefits of avoiding fevers on immunity and the effect of sub-therapeutic levels of SP on parasite dynamics. The baseline model reproduced the pattern of results reasonably well. None of the models based on alternative hypotheses improved the fit between the model predictions and observed data. Predictions suggest that IPTi would have a beneficial effect across a range of transmission intensities. IPTi was predicted to avert a greater number of episodes where IPTi coverage was higher, the health system treatment coverage lower, and for drugs which were more efficacious and had longer prophylactic periods. The predicted cumulative benefits were proportionately slightly greater for severe malaria episodes and malaria-attributable mortality than for acute episodes in the settings modelled. Modest increased susceptibility was predicted between doses and following the last dose, but these were outweighed by the cumulative benefits. The impact on transmission intensity was negligible. CONCLUSIONS: The pattern of trial results can be accounted for by differences between the trial sites together with known features of malaria epidemiology and the action of SP. Predictions suggest that IPTi would have a beneficial impact across a variety of epidemiological settings

Georgia College & State University Nursing Program

In order to evaluate the effectiveness of the Georgia College & State University (GC&SU) Nursing Program, a non-experimental, survey research study was conducted by senior nursing students in the Nursing Research class. The survey evaluated the teaching and learning strategies used in the program, the students\u27 perceptions of preparedness for nursing after graduation, and the students\u27 perceptions of the strengths and weaknesses of the GC&SU nursing curriculum. Each participant signed an informed consent form. Forty-five out of a possible 142 nursing students responded to the survey. A statistical analysis of the responses was conducted and comparisons of answers were analyzed across the different nursing cohorts. Implications and recommendations for changes for the GC&SU Nursing Program were stated. As demand for registered nurses continues to increase, nursing programs in the United States are rising to meet this need by educating clinically proficient nurses. GC&SU nursing program graduates approximately 80 nursing students per year. In May 2003, 94% of the nursing graduates passed the licensure exam, helping fill the need in healthcare settings. Nursing faculty realize that they must prepare nurses who are adept at performing essential nursing skills including assessment, safe medication administration, nursing care for ill clients and health teaching

Inhibition of acetyl-CoA carboxylase suppresses fatty acid synthesis and tumor growth of non-small-cell lung cancer in preclinical models.

Continuous de novo fatty acid synthesis is a common feature of cancer that is required to meet the biosynthetic demands of a growing tumor. This process is controlled by the rate-limiting enzyme acetyl-CoA carboxylase (ACC), an attractive but traditionally intractable drug target. Here we provide genetic and pharmacological evidence that in preclinical models ACC is required to maintain the de novo fatty acid synthesis needed for growth and viability of non-small-cell lung cancer (NSCLC) cells. We describe the ability of ND-646-an allosteric inhibitor of the ACC enzymes ACC1 and ACC2 that prevents ACC subunit dimerization-to suppress fatty acid synthesis in vitro and in vivo. Chronic ND-646 treatment of xenograft and genetically engineered mouse models of NSCLC inhibited tumor growth. When administered as a single agent or in combination with the standard-of-care drug carboplatin, ND-646 markedly suppressed lung tumor growth in the Kras;Trp53-/- (also known as KRAS p53) and Kras;Stk11-/- (also known as KRAS Lkb1) mouse models of NSCLC. These findings demonstrate that ACC mediates a metabolic liability of NSCLC and that ACC inhibition by ND-646 is detrimental to NSCLC growth, supporting further examination of the use of ACC inhibitors in oncology

Clinical evaluation of magnetic resonance imaging in coronary heart disease: The CE-MARC study

<p>Abstract</p> <p>Background</p> <p>Several investigations are currently available to establish the diagnosis of coronary heart disease (CHD). Of these, cardiovascular magnetic resonance (CMR) offers the greatest information from a single test, allowing the assessment of myocardial function, perfusion, viability and coronary artery anatomy. However, data from large scale studies that prospectively evaluate the diagnostic accuracy of multi-parametric CMR for the detection of CHD in unselected populations are lacking, and there are few data on the performance of CMR compared with current diagnostic tests, its prognostic value and cost-effectiveness.</p> <p>Methods/design</p> <p>This is a prospective diagnostic accuracy cohort study of 750 patients referred to a cardiologist with suspected CHD. Exercise tolerance testing (ETT) will be preformed if patients are physically able. Recruited patients will then undergo CMR and single photon emission tomography (SPECT) followed in all patients by invasive X-ray coronary angiography. The order of the CMR and SPECT tests will be randomised. The CMR study will comprise rest and adenosine stress perfusion, cine imaging, late gadolinium enhancement and whole-heart MR coronary angiography. SPECT will use a gated stress/rest protocol. The primary objective of the study is to determine the diagnostic accuracy of CMR in detecting significant coronary stenosis, as defined by X-ray coronary angiography. Secondary objectives include an assessment of the prognostic value of CMR imaging, a comparison of its diagnostic accuracy against SPECT and ETT, and an assessment of cost-effectiveness.</p> <p>Discussion</p> <p>The CE-MARC study is a prospective, diagnostic accuracy cohort study of 750 patients assessing the performance of a multi-parametric CMR study in detecting CHD using invasive X-ray coronary angiography as the reference standard and comparing it with ETT and SPECT.</p> <p>Trial Registration</p> <p>Current Controlled Trials ISRCTN77246133</p

Maternal iodine status in a multi-ethnic UK birth cohort:Associations with child cognitive and educational development

Background: Maternal iodine requirements increase during pregnancy to supply thyroid hormones critical for fetal neurodevelopment. Iodine insufficiency may result in poorer cognitive or child educational outcomes but current evidence is sparse and inconsistent. Objectives: To quantify the association between maternal iodine status and child educational outcomes. Methods: Urinary iodine concentrations (UIC) and iodine/creatinine ratios (I:Cr) were measured in 6971 mothers at 26-28 weeks' gestation participating in the Born in Bradford cohort. Maternal iodine status was examined in relation to child school achievement (early years foundation stage (EYFS), phonics, and Key Stage 1 (KS1)), other learning outcomes, social and behavioural difficulties, and sensorimotor control in 5745 children aged 4-7 years. Results: Median (interquartile range) UIC was 76 µg/L (46, 120), and I:Cr was 83 µg/g (59, 121). Overall, there was no strong or consistent evidence to support associations between UIC or I:Cr and neurodevelopmental outcomes. For instance, predicted EYFS and phonics scores (primary outcomes) at the 25th vs 75th I:Cr percentiles (99% confidence intervals) were similar, with no evidence of associations: EYFS scores were 32 (99% CI 31, 33) and 33 (99% CI 32, 34), and phonics scores were 34 (99% CI 33, 35) and 35 (99% CI 34, 36), respectively. Conclusions: In the largest single study of its kind, there was little evidence of detrimental neurodevelopmental outcomes in children born to pregnant women with iodine insufficiency as defined by World Health Organization–outlined thresholds. Alternative functional biomarkers for iodine status in pregnancy and focused assessment of other health outcomes may provide additional insight.</p

Poor Potential Coverage for 7-Valent Pneumococcal Conjugate Vaccine, Malawi

Streptococcus pneumoniae infections can be prevented by using new conjugate vaccines, but these vaccines have limited serogroup coverage. We report the first serogrouping data from carried and invasive isolates obtained from children and adults in Malawi. The 7-valent vaccine would cover 41% of invasive isolates from children and 25% from adults. A 9-valent vaccine, including types 1 and 5, would cover 66% of invasive isolates from children and 55% from adults

Phase 2a randomised controlled feasibility trial of a new ‘balanced binocular viewing’ treatment for unilateral amblyopia in children age 3–8 years : trial protocol

Introduction Treatments for amblyopia, the most common vision deficit in children, often have suboptimal results. Occlusion/atropine blurring are fraught with poor adherence, regression and recurrence. These interventions target only the amblyopic eye, failing to address imbalances of cortical input from the two eyes (‘suppression’). Dichoptic treatments manipulate binocular visual experience to rebalance input. Poor adherence in early trials of dichoptic therapies inspired our development of balanced binocular viewing (BBV), using movies as child-friendly viewable content. Small observational studies indicate good adherence and efficacy. A feasibility trial is needed to further test safety and gather information to design a full trial. Methods/analysis We will carry out an observer-masked parallel-group phase 2a feasibility randomised controlled trial at two sites, randomising 44 children aged 3–8 years with unilateral amblyopia to either BBV or standard occlusion/atropine blurring, with 1:1 allocation ratio. We will assess visual function at baseline, 8 and 16 weeks. The primary outcome is intervention safety at 16 weeks, measured as change in interocular suppression, considered to precede the onset of potential diplopia. Secondary outcomes include safety at other time points, eligibility, recruitment/retention rates, adherence, clinical outcomes. We will summarise baseline characteristics for each group and assess the treatment effect using analysis of covariance. We will compare continuous clinical secondary endpoints between arms using linear mixed effect models, and report feasibility endpoints using descriptive statistics. Ethics/dissemination This trial has been approved by the London-Brighton & Sussex Research Ethics Committee (18/LO/1204), National Health Service Health Research Authority and Medicines and Healthcare products Regulatory Agency. A lay advisory group will be involved with advising on and disseminating the results to non-professional audiences, including on websites of funder/participating institutions and inputting on healthcare professional audience children would like us to reach. Reporting to clinicians and scientists will be via internal and external meetings/conferences and peer-reviewed journals

Achieving consensus on psychosocial and physical rehabilitation management for people living with kidney disease

From Crossref journal articles via Jisc Publications RouterHistory: epub 2023-05-19, issued 2023-05-19Article version: AMPublication status: PublishedPelagia Koufaki - ORCID: 0000-0002-1406-3729 https://orcid.org/0000-0002-1406-3729Background People living with chronic kidney disease (CKD) need to be able to live well with their condition. The provision of psychosocial interventions (psychological, psychiatric, and social care) and physical rehabilitation management is variable across England, as well as the rest of the United Kingdom. There is a need for clear recommendations for standards of psychosocial and physical rehabilitation care for people living with CKD, and guidance for the commissioning and measurement of these services. The NHS England Renal Services Transformation Programme (RSTP) supported a programme of work and modified Delphi process to address the management of psychosocial and physical rehabilitation care as part of a larger body of work to formulate a comprehensive commissioning toolkit for renal care services across England. We sought to achieve expert consensus regarding the psychosocial and physical rehabilitation management of people living with CKD in England and the rest of the UK. Method A Delphi consensus method was used to gather and refine expert opinions of senior members of the kidney multi-disciplinary team (MDT) and other key stakeholders in the UK. An agreement was sought on 16 statements reflecting aspects of psychosocial and physical rehabilitation management for people living with CKD. Results Twenty-six expert practitioners and other key stakeholders, including lived experience representatives, participated in the process. The consensus (&amp;gt;80% affirmative votes) amongst the respondents for all 16 statements was high. Nine recommendation statements were discussed and refined further to be included in the final iteration of the ‘Systems’ section of the NHS England RSTP commissioning toolkit. These priority recommendations reflect pragmatic solutions that can be implemented in renal care and include recommendations for a holistic well-being assessment for all people living with CKD who are approaching dialysis, or who are at listing for kidney transplantation, which includes the use of validated measurement tools to assess the need for further intervention in psychosocial and physical rehabilitation management. It is recommended that the scores from these measurement tools be included in the NHS England Renal Data Dashboard. There was also a recommendation for referral as appropriate to NHS Talking therapies, psychology, counselling or psychotherapy, social work or liaison psychiatry for those with identified psychosocial needs. The use of digital resources was recommended to be used in addition to face-to-face care to provide physical rehabilitation, and all healthcare professionals should be educated to recognise psychosocial and physical rehabilitation needs and refer/sign-post people with CKD to appropriate services. Conclusion There was high consensus amongst senior members of the kidney MDT and other key stakeholders, including those with lived experience, in the UK on all aspects of the psychosocial and physical rehabilitation management of people living with CKD. The results of this process will be used by NHS England to inform the ‘Systems’ section of the commissioning toolkit and data dashboard and to inform the National Standards of Care for people living with CKD.inpressinpres