By C. Pakwan. Westminster College, Salt Lake City.
Many studies have provided information on the safety and efficacy of catheter ablation of AF cheap ketoconazole cream 15gm on line. These studies vary from small and large single-center nonrandomized studies to multicenter prospective randomized controlled trials (RCTs) cheap ketoconazole cream 15gm visa. The relatively small number of patients included in each trial makes definitive conclusions about the safety and efficacy of PVI based on an individual study difficult and does not permit meaningful analyses of key subgroups of patients (e. None of the trials provides data on final outcomes such as mortality and stroke. Although the ongoing Catheter Ablation versus Antiarrhythmic Drug Therapy for AF (CABANA) study will provide important information on the effect of catheter ablation on final 19 outcomes, this trial is not expected to end until several years from now. The present review will increase the power of existing studies by synthesizing the evidence on this procedure by pooling data from existing studies and by exploring whether other types of studies or comparative effectiveness research would be helpful. Several other procedures for the treatment of AF have been investigated. One such procedure is the surgical Maze procedure, which appears to confer some benefit to selected patients with 20 AF. Implantation of a cardiac resynchronization therapy (CRT) device is another procedure that may decrease the burden of AF in patients who are eligible for this device based on a left ventricular ejection fraction ≤35 percent, a wide QRS complex, and heart failure symptoms despite optimal medical therapy. Secondary analyses of major clinical trials have provided 21,22 conflicting findings on the effect of CRT on AF burden. This report reviews and synthesizes current published data on these novel procedures and helps to better define their risks and benefits in contemporary clinical practice. Rate Control Versus Rhythm Control Although several studies of rate- and rhythm-control strategies exist, to date no study has shown that maintaining patients with AF in sinus rhythm provides a long-term survival benefit. ES-3 We also do not know whether the risks and benefits of different therapies vary by AF type. Our review seeks to systematically review the comparative risks and benefits of specific outcomes to allow patients and providers to assess the patient-specific tradeoffs of the differing strategies. Scope and Key Questions This CER was funded by AHRQ and is designed to evaluate the comparative safety and effectiveness of a wide range of pharmacological and procedural rate- and rhythm-control strategies for the treatment of adult patients with paroxysmal, persistent, or permanent AF (including atrial flutter). With input from our Key Informants, we constructed Key Questions (KQs) using the general approach of specifying the populations, interventions, comparators, outcomes, timing, and settings of interest (PICOTS). See the section “Inclusion and Exclusion Criteria” in the Methods chapter of the full report for details. The first three KQs considered in this CER focus on rate-control therapies. Specifically: • KQ 1: What are the comparative safety and effectiveness of pharmacological agents used for ventricular rate control in patients with atrial fibrillation? Do the comparative safety and effectiveness of these therapies differ among specific patient subgroups of interest? Do the comparative safety and effectiveness of these therapies differ among specific patient subgroups of interest? Do the comparative safety and effectiveness of these therapies differ among specific patient subgroups of interest? The next two KQs focus specifically on rhythm-control therapies: • KQ 4: What are the comparative safety and effectiveness of available antiarrhythmic agents and electrical cardioversion for conversion of atrial fibrillation to sinus rhythm? Do the comparative safety and effectiveness of these therapies differ among specific patient subgroups of interest? Do the comparative safety and effectiveness of these therapies differ among specific patient subgroups of interest? The final KQ seeks to evaluate the comparison of the available rate- and rhythm-control therapies: • KQ 6: What are the comparative safety and effectiveness of rate-control therapies versus rhythm-control therapies in patients with atrial fibrillation? Do the comparative safety and effectiveness of these therapies differ among specific patient subgroups of interest? Figure A depicts the KQs within the context of the PICOTS. Analytic framework Note: AF = atrial fibrillation; CV = cardiovascular; KQ = Key Question. Methods The methods for this CER follow those suggested in the AHRQ Methods Guide for Effectiveness and Comparative Effectiveness Reviews (hereafter referred to as the Methods 23 Guide). Input From Stakeholders During the topic refinement stage, we solicited input from Key Informants representing medical professional societies/clinicians in the areas of general internal medicine, geriatrics, cardiology, electrophysiology, and primary care; patients; scientific experts; Federal agencies; and payers to help define the KQs. The KQs were then posted for public comment for 4 weeks from September 27 to October 25, 2011, and the comments received were considered in the development of the research protocol. We next convened a Technical Expert Panel (TEP) comprising clinical, content, and methodological experts to provide input to the draft protocol in defining populations, interventions, comparisons, and outcomes, and in identifying particular 24 studies or databases to search. Before involvement in the CER process, the Key Informants and members of the TEP were required to disclose any financial conflicts of interest greater than $10,000 and any other relevant business or professional conflicts. Any potential conflicts of interest were balanced or mitigated. Neither Key Informants nor members of the TEP performed analysis of any kind, nor did any of them contribute to the writing of this report. ES-5 Literature Search Strategy ® ® To identify relevant published literature, we searched PubMed , Embase , and the Cochrane Database of Systematic Reviews (CDSR), limiting the search to studies published from January 1, 2000, to August 1, 2012.
Bion JF cheap ketoconazole cream 15gm free shipping, Aitchison TC generic ketoconazole cream 15 gm amex, Edlin SA, Ledingham IM : Sickness scoring and system: Risk prediction of hospital mortality for critically ill hospitalized response to treatm ent as predictors of outcom e from critical illness. Chew SL, Lins RL, Daelem ans R, De Broe M E: O utcom e in acute score for ICU patients. Liaño F: Severity of acute renal failure: The need of m easurem ent. Le Gall, Lem eshow S, Saulnier F: A new Sim plified Acute Phisiology N ephrol D ial Transplant 1994, 9(Suppl. Score (SAPS II) based on a European/N orth Am erican m ulticenter study. Bonom ini V, Stefoni S, Vangelista A: Long-term patient and renal prognosis in acute renal failure. Turney JH : W hy is m ortality persistently high in acute renal failure? Knaus W A, Draper EA, W agner DP, Zim m erm an JE: Prognosis in APACH E II en el fracaso renal agudo de las unidades de cuidados acute organ-system failure. Racusen cute renal failure (ARF) in the transplanted kidney represents a high-stakes area of nephrology and of transplantation practice. AA correct diagnosis can lead to rapid return of renal function; an incorrect diagnosis can lead to loss of the graft and severe sequelae for the patient. In transplant-related ARF percutaneous kidney allograft biopsy is crucial in differentiating such diverse entities as acute rejection (Figs. In the case of acute rejection, standardization of transplant biopsy interpretation and reporting is necessary to guide therapy and to estab- lish an objective endpoint for clinical trials of new immunosuppressive agents. The Banff Classification of Renal Allograft Pathology is an internationally accepted standard for the assessment of renal allograft biopsies sponsored by the International Society of N ephrology Commission of Acute Renal Failure. The classification had its origins in a meeting held in Banff, Alberta, in the Canadian Rockies, in August, 1991, where subsequent meetings have been held every 2 years. Hot topics likely to influence the Banff Classification of Renal Allograft Pathology in 1999 and beyond are shown in Figs. Prerenal azotemia FIGURE 10-2 Diagnosis of rejection in the Banff classification makes use of two basic lesions, tubulitis and intimal arteritis. The 1993–1995 Banff classification depicted in this figure is the standard in use in virtually all current clinical trials and in many individual transplant units. In this construct, rejection is regarded as a continuum of mild, moderate, and severe forms. The 1997 Banff classification is similar, having the same threshold for rejection diagnosis, but it recognizes three different histologic types of acute rejection: tubulointersititial, vascular, and transmural. The quotation marks emphasize the possible overlap of features of the various types (eg, the finding of tubulitis should not None Borderline M ild M oderate Severe Rejection dissuade the pathologist from conducting a thorough search for intim al arteritis). No tubulitis FIGURE 10-3 Tubulitis is not absolutely specific for acute rejection. It can be found in m ild form s in acute tubular necrosis, norm ally functioning kidneys, and in cyclosporine toxicity and in conditions not related to rejection. The num ber of lym phocytes situated between and beneath tubular epithelial cells is com pared with the num ber of tubular cells to determ ine the severity of tubulitis. Four lym phocytes per m ost inflam ed tubule cross sec- tion or per ten tubular cells is required to reach the threshold for diagnosing rejection. In this figure, the two tubule cross sections in the center have eight m ononuclear cells each. Rejection with intim al arteritis or transm ural arteritis can occur without any tubulitis whatsoever, although usually in well-established rejection both tubulitis and intim al arteritis are observed. N ote that m ore than with thickened tubular basem ent m em branes. There are 13 or 14 20 lym phocytes are present in the thickened intim a. This is an exam ple of how a lesion, however, even a single lym phocyte in this site is sufficient properly perform ed periodic acid-Schiff (PAS) stain should look. Thus, the pathologist m ust search for subtle The Banff classification is critically dependent on proper performance intim al arteritis lesions, which are highly reliable and specific for of PAS staining. The invading lym phocytes are readily apparent and rejection. In the Banff 1997 classification one avoids counting lym phocytes in atrophic tubules, as tubulitis there is m ore “nonspecific” than in nonatrophed tubules. In addition to the influx of than that in Figure 10-5. Aggregation of lym phocytes is also seen inflammatory cells there has been proliferation of modified smooth in the lum en, but this is a nonspecific change.
In contrast buy ketoconazole cream 15 gm on line, ASO-RAD is generic 15gm ketoconazole cream with visa, technically, much less amenable to PTRA (particularly Ischemic atrophy common Ischemic atrophy rare ostial lesions), and surgical intervention or Surgical intervention or angioplasty: Surgical intervention or angioplasty: PTRA produce mediocre-to-poor cure rates Mediocre cure rates of the hypertension Good cure rates of the hypertension of the hypertension. ASO-RAD and medial Less amenable to PTRA More amenable to PTRA fibroplasia m ay cause hypertension and when the hypertension is cured or markedly improved following intervention, the patient m ay be viewed as having “renovascular FIGURE 3-8 hypertension. The m ost far m ore likely to occur in patients with com m on types of renal artery disease (atherosclerotic renal artery disease [ASO -RAD] and m edial fibroplasia than in patients with m edial fibroplasia) are com pared here. In general, ASO -RAD is observed in m en and ASO-RAD. ASO-RAD and medial fibroplasia wom en older than 50 to 55 years of age, whereas m edial fibroplasia is observed prim arily involve both main renal arteries in approxi- in younger white wom en. Total occlusion of the renal artery and, hence, atrophy of the mately 30% to 40% of patients. In the Stenotic presence of hem odynam ically sufficient unilateral renal artery kidney stenosis, the kidney distal to the stenosis is rendered ischem ic, activating the renin angiotensin system , and producing high levels of angiotensin II, causing a “vasoconstrictor” type of hypertension. N um erous studies have established the causal relationship between angiotensin II–m ediated vasoconstriction Contralateral Ischemia and hypertension in the early phase of this experim ental m odel. This sec- • Pressure natriuresis Angiotensin II ondary aldosteronism also produces hypokalem ia. The degree of renal artery stenosis necessary to produce hem odynam ically Vasoconstriction Aldosterone significant reductions in perfusion, triggering renal ischem ia and activation of the renin angiotensin system , generally does • Intrarenal hemodynamics not occur until a reduction of 80% or m ore in both lum en diam eter • Sodium retention and cross-sectional area of the renal artery takes place. Lesser degrees of renal artery constriction do not initiate this sequence of events. This m odel of 2K,1C Goldblatt hypertension im plies that FIGURE 3-9 the contralateral (nonaffected) kidney is present, and that its Schematic representation of renovascular hypertension. Renovascular renal artery is not hem odynam ically significantly narrowed. In addition, the high Clip III levels of angiotensin II stim ulate thirst, which further augm ents Blood pressure expansion of the extracellular fluid volum e. The expanded extra- cellular fluid volume results in a progressive suppression of peripheral renin activity. During this transition phase, the hypertension is still Renin responsive to rem oval of the unilateral renal artery stenosis, to angiotensin II blockade, or unilateral nephrectom y, although these Change in blood pressure m aneuvers do not norm alize the blood pressure as prom ptly and on removing clip consistently as in the acute phase. After several weeks, a chronic phase (phase III) ensues wherein unclipping the renal artery of the experimental animal does not lower the blood pressure. This failure of “unclipping” to lower the blood pressure in this chronic phase (III) of 2K,1C hypertension is due to FIGURE 3-10 widespread arteriolar damage to the “contralateral kidney,” conse- Sequential phases in two-kidney, one-clip (2K,1C) experimental reno- quent to prolonged exposure to high blood pressure and high levels vascular hypertension. The schematic representation of renovascular of angiotensin II. In this chronic phase of 2K,1C renovascular hyper- hypertension depicted in Figure 3-9 is an oversim plification. In tension, extracellular fluid volum e expansion and system ic vasocon- fact, the course of experimental 2K,1C hypertension may be divided striction are the m ain pathophysiologic abnorm alities. In phase I, renal ischemia and activation natriuresis of the “contralateral kidney” blunts the extracellular of the renin angiotensin system are of fundam ental im portance, fluid volum e expansion caused by the “stenotic kidney;” but as the and in this early phase of experim ental hypertension, the blood contralateral kidney suffers vascular damage from extended exposure pressure elevation is renin- or angiotensin II–dependent. Acute to elevated arterial pressure, its excretory function diminishes and adm inistration of angiotensin II antagonists, adm inistration of extracellular fluid volume expansion persists. In this third phase of angiotensin-converting enzym e (ACE) inhibitors, rem oval of the experim ental 2K,1C hypertension, acute blockade of the renin renal artery stenosis (ie, rem oval of the clip in the experim ental angiotensin system fails to lower blood pressure. Sodium depletion anim al or rem oval of the “stenotic kidney”) prom ptly norm alizes m ay am eliorate the hypertension but does not norm alize it. Several days after renal artery clamping, renin levels clinical surrogate of phase III experimental 2K,1C hypertension is fall, but blood pressure rem ains elevated. W idespread clinical experience indicates experim ental 2K,1C hypertension m ay be viewed as a pathophysio- that major improvements in blood pressure control or cure of the logic transition phase that, depending on the experim ental m odel hypertension following renal revascularization or even removal of and species, m ay last from a few days to several weeks. During this the kidney ipsilateral to the renal artery stenosis are rarely observed transition phase (phase II), salt and water retention are observed as in patients with a long duration (ie, >5 years) of hypertension. The discussion so far of the pathophysiology of renovascular hypertension has focused on the two-kidney, one-clip m odel of renovascular hypertension (“two-kidney hypertension”), wherein the artery to the “contralateral kidney” is patent and the “contralateral” nonaffected kidney is present. Elevated peripheral renin activity, norm al plasm a volum e, and hypokalem ia are typically associated with the elevated arterial pressure. There is another type of “reno- Blood Renin Volume Blood Renin Volume vascular hypertension” known as “one-kidney” hypertension, pressure pressure wherein in the experim ental m odel, one renal artery is constricted High Normal Normal High and the contralateral kidney is removed. Although there is an initial increase in renin release responsible for the early rise in blood pressure in “one-kidney” hypertension as in “two-kidney” hypertension, the absence of an unclipped contralateral kidney allows for sodium retention early in the course of this one-kidney, one-clip (1K,1C) m odel. Renin levels are suppressed to norm al levels in conjunction with high blood pressure which is m aintained by salt and water retention. Thus, extracellular fluid volum e expansion is a prim e feature of “one-kidney” hypertension. LESIONS PRODUCING THE SYNDROM E OF RENOVASCULAR Lesions producing the syndrom e of reno- HYPERTENSION (“TW O-KIDNEY HYPERTENSION”)* vascular hypertension. The m ost com m on clinical counterpart to “two-kidney” hypertension Unilateral atherosclerotic renal arterial disease is unilateral renal artery stenosis due to either Unilateral fibrous renal artery disease atherosclerotic or fibrous renal artery disease. Unilateral renal traum a, with developm ent Renal artery aneurysm of a calcified fibrous capsule surrounding Arterial embolus the injured kidney causing com pression of Arteriovenous fistula (congenital and traumatic) the renal parenchym a, m ay produce reno- Segmental arterial occlusion (traumatic) vascular hypertension; this clinical situation is Pheochromocytoma compressing renal artery analogous to the experimental Page kidney, Unilateral perirenal hematoma or subcapsular hematoma (compressing renal parenchyma) wherein cellophane wrapping of one of two kidneys causes hypertension, which is *Implies contralateral (nonaffected) kidney present.