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Fluoroquinolones, a popular antibiotic class that inhibits nucleic acid synthesis of bacteria by disrupting the activity of the enzyme's topoisomerase IV and DNA gyrase, are used to treat bacterial infections. However, the widespread use of these drugs has allowed for the development of microbial resistance in recent years. Quinolones also have many clinically relevant side effects, including psychosis, confusion, seizures, headaches, dizziness, and nausea. Common side effects include tendinitis, myopathy, depression, and fatigue. Cardiovascular side effects include increased risk of aortic aneurysm, aortic dissection, and QT interval prolongation. Overall, quinolones can be an effective choice for treating bacterial infections. Still, the side effect profile and decreased efficacy secondary to microbial resistance no longer make the quinolone class an ideal choice for many types of infection. A better understanding of the role of quinolone-mediated or neurological damage, cardiovascular impairment, and musculoskeletal involvement is imperative to determine the risks/benefits for the clinician.
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Duchenne muscular dystrophy (DMD) is one of the most prevalent X-linked inherited neuromuscular disorders, with an estimated incidence between 1 in 3500 and 5000 live male births. The median life expectancy at birth is around 30 years due to a rapid and severe disease progression. Currently, there is no cure for DMD, and the standard of care is mainly palliative therapy and glucocorticoids to mitigate symptoms and improve quality of life. Recent advances in phosphorodiamidate morpholino antisense oligonucleotide (PMO) technology has proven optimistic in providing a disease-modifying therapy rather than a palliative treatment option through correcting the primary genetic defect of DMD by exon skipping. However, as a result of the high variance in mutations of the dystrophin gene causing DMD, it has been challenging to tailor an effective therapy in most patients. Viltolarsen is effective in 8% of patients and accurately skips exon 53, reestablishing the reading frame and producing a functional form of dystrophin and milder disease phenotype. Results of recently concluded preclinical and clinical trials show significantly increased dystrophin protein expression, no severe adverse effects, and stabilization of motor function. In summary, viltolarsen has provided hope for those working toward giving patients a safe and viable treatment option for managing DMD. This review summarizes an overview of the presentation, pathophysiology, genetics, and current treatment guidelines of DMD, pharmacological profile of viltolarsen, and a summary of the safety and efficacy with additional insights using recent clinical trial data.
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Distrofia Muscular de Duchenne , Recém-Nascido , Humanos , Masculino , Distrofia Muscular de Duchenne/tratamento farmacológico , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/metabolismo , Distrofina/genética , Distrofina/metabolismo , Qualidade de Vida , Oligonucleotídeos/uso terapêuticoRESUMO
Hyperkalemia has been defined as a condition where a serum potassium level is >5.5 mmol/l. It is associated with fatal dysrhythmias and muscular dysfunction. Certain medical conditions, such as chronic kidney disease (CKD), diabetes mellitus, and others, can lead to hyperkalemia. Many of the signs of hyperkalemia are nonspecific. A history and physical examination can be beneficial in the diagnosis of the condition. In this regard, certain characteristic electrocardiogram findings are associated with hyperkalemia along with laboratory potassium levels. In acute and potentially lethal conditions, hyperkalemia treatments include glucose and insulin, bicarbonate, calcium gluconate, beta-2 agonists, hyperventilation, and dialysis. There are several drugs, both old and new, that can additionally aid in the reduction of serum potassium levels. The present investigation evaluated some of these different drugs, including sodium polystyrene sulfonate (SPS), sodium zirconium cyclosilicate (SZC), and patiromer. These drugs each have increased selectivity for potassium and work primarily in the gastrointestinal (GI) tract. Each of these medications has unique benefits and contraindications. Clinicians must be aware of these medications when managing patients with hyperkalemia.
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AIMS: To assess the real-world evidence for flash glucose monitoring (Abbott FreeStyle Libre) for children with type 1 diabetes in terms of glucose control, secondary healthcare resources and costs. RESEARCH DESIGN AND METHODS: We conducted a controlled before and after study (approximately 12 months before and after) using routinely collected health record data on children who start using flash monitors and a control population of children with self-monitoring of blood glucose (SMBG). Our population-based sample of eligible individuals using flash monitoring (n=114) and controls (n=80) aged between 4 and 18 years was drawn from four paediatric diabetes clinics (secondary care) in the South West England. Outcome measures included: glycated hemoglobin (HbA1c), frequency of BG tests; frequency of sensor scans; time in recommended glucose range; short-term complications (hypoglycemia, diabetic ketoacidosis and related illness resulting in investigation) and secondary care costs. RESULTS: After adjustment for age, time since diagnosis, deprivation and the test modality (point of care or laboratory), the mean HbA1c reading for controls was 61.2 (mmol/mol) for the period before and 63.9 after. For individuals using flash monitoring, the adjusted mean HbA1c reading was 64.6 for the period before implementation and 63.8 after. Rates of short-term complications were low across all groups in the study. Whereas the 'after' flash monitoring group had substantially higher incremental costs (+£703 vs the flash monitoring 'before' comparison and +£841 vs contemporaneous SMBG controls), these cost differences were driven by primary care prescribing (sensor costs). CONCLUSIONS: There was some indication that flash monitoring might help young people improve the control of their diabetes but for our sample, the difference between finger-prick testing and flash monitoring was not clinically significant (HbA1c improvement <5 mmol/mol). Given the pace of technological change within diabetes, research efforts should now facilitate the real-time analysis of long-term routine data on flash and continuous glucose monitors.
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Glicemia , Diabetes Mellitus Tipo 1 , Humanos , Criança , Adolescente , Pré-Escolar , Automonitorização da Glicemia , Hemoglobinas Glicadas , GlucoseRESUMO
Bupropion had been in use since the late 1980s as an unconventional treatment for depression. Unlike other antidepressants, bupropion has no serotonergic activity and inhibits the reuptake of norepinephrine and dopamine. The drug has been used to treat depression, Attention Deficit Hyperactivity Disorder (ADHD), and smoking cessation. This investigation reviews the pharmacokinetic and pharmacodynamic effects of bupropion and its mechanisms of action and interactions with other drugs. We evaluated the efficacy of major on and off-label uses of bupropion, focusing on the indications, benefits, and adverse effects. Our review demonstrates that bupropion is superior to placebo and non-inferior to SSRIs such as escitalopram in treating major depressive disorder. More research is needed to determine positive patient-centered outcomes such as increases in quality of life. In the case of ADHD, the evidence for efficacy is mixed with poorly conducted randomized clinical trials, small sample sizes, and a lack of long-term assessments. The same is true in the case of bipolar disorder in which there is still limited and controversial data available on bupropion's safety and efficacy. In the case of smoking cessation, bupropion is found to be an effective anti-smoking drug with synergistic benefits when used as a combination therapy. We conclude that bupropion has the potential to provide benefit for a subset of patients who do not tolerate other typical antidepressants or anti-smoking therapies or for those whose treatment goals align with bupropion's unique side effect profile, such as smokers who wish to quit and lose weight. Additional research is needed to determine the drug's full clinical potential, particularly in the areas of adolescent depression and combination therapy with varenicline or dextromethorphan. Clinicians should use this review to understand the varied uses of the drug and identify the situations and patient populations in which bupropion can lend its greatest benefit.
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OBJECTIVES: Flash glucose monitoring for patients with T1 diabetes avoids frequent painful finger-prick testing, thus potentially improving frequency of glucose self-monitoring. Our study aimed to explore experiences of young people using Freestyle Libre sensors and their parents, and to identify benefits and challenges to National Health Service (NHS) staff of its adoption in their care provision. PARTICIPANTS: Young people with T1 diabetes, their parents and healthcare professionals were interviewed between February and December 2021. Participants were recruited via social media and through NHS diabetes clinic staff. DESIGN: Semistructured interviews were conducted online and analysed using thematic methods. Staff themes were mapped onto normalisation process theory (NPT) constructs. RESULTS: Thirty-four participants were interviewed: 10 young people, 14 parents and 10 healthcare professionals. Young people reported that life was much easier since changing to flash glucose monitoring, increasing confidence and independence to manage their condition. Parents' quality of life improved and they appreciated access to real-time data. Using the NPT concepts to understand how technology was integrated into routine care proved useful; health professionals were very enthusiastic about flash glucose monitoring and coped with the extra data load to facilitate more tailored patient support within and between clinic visits. CONCLUSION: This technology empowers young people and their parents to understand their diabetes adherence more completely; to feel more confident about adjusting their own care between clinic appointments; and provides an improved interactive experience in clinic. Healthcare teams appear committed to delivering improving technologies, acknowledging the challenge for them to assimilate new information required to provide expert advice.
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Diabetes Mellitus Tipo 1 , Humanos , Adolescente , Diabetes Mellitus Tipo 1/terapia , Glicemia , Qualidade de Vida , Automonitorização da Glicemia , Medicina Estatal , PaisRESUMO
Collaboration on annual training between a medical school and a National Guard Special Forces Group can be accomplished with great benefit to both parties. The authors describe the involvement by the Edward Via College of Osteopathic Medicine in providing training for the 20th Special Forces Group Medical Sergeants of the Alabama Army National Guard.
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Militares , Faculdades de Medicina , Competência Clínica , Escolaridade , Humanos , Militares/educaçãoRESUMO
The use of antimalarial drugs is an effective strategy in the fight against malaria. However, selection of drug resistant parasites is a constant threat to the continued use of this approach. Antimalarial drugs are used not only to treat infections but also as part of population-level strategies to reduce malaria transmission toward elimination. While there is strong evidence that the ongoing use of antimalarial drugs increases the risk of the emergence and spread of drug-resistant parasites, it is less clear how population-level use of drug-based interventions like seasonal malaria chemoprevention (SMC) or mass drug administration (MDA) may contribute to drug resistance or loss of drug efficacy. Critical to sustained use of drug-based strategies for reducing the burden of malaria is the surveillance of population-level signals related to transmission reduction and resistance selection. Here we focus on Plasmodium falciparum and discuss the genetic signatures of a parasite population that are correlated with changes in transmission and related to drug pressure and resistance as a result of drug use. We review the evidence for MDA and SMC contributing to malaria burden reduction and drug resistance selection and examine the use and impact of these interventions in Senegal. Throughout we consider best strategies for ongoing surveillance of both population and resistance signals in the context of different parasite population parameters. Finally, we propose a roadmap for ongoing surveillance during population-level drug-based interventions to reduce the global malaria burden.
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Antimaláricos , Malária Falciparum , Malária , Preparações Farmacêuticas , Antimaláricos/farmacologia , Antimaláricos/uso terapêutico , Resistência a Medicamentos/genética , Humanos , Malária/tratamento farmacológico , Malária Falciparum/tratamento farmacológico , Malária Falciparum/epidemiologia , Malária Falciparum/prevenção & controle , Plasmodium falciparum/genéticaRESUMO
Distribution of long-lasting insecticide-treated nets (LLINs), passive detection and treatment with artemisinin-based combination therapy (ACT), and intermittent preventive treatment in pregnancy (IPTp) are the mainstay malaria control measures of Guinea-Bissau's national control programme. This study aimed to estimate the prevalence of Plasmodium falciparum on Bubaque, the most populous island of the country's remote Bijagos archipelago. A cross-sectional survey was performed at the start of the rainy season in August 2017. Participants were recruited using systematic random sampling in a two-stage stratified cluster design. Malaria parasitemia was detected using rapid diagnostic tests (RDTs) and quantitative PCR (qPCR). Data on housing, education, larval source management, socioeconomic status, anemia, and malaria preventive measures were collected. Multivariable logistic regression models were constructed to identify associations with P. falciparum infection. Four hundred four persons (aged 6 months-79 years, median 17 years) were enrolled in the study. The prevalence of P. falciparum parasitemia was 5.8% by RDT (95% CI: 3.55-9.33) and 16.9% by qPCR (95% CI: 13.09-21.71). The prevalence of anemia was 74.3% (95% CI: 69.04-78.85) as defined by the WHO criteria. All sampled houses were found to have open eaves; 99.5% of the surveyed population reported sleeping under a bednet (95% CI: 97.8-99.9). Although reported LLIN use is high, there remains an appreciable prevalence of malaria, suggesting that transmission is ongoing and further tools are required to reduce the burden of the disease.
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Malária Falciparum/epidemiologia , Controle de Mosquitos/métodos , Parasitemia/epidemiologia , Adolescente , Adulto , Idoso , Anemia/epidemiologia , Anemia/parasitologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Guiné-Bissau/epidemiologia , Humanos , Lactente , Mosquiteiros Tratados com Inseticida/provisão & distribuição , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Plasmodium falciparum/genética , População , Prevalência , Adulto JovemRESUMO
Dermatofibrosarcoma protuberans (DFSP) is a low-grade, fibroblastic tumor that is rarely seen in the breast with only a few cases reported in the literature. DFSP poses a diagnostic challenge as there is significant cytomorphological overlap with other spindle cell lesions. We report a case of a 42-year-old female who presented with a nodule in the right breast. Histology revealed a hypercellular lesion composed of spindle cells infiltrating the fat. A diagnosis of spindle cell lipoma was made. However, two years later, the patient developed a recurrent mass in the right breast that was histologically consistent with DFSP with a predominant myxoid stroma obscuring the characteristic storiform architecture with a focal component of giant cell fibroblastoma. A careful histomorphological examination is warranted as DFSP tends to recur if not completely excised.
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Objectives Prader-Willi Syndrome (PWS) is characterised by hyperphagia often leading to obesity; a known risk factor for insulin resistance and type 2 (T2) diabetes. We present a prepubertal girl with PWS who developed diabetes. Case presentation Our case was diagnosed with PWS in infancy following investigation for profound central hypotonia and feeding difficulties. She commenced growth hormone (GH) aged 8 years for short stature and treatment improved linear growth. At age 12 years, she presented with polydipsia, polyuria and vulvovaginitis. She was overweight (BMI SDS +1.43). Diabetes was diagnosed (Blood glucose = 24.2 mmol/L, HbA1c = 121 mmol/mol or 13.2%). She was not acidotic and had negative blood ketones. Autoantibodies typical of type 1 diabetes were negative. She was initially treated with basal bolus insulin regime. GH was discontinued 3 months later due to concerns regarding GH-induced insulin resistance. Off GH, insulin requirements reduced to zero, allowing Metformin monotherapy. However off GH, she reported significant lethargy with static growth and increased weight. Combinations of Metformin with differing insulin regimes did not improve glucose levels. Liraglutide (GLP-1 agonist) and Metformin did not improve glucose levels nor her weight. Liraglutide and Empaglifozin (SGLT-2 inhibitor) therapy used in combination were well tolerated and demonstrated rapid normalisation of blood glucose and improvement in her HbA1c to within target (48 mmol/mol) which was sustained after 6 months of treatment. Conclusions Newer treatments for type 2 diabetes (e. g. GLP-1 agonists or SGLT-2 inhibitors) offer potential treatment options for those with diabetes and PWS when conventional treatments are ineffective.
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Compostos Benzidrílicos/administração & dosagem , Diabetes Mellitus/tratamento farmacológico , Glucosídeos/administração & dosagem , Liraglutida/administração & dosagem , Síndrome de Prader-Willi/tratamento farmacológico , Adolescente , Compostos Benzidrílicos/farmacologia , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Criança , Diabetes Mellitus/sangue , Diabetes Mellitus/etiologia , Quimioterapia Combinada , Feminino , Peptídeo 1 Semelhante ao Glucagon/agonistas , Glucosídeos/farmacologia , Humanos , Liraglutida/farmacologia , Síndrome de Prader-Willi/sangue , Síndrome de Prader-Willi/complicações , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Resultado do TratamentoRESUMO
BACKGROUND: Fluid overload in patients undergoing hemodialysis contributes to cardiovascular morbidity and mortality. There is a global trend to lower dialysate sodium with the goal of reducing fluid overload. METHODS: To investigate whether lower dialysate sodium during hemodialysis reduces left ventricular mass, we conducted a randomized trial in which patients received either low-sodium dialysate (135 mM) or conventional dialysate (140 mM) for 12 months. We included participants who were aged >18 years old, had a predialysis serum sodium ≥135 mM, and were receiving hemodialysis at home or a self-care satellite facility. Exclusion criteria included hemodialysis frequency >3.5 times per week and use of sodium profiling or hemodiafiltration. The main outcome was left ventricular mass index by cardiac magnetic resonance imaging. RESULTS: The 99 participants had a median age of 51 years old; 67 were men, 31 had diabetes mellitus, and 59 had left ventricular hypertrophy. Over 12 months of follow-up, relative to control, a dialysate sodium concentration of 135 mmol/L did not change the left ventricular mass index, despite significant reductions at 6 and 12 months in interdialytic weight gain, in extracellular fluid volume, and in plasma B-type natriuretic peptide concentration (ratio of intervention to control). The intervention increased intradialytic hypotension (odds ratio [OR], 7.5; 95% confidence interval [95% CI], 1.1 to 49.8 at 6 months and OR, 3.6; 95% CI, 0.5 to 28.8 at 12 months). Five participants in the intervention arm could not complete the trial because of hypotension. We found no effect on health-related quality of life measures, perceived thirst or xerostomia, or dietary sodium intake. CONCLUSIONS: Dialysate sodium of 135 mmol/L did not reduce left ventricular mass relative to control, despite improving fluid status. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: The Australian New Zealand Clinical Trials Registry, ACTRN12611000975998.
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Ventrículos do Coração/efeitos dos fármacos , Soluções para Hemodiálise/farmacologia , Hemodiálise no Domicílio/métodos , Hipertrofia Ventricular Esquerda/patologia , Diálise Renal/efeitos adversos , Sódio/administração & dosagem , Idoso , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/terapia , Feminino , Hemodiálise no Domicílio/efeitos adversos , Humanos , Hipertrofia Ventricular Esquerda/etiologia , Hipertrofia Ventricular Esquerda/prevenção & controle , Hipotensão/etiologia , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão/efeitos dos fármacos , Ambulatório Hospitalar , Autocuidado , Resultado do Tratamento , Equilíbrio Hidroeletrolítico , Desequilíbrio Hidroeletrolítico/etiologia , Desequilíbrio Hidroeletrolítico/prevenção & controleRESUMO
BACKGROUND: There is little published data investigating non-invasive cardiac output monitoring in the emergency department (ED). We assess here the accuracy of five non-invasive methods in detecting fluid responsiveness in the ED: (1) common carotid artery blood flow, (2) suprasternal aortic Doppler, (3) bioreactance, (4) plethysmography with digital vascular unloading method, and (5) inferior vena cava collapsibility index. Left ventricular outflow tract echocardiography derived velocity time integral is the reference standard. This follows an assessment of feasibility and repeatability of these methods in the same cohort of ED patients. METHODS: This is a prospective observational study of non-invasive methods for assessing fluid responsiveness in the ED. Participants were non-ventilated ED adult patients requiring intravenous fluid resuscitation. Sensitivity and specificity of each method in determining the fluid responsiveness status of participants is determined in comparison to the reference standard. RESULTS: Thirty-three patient data sets were included for analysis. The specificity and sensitivity to detect fluid responders was 46.2 and 45% for common carotid artery blood flow (CCABF), 61.5 and 63.2% for suprasternal artery Doppler (SSAD), 46.2 and 50% for bioreactance, 50 and 41.2% for plethysmography vascular unloading technique (PVUT), and 63.6 and 47.4% for inferior vena cava collapsibility index (IVCCI), respectively. Analysis of agreement with Cohen's Kappa - 0.08 for CCABF, 0.24 for SSAD, - 0.04 for bioreactance, - 0.08 for PVUT, and 0.1 for IVCCI. CONCLUSION: In this study, non-invasive methods were not found to reliably identify fluid responders. Non-invasive methods of identifying fluid responders are likely to play a key role in improving patient outcome in the ED in fluid depleted states such as sepsis. These results have implications for future studies assessing the accuracy of such methods.
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Débito Cardíaco/fisiologia , Artérias Carótidas/diagnóstico por imagem , Serviço Hospitalar de Emergência , Monitorização Fisiológica/métodos , Ressuscitação/métodos , Sepse/fisiopatologia , Veia Cava Inferior/diagnóstico por imagem , Feminino , Hidratação/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Reprodutibilidade dos Testes , Sepse/diagnóstico , Ultrassonografia Doppler/métodosRESUMO
Proposed interventions for eliminating drug-resistant Plasmodium falciparum malaria include the targeting of asymptomatic carriers through screening and treatment. We report on the diagnostic performance of the recently developed ultrasensitive rapid diagnostic test (uRDT) compared with screening with conventional RDTs (cRDT) and polymerase chain reaction (PCR) under field conditions in Cambodia in a total of 2,729 individuals. The P. falciparum positivity by quantitative PCR (qPCR) was 3.8% (26/678) in those screened during active case detection and 0.5% (10/2,051) in the cross-sectional survey. Compared with qPCR, the sensitivity of the uRDTs was 53.8% (95% CI: 33.4-73.4%) when used in active case detection and 60.0% (95% CI: 26.2-87.8%) in the cross-sectional survey. The uRDTs did not show a significant improvement in diagnostic performance over cRDTs when used for active case detection and for a malaria prevalence survey in the context of this low-transmission setting.
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Testes Diagnósticos de Rotina/métodos , Testes Diagnósticos de Rotina/normas , Malária Falciparum/diagnóstico , Plasmodium falciparum , Camboja/epidemiologia , Humanos , Malária Falciparum/epidemiologia , Reação em Cadeia da Polimerase/métodos , Sensibilidade e Especificidade , Tailândia/epidemiologia , Fatores de TempoRESUMO
BACKGROUND: People who have chronic kidney disease (CKD) have important changes to bone structure, strength, and metabolism. Children experience bone deformity, pain, and delayed or impaired growth. Adults experience limb and vertebral fractures, avascular necrosis, and pain. The fracture risk after kidney transplantation is four times that of the general population and is related to Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD) occurring with end-stage kidney failure, steroid-induced bone loss, and persistent hyperparathyroidism after transplantation. Fractures may reduce quality of life and lead to being unable to work or contribute to community roles and responsibilities. Earlier versions of this review have found low certainty evidence for effects of treatment. This is an update of a review first published in 2005 and updated in 2007. OBJECTIVES: This review update evaluates the benefits and harms of interventions for preventing bone disease following kidney transplantation. SEARCH METHODS: We searched the Cochrane Kidney and Transplant Register of Studies up to 16 May 2019 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA: RCTs and quasi-RCTs evaluating treatments for bone disease among kidney transplant recipients of any age were eligible. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial risks of bias and extracted data. Statistical analyses were performed using random effects meta-analysis. The risk estimates were expressed as a risk ratio (RR) for dichotomous variables and mean difference (MD) for continuous outcomes together with the corresponding 95% confidence interval (CI). The primary efficacy outcome was bone fracture. The primary safety outcome was acute graft rejection. Secondary outcomes included death (all cause and cardiovascular), myocardial infarction, stroke, musculoskeletal disorders (e.g. skeletal deformity, bone pain), graft loss, nausea, hyper- or hypocalcaemia, kidney function, serum parathyroid hormone (PTH), and bone mineral density (BMD). MAIN RESULTS: In this 2019 update, 65 studies (involving 3598 participants) were eligible; 45 studies contributed data to our meta-analyses (2698 participants). Treatments included bisphosphonates, vitamin D compounds, teriparatide, denosumab, cinacalcet, parathyroidectomy, and calcitonin. Median duration of follow-up was 12 months. Forty-three studies evaluated bone density or bone-related biomarkers, with more recent studies evaluating proteinuria and hyperparathyroidism. Bisphosphonate therapy was usually commenced in the perioperative transplantation period (within 3 weeks) and regardless of BMD. Risks of bias were generally high or unclear leading to lower certainty in the results. A single study reported outcomes among 60 children and adolescents. Studies were not designed to measure treatment effects on fracture, death or cardiovascular outcomes, or graft loss.Compared to placebo, bisphosphonate therapy administered over 12 months in transplant recipients may prevent fracture (RR 0.62, 95% CI 0.38 to 1.01; low certainty evidence) although the 95% CI included the possibility that bisphosphonate therapy might make little or no difference. Fracture events were principally vertebral fractures identified during routine radiographic surveillance. It was uncertain whether any other drug class decreased fracture (low or very low certainty evidence). It was uncertain whether interventions for bone disease in kidney transplantation reduce all-cause or cardiovascular death, myocardial infarction or stroke, or graft loss in very low certainty evidence. Bisphosphonate therapy may decrease acute graft rejection (RR 0.70, 95% CI 0.55 to 0.89; low certainty evidence), while it is uncertain whether any other treatment impacts graft rejection (very low certainty evidence). Bisphosphonate therapy may reduce bone pain (RR 0.20, 95% CI 0.04 to 0.93; very low certainty evidence), while it was very uncertain whether bisphosphonates prevent spinal deformity or avascular bone necrosis (very low certainty evidence). Bisphosphonates may increase to risk of hypocalcaemia (RR 5.59, 95% CI 1.00 to 31.06; low certainty evidence). It was uncertain whether vitamin D compounds had any effect on skeletal, cardiovascular, death, or transplant function outcomes (very low certainty or absence of evidence). Evidence for the benefits and harms of all other treatments was of very low certainty. Evidence for children and young adolescents was sparse. AUTHORS' CONCLUSIONS: Bisphosphonate therapy may reduce fracture and bone pain after kidney transplantation, however low certainty in the evidence indicates it is possible that treatment may make little or no difference. It is uncertain whether bisphosphonate therapy or other bone treatments prevent other skeletal complications after kidney transplantation, including spinal deformity or avascular bone necrosis. The effects of bone treatment for children and adolescents after kidney transplantation are very uncertain.
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OBJECTIVES: Bedside ultrasound is increasingly being used to guide fluid management in shocked patients. Little data exist on the inter-rater reliability of techniques used, especially when performed by nonexpert trainee doctors. The primary aim of this study is to measure the inter-rater reliability of five ultrasound techniques commonly used to guide fluid management: inferior vena cava collapsibility index (IVCCI), transthoracic echocardiography (TTE)-derived stroke volumes, ultrasound cardiac output monitor (USCOM) derived stroke volume and carotid artery blood flow and corrected flow time measurements. METHODS: Two Royal College of Emergency Medicine level one ultrasound-certified emergency medicine trainees performed paired ultrasound measurements on 31 healthy nonpatient volunteers. Inter-rater reliability was assessed through three indices: interclass correlation coefficient (ICC), limits of agreements (LOAs) derived from Band-Altman plots and the proportion of paired scans with absolute differences of less that 15% (defined as agreement). RESULTS: TTE-derived measurements performed the best overall, with an LOA of 22%, an ICC of 0.55 and an agreement of 80%. USCOM also performed well, with an LOA of 33%, an ICC of 0.68 and an agreement of 58%. IVCCI and carotid artery-derived measurements performed poorly across all indices. CONCLUSION: TTE-derived measurements showed the highest level of inter-rater reliability and can thus be expected to provide reliable measures over time with different sonographer clinicians. USCOM interobserver reliability was also adequate for clinical use. However, on the basis of inter-reliability measures, IVCCI and carotid artery measurements were found to be inadequate for clinical use.
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Competência Clínica , Ecocardiografia/métodos , Educação de Pós-Graduação em Medicina/métodos , Monitorização Hemodinâmica/métodos , Hospitais de Ensino/organização & administração , Testes Imediatos , Adulto , Feminino , Voluntários Saudáveis , Humanos , Masculino , Variações Dependentes do Observador , Medição de Risco , Análise e Desempenho de Tarefas , Reino UnidoRESUMO
Aims. To examine the outcome of potential live kidney donors (PLKD) assessment program at Christchurch Hospital and, also, to review findings of Computed Tomographic (CT) renal angiograms that led to exclusion in the surgical assessment. Methods. Clinical data was obtained from the database of kidney transplants, Proton. Radiological investigations were reviewed using the hospital database, Éclair. The transplant coordinator was interviewed to clarify information about PLKD who did not proceed to surgery, and a consultant radiologist was interviewed to explain unfavorable findings on CT renal angiograms. Results. 162 PLKD were identified during the period January 04-June 08. Of those, 65 (40%) proceeded to have nephrectomy, 15 were accepted and planned to proceed to surgery, 13 were awaiting further assessment, and 69 (42.5%) did not proceed to nephrectomy. Of the 162 PLKD, 142 (88%) were directed donors. The proportion of altruistic PLKD who opted out was significantly higher than that of directed PLKD (45% versus 7%, P = 0.00004). Conclusions. This audit demonstrated a positive experience of live kidney donation at Christchurch Hospital. CT renal angiogram can potentially detect incidental or controversial pathologies in the kidney and the surrounding structures. Altruistic donation remains controversial with higher rates of opting out.
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After the publication of our paper Dunlop et al. "Rationale and design of the Sodium Lowering In Dialysate (SoLID) trial: a randomised controlled trial of low versus standard dialysate sodium concentration during hemodialysis for regression of left ventricular mass", we became aware of further data correlating left ventricular (LV) mass index at baseline and their corresponding mass at 12 months, using cardiac magnetic resonance imaging (MRI) in patients on hemodialysis. The original published sample size for the SoLID trial of 118 was a conservative estimate, calculated using analysis of covariance and a within person Pearson's correlation for LV mass index of 0.75. New data communicated to the SoLID trial group has resulted in re-calcuation of the sample size, based upon a within person Pearson's correlation of 0.8 but otherwise unchanged assumptions. As a result, the SoLID trial will now recruit 96 participants.
Assuntos
Soluções para Diálise/química , Projetos de Pesquisa , Tamanho da Amostra , Sódio/administração & dosagem , Ventrículos do Coração/patologia , Humanos , Imageamento por Ressonância Magnética , Tamanho do Órgão , Diálise RenalRESUMO
BACKGROUND: The Sodium Lowering in Dialysate (SoLID) trial is an ongoing a multi-center, prospective, randomised, single-blind (assessor), controlled, parallel assignment clinical trial, enrolling 96 home and self-care hemodialysis (HD) patients from 7 centers in New Zealand. The trial will evaluate the hypothesis that lower dialysate [Na+] during HD results in lower left ventricular (LV) mass. Since it's inception, observational evidence has suggested increased mortality risk with lower dialysate [Na+], possibly due to exacerbation of intra-dialytic hypotension and subsequent myocardial micro-injury. The Myocardial Micro-injury and Cardiac Remodeling Extension Study in the Sodium Lowering In Dialysate Trial (Mac-SoLID study) aims to determine whether lower dialysate [Na+] results in (i) increased levels of high-sensitivity Troponin T (hsTnT), a well-established marker of intra-dialytic myocardial micro-injury in HD populations, and (ii) increased fixed LV segmental wall motion abnormalities, a marker of recurrent myocardial stunning and micro-injury, and (iii) detrimental changes in LV geometry due to maladaptive homeostatic mechanisms. METHODS/DESIGN: The SoLID trial and the Mac-SoLID study are funded by the Health Research Council of New Zealand. Key exclusion criteria: patients who dialyse > 3.5 times per week, pre-dialysis serum sodium <135 mM, and maintenance haemodiafiltration. In addition, some medical conditions, treatments or participation in other dialysis trials that contraindicate the study intervention or confound its effects, will be exclusion criteria. The intervention and control groups will receive dialysate sodium 135 mM and 140 mM respectively, for 12 months. The primary outcome measure for the Mac-SOLID study is repeated measures of [hsTnT] at 0, 3, 6, 9, and 12 months. The secondary outcomes will be assessed using cardiac magnetic resonance imaging (MRI), and comprise LV segmental wall motion abnormality scores, LV mass to volume ratio and patterns of LV remodeling at 0 and 12 months. DISCUSSION: The Mac-SoLID study enhances and complements the SoLID trial. It tests whether potential gains in cardiovascular health (reduced LV mass) which low dialysate [Na+] is expected to deliver, are counteracted by deterioration in cardiovascular health through alternative mechanisms, namely repeated LV stunning and micro-injury. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry number: ACTRN12611000975998.