Impact of pregnancy vaccine uptake and socio-demographic determinants on subsequent childhood Measles, Mumps and Rubella vaccine uptake: A UK birth cohort study.

BACKGROUND: We examined the association between socio-demographic determinants and uptake of childhood Measles, Mumps & Rubella (MMR) vaccines and the association between pregnant women's pertussis vaccine uptake and their children's MMR vaccine uptake. METHODS: We used nationally-representative linked mother-baby electronic records from the United Kingdom's Clinical-Practice-Research-Datalink. We created a birth cohort of children born between 01.01.2000 and 12.12.2020. We estimated the proportion vaccinated with first MMR vaccine by age 2 years and first and second MMR vaccines by age 5 years. We used survival-analysis and Cox proportional hazard models to examine the association between deprivation, ethnicity and maternal age and pertussis vaccination in pregnancy and children's MMR uptake. RESULTS: Overall, 89.4 % (710,797/795,497) of children had first MMR by age 2 years and 92.6 % (736,495/795,497) by age 5 years. Among children still in the cohort when second MMR was due, 85.9 % (478,480/557,050) had two MMRs by age 5 years. Children from the most-deprived areas, children of Black ethnicity and children of mothers aged < 20 years had increased risk of being unvaccinated compared with children from the least-deprived areas, White children and children of mothers aged 31-40 years: first MMR by 5 years, adjusted Hazard Ratios (HR):0.86 (CI:0.85-0.87), HR:0.87 (CI:0.85-0.88) & HR:0.89 (CI:0.88-0.90) respectively. Deprivation was the determinant associated with the greatest risk of missed second MMR: adjusted HR:0.82 (CI:0.81-0.83). Children of mothers vaccinated in pregnancy were more likely than children of unvaccinated mothers to have MMR vaccines after adjusting for ethnicity, deprivation, and maternal age (First and Second MMRs adjusted HRs:1.43 (CI:1.41-1.45), 1.49 (CI:1.45-1.53). CONCLUSION: Children from most-deprived areas are less likely to have MMR vaccines compared with children from least-deprived areas. Mothers who take up pregnancy vaccines are more likely to have their children vaccinated with MMR. Healthcare services should promote and facilitate access to both maternal and childhood vaccines during pregnancy.

Challenges and recommendations for high quality research using electronic health records.

Harnessing Real World Data is vital to improve health care in the 21st Century. Data from Electronic Health Records (EHRs) are a rich source of patient centred data, including information on the patient's clinical condition, laboratory results, diagnoses and treatments. They thus reflect the true state of health systems. However, access and utilisation of EHR data for research presents specific challenges. We assert that using data from EHRs effectively is dependent on synergy between researchers, clinicians and health informaticians, and only this will allow state of the art methods to be used to answer urgent and vital questions for patient care. We propose that there needs to be a paradigm shift in the way this research is conducted - appreciating that the research process is iterative rather than linear. We also make specific recommendations for organisations, based on our experience of developing and using EHR data in trusted research environments.

The lumbar artery perforator flap: clinical review and guidance on image reporting.

The lumbar artery perforator (LAP) flap is a relatively new procedure that can be utilized to manage lumbosacral defects in addition to reconstructing distal body parts as well, such as breast reconstruction. This fasciocutaneous flap is designed based on the LAPs small arteries that emerge from the lumbar arteries then move superficially piercing overlying tissues to perforate the lumbar fascia and supply the skin and subcutaneous tissue; However, anatomical and clinical studies regarding the LAP flap and its perforators are sparse in the literature, and the results are even contradicting. This article will discuss the LAP flap, the anatomy of its perforators, and the clinical aspects about its usage. In addition, we explore its preoperative imaging evaluation, and deliver a guide on image reporting and radiological data that will benefit the surgeon most during the procedure.

Imaging bone metastases in breast cancer: evidence on comparative test accuracy.

BACKGROUND: Numerous imaging modalities may be used to detect bone metastases (BM) in women with breast cancer. METHODS: Systematic evidence review, including quality appraisal, of studies reporting on comparative imaging accuracy for detection of BM from breast cancer. RESULTS: Eligible studies (N = 16) included breast cancer subjects who had imaging evaluation for suspected BM or for staging/restaging in suspected local or distant relapse. Median prevalence of BM was 34.0% (range 10.0%-66.7%). There was substantial heterogeneity in the quality of reference standards and in the prevalence of BM, which could account for some of the differences in reported comparative accuracy. Most frequently, bone scan (BS) was compared with newer imaging modalities in subjects selected to both tests; therefore, results could be affected by selection bias. There was some evidence that positron emission tomography (PET), and limited evidence that PET/computed tomography (CT), CT, and magnetic resonance imaging (MRI), may provide small increments in accuracy relative to BS as add-on tests; there was little evidence regarding single photon emission computed tomography or whole-body MRI. CONCLUSIONS: There is some evidence of enhanced incremental accuracy for some of the above-mentioned tests where used as add-on in subjects selected to more than one imaging modality, with little evidence to support their application as a replacement to BS in first-line imaging of BM. PET/CT appears to have high accuracy and is recommended for further evaluation.

Tumour response interpretation with new tumour response criteria vs the World Health Organisation criteria in patients with bone-only metastatic breast cancer.

BACKGROUND: We compared the utility of a new response classification (MDA; based on computed tomography (CT), magnetic resonance imaging (MRI), plain radiography (XR), and skeletal scintigraphy (SS)) and the World Health Organisation response classification (WHO; based on XR and SS) in stratifying breast cancer patients with bone-only metastases with respect to progression-free survival (PFS), overall survival (OS), and clinical response. METHODS: We retrospectively reviewed 41 patients with bone-only metastatic breast cancer and assigned responses according to the MDA and WHO criteria. We analysed whether the MDA or WHO response classifications correlated with PFS and OS. RESULTS: With the MDA criteria, there were significant differences in PFS between patients classified as responders and those classified as nonresponders (P=0.025), but with the WHO criteria, there were not. Neither criteria distinguished responders from nonresponders in terms of OS. MDA response criteria correlated better than WHO response criteria with clinical response assessment. CONCLUSIONS: The MDA classification is superior to the WHO classification in differentiating between responders and nonresponders among breast cancer patients with bone-only metastases. Application of the MDA classification may allow bone lesions to be considered measurable disease. Prospective study is needed to test the MDA classification among patients with bone metastasis.

Paracetamol and ibuprofen for the treatment of fever in children: the PITCH randomised controlled trial.

OBJECTIVES: To establish the relative clinical effectiveness and cost-effectiveness of paracetamol plus ibuprofen compared with paracetamol and ibuprofen separately for time without fever, and the relief of fever-associated discomfort in young children who can be managed at home. DESIGN: The trial design was a single-centre (multisite), individually randomised, blinded, three-arm trial comparing paracetamol and ibuprofen together with paracetamol or ibuprofen separately. SETTING: There were three recruitment settings, as follows: 'local' where research nurses were recruited from NHS primary care sites; 'remote' where NHS sites notified the study of potentially eligible children; and 'community' where parents contacted the study in response to local media advertisements. PARTICIPANTS: Children aged between 6 months and 6 years with fever > or = 37.8 degrees C and < or = 41 degrees C due to an illness that could be managed at home. INTERVENTIONS: The intervention was the provision of, and advice to give, the medicines for up to 48 hours: paracetamol every 4-6 hours (maximum of four doses in 24 hours) and ibuprofen every 6-8 hours (maximum of three doses in 24 hours). Every parent received two bottles, with at least one containing an active medicine. Parents, research nurses and investigators were blinded to treatment allocation by the use of identically matched placebo medicines. The dose of medicine was determined by the child's weight: paracetamol 15 mg/kg and ibuprofen 10 mg/kg per dose. RESULTS: For additional time without fever in the first 4 hours, use of both medicines was superior to use of paracetamol alone [adjusted difference 55 minutes, 95% confidence interval (CI) 33 to 77 minutes; p < 0.001] and may have been as good as ibuprofen (adjusted difference 16 minutes, 95% CI -6 to 39 minutes; p = 0.2). Both medicines together cleared the fever 23 minutes (95% CI 2-45 minutes; p = 0.015) faster than paracetamol alone, but no faster than ibuprofen alone (adjusted difference -3 minutes, 95% CI 24-18 minutes; p = 0.8). For additional time without fever in the first 24 hours, both medicines were superior to paracetamol (adjusted difference 4.4 hours, 95% CI 2.4-6.3 hours; p < 0.001) or ibuprofen (adjusted difference 2.5 hours, 95% CI 0.6-4.5 hours; p = 0.008) alone. No reduction in discomfort or other fever-associated symptoms was found, although power was low for these outcomes. An exploratory analysis showed that children with higher discomfort levels had higher mean temperatures. No difference in adverse effects was observed between treatment groups. The recommended maximum number of doses of paracetamol and ibuprofen in 24 hours was exceeded in 8% and 11% of children respectively. Over the 5-day study period, paracetamol and ibuprofen together was the cheapest option for the NHS due to the lower use of health-care services:14 pounds [standard deviation (SD) 23 pounds] versus 20 pounds (SD 38 pounds) for paracetamol and 18 pounds (SD 40 pounds) for ibuprofen. Both medicines were also cheapest for parents because the lower use of health care services resulted in personal saving on travel costs and less time off work: 24 pounds (SD 46 pounds) versus 26 pounds (SD 63 pounds) for paracetamol and 30 pounds (SD 91 pounds) for ibuprofen. This more than compensated for the extra cost of medication. However, statistical evidence for these differences was weak due to lack of power. Overall, a quarter of children were 'back to normal' by 48 hours and one-third by day 5. Five (3%) children were admitted to hospital, two with pneumonia, two with bronchiolitis and one with a severe, but unidentified 'viral illness'. CONCLUSIONS: Young children who are unwell with fever should be treated with ibuprofen first, but the relative risks (inadvertently exceeding the maximum recommended dose) and benefits (extra 2.5 hours without fever) of using paracetamol plus ibuprofen over 24 hours should be considered. However, if two medicines are used, it is recommended that all dose times are carefully recorded to avoid accidentally exceeding the maximum recommended dose. Manufacturers should consider supplying blank charts for this purpose. Use of both medicines should not be discouraged on the basis of cost to either parents or the NHS. Parents and clinicians should be aware that fever is a relatively short-lived symptom, but may have more serious prognostic implications than the other common symptom presentations of childhood.

Thoracic outlet syndrome: case report and review.

Thoracic outlet syndrome is caused by a large number of etiologies, which can affect the elements of the neurovascular bundle in combination or separately. The radiology department offers many imaging modalities which can assist in determining which structures may be involved as well as suggest possible etiology. The interventional radiologist, often working in conjunction with the surgeon, can assist in the treatment of many arterial or venous disorders, such as stenosis or thrombosis commonly seen in patients with Thoracic outlet syndrome.

Sequence selectivity, cross-linking efficiency and cytotoxicity of DNA-targeted 4-anilinoquinoline aniline mustards.

We have investigated the sequence selectivity, DNA binding site characteristics, interstrand cross-linking ability and cytotoxicity of four 4-anilinoquinoline aniline mustards related to the AT-selective minor groove-binding bisquaternary ammonium heterocycles. The compounds studied include two full mustards that differ in alkylating power, a half mustard and a quaternary anilinoquinolinium bismustard. We have also compared their cytotoxicity with their precursor diols and their toxicity and cross-linking ability with the classical alkylating agents melphalan and chlorambucil. We find that the anilinoquinoline aniline mustards weakly and non-specifically alkylate guanines in the major groove and that they bind strongly to AT-rich sequences in the minor groove, where they alkylate both adenines and guanines at the N3 position. The most preferred sites are classical minor groove binder AT-tracts to which all four ligands bind equally well. The remaining sites are AT-rich, but include GC base pairs, to which the ligands bind with preferences depending on their structure. The full mustards alkylate at the 3' ends of the binding site in an orientation that depends on the spatial disposition of the purines within the two strands. Generally speaking guanines are found to be much less reactive than adenines. The anilinoquinoline aniline mustards are interstrand cross-linking agents that are 60- to 100-fold more effective than melphalan, with the quaternary compound being the most efficacious. However, the type of binding site at which the cross-links occur is not clear, since distamycin challenge fails to antagonize them fully. The full mustards are 20- to 50-fold more cytotoxic than their diol precursors, are more cytotoxic than the half mustard and are 20- to 30-fold more active than melphalan and chlorambucil. The quaternary ligand is the most potent. Given the evidence to hand, it appears that antitumour activity correlates with capacity to cause interstrand cross-links at classical or near-classical AT-minor groove binder sites, rather than with ability to discriminate between the subsets of potential anilinoquinoline aniline mustard binding sites.