Drug interactions in primary health care in the George subdistrict, South Africa: a cross-sectional study

Objectives: To investigate the prevalence of potential drug-drug interactions in primary healthcare clinics in the George subdistrict, to determine which drugs were involved, and to identify associated risk factors. Design: A cross-sectional retrospective folder review was performed. Setting and subjects: Four hundred randomly selected patient files from four primary care clinics in the George subdistrict. Outcome measures: The prevalence of potential drug-drug interactions in primary care, drugs involved in potential drugdrug interactions and associated risk factors. Results: The prevalence of scripts containing at least one moderate potential interaction was 42%; severe potential interaction, 5.25%; and contraindicated combinations, 0.5%. The most common drugs involved were enalapril, aspirin, ibuprofen, furosemide and fluoxetine. The most common implicated drugs in potentially severe interactions were warfarin, aspirin, fluoxetine, tramadol and allopurinol. Two contraindicated combinations were found, namely verapamil plus simvastatin, and hyoscine butyl bromide plus oral potassium chloride. Advancing age and polypharmacy were associated with an increased risk of potential drug-drug interactions. Input from the regional hospital specialist departments greatly increased the risk of a patient being given a prescription that contained a potential drug-drug interaction. Eighty one per cent of severe interactions were from this group. Conclusion: The potential for drug-drug interactions occurring was common in primary healthcare clinics in the George subdistrict. Drug interactions are predictable and preventable. The risk factors identified in this study may assist in the design of interventions that reduce the risk.Keywords: potential drug-drug interactions, adverse drug events, polypharmacy, primary health care, pharmacokinetic interactions, pharmacodynamic interaction

The role of sonographic phenotyping in delivering an efficient non-invasive prenatal diagnosis (NIPD) service for FGFR3-related skeletal dysplasias

Objectives: To evaluate the diagnostic yield of noninvasive prenatal diagnosis (NIPD) for FGFR3‐related skeletal dysplasias and assess the accuracy of referrals based on sonographic findings to inform guidelines for referral. Methods: We retrospectively reviewed laboratory and referral records from 2012 to 2018 to ascertain all NIPD tests performed using our next generation sequencing panel to detect FGFR3 mutations. We calculated the diagnostic yield of the test overall and when sub‐divided according to the phenotypic features identified on ultrasound before testing. Pregnancy outcomes were ascertained wherever possible from referring centers. Results: Of 335 tests, 261 were referred because of sonographic findings, of which 80 (31.3%) had a mutation. The diagnostic yield when short limbs were the only abnormal sonographic feature reported was 17.9% (30/168), increasing to 48.9% (23/47) in the presence of one, and 82.6% (19/23) in the presence of two or more characteristic features in addition to short limbs. Conclusions: Accurate sonographic phenotyping can maximise the diagnostic yield of NIPD in fetuses suspected to have FGFR3‐related skeletal dysplasias. We suggest that clear guidelines for referral are necessary to increase benefits, decrease costs by preventing unnecessary NIPD, and potentially allow first‐line broader spectrum testing for fetuses where the aetiology may be more heterogeneous

Non-invasive prenatal diagnosis (NIPD) for single gene disorders: cost analysis of NIPD and invasive testing pathways

OBJECTIVE: Evaluate the costs of offering non-invasive prenatal diagnosis (NIPD) for single gene disorders compared to traditional invasive testing to inform NIPD implementation into clinical practice. METHOD: Total costs of diagnosis using NIPD or invasive testing pathways were compared for a representative set of single gene disorders. RESULTS: For autosomal dominant conditions, where NIPD molecular techniques are straightforward, NIPD cost £314 less than invasive testing. NIPD for autosomal recessive and X-linked conditions requires more complicated technical approaches and total costs were more than invasive testing, e.g. NIPD for spinal muscular atrophy was £1090 more than invasive testing. Impact of test uptake on costs was assessed using sickle cell disorder as an example. Anticipated high uptake of NIPD resulted in an incremental cost of NIPD over invasive testing of £48 635 per 100 pregnancies at risk of sickle cell disorder. CONCLUSIONS: Total costs of NIPD are dependent upon the complexity of the testing technique required. Anticipated increased demand for testing may have economic implications for prenatal diagnostic services. Ethical issues requiring further consideration are highlighted including directing resources to NIPD when used for information only and restricting access to safe tests if it is not cost-effective to develop NIPD for rare conditions

Bunch length measurements using a transverse deflecting cavity on VELA

The VELA facility at Daresbury Laboratory in the UK includes a 5 MeV/c 2.5 cell S-band photoinjector gun. This gun operates in the "blow-out" regime with a sub-200 fs length drive laser: the resulting bunch length is determined by space-charge effects. We present measurements made with an S-band transverse deflecting cavity to characterise the bunch length as a function of charge, and as a function of the gun operating phase

Noninvasive Prenatal Diagnosis for Cystic Fibrosis: Implementation, Uptake, Outcome, and Implications

BACKGROUND: Noninvasive prenatal diagnosis (NIPD) for monogenic disorders has a high uptake by families. Since 2013, our accredited public health service laboratory has offered NIPD for monogenic disorders, predominantly for de novo or paternally dominantly inherited mutations. Here we describe the extension of this service to include definitive NIPD for a recessive condition, cystic fibrosis (CF). // METHODS: Definitive NIPD for CF was developed using next-generation sequencing. Validation was performed on 13 cases from 10 families before implementation. All cases referred for CF NIPD were reviewed to determine turnaround times, genotyping results, and pregnancy outcomes. // RESULTS: Of 38 referrals, 36 received a result with a mean turnaround of 5.75 days (range, 3-11 days). Nine cases were initially inconclusive, with 3 reported unaffected because the low-risk paternal allele was inherited and 4 cases in which the high-risk paternal allele was inherited, receiving conclusive results following repeat testing. One case was inconclusive owing to a paternal recombination around the mutation site, and one case was uninformative because of no heterozygosity. Before 2016, 3 invasive referrals for CF were received annually compared with 38 for NIPD in the 24 months since offering a definitive NIPD service. // CONCLUSIONS: Timely and accurate NIPD for definitive prenatal diagnosis of CF is possible in a public health service laboratory. The method detects recombinations, and the service is well-received as evidenced by the significant increase in referrals. The bioinformatic approach is gene agnostic and will be used to expand the range of conditions tested for

Time-Delay Interferometry

Equal-arm interferometric detectors of gravitational radiation allow phase measurements many orders of magnitude below the intrinsic phase stability of the laser injecting light into their arms. This is because the noise in the laser light is common to both arms, experiencing exactly the same delay, and thus cancels when it is differenced at the photo detector. In this situation, much lower level secondary noises then set overall performance. If, however, the two arms have different lengths (as will necessarily be the case with space-borne interferometers), the laser noise experiences different delays in the two arms and will hence not directly cancel at the detector. In order to solve this problem, a technique involving heterodyne interferometry with unequal arm lengths and independent phase-difference readouts has been proposed. It relies on properly time-shifting and linearly combining independent Doppler measurements, and for this reason it has been called Time-Delay Interferometry (or TDI). This article provides an overview of the theory and mathematical foundations of TDI as it will be implemented by the forthcoming space-based interferometers such as the Laser Interferometer Space Antenna (LISA) mission. We have purposely left out from this first version of our ``Living Review'' article on TDI all the results of more practical and experimental nature, as well as all the aspects of TDI that the data analysts will need to account for when analyzing the LISA TDI data combinations. Our forthcoming ``second edition'' of this review paper will include these topics.Comment: 51 pages, 11 figures. To appear in: Living Reviews. Added conten

Discipline-Specific Compared to Generic Training of Teachers in Higher Education

A recurrent theme arising in the higher education sector is the suitability and effectiveness of generic versus discipline-specific training of university teachers, who are often recruited based on their disciplinary specialties to become teachers in higher education. We compared two groups of participants who had undergone training using a generic post-graduate certificate in higher education (PGCertGeneric) versus a discipline-specific course in veterinary education (PGCertVetEd). The study was conducted using a survey that allowed comparison of participants who completed PGCertGeneric (n=21) with PGCertVetEd (n=22). Results indicated that participants from both PGCertGeneric and PGCertVetEd considered teaching to be satisfying and important to their careers, valued the teaching observation component of the course, and identified similar training needs. However, the participants of the PGCertVetEd felt that the course made them better teachers, valued the relevance of the components taught, understood course design better, were encouraged to do further courses/reading in teaching and learning, changed their teaching as a result of the course, and were less stressed about teaching as compared to the PGCertGeneric participants (p<.05). It is likely that the PGCertVetEd, which was designed and developed by veterinarians with a wider understanding of the veterinary sector, helped the participants perceive the training course as suited to their needs

Uptake, outcomes, and costs of implementing non-invasive prenatal testing for Down's syndrome into NHS maternity care: prospective cohort study in eight diverse maternity units.

OBJECTIVE:  To investigate the benefits and costs of implementing non-invasive prenatal testing (NIPT) for Down's syndrome into the NHS maternity care pathway. DESIGN:  Prospective cohort study. SETTING:  Eight maternity units across the United Kingdom between 1 November 2013 and 28 February 2015. PARTICIPANTS:  All pregnant women with a current Down's syndrome risk on screening of at least 1/1000. MAIN OUTCOME MEASURES:  Outcomes were uptake of NIPT, number of cases of Down's syndrome detected, invasive tests performed, and miscarriages avoided. Pregnancy outcomes and costs associated with implementation of NIPT, compared with current screening, were determined using study data on NIPT uptake and invasive testing in combination with national datasets. RESULTS:  NIPT was prospectively offered to 3175 pregnant women. In 934 women with a Down's syndrome risk greater than 1/150, 695 (74.4%) chose NIPT, 166 (17.8%) chose invasive testing, and 73 (7.8%) declined further testing. Of 2241 women with risks between 1/151 and 1/1000, 1799 (80.3%) chose NIPT. Of 71 pregnancies with a confirmed diagnosis of Down's syndrome, 13/42 (31%) with the diagnosis after NIPT and 2/29 (7%) after direct invasive testing continued, resulting in 12 live births. In an annual screening population of 698 500, offering NIPT as a contingent test to women with a Down's syndrome screening risk of at least 1/150 would increase detection by 195 (95% uncertainty interval -34 to 480) cases with 3368 (2279 to 4027) fewer invasive tests and 17 (7 to 30) fewer procedure related miscarriages, for a non-significant difference in total costs (£-46 000, £-1 802 000 to £2 661 000). The marginal cost of NIPT testing strategies versus current screening is very sensitive to NIPT costs; at a screening threshold of 1/150, NIPT would be cheaper than current screening if it cost less than £256. Lowering the risk threshold increases the number of Down's syndrome cases detected and overall costs, while maintaining the reduction in invasive tests and procedure related miscarriages. CONCLUSIONS:  Implementation of NIPT as a contingent test within a public sector Down's syndrome screening programme can improve quality of care, choices for women, and overall performance within the current budget. As some women use NIPT for information only, the Down's syndrome live birth rate may not change significantly. Future research should consider NIPT uptake and informed decision making outside of a research setting

Dietary glycemic load and gastric cancer risk in Italy

We investigated gastric cancer risk in relation to dietary glycemic index (GI) and glycemic load (GL), which represent indirect measures of carbohydrate absorption and consequently of dietary insulin demand, in a case-control study conducted in northern Italy between 1997 and 2007, including 230 patients with the incident, histologically confirmed gastric cancer and 547 frequency matched controls, admitted to the same hospitals as cases with acute non-neoplastic conditions. We used conditional logistic regression models, including terms for major recognised gastric cancer risk factors and non-carbohydrate energy intake. The odds ratios (ORs) in the highest vs lowest quintile were 1.9 (95% CI: 1.0–3.3) for GI and 2.5 (95% CI: 1.3–4.9) for GL. Compared with participants reporting low GL and high fruits/vegetables intake, the OR rose across strata of high GL and low fruits/vegetables, to reach 5.0 (95% CI: 2.2–11.5) for those reporting low fruits/vegetables intake and high GL. Our study may help to explain the direct relation observed in several studies between starchy foods and gastric cancer risk

Ensuring high standards for the delivery of NIPT world-wide: Development of an international external quality assessment scheme

OBJECTIVE: To ensure accurate and appropriate reporting of non-invasive prenatal testing (NIPT) results, the standard of testing should be measured and monitored by participation in external quality assessment (EQA) schemes. The findings from international pilot EQAs for NIPT for the common trisomies are presented. METHODS: In the first pilot, three EQA providers used artificially manufactured reference materials to deliver an EQA for NIPT. The second pilot used clinically collected maternal plasma samples. The testing and reporting for aneuploidy status was performed by participating laboratories using routine procedures. Reports were assessed against peer ratified criteria and EQA scores were returned to participants. RESULTS: Forty-laboratories participated in the first. Genotyping accuracy was high; four laboratories reported a critical genotyping error (10%) and two reported partial results. Eighty-seven laboratories participated in the second pilot using maternal plasma, two reporting a critical genotyping error (2.3%). For both rounds, report content was variable with key information frequently omitted or difficult to identify within the report. CONCLUSIONS: We have successfully delivered an international pilot EQA for NIPT. When compared with currently available manufactured materials, EQA for NIPT was best performed using clinically collected maternal plasma. Work is required to define and improve the standard of reporting