Valued Components of a Consultant Letter from Referring Physicians' Perspective: a Systematic Literature Synthesis.

BACKGROUND: Effective communication between the consultants and physicians form an integral foundation of effective and expert patient care. A broad review of the literature has not been undertaken to determine the components of a consultant's letter of most value to the referring physician. We aimed to identify the components of a consultant's letter preferred by referring physicians. METHODS: We searched Embase and MEDLINE (OVID) Medicine (EBM) Reviews and Cochrane Database of Systematic Reviews for English articles with no restriction on initial date to January 6, 2017. Articles containing letters from specialists to referring physicians regarding outpatient assessments with either an observational or experimental design were included. Studies were excluded if they pertained to communications from referring physicians to consultant specialists, or pertained to allied health professionals, inpatient documents, or opinion articles. We enumerated the frequencies with which three common themes were addressed, and the positive or negative nature of the comments. The three themes were the structure of consultant letters, their contents, and whether referring physicians and consultants shared a common opinion about the items. RESULTS: Eighteen articles were included in our synthesis. In 11 reports, 91% of respondents preferred structured formats. Other preferred structural features were problem lists and brevity (four reports each). The most preferred contents were oriented to insight: diagnosis, prognosis, and management plan (16/21 mentions in the top tertile). Data items such as history, physical examination, and medication lists were less important (1/23 mentions in the top tertile). Reports varied as to whether referring physicians and consultants shared common opinions about letter features. CONCLUSIONS: Referring physicians prefer brief, structured letters from consultants that feature diagnostic and prognostic opinions and management plans over unstructured letters that emphasize data elements such as detailed histories and medication lists. Whether these features improve outcomes is unknown.

Assessment of endothelin and copeptin as biomarkers for vasovagal syncope.

BACKGROUND: The diagnosis of vasovagal syncope continues to be difficult despite the use of accurate histories, tilt testing and implantable loop recorders. A circulating biomarker might be useful to facilitate diagnoses. Both endothelin-1 and vasopressin are increased during positive tilt tests resulting in syncope. Copeptin is a stable cleavage product of vasopressin formation. We conducted a pilot study to assess the utility of endothelin-1 and copeptin as circulating biomarkers of vasovagal syncope. METHODS: Three populations were studied: syncope patients, epilepsy patients and controls. Vasovagal syncope diagnosis was ascertained with the Calgary Syncope Score and epilepsy diagnosis was confirmed with EEG. Plasma levels of endothelin-1 were measured using by ELISA and copeptin levels were determined using an EIA kit. RESULTS: Asymptomatic control subjects had mean age 35 ± 11 years (7/22 male); epileptic subjects had mean age 32 ± 7 years (4/15 male); and syncope subjects had mean age 33 ± 16 years (4 of 21 male). Circulating plasma levels of endothelin-1 and copeptin were no different among the three groups. Mean concentrations of endothelin-1 were as follows: syncope, 23 ± 32 pg/mL; controls, 21 ± 17 pg/mL; and epileptics, 18 ± 12 pg/mL. Mean concentrations of copeptin were as follows: syncope, 1·29 ± 0·79 ng/mL; controls, 1·25 ± 0·79 ng/mL; and seizures, 1·23 ± 0·45 ng/mL. There were no significant correlations between syncope frequency and copeptin or endothelin-1 levels. CONCLUSION: Circulating plasma endothelin-1 and copeptin levels are not significantly different among populations of controls, syncope patients and seizure patients.

The effect of chronic candesartan therapy on the metabolic profile and renal tissue cytokine levels in the obese Zucker rat.

The effect of candesartan, an angiotensin-II type-1 receptor antagonist, on the metabolic profile and renal inflammation is unclear. We evaluated this relationship by feeding male lean (LZ) and obese (OZ) Zucker rats chow or chow with candesartan (23.5 mg/kg . diet) for 14 weeks (n = 6-8/treatment/body type). Candesartan reduced serum triglycerides, plasma creatinine, urine albumin, and renal cortical collagen and glycogen deposition in the OZ. An ELISA-based cytokine array revealed that candesartan normalized elevated renal interleukin (IL) 1-beta and monocyte chemoattractant protein-1 (MCP-1) levels in OZ. Nonetheless, candesartan impaired glucose tolerance, and did not lower blood insulin or glucose levels. Moreover, renal IL-1alpha, -2, -4, -6 and -10 tumor necrosis factor-alpha, interferon-gamma, were significantly reduced in OZ relative to LZ, and increased by candesartan. Furthermore, candesartan increased growth-regulated oncogene, transforming growth factor-beta1 and IL-18 in OZ kidneys to a level higher than LZ or untreated OZ. Candesartan did not affect renal cytokine levels in LZ. Overall, candesartan attenuated renal disease and improved renal function in OZ, despite mixed effects on metabolic factors and cytokines. Reduced plasma triglycerides and/or renal MCP-1 and IL-1beta may have had a role in this protection. However, these effects were clearly independent of any improvement in glucose tolerance.

Abundance of the Na-K-2Cl cotransporter NKCC2 is increased by high-fat feeding in Fischer 344 X Brown Norway (F1) rats.

Insulin resistance is associated with hypertension by mechanisms likely involving the kidney. To determine how the major apical sodium transporter of the thick ascending limb, the bumetanide-sensitive Na-K-2Cl cotransporter (NKCC2) is regulated by high-fat feeding, we treated young male, Fischer 344 X Brown Norway (F344BN) rats for 8 wk with diets containing either normal (NF, 4%) or high (HF, 36%) fat, by weight, primarily as lard. HF-fed rats had impaired glucose tolerance, increased urine excretion of 8-isoprostane (a marker of oxidative stress), increased protein levels for NKCC2 (50-125%) and the renal outer medullary potassium channel (106%), as well as increased natriuretic response to furosemide (20-40%). To test the role of oxidative stress in this response, in study 2, rats were fed the NF or HF diet plus plain drinking water, or water containing N(G)-nitro-l-arginine methyl ester (l-NAME), a nitric oxide synthase inhibitor (100 mg/l), or tempol, a superoxide dismutase mimetic (1 mmol/l). The combination of tempol with HF nullified the increase in medullary NKCC2, while l-NAME with HF led to the highest expression of medullary NKCC2 (to 498% of NF mean). However, neither of these drugs dramatically affected the elevated natriuretic response to furosemide with HF. Finally, l-NAME led to a marked increase in blood pressure (measured by radiotelemetry), which was significantly enhanced with HF. Mean arterial blood pressure at 7 wk was as follows (mmHg): NF, 100 +/- 2; NF plus l-NAME, 122 +/- 3; and HF plus l-NAME, 131 +/- 2. Overall, HF feeding increased the abundance of NKCC2. Inappropriately high sodium reabsorption in the thick ascending limb via NKCC2 may contribute to hypertension with insulin resistance.

Candesartan Differentially Regulates Epithelial Sodium Channel in Cortex Versus Medulla of Streptozotocin-Induced Diabetic Rats.

Diabetes is associated with an activated renal renin-angiotensin-aldosterone system (RAAS) and it was shown that streptozotocin (STZ)-induced diabetic rats had increased whole kidney protein levels of the epithelial sodium channel subunits (α-, ß- and γ-ENaC). However, the role of the RAAS on the regional, i.e., cortical versus medullary, regulation of ENaC is unclear. Male Sprague-Dawley rats were injected with STZ (intravenous, 65 mg/kg·bw, n=12/group). After 14 days, half of them received drinking water with candesartan (2 mg/kg·bw/day), an angiotensin-II type-1 receptor (AT1R) antagonist, for one week. In the medulla, i.e., inner stripe of the outer medulla (ISOM), base and/or tip of the inner medulla, immunoblotting revealed increased protein abundances of α1 Na-K-ATPase and ENaC subunits with diabetes (200-600% of controls), which were not reversed by candesartan. In fact, candesartan increased all ENaC subunits and α1 Na-K-ATPase in the ISOM and/or base in control rats. In contrast, in the cortex, diabetes did not increase these proteins. However, candesartan reduced cortical ß- and γ-ENaC regardless of diabetic state. In summary, diabetes-induced increases in ENaC were seen preferentially in the medulla. These changes appeared to be due to a mechanism clearly distinct from AT1R activation, because they were not abolished by candesartan. In fact, candesartan treatment tended to increase some of these medullary proteins, perhaps in compensation for increased NaCl load. In contrast, cortical ß- and γ-ENaC were reduced by candesartan regardless of diabetic state suggesting their regulation by AT1R at this site; however this did not appear to be a site of diabetes-induced ENaC up-regulation.