Relationship between medication adherence and treatment outcomes: the COMBINE study

Background: Within the alcoholism field, there is mounting evidence supporting an important relationship between medication adherence and drinking outcomes. Little is known however, about the complex relationships between medication and treatment variables and drinking outcomes. The present paper reports on the differential impact of medication adherence and treatment factors on drinking outcomes. Data derived from the COMBINE Study was used to investigate the interrelationships between medication adherence, combination treatments and drinking outcomes. Methods: Twelve hundred and twenty‐six patients were randomized to 1 of 8 different combination treatments involving 2 medications—naltrexone and acamprosate and placebo, and 2 behavioral treatments—medical management (MM) and combined behavioral intervention (CBI). Two primary drinking outcomes were percent days abstinent (PDA) and time to first heavy drinking day. Medication adherence was defined as a proportion that reflects the number of pills taken by the maximum number of pills expected to be taken over the course of the trial. A generalized linear mixed model was used to estimate the effects of adherence on PDA while proportional hazards model was used to examine similar co‐variate effects on time to first heavy drinking day. Results: Concerning time to first heavy drinking day, a significant three‐way interaction was found between medication adherence, CBI and naltrexone (p = 0.0160). Within the MM only plus placebo group (no CBI), significant differences were found in “recovery” (i.e., no heavy drinking days) rates between adherers and nonadherers (40% vs. 10%, p < 0.0001). Such differences became nonsignificant (p = 0.12) when CBI was introduced into the relationship. CBI did not add any such advantage to naltrexone‐treated patients. Conclusions: CBI might serve a protective function for nonadherers in the placebo group; the median relapse time was reduced when these nonadherers were exposed to the alcohol specialty intervention. CBI offered little additional benefit to nonadherers in the naltrexone group. Among nonadherers in the naltrexone group, relapse rates appear to be more a function of inadequate exposure to the active medication and less influenced by CBI.     

Closed loop intestinal obstruction: role of computerized tomography]

PURPOSE: The obstruction of a bowel segment at both ends results in a closed loop obstruction. Progression to strangulation frequently occurs if surgical intervention is delayed. The role of plain radiography in the diagnosis of closed loop obstruction and strangulation has been shown to be limited, while the recent literature has demonstrated the growing role of computed tomography (CT). This paper reports our experience in the study of closed loop obstruction by CT. MATERIAL AND METHODS: The CT studies of 12 patients with surgically confirmed closed loop obstruction were retrospectively reviewed. The following CT signs were used for the diagnosis: a) fluid-filled distended loops, b) C-shaped incarcerated loop, c) radial distribution of several dilated bowel loops and mesenteric vessels converging toward the point of obstruction, d) triangular or fusiform tapering of the closed loop and/or whirl sign in the site of obstruction. RESULTS: On the basis of these signs, the diagnosis was made in 11 of 12 patients. Only 1 patient, who had a negative CT study, was positive at a subsequent enteroclysis. CT findings of strangulation were associated in 3 cases: slight wall thickening with vascular congestion and mesenteric ascites, confirmed at surgery. DISCUSSION AND CONCLUSIONS: Small bowel obstruction can be distinguished into simple and closed loop obstructions. The latter is a more severe condition which is often complicated by strangulation with vascular impairment, edema and intramural and mesenteric hemorrhage. Consequent arterial insufficiency rapidly leads to ischemia, infarction and necrosis. The radiologist plays a role in the early recognition of the closed loop obstruction and of any sign of strangulation. The role of CT in the diagnosis and workup of patients with suspected intestinal occlusion has been analyzed in the literature with reported 63% sensitivity, 78% specificity and 66% accuracy. CT is also capable of revealing the causes of occlusion in 73-95% of cases. The above CT signs, as confirmed in our experience, allow to identify closed loop obstruction and also small bowel strangulation, thus supplying a valuable contribution to diagnosis and accurate preoperative evaluation. We conclude that CT can accurately demonstrate the presence of closed loop obstruction and can be the technique of choice in patients in whom obstruction is associated with clinical signs suggestive of strangulation.     

Relationship between complex fractionated electrograms (CFE) and dominant frequency (DF) sites and prospective assessment of adding DF-guided ablation to pulmonary vein isolation in persistent atrial fibrillation (AF)

Dominant Frequency Mapping and Ablation . Background: Sites of high DF are potential targets for AF ablation, but it is unknown if addition of DF ablation can improve procedural outcome. Objectives: We sought to (1) examine the relationship between DF sites and complex fractionated electrograms (CFE) and (2) prospectively assess the long‐term outcome of adding DF ablation to pulmonary vein antral isolation (PVAI) for persistent AF. Methods: First, 20 patients with persistent AF who underwent previous CFE‐guided ablation and who had AF terminate during ablation were studied retrospectively (group I). Bipolar, 8‐second electrograms were collected by a circular catheter (288 ± 86 points/map). The EnSite NavX system allows for automated display of both CFE and DF maps. Electrograms with cycle length <120 ms were considered CFE and were compared to DF sites > 8 Hz (direct inverse relationship). Sites of AF termination were related to CFE and DF sites. Based on these observations, 30 different patients (group II) with persistent AF prospectively underwent DF‐guided ablation plus PVAI. They were followed every 3 months for 1 year (visit, Holter, ECG). These patients were compared to case‐matched controls undergoing PVAI alone (group III). Results: In group I, there was a significant, inverse correlation between DF and CFE values at each point (r =–0.24, P < 0.001). DF surface area was less than CFE area (27 ± 5 cm² vs 34 ± 4 cm², P = 0.03). CFE sites overlapped 48 ± 27% with the DF surface area. Nonoverlapping CFE sites were contiguous to DF sites. AF termination occurred where DF and CFE overlapped, and at these sites, DF was always greater than the mean DF for the map. In group II, all DF sites above the mean value were prospectively ablated during AF. AF termination was noted in only 2/30 (7%) patients. After DF ablation, PVAI was performed and termination increased to 4/30 patients (14%). At 1 year, freedom from atrial arrhythmia > 30 seconds occurred in 57% of DF+PVAI compared to 60% in patients receiving PVAI alone (P = 0.18). Conclusions: DF and CFE regions overlap only about 50%. AF termination retrospectively occurred on overlapping CFE/DF sites where DF was above the mean. However, prospective ablation of DF sites plus PVAI resulted in low AF termination rates, and did not improve 1 year success over PVAI alone. (J Cardiovasc Electrophysiol, Vol. 22, pp. 1309‐1316, December 2011)     

Thiazide and loop diuretics

J Clin Hypertens (Greenwich). 2011;13:639–643. ©2011 Wiley Periodicals, Inc.Key Points and Practical Recommendations

• • Although chlorthalidone and hydrochlorothiazide are structurally similar, they are very different pharmacokinetically, with chlorthalidone having both an extremely long half‐life (approximately 40 to 60 hours) and a large volume of distribution, with gradual elimination from the plasma compartment by tubular secretion.
• • Furosemide usage, the most widely used diuretic in the loop diuretic class, can be complicated by extremely erratic absorption, with a bioavailability range of 12% to 112%.
• • Chlorthalidone, at a dose of 25 mg, is comparatively more potent than 50 mg of hydrochlorothiazide, particularly as related to overnight blood pressure reduction.
• • In ALLHAT, there was no difference among chlorthalidone, amlodipine, lisinopril, and doxazosin for the primary outcome or mortality.
• • Secondary outcomes were similar except for a 38% higher rate of heart failure with amlodipine; a 10% higher rate of combined cardiovascular disease, a 15% higher rate of stroke, and a 19% higher rate of heart failure with lisinopril; and a 20% higher rate of cardiovascular disease, a 20% higher rate of stroke (40% higher rate in blacks), and an 80% higher rate of heart failure with doxazosin, compared with chlorthalidone.
• • The ACCOMPLISH study may affect future practice guidelines as a result of its findings favoring the amlodipine/benazepril combination; however, the generalizability to patient populations with a lesser cardiovascular risk profile remains in question and the dose of hydrochlorothiazide was only 12.5 mg to 25 mg daily, which was a dose lower than that used in placebo‐controlled trials using hydrochlorothiazide.
• • Certain low‐renin patient groups (eg, blacks, the elderly, and diabetics) as well as those who manifest the metabolic syndrome are commonly more responsive to thiazide‐type diuretic therapy.
• • Diuretics can be successfully combined with β‐blockers, angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, centrally acting agents, and even calcium channel blockers.
• • Although thiazide‐type diuretics are among the best‐tolerated antihypertensive agents in terms of symptomatic adverse effects, diuretic‐related adverse side effects include those with established mechanisms (eg, such as electrolyte changes and/or metabolic abnormalities) and other side effects, which are less well understood mechanistically (eg, impotence), although the latter is not universally accepted as a diuretic‐related side effect.
• • Thiazide‐induced hypokalemia is associated with increased blood glucose, and treatment of thiazide‐induced hypokalemia may reverse glucose intolerance and possibly prevent diabetes.
• • Thiazide‐induced hyperuricemia occurs as a result of volume contraction and competition with uric acid for renal tubular secretion, but does not necessarily contraindicate using a thiazide, especially if a uric acid–lowering drug such as allopurinol is being used.
• • Adverse interactions include the blunting of thiazide effects by nonsteroidal anti‐inflammatory drugs and the potential to increase fatigue, lethargy, and increase in glucose when combined with β‐blockers.
• • Thiazide‐type diuretics are useful first‐line agents in the treatment of hypertension because they have been proven to reduce cardiovascular mortality and morbidity in systolic and diastolic forms of hypertension and do so at low cost.
• • Loop diuretics should not be used as first‐line therapy in hypertension since there are no outcome data with them. They should be reserved for conditions of clinically significant fluid overload (eg, heart failure and significant fluid retention with vasodilator drugs, such as minoxidil) or with advanced renal failure and can be combined with thiazide‐type diuretics.

Diuretics are tools of considerable therapeutic importance in hypertension. First, they effectively reduce blood pressure (BP), while at the same time decrease the morbidity and mortality associated with hypertension. Diuretics are currently recommended by the Seventh Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) as first‐line therapy for the treatment of hypertension. ¹ In addition, they remain an important component of therapy for volume‐overload conditions, such as heart failure (HF), nephrotic syndrome, and cirrhosis, in that they improve the symptoms of edema and congestion. ²      

What is the Role of Aldosterone Excess in Resistant Hypertension and How Should It Be Investigated and Treated?

Resistant hypertension has evolved as an important global health care problem. Primary aldosteronism is one of several potentially reversible causes of resistant hypertension. Primary aldosteronism can be effectively treated, when recognized, with a mineralocorticoid receptor antagonist, such as spironolactone and eplerenone. Each of these compounds can reduce blood pressure as monotherapy or when given with a range of other antihypertensive drug classes. These compounds have distinctive pharmacokinetic and pharmacodynamic patterns that require some forethought in their use before they are prescribed. However, as the use of mineralocorticoid-blocking agents has gradually increased, the hazards inherent to use of such drugs has become more apparent. Whereas the endocrine side effects of spironolactone are in most cases little more than a cosmetic annoyance, the potassium-sparing effects of both spironolactone and eplerenone can prove fatal if sufficient degrees of hyperkalemia develop. However, for most patients the risk of developing hyperkalemia in and of itself should not discourage the prudent clinician from bringing these compounds into play. Hyperkalemia should always be considered as a likelihood in any patient receiving one or the other of these medications. As such, steps should be taken to lessen the likelihood of it occurring if therapy is being contemplated with agents in this class.     

Spouses of Persian Gulf War I veterans: medical evaluation of a U.S. cohort

Ten years after the 1991 Persian Gulf War (GW I), a comprehensive evaluation of a national cohort of deployed veterans (DV) demonstrated a higher prevalence of several medical conditions, in comparison to a similarly identified cohort of nondeployed veterans (NDV). The present study determined the prevalence of medical conditions among nonveteran spouses of these GW I DV and NDV. A cohort of 490 spouses of GW I DV and 537 spouses of GW I NDV underwent comprehensive face-to-face examinations. No significant differences in health were detected except that spouses of DV were less likely to have one or more of a group of six common skin conditions. We conclude that, 10 years after GW I, the general physical health of spouses of GW I DV is similar to that of spouses of NDV.     

True Crime Consumption as Defensive Vigilance: Psychological Mechanisms of a Rape Avoidance System

Archives of Sexual Behavior - The circumvention of female reproductive choice via rape is a costly and evolutionarily persistent threat to women’s reproductive fitness. This is argued to have...