Gender-affirming care in the context of medical ethics – gatekeeping v. informed consent

Introduction. For many transgender patients, access to healthcare – and specifically gender-affirming care (such as hormone replacement therapy) – is limited by a variety of different barriers. Despite evidence showing that access to medical transition is not only safe, but also improves suicide risk in transgender patients, these services are often subject to excessive gatekeeping by medical professionals and healthcare workers.Objectives. To evaluate the ethical merits of the two most prominent models of providing gender-affirming care to patients who identify as transgender.Methods. The author compares the gatekeeping model and the informed consent model of providing gender-affirming care, in terms of the well-recognised four fundamental ‘pillars’ of medical ethics, namely respect for autonomy, non-maleficence, beneficence and distributive justice.Results. The gatekeeping model is found to be in violation of all four principles, while an informed consent model of care respects these ethical pillars.Discussion. A variety of ethical factors are at play in the provision of gender-affirming care to transgender patients, and these need to be considered carefully in formulating approaches or models. There are many other factors that can present a barrier to gender-affirming care in a South African context, but an examination of the ethical considerations can be of immediate benefit to an already marginalised population.Conclusion. Clinicians should be aware of the ethical factors in withholding gender-affirming care from transgender patients, and the potential consequences thereof. An approach based on a model of informed consent, which respects a patient’s agency over their own body, is both clinically safe and ethically sound

Randomized trial comparing proactive, high-dose versus reactive, low-dose intravenous iron supplementation in hemodialysis (PIVOTAL) : Study design and baseline data

Background: Intravenous (IV) iron supplementation is a standard maintenance treatment for hemodialysis (HD) patients, but the optimum dosing regimen is unknown. Methods: PIVOTAL (Proactive IV irOn Therapy in hemodiALysis patients) is a multicenter, open-label, blinded endpoint, randomized controlled (PROBE) trial. Incident HD adults with a serum ferritin 700 μg/L and/or TSAT ≥40%) or a reactive, low-dose IV iron arm (iron sucrose administered if ferritin <200 μg/L or TSAT < 20%). We hypothesized that proactive, high-dose IV iron would be noninferior to reactive, low-dose IV iron for the primary outcome of first occurrence of nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for heart failure or death from any cause. If noninferiority is confirmed with a noninferiority limit of 1.25 for the hazard ratio of the proactive strategy relative to the reactive strategy, a test for superiority will be carried out. Secondary outcomes include infection-related endpoints, ESA dose requirements, and quality-of-life measures. As an event-driven trial, the study will continue until at least 631 primary outcome events have accrued, but the expected duration of follow-up is 2-4 years. Results: Of the 2,589 patients screened across 50 UK sites, 2,141 (83%) were randomized. At baseline, 65.3% were male, the median age was 65 years, and 79% were white. According to eligibility criteria, all patients were on ESA at screening. Prior stroke and MI were present in 8 and 9% of the cohort, respectively, and 44% of patients had diabetes at baseline. Baseline data for the randomized cohort were generally concordant with recent data from the UK Renal Registry. Conclusions: PIVOTAL will provide important information about the optimum dosing of IV iron in HD patients representative of usual clinical practice. Trial Registration: EudraCT number: 2013-002267-25.Peer reviewedFinal Published versio

ACE inhibitor and angiotensin receptor-II antagonist prescribing and hospital admissions with acute kidney injury:a longitudinal ecological study

BACKGROUND: ACE Inhibitors (ACE-I) and Angiotensin-Receptor Antagonists (ARAs) are commonly prescribed but can cause acute kidney injury (AKI) during intercurrent illness. Rates of hospitalization with AKI are increasing. We aimed to determine whether hospital AKI admission rates are associated with increased ACE-I/ARA prescribing. METHODS AND FINDINGS: English NHS prescribing data for ACE-I/ARA prescriptions were matched at the level of the general practice to numbers of hospital admissions with a primary diagnosis of AKI. Numbers of prescriptions were weighted for the demographic characteristics of general practices by expressing prescribing as rates where the denominator is Age, Sex, and Temporary Resident Originated Prescribing Units (ASTRO-PUs). We performed a mixed-effect Poisson regression to model the number of admissions for AKI occurring in each practice for each of 4 years from 1/4/2007. From 2007/8-2010/11, crude AKI admission rates increased from 0.38 to 0.57 per 1000 patients (51.6% increase), and national annual ACE-I/ARA prescribing rates increased by 0.032 from 0.202 to 0.234 (15.8% increase). There was strong evidence (p<0.001) that increases in practice-level prescribing of ACE-I/ARA over the study period were associated with an increase in AKI admission rates. The increase in prescribing seen in a typical practice corresponded to an increase in admissions of approximately 5.1% (rate ratio = 1.051 for a 0.03 per ASTRO-PU increase in annual prescribing rate, 95%CI 1.047-1.055). Using the regression model we predict that 1,636 (95%CI 1,540-1,780) AKI admissions would have been avoided if prescribing rates were at the 2007/8 level, equivalent to 14.8% of the total increase in AKI admissions. CONCLUSION: In this ecological analysis, up to 15% of the increase in AKI admissions in England over a 4-year time period is potentially attributable to increased prescribing of ACE-I and ARAs. However, these findings are limited by the lack of patient level data such as indication for prescribing and patient characteristics

Patterns of resistance and DHFR/DHPS genotypes of Plasmodium falciparum in rural Tanzania prior to the adoption of sulfadoxine-pyrimethamine as first-line treatment.

A study was carried out to assess the patterns of resistance and occurrence of DHFR/DHPS genotypes of Plasmodium falciparum prior to the adoption of sulfadoxine-pyrimethamine (SP) as first-line treatment for uncomplicated malaria in Tanzania. Children under five years (n = 117) with clinical, uncomplicated malaria were randomly allocated to standard treatments of either chloroquine (CQ) (25 mg/kg) or SP (25 mg sulfadoxine and 1.25 mg pyrimethamine/kg). Patients were monitored for 28 days. Clinical recovery was achieved in 98% (n = 58) and 90% (n = 59) of the patients in the SP and CQ groups, respectively. Parasitologically, 14% of the patients in the SP group and 51% in the CQ group exhibited RII/RIII resistance. When relating pre-treatment blood drug levels to treatment outcome and the degree of parasite resistance to the number of mutations, no relationships could be detected. There was an overall significant increase in haemoglobin levels from day 0 to day 28 in both patient groups. Sulfadoxine-pyrimethamine produced an acceptable clinical response but the high degree of parasitological resistance (RII/RIII) observed two years prior to the introduction of the drug as first-line treatment is of concern, especially considering the long half-lives of sulfadoxine and pyrimethamine

The influence of irrigant activation, concentration and contact time on sodium hypochlorite penetration into root dentine: an ex vivo experiment

Aim To establish if irrigant activation techniques, namely manual‐dynamic‐activation (MDA), passive‐ultrasonic‐irrigation (PUI) and sonic‐irrigation (SI), improve the tubular penetration of sodium hypochlorite (NaOCl) into root dentine when compared with conventional‐needle‐irrigation (CNI). Secondly, investigate if increasing NaOCl concentration and/or contact‐time improves the performance of these techniques. Methodology A total of 83 extracted human maxillary permanent canines were decoronated to 15 mm and root canals prepared to a size 40,.10 taper. Root dentine was stained with crystal violet for 72 h and embedded in silicone. Eighty specimens were randomly distributed into 16 groups (n = 5) according to the irrigant activation technique, NaOCl concentration (2%; 5.25%) and irrigant contact‐time (10 min; 20 min). All activation techniques were used for 60 s in the last minute of irrigation. Additionally, 3 teeth were not exposed to NaOCl to confirm adequate dentine staining had occurred (i.e. negative control). All specimens were subsequently dissected, observed under a light microscope and NaOCl penetration depth (µm) determined by measuring the average width of bleached dentine using ImageJ software. Statistical comparisons were made with paired and unpaired t‐tests, ANOVAs followed by post‐hoc Tukey and Dunnett’s tests, and a general linear model (α < 0.05). Results Overall, NaOCl penetration ranged from 38.8 µm – 411.0 µm with MDA, PUI and SI consistently resulting in significantly greater tubular infiltration than CNI (P < 0.05). The deepest measurements in the coronal, middle and apical segments were all recorded in the MDA; 5.25%; 20 min group and the least in the CNI; 2%; 10 min group. Increasing either irrigant concentration or contact‐time resulted in significantly greater NaOCl penetration depths for all techniques and segments of the canal (P < 0.05). However, when irrigant concentration and contact‐time were increased together, a significant interaction effect between these two independent variables was observed on overall NaOCl penetration (P < 0.05). Conclusions Agitating irrigants with MDA, PUI or SI, as well as using greater irrigant concentrations or contact‐times, potentiated NaOCl penetration into root dentine. However, longer durations of NaOCl exposure at lower concentrations resulted in similar depths of tubular penetration as those achieved at higher concentrations

The accuracy of diagnostic coding for acute kidney injury in England - a single centre study.

BACKGROUND: Acute kidney injury (AKI) is an independent risk factor for mortality and is responsible for a significant burden of healthcare expenditure, so accurate measurement of its incidence is important. Administrative coding data has been used for assessing AKI incidence, and shows an increasing proportion of hospital bed days attributable to AKI. However, the accuracy of coding for AKI and changes in coding over time have not been studied in England. METHODS: We studied a random sample of admissions from 2005 and 2010 where ICD-10 code N17 (acute renal failure) was recorded in the administrative coding data at one acute NHS Foundation Trust in England. Using the medical notes and computerised records we examined the demographic and clinical details of these admissions. RESULTS: Against a 6.3% (95% CI 4.8-7.9%) increase in all non-elective admissions, we found a 64% increase in acute renal failure admissions (95% CI 41%-92%, p < 0.001) in 2010 compared to 2005. Median age was 78 years (IQR 72-87), 11-25% had a relevant pre-admission co-morbidity and 64% (55-73%) were taking drugs known to be associated with AKI. Over both years, 95% (91-99%) of cases examined met the Kidney Disease: Improving Global Outcomes criteria for AKI. CONCLUSIONS: Patients with hospital admissions where AKI has been coded are elderly with multiple co-morbidities. Our results demonstrate a high positive predictive value of coding data for a clinical diagnosis of AKI, with no suggestion of marked changes in coding of AKI between 2005 and 2010.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Randomized multicentre pilot study of sacubitril/valsartan versus irbesartan in patients with chronic kidney disease: United Kingdom Heart and Renal Protection (HARP)- III—rationale, trial design and baseline data

BACKGROUND: Patients with chronic kidney disease (CKD) are at risk of progression to end-stage renal disease and cardiovascular disease. Data from other populations and animal experiments suggest that neprilysin inhibition (which augments the natriuretic peptide system) may reduce these risks, but clinical trials among patients with CKD are required to test this hypothesis. METHODS: UK Heart and Renal Protection III (HARP-III) is a multicentre, double-blind, randomized controlled trial comparing sacubitril/valsartan 97/103 mg two times daily (an angiotensin receptor-neprilysin inhibitor) with irbesartan 300 mg one time daily among 414 patients with CKD. Patients ≥18 years of age with an estimated glomerular filtration rate (eGFR) of ≥45 but &lt;60 mL/min/1.73 m2 and urine albumin:creatinine ratio (uACR) &gt;20 mg/mmol or eGFR ≥20 but &lt;45 mL/min/1.73 m2 (regardless of uACR) were invited to be screened. Following a 4- to 7-week pre-randomization single-blind placebo run-in phase (during which any current renin-angiotensin system inhibitors were stopped), willing and eligible participants were randomly assigned either sacubitril/valsartan or irbesartan and followed-up for 12 months. The primary aim was to compare the effects of sacubitril/valsartan and irbesartan on measured GFR after 12 months of therapy. Important secondary outcomes include effects on albuminuria, change in eGFR over time and the safety and tolerability of sacubitril/valsartan in CKD. RESULTS: Between November 2014 and January 2016, 620 patients attended a screening visit and 566 (91%) entered the pre-randomization run-in phase. Of these, 414 (73%) participants were randomized (mean age 63 years; 72% male). The mean eGFR was 34.0 mL/min/1.73 m2 and the median uACR was 58.5 mg/mmol. CONCLUSIONS: UK HARP-III will provide important information on the short-term effects of sacubitril/valsartan on renal function, tolerability and safety among patients with CKD

Teratogenic risk and contraceptive counselling in psychiatric practice: analysis of anticonvulsant therapy

&lt;p&gt;Background: Anticonvulsants have been used to manage psychiatric conditions for over 50 years. It is recognised that some, particularly valproate, carbamazepine and lamotrigine, are human teratogens, while others including topiramate require further investigation. We aimed to appraise the documentation of this risk by psychiatrists and review discussion around contraceptive issues.&lt;/p&gt; &lt;p&gt;Methods: A retrospective review of prescribing patterns of four anticonvulsants (valproate, carbamazepine, lamotrigine and topiramate) in women of child bearing age was undertaken. Documented evidence of discussion surrounding teratogenicity and contraceptive issues was sought.&lt;/p&gt; &lt;p&gt;Results: Valproate was most commonly prescribed (n=67). Evidence of teratogenic risk counselling at medication initiation was sub-optimal – 40% of individuals prescribed carbamazepine and 22% of valproate. Documentation surrounding contraceptive issues was also low- 17% of individuals prescribed carbamazepine and 13% of valproate.&lt;/p&gt; &lt;p&gt;Conclusion: We found both low rates of teratogenic risk counselling and low rates of contraception advice in our cohort. Given the high rates of unplanned pregnancies combined with the relatively high risk of major congenital malformations, it is essential that a detailed appraisal of the risks and benefits associated with anticonvulsant medication occurs and is documented within patients’ psychiatric notes.&lt;/p&gt