Arthroscopic suture bridge fixation for acute bony Bankart with anterior glenohumeral instability: a case report and narrative review.

Background and Objective: Anterior shoulder dislocations can result in acute glenoid rim fractures that compromise the bony stability of the glenohumeral joint. Adequate fixation of these fractures is required to restore stability, decrease shoulder pain, and facilitate return to activity. The double-row suture bridge is a relatively novel fixation technique, first described in 2009, that accomplishes internal fixation with sufficient stability using an all-arthroscopic technique to restore the glenoid footprint. A 40-year-old female with recurrent anterior shoulder instability in the setting of seizure disorder was found to have a bony Bankart lesion of 25% to 30% with a concomitant superior labral tear. The patient was treated with a double-row bony Bankart bridge and labral repair. At six months follow-up, she has progressed to a full recovery with no recurrence. Methods: A search was conducted in May 2023 in PubMed, EMBASE, and CINAHL with the search terms bony Bankart, bone Bankart, osseous Bankart, acute, bridge, suture bridge, double row. Key Content and Findings: Double-row suture bridge repairs result in improvement in shoulder function as determined by ASES (93.5), QuickDASH (4.5), SANE (95.9), and SF-12 (55.6). The overall recurrence rate of anterior instability after a bony Bankart bridge repair is 8%. When examining the return to prior level of function, 81.4% of patients were able to do so with only 7.9% of patients reporting significant modifications to their activity level. In mid-term results, double row suture bridge demonstrates similar outcomes to other all-arthroscopic fixation methods of bony Bankart injuries. Importantly, bony Bankart bridge remains a viable option for critical glenoid lesions over the 20% cutoff used in other all arthroscopic techniques. Biomechanically, the double-row suture bridge offers distinct benefits over its single-row counterpart including increased compression, reduced displacement, and reduced step-off. Conclusions: Although there is limited data, the studies discussed and the demonstrative case show the potential benefit of all-arthroscopic double-row suture bridge fixation including increased compression, decreased displacement, and a lower complication rate in patients with large bony Bankart lesions traditionally requiring bony augmentation. However, more robust studies are necessary to determine the long-term success of the double-row suture bridge.

Batter's Shoulder: All-Knotless Posterior Labral Repair With Retensionable Anchors for Treatment of Batter's Shoulder.

Batter's Shoulder is a unique injury that may be associated with recurrent microtrauma followed by acute subluxation of the humeral head on the posterior glenoid edge, leading to posterior labral tears. Early identification of this injury is critical, as it may be treated with conservative nonsurgical treatments prior to labral tear onset. If conservative treatment fails and pain persists, surgical options include arthroscopic fixation to reapproximate the posterior labrum to the glenoid and restore capsular tension. Previous studies have shown the benefit of using knotless suture anchors in arthroscopic shoulder fixation. This technical note demonstrates that Batter's Shoulder is a unique injury associated with posterior labral tears of the shoulder and provides a contemporary method of arthroscopic fixation of a posterior labral tear using retensionable knotless all-suture anchors.

An Expedited Sling Immobilization Protocol After Isolated Biceps Tenodesis Results in Clinical and Patient-Reported Postoperative Outcomes Equivalent to a Standard Rehabilitation Protocol.

Purpose: To characterize clinical and patient-reported outcomes for patients after isolated biceps tenodesis (BT) who underwent either standard or expedited sling immobilization protocols following surgery. Methods: This retrospective cohort study compared patients who were assigned to use a sling for either 4 to 6 weeks (standard) or 0 to 2 weeks (expedited) following an isolated BT. Primary endpoint included rate of re-rupture, surgical revision, loss of fixation, and Popeye deformity. Secondary endpoints included shoulder range of motion (ROM) as well as pre- and postoperative patient-reported outcomes (PROs) of pain and function. Missing data were managed via multiple imputation with chained equations. Complication prevalence 95% confidence intervals were calculated using the Clopper Pearson method and a series of hierarchical mixed effects linear regressions were performed to assess differences between sling interventions in PROs and ROM. Results: The average age of the standard cohort (n = 66) was 49 years (±14 years), and the average age of the expedited cohort (n = 69) was 47 years (±14 years). The expedited and standardized cohorts demonstrated 0.4 and 0.3 complications per 10,000 exposure days, respectively, with no significant difference between groups (1.4 [95% confidence interval 0.2-10.0], P = .727). There was no demonstrated difference in forward flexion, abduction, or external ROM. The expedited group had less improvement in visual analog scale for pain scores that was not clinically significant and there were no differences in PROs of function. Conclusions: No statistically significant difference in the rate of re-rupture, surgical revision, loss of fixation, or Popeye deformity was noted between protocols after isolated BT. Furthermore, there were no clinically significant differences in ROM or PROs identified between protocols after isolated BT. This study suggests that patients who have undergone isolated BT may safely discontinue sling use within 2 weeks after surgery. Level of Evidence: Level III, retrospective comparative study.

Diagnosis and management of primary hyperaldosteronism in patients with hypertension: a practical approach endorsed by the British and Irish Hypertension Society.

Alongside the lack of homogeneity among international guidelines and consensus documents on primary hyperaldosteronism, the National UK guidelines on hypertension do not provide extensive recommendations regarding the diagnosis and management of this condition. Local guidelines vary from area to area, and this is reflected in the current clinical practice in the UK. In an attempt to provide support to the clinicians involved in the screening of subjects with hypertension and clinical management of suspected cases of primary hyperaldosteronism the following document has been prepared on the behalf of the BIHS Guidelines and Information Service Standing Committee. Through remote video conferences, the authors of this document reviewed an initial draft which was then circulated among the BIHS Executive members for feedback. A survey among members of the BIHS was carried out in 2022 to assess screening strategies and clinical management of primary hyperaldosteronism in the different regions of the UK. Feedback and results of the survey were then discussed and incorporated in the final document which was approved by the panel after consensus was achieved considering critical review of existing literature and expert opinions. Grading of recommendations was not performed in light of the limited available data from properly designed randomized controlled trials.

Low Recurrence of Instability and Satisfying Patient-Reported Outcomes Following Various Surgical Treatments of Reverse Hill-Sachs Lesions in the Setting of Posterior Instability: A Systematic Review.

PURPOSE: To systematically review the literature and report the outcomes of various surgical treatments for reverse Hill-Sachs lesions (RHSL) in the setting of posterior shoulder instability. METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. All studies assessing outcomes of surgical treatment of RHSL from inception to January 2023 were identified in PubMed, Embase, and Cochrane Library. Inclusion criteria consisted of studies reporting outcomes, minimum mean 1-year follow-up, and minimum Level IV evidence. Outcomes were assessed using Forest plots with random effects models using R software. RESULTS: A total of 29 studies consisting of 291 patients were included with a mean age of 42 years (range 16-88 years), 87% male gender, and mean follow-up of 4.5 years. The mean size of impacted or affected cartilage was 35%, and time from injury to surgery was mean 15 weeks. Nearly all studies were Level IV evidence, and quality of studies was low. Random effect models were performed, and data are presented as range. A low incidence of instability was noted for all surgical techniques with good patient-reported outcome measures. Most studies reported outcomes of the modified McLaughlin procedure (13 studies, 126 patients) with overall Constant-Murley Score of 65 to 92. Trends were seen towards better Constant-Murley Score and external rotation with a shorter delay between injury, and when arthroscopic and joint preserving treatments were performed. CONCLUSIONS: This systematic review showed low rates of instability recurrence, reproducible range of motion, and favorable patient-reported outcome measures were reported following all treatments for RHSLs with posterior instability. There was a significant association between better outcomes and a shorter delay between injury and surgery. The level of evidence is limited, given the small and retrospective studies which can be explained by the rarity of these injuries. LEVEL OF EVIDENCE: Level IV; systematic review of Level IV or better investigations.

Liquid-Liquid Phase Separation of the DEAD-Box Cyanobacterial RNA Helicase Redox (CrhR) into Dynamic Membraneless Organelles in Synechocystis sp. Strain PCC 6803.

Compartmentalization of macromolecules into discrete non-lipid-bound bodies by liquid-liquid phase separation (LLPS) is a well-characterized regulatory mechanism frequently associated with the cellular stress response in eukaryotes. In contrast, the formation and importance of similar complexes is just becoming evident in bacteria. Here, we identify LLPS as the mechanism by which the DEAD-box RNA helicase, cyanobacterial RNA helicase redox (CrhR), compartmentalizes into dynamic membraneless organelles in a temporal and spatial manner in response to abiotic stress in the cyanobacterium Synechocystis sp. strain PCC 6803. Stress conditions induced CrhR to form a single crescent localized exterior to the thylakoid membrane, indicating that this region is a crucial domain in the cyanobacterial stress response. These crescents rapidly dissipate upon alleviation of the stress conditions. Furthermore, CrhR aggregation was mediated by LLPS in an RNA-dependent reaction. We propose that dynamic CrhR condensation performs crucial roles in RNA metabolism, enabling rapid adaptation of the photosynthetic apparatus to environmental stresses. These results expand our understanding of the role that functional compartmentalization of RNA helicases and thus RNA processing in membraneless organelles by LLPS-mediated protein condensation performs in the bacterial response to environmental stress. IMPORTANCE Oxygen-evolving photosynthetic cyanobacteria evolved ~3 billion years ago, performing fundamental roles in the biogeochemical evolution of the early Earth and continue to perform fundamental roles in nutrient cycling and primary productivity today. The phylum consists of diverse species that flourish in heterogeneous environments. A prime driver for survival is the ability to alter photosynthetic performance in response to the shifting environmental conditions these organisms continuously encounter. This study demonstrated that diverse abiotic stresses elicit dramatic changes in localization and structural organization of the RNA helicase CrhR associated with the photosynthetic thylakoid membrane. These dynamic changes, mediated by a liquid-liquid phase separation (LLPS)-mediated mechanism, reveal a novel mechanism by which cyanobacteria can compartmentalize the activity of ribonucleoprotein complexes in membraneless organelles. The results have significant consequences for understanding bacterial adaptation and survival in response to changing environmental conditions.

Management of hypertensive crisis: British and Irish Hypertension Society Position document.

Patients with hypertensive emergencies, malignant hypertension and acute severe hypertension are managed heterogeneously in clinical practice. Initiating anti-hypertensive therapy and setting BP goal in acute settings requires important considerations which differ slightly across various diagnoses and clinical contexts. This position paper by British and Irish Hypertension Society, aims to provide clinicians a framework for diagnosing, evaluating, and managing patients with hypertensive crisis, based on the critical appraisal of available evidence and expert opinion.

Degron-mediated proteolysis of CrhR-like DEAD-box RNA helicases in cyanobacteria.

Conditional proteolytic degradation is an irreversible and highly regulated process that fulfills crucial regulatory functions in all organisms. As proteolytic targets tend to be critical metabolic or regulatory proteins, substrates are targeted for degradation only under appropriate conditions through the recognition of an amino acid sequence referred to as a "degron". DEAD-box RNA helicases mediate all aspects of RNA metabolism, contributing to cellular fitness. However, the mechanism by which abiotic-stress modulation of protein stability regulates bacterial helicase abundance has not been extensively characterized. Here, we provide in vivo evidence that proteolytic degradation of the cyanobacterial DEAD-box RNA helicase CrhR is conditional, being initiated by a temperature upshift from 20 to 30 °C in the model cyanobacterium, Synechocystis sp. PCC 6803. We show degradation requires a unique, highly conserved, inherently bipartite degron located in the C-terminal extension found only in CrhR-related RNA helicases in the phylum Cyanobacteria. However, although necessary, the degron is not sufficient for proteolysis, as disruption of RNA helicase activity and/or translation inhibits degradation. These results suggest a positive feedback mechanism involving a role for CrhR in expression of a crucial factor required for degradation. Furthermore, AlphaFold structural prediction indicated the C-terminal extension is a homodimerization domain with homology to other bacterial RNA helicases, and mass photometry data confirmed that CrhR exists as a dimer in solution at 22 °C. These structural data suggest a model wherein the CrhR degron is occluded at the dimerization interface but could be exposed if dimerization was disrupted by nonpermissive conditions.

Lumbopelvic postural differences in adolescent idiopathic scoliosis: A pilot study.

BACKGROUND: A primary etiology of adolescent idiopathic scoliosis (AIS) is currently unknown, but poor postural control of the spinal extensor musculature has been identified as an AIS risk factor. Identifiable postural differences would aid in advancing the precise postural behaviors that should be modified during Physiotherapy Scoliosis Specific Exercise (PSSE) to help limit the progression of AIS. RESEARCH QUESTION: Are there any determinable differences in lumbopelvic posture or range of motion between subjects with AIS and controls? METHODS: This prospective cohort pilot study consisted of 53 subjects (27 AIS and 26 control) aged 11-17 years. Subjects had their lumbopelvic posture assessed and monitored using the ViMove DorsaVi sensor package. All subjects underwent a live assessment to obtain initial lumbopelvic (LP) range of motion (ROM) measurements. Subjects were then monitored while continuing with normal activities of daily living (ADLs) for 12 h. With an alpha level of 0.05, nonparametric analyses were performed for each variable via a Mann-Whitney U-test. RESULTS: During the live assessment, controls exhibited a significantly greater anterior pelvic tilt ROM in the sitting position than the AIS group (p = 0.0433). When compared to female controls, females with AIS had a sitting pelvic tilt ROM that was significantly more retroverted (p = 0.0232) and less anteverted (p = 0.0010). During ADLs, female controls exhibited a higher total number of extension events than their female with AIS (p = 0.0263). These associations did not strengthen with greater spinal deformity. SIGNIFICANCE: This work demonstrates postural differences between patients with AIS and controls. Further study is necessary to determine why patients with AIS adopt these postures, and if PSSEs can be utilized to limit the progression of AIS.

Case report: Physiological changes due to a rapid ascent from 55 metres underwater.

We present the case of a diver who experienced an uncontrolled ascent from 55 m and presented with a severe decompression illness. She was clinically shocked and in multi organ failure due to massive fluid shifts. She demonstrated bilateral lower limb loss of power and sensation and required multiple hyperbaric therapy sessions. With joint critical care, hyperbaric and physical therapy involvement, she was discharged some five weeks after her presentation with an independent level of function.

Pet Food-Associated Dietary Exogenous Thyrotoxicosis: Retrospective Study (2016-2018) and Clinical Considerations.

Dietary exogenous thyrotoxicosis is infrequently observed in pet food. A retrospective evaluation of pet food investigations (PFI) was conducted for 17 dogs, including review of medical records, dietary and environmental exposure interviews, food testing, and regulatory action. Five PFIs occurring between 2016 and 2018 involved 7 food products including 2 food types, jerky treats or canned food, made from beef or bison. The dogs' serum thyroid hormone concentrations were evaluated before and after diet change. The foods were tested for active thyroid hormones and hormone precursors using high performance liquid chromatography with inductively coupled plasma mass spectrometry detection. The foods were also examined microscopically. Serum thyroid hormone concentrations of thyroxine (T4) varied depending on the food type consumed. Dogs that consumed dried jerky containing greater T4 concentrations often had increased serum T4 concentrations, whereas dogs that consumed canned products containing greater and 3,4,5- and 3,5,3'-triiodothyronine (T3) concentrations often had decreased serum T4 concentrations. After the diets were changed, serum T4 and T3 concentrations normalized at 1 month. Seven foods containing beef or bison had iodine concentrations greater than 11 mg/kg, and iodine speciation identified variable concentrations of iodide, T4, T3, monoiodotyrosine (MIT), and di-iodotyrosine (DIT). Thyroid gland was found in microscopic sections from one finished food and one ingredient, gullet. FDA performed Health Hazard Evaluations to categorize the exposure risk, and 5 foods were recalled for which the product packaging had not been discarded. Dietary exogenous thyrotoxicosis should be considered in dogs exhibiting clinical signs compatible with hyperthyroidism, especially if consuming beef-based food. A thyroid panel that includes serum iodine, coupled with a thorough feeding history can aid in diagnosis. Thyrotoxicosis is typically reversible after removing the contaminated food from the diet.

Options for the diagnosis of high blood pressure in primary care: a systematic review and economic model.

The 2011 NICE hypertension guideline (CG127) undertook a systematic review of the diagnostic accuracy of different blood pressure (BP) assessment methods to confirm the diagnosis of hypertension. The guideline also undertook a cost-utility analysis exploring the cost-effectiveness of the monitoring methods. A new systematic review was undertaken as part of the 2019 NICE hypertension guideline update (NG136). BP monitoring methods compared included Ambulatory BP, Clinic BP and Home BP. Ambulatory BP was the reference standard. The economic model from the 2011 guideline was updated with this new accuracy data. Home BP was more sensitive and specific than Clinic BP. Specificity improved more than sensitivity since the 2011 review. A higher specificity translates into fewer people requiring unnecessary treatment. A key interest was to compare Home BP and Ambulatory BP, and whether any improvement in Home BP accuracy would change the model results. Ambulatory BP remained the most cost-effective option in all age and sex subgroups. In all subgroups, Ambulatory BP was associated with lower costs than Clinic BP and Home BP. In all except one subgroup (females aged 40), Ambulatory BP was dominant. However, Ambulatory BP remained the most cost-effective option in 40-year-old females as the incremental cost-effectiveness ratio for Home BP versus Ambulatory BP was above the NICE £20,000 threshold. The new systematic review showed that the accuracy of both Clinic BP and Home BP has increased. However, Ambulatory BP remains the most cost-effective option to confirm a diagnosis of hypertension in all subgroups evaluated.

Cost-Effectiveness of Initiating Pharmacological Treatment in Stage One Hypertension Based on 10-Year Cardiovascular Disease Risk: A Markov Modeling Study.

Antihypertensive drug treatment is cost-effective for adults at high risk of developing cardiovascular disease (CVD). However, the cost-effectiveness in people with stage 1 hypertension (140-159 mm Hg systolic blood pressure) at lower CVD risk remains unclear. The objective was to establish the 10-year CVD risk threshold where initiating antihypertensive drug treatment for primary prevention in adults, with stage 1 hypertension, becomes cost-effective. A lifetime horizon Markov model compared antihypertensive drug versus no treatment, using a UK National Health Service perspective. Analyses were conducted for groups ranging between 5% and 20% 10-year CVD risk. Health states included no CVD event, CVD and non-CVD death, and 6 nonfatal CVD morbidities. Interventions were compared using cost-per-quality-adjusted life-years. The base-case age was 60, with analyses repeated between ages 40 and 75. The model was run separately for men and women, and threshold CVD risk assessed against the minimum plausible risk for each group. Treatment was cost-effective at 10% CVD risk for both sexes (incremental cost-effectiveness ratio £10 017/quality-adjusted life-year [$14 542] men, £8635/QALY [$12 536] women) in the base-case. The result was robust in probabilistic and deterministic sensitivity analyses but was sensitive to treatment effects. Treatment was cost-effective for men regardless of age and women aged >60. Initiating treatment in stage 1 hypertension for people aged 60 is cost-effective regardless of 10-year CVD risk. For other age groups, it is also cost-effective to treat regardless of risk, except in younger women.

HOPON (Hyperbaric Oxygen for the Prevention of Osteoradionecrosis): A Randomized Controlled Trial of Hyperbaric Oxygen to Prevent Osteoradionecrosis of the Irradiated Mandible After Dentoalveolar Surgery.

PURPOSE: Hyperbaric oxygen (HBO) has been advocated in the prevention and treatment of osteoradionecrosis (ORN) of the jaw after head and neck radiation therapy, but supporting evidence is weak. The aim of this randomized trial was to establish the benefit of HBO in the prevention of ORN after high-risk surgical procedures to the irradiated mandible. METHODS AND MATERIALS: HOPON was a randomized, controlled, phase 3 trial. Participants who required dental extractions or implant placement in the mandible with prior radiation therapy >50 Gy were recruited. Eligible patients were randomly assigned 1:1 to receive or not receive HBO. All patients received chlorhexidine mouthwash and antibiotics. For patients in the HBO arm, oxygen was administered in 30 daily dives at 100% oxygen to a pressure of 2.4 atmospheres absolute for 80 to 90 minutes. The primary outcome measure was the diagnosis of ORN 6 months after surgery, as determined by a blinded central review of clinical photographs and radiographs. The secondary endpoints included grade of ORN, ORN at other time points, acute symptoms, pain, and quality of life. RESULTS: A total of 144 patients were randomized, and data from 100 patients were analyzed for the primary endpoint. The incidence of ORN at 6 months was 6.4% and 5.7% for the HBO and control groups, respectively (odds ratio, 1.13; 95% confidence interval, 0.14-8.92; P = 1). Patients in the hyperbaric arm had fewer acute symptoms but no significant differences in late pain or quality of life. Dropout was higher in the HBO arm, but the baseline characteristics of the groups that completed the trial were comparable between the 2 arms. CONCLUSIONS: The low incidence of ORN makes recommending HBO for dental extractions or implant placement in the irradiated mandible unnecessary. These findings are in contrast with a recently published Cochrane review and previous trials reporting rates of ORN (non-HBO) of 14% to 30% and challenge a long-established standard of care.

Urinary Extracellular Vesicle Protein Profiling and Endogenous Lithium Clearance Support Excessive Renal Sodium Wasting and Water Reabsorption in Thiazide-Induced Hyponatremia.

INTRODUCTION: Thiazide diuretics are among the most widely used antihypertensive medications worldwide. Thiazide-induced hyponatremia (TIH) is 1 of their most clinically significant adverse effects. A priori TIH must result from excessive saliuresis and/or water reabsorption. We hypothesized that pathways regulating the thiazide-sensitive sodium-chloride cotransporter NCC and the water channel aquaporin-2 (AQP2) may be involved. Our aim was to assess whether patients with TIH would show evidence of altered NCC and AQP2 expression in urinary extracellular vesicles (UEVs), and also whether abnormalities of renal sodium reabsorption would be evident using endogenous lithium clearance (ELC). METHODS: Blood and urine samples were donated by patients admitted to hospital with acute symptomatic TIH, after recovery to normonatremia, and also from normonatremic controls on and off thiazides. Urinary extracellular vesicles were isolated and target proteins evaluated by western blotting and by nanoparticle tracking analysis. Endogenous lithium clearance was assessed by inductively coupled plasma mass spectrometry. RESULTS: Analysis of UEVs by western blotting showed that patients with acute TIH displayed reduced total NCC and increased phospho-NCC and AQP2 relative to appropriate control groups; smaller differences in NCC and AQP2 expression persisted after recovery from TIH. These findings were confirmed by nanoparticle tracking analysis. Renal ELC was lower in acute TIH compared to that in controls and convalescent case patients. CONCLUSION: Reduced NCC expression and increased AQP2 expression would be expected to result in saliuresis and water reabsorption in TIH patients. This study raises the possibility that UEV analysis may be of diagnostic utility in less clear-cut cases of thiazide-associated hyponatremia, and may help to identify patients at risk for TIH before thiazide initiation.

Impact of hydration status on haemodynamics, effects of acute blood pressure-lowering treatment, and prognosis after stroke.

AIMS: Although high blood pressure (BP) is common in acute stroke and associated with poor outcome, the Efficacy of Nitric Oxide in Stroke (ENOS) trial showed no beneficial effect of antihypertensive treatment in this situation. Antihypertensive agents have accentuated effects in dehydrated patients. We assessed the impact of dehydration on haemodynamics, the effects of antihypertensive treatment, and prognosis in the ENOS trial. METHODS: ENOS randomized 4011 patients with acute stroke and raised systolic BP to a glyceryl trinitrate (GTN) patch or no GTN patch, and to continue or to stop existing antihypertensive treatment within 48 h of onset. The primary outcome was functional outcome (modified Rankin Scale, mRS) at day 90. Blood markers of dehydration at baseline were collected at two sites (n = 310) and their relationship with haemodynamics and outcome was assessed. RESULTS: There were no significant associations between dehydration markers and fall in blood pressure from baseline to day 1, and no significant interaction with allocated treatment. Overall, increasing urea was associated with an unfavourable shift in mRS [odds ratio 3.43, 95% confidence interval (CI) 1.42, 8.32; P = 0.006] and increased risk of death at day 90 (hazard ratio 4.55, 95% CI 1.51, 13.66; P = 0.007). CONCLUSIONS: Blood pressure-lowering treatment was safe in dehydrated patients, with no precipitous changes in BP, thus supporting its use in acute stroke prior to blood markers of dehydration becoming available. Increased baseline urea was associated with poor prognosis after stroke.

A randomized controlled crossover trial evaluating differential responses to antihypertensive drugs (used as mono- or dual therapy) on the basis of ethnicity: The comparIsoN oF Optimal Hypertension RegiMens; part of the Ancestry Informative Markers in HYpertension program-AIM-HY INFORM trial.

BACKGROUND: Ethnicity, along with a variety of genetic and environmental factors, is thought to influence the efficacy of antihypertensive therapies. Current UK guidelines use a "black versus white" approach; in doing so, they ignore the United Kingdom's largest ethnic minority: Asians from South Asia. STUDY DESIGN: The primary purpose of the AIM-HY INFORM trial is to identify potential differences in response to antihypertensive drugs used as mono- or dual therapy on the basis of self-defined ethnicity. A multicenter, prospective, open-label, randomized study with 2 parallel, independent trial arms (mono- and dual therapy), AIM-HY INFORM plans to enroll a total of 1,320 patients from across the United Kingdom. Those receiving monotherapy (n = 660) will enter a 3-treatment (amlodipine 10 mg od; lisinopril 20 mg od; chlorthalidone 25 mg od), 3-period crossover, lasting 24 weeks, whereas those receiving dual therapy (n = 660) will enter a 4-treatment (amlodipine 5 mg od and lisinopril 20 mg od; amlodipine 5 mg od and chlorthalidone 25 mg od; lisinopril 20 mg od and chlorthalidone 25 mg od; amiloride 10 mg od and chlorthalidone 25 mg od), 4-period crossover, lasting 32 weeks. Equal numbers of 3 ethnic groups (white, black/black British, and Asian/Asian British) will ultimately be recruited to each of the trial arms (ie, 220 participants per ethnic group per arm). Seated, automated, unattended, office, systolic blood pressure measured 8 weeks after each treatment period begins will serve as the primary outcome measure. CONCLUSION: AIM-HY INFORM is a prospective, open-label, randomized trial which aims to evaluate first- and second-line antihypertensive therapies for multiethnic populations.

Clinical and Molecular Features of Thiazide-Induced Hyponatremia.

PURPOSE OF REVIEW: Hypertension affects more than 30% of the world's adult population and thiazide (and thiazide-like) diuretics are amongst the most widely used, effective, and least costly treatments available, with all-cause mortality benefits equivalent to angiotensin-converting enzyme inhibitors or calcium channel antagonists. A minority of patients develop thiazide-induced hyponatremia (TIH) and this is largely unpredictable at the point of thiazide prescription. In some cases, TIH can cause debilitating symptoms and require hospital admission. Although TIH affects only a minority of patients exposed to thiazides, the high prevalence of hypertension leads to TIH being the most common cause of drug-induced hyponatremia requiring hospital admission in the UK. This review examines current clinical and scientific understanding of TIH. Consideration is given to demographic associations, limitations of current electrolyte monitoring regimens, clinical presentation, the phenotype evident on routine clinical blood and urine tests as well as more extensive analyses of blood and urine in research settings, recent genetic associations with TIH, and thoughts on management of the condition. RECENT FINDINGS: Recent genetic and phenotyping analysis has suggested that prostaglandin E2 pathways in the collecting duct may have a role in the development of TIH in a subgroup of patients. Greater understanding of the molecular pathophysiology of TIH raises the prospect of pre-prescription TIH risk profiling and may offer novel insights into how TIH may be avoided, prevented and treated. The rising prevalence of hypertension and the widespread use of thiazides mean that further understanding of TIH will continue to be a pressing issue for patients, physicians, and scientists alike for the foreseeable future.