Active surveillance is superior to radical nephrectomy and equivalent to partial nephrectomy for preserving renal function in patients with small renal masses: Results from the DISSRM registry.

PURPOSE: We compared renal function outcomes among patients in the surveillance and intervention arms of the DISSRM registry. MATERIALS AND METHODS: Patients were grouped into chronic kidney disease stages by estimated glomerular filtration rate range. Cases were considered up staged if a more advanced chronic kidney disease stage was entered during followup. Chronic kidney disease up staging-free survival was compared among groups using Kaplan-Meier analysis and paired comparisons log rank tests. Multivariate Cox regression identified independent predictors of chronic kidney disease up staging-free survival. RESULTS: A total of 162 patients met the study inclusion criteria, with 68 in the surveillance arm, 65 undergoing partial nephrectomy, 15 undergoing radical nephrectomy, and 14 undergoing cryoablation. Median tumor size was 2.2cm. Mean estimated glomerular filtration rate change was significantly larger for radical nephrectomy vs. surveillance (-9.2 vs. -0.5ml/min/1.73m2) and for radical vs. partial nephrectomy (-9.2 vs. -1.9ml/min/1.73m2) (P = 0.001). No other groups differed significantly. On Kaplan-Meier analysis, patients undergoing radical nephrectomy had significantly worse chronic kidney disease up staging-free survival vs. those treated with partial nephrectomy (P = 0.029), surveillance (P = 0.007), and cryoablation (P = 0.019). No other groups differed significantly. On multivariate analysis, radical nephrectomy independently predicted poor chronic kidney disease up staging-free survival (odds ratio vs. surveillance 30.6, P = 0.001). Neither partial nephrectomy (P = 0.985) nor cryoablation (P = 0.976) predicted poor chronic kidney disease up staging-free survival relative to surveillance. CONCLUSIONS: Patients in the surveillance arm had superior estimated glomerular filtration rate preservation compared to those in the radical nephrectomy but not the partial nephrectomy arm. In certain patients with small renal masses, surveillance and partial nephrectomy may offer comparable renal functional outcomes. This could be partly attributable to a modest estimated glomerular filtration rate decrease associated with surveillance itself. A thorough understanding of the renal functional impacts of treatment modalities is critical in the management of small renal masses.

Patient profiles and outcomes following repair of irreducible and reducible Ventral Wall Hernias.

PURPOSE: The belief that irreducible hernias are repaired less successfully and with higher morbidity drives patients to seek elective repair. The aims of this study were threefold. First, this study sought to compare characteristics of patients undergoing irreducible and reducible ventral hernia repair. Second, to compare morbidity rates. Third, to determine which factors, including irreducibility, might be associated with recurrence. METHODS: This observational study was a retrospective review of 252 consecutive ventral hernia patients divided into two cohorts: 101 patients who underwent repair of an irreducible ventral hernia, and 152 patients underwent repair of a reducible ventral hernia. The mean follow-up time was approximately 4 years in both groups. RESULTS: Patients undergoing repair of irreducible hernias had higher median BMI (31 vs. 27 kg/m2, p = 0.005), had their hernias longer (median 34 months compared to 12 months, p = 0.043), had more defects on average (mean 1.8 vs. 1.4, p < 0.001), and were more likely to be symptomatic (83 vs. 55%, p = 0.002). Interestingly, neither hernia size (p = 0.821), nor the location of hernia (p = 0.261) differed significantly between the two groups. Morbidity rates, including rates of surgical site infection, obstruction, and recurrence, did not differ significantly; nor did recurrence-free survival (RFS) distributions. Risk factors for hernia recurrence on multivariate analysis included the repaired hernia being itself recurrent (HR = 2.06, 95% CI = 1.07-3.99, p = 0.031), the occurrence of post-operative surgical site infection (HR = 5.10, 95% CI = 2.18-11.91, p < 0.001), and the occurrence of post-operative intestinal obstruction (HR = 5.18, 95% CI = 1.82-14.75, p = 0.002). Irreducibility was not a significant predictor of recurrence (p = 0.152). CONCLUSION: Despite differing profiles, patients with these two types of hernias did not have statistically significant differences in morbidity. Recurrence was not observed to be associated with irreducibility but was found to be associated with other post-operative complications.

Synergism between metformin and statins in modifying the risk of biochemical recurrence following radical prostatectomy in men with diabetes.

BACKGROUND: To determine the effect of statins and metformin in combination on biochemical recurrence (BCR) among diabetic men undergoing radical prostatectomy (RP). METHODS: Diabetic men undergoing RP at our institution from January 1995 to March 2012 were retrospectively reviewed. Recipients of adjuvant radiation or hormonal therapy were excluded. Statin and/or metformin use was determined through review of electronic records. BCR-free survival was plotted using Kaplan-Meier analysis, and the effect of statins and metformin on BCR was assessed via a multivariate Cox proportional hazards model. RESULTS: Seven hundred and sixty-seven men met the inclusion criteria. Seventy-six (9.9%) were users of statins only, 56 (7.3%) were users of metformin only and 42 (5.5%) were dual users. Median follow-up time was 27 months. Dual users were less likely than nonusers or users of either medication alone to have a biopsy Gleason sum of 8-10 (P=0.033), and tended towards a lower rate of pathological T stage of pT3 or higher (P=0.064). Dual users had the highest 2-year and 5-year BCR-free survival, although this was not statistically significant (P=0.205). On multivariate regression, neither statin nor metformin use alone was significantly associated with BCR-free survival. However, their interaction led to a significantly lower BCR risk than would be expected from each medication's independent effects (hazard ratio=0.2; P=0.037). CONCLUSIONS: The combination of statins and metformin in men undergoing RP for prostate cancer (PCa) may be associated with a lower BCR risk than would be predicted based on the independent effects of both medications. A synergism between these two agents is biologically plausible based on our current understanding of their diverse molecular pathways of action. The results of future clinical trials involving the use of either medication in men with PCa should be carefully assessed for confirmatory evidence of such a relationship.

Prophylactic management of children at risk for recurrent upper respiratory infections: the Preventia I Study.

BACKGROUND: Given the morbidity and mortality of asthma and the recent dramatic increase in its prevalence, pharmacologic prophylaxis of this disease in children at risk would represent a major medical advance. OBJECTIVES: The Preventia I Study was designed to evaluate the efficacy and long-term safety of loratadine in reducing the number of respiratory infections in children at 24 months. A secondary objective was to investigate the benefit of loratadine treatment in preventing the onset of respiratory exacerbations. METHODS: Preventia I was a randomized placebo-controlled study involving 22 countries worldwide. The children were 12-30 months of age at enrollment and had experienced at least five episodes of ENT infections, and no more than two episodes of wheezing during the previous 12 months. Phase I was a 12-month double-blind period during which the children were treated with loratadine 5 mg/day (2.5 mg/day for children

Added relief in the treatment of acute recurrent sinusitis with adjunctive mometasone furoate nasal spray. The Nasonex Sinusitis Group.

BACKGROUND: Intranasal glucocorticoids are effective in the treatment of allergic rhinitis. Their effectiveness as an anti-inflammatory adjunct in the treatment of acute recurrent sinusitis has not been adequately established in a controlled clinical study. OBJECTIVE: The purpose of this study was to test the hypothesis that intranasal corticosteroid treatment produces additional relief in the treatment of acute sinusitis with oral antibiotics. METHODS: Patients who were 12 years old and older with a history of recurrent sinusitis were treated while experiencing a new episode of acute sinusitis, which was diagnosed by symptoms and confirmed by computed tomography scan of the paranasal sinuses. Patients were treated for 21 days with amoxicillin clavulanate potassium and randomized to receive concurrent mometasone furoate nasal spray (MFNS; Nasonex [400 microg, twice daily]; n = 200 patients) or placebo spray (twice daily; n = 207 patients). Symptom scores for headache, facial pain, congestion, purulent rhinorrhea, postnasal drip, and cough were recorded at baseline and throughout treatment. RESULTS: Baseline symptom scores showed a moderate level of symptom severity comparable in both groups. Patient-recorded twice daily symptom scores showed that adjunctive treatment with MFNS caused a significantly greater decrease in total symptom score (primary efficacy variable) and in individual scores of inflammatory symptoms associated with the obstruction process (headache, congestion, and facial pain) compared with placebo. Symptoms associated with the secretory processes were improved to a lesser degree. Therapy-related local adverse events were not significantly different between groups. CONCLUSION: The addition of intranasal corticosteroid, MFNS 400 microg twice daily, to antibiotics significantly reduces symptoms of acute sinusitis compared with antibiotic treatment alone.

Comparative efficacy and safety of once-daily versus twice-daily loratadine-pseudoephedrine combinations versus placebo in seasonal allergic rhinitis.

The objective of this study was to compare the efficacy and safety of Claritin-D 24 Hour (once daily) with that of Claritin-D 12 Hour (twice daily) and placebo in the treatment of patients with seasonal allergic rhinitis (SAR). In this double-blind, placebo-controlled, multicenter study, 469 patients with moderate-to-severe SAR symptoms were treated for 2 weeks with one of the following: Claritin-D 24 Hour (a combination tablet formulation of loratadine 10 mg in the coating and pseudoephedrine sulfate 240 mg in an extended-release core), Claritin-D 12 Hour (a combination tablet formulation of loratadine 5 mg in the tablet coating and 120 mg pseudoephedrine sulfate, 60 mg in the coating and 60 mg in the core), or placebo. Claritin-D 24 Hour and Claritin-D 12 Hour were consistently superior to placebo (P < 0.01) in reducing total, nasal, and nonnasal symptom scores. Patients in the Claritin-D 24 Hour and Claritin-D 12 Hour groups also had significantly greater (P

Multicenter comparison of clotrimazole vaginal tablets, oral metronidazole, and vaginal suppositories containing sulfanilamide, aminacrine hydrochloride, and allantoin in the treatment of symptomatic trichomoniasis.

BACKGROUND AND OBJECTIVES: Trichomonas vaginalis is a common vaginal pathogen. Oral metronidazole is the drug of choice for the treatment of trichomoniasis. Oral metronidazole, however, may cause unpleasant side effects and is contraindicated during the first trimester of pregnancy. In vitro studies and preliminary clinical data have suggested that intravaginal clotrimazole may be effective against this pathogen. GOALS: To compare the efficacy of clotrimazole vaginal tablets, oral metronidazole, and vaginal suppositories containing sulfanilamide, aminacrine, and allantoin (AVC suppositories) in the treatment of women with symptomatic trichomoniasis. STUDY DESIGN: In a multicenter, open-label trial conducted in 1982 and 1983, 168 symptomatic women with microscopically evident vaginal trichomoniasis were randomized to receive any of 2 g of metronidazole as a single oral dose, two 100-mg clotrimazole vaginal tablets once a day for 7 days, or vaginal suppositories containing 1.05 g of sulfanilamide, 14 mg of aminacrine hydrochloride, and 140 mg of allantoin (AVC suppositories) twice a day for 7 days. Wet mounts and cultures were repated at 1 to 2 and 4 to 6 weeks after completion of treatment. RESULTS: The number of patients who had positive cultures after treatment were 40/45 (88.9%) in the clotrimazole group, 35/43 (81.4%) in the AVC suppository group, and 9/45 (20%) in the metronidazole group (P < 0.001). All treatments were associated with a reduction in reported symptoms. Oral metrohidazole was more effective in reducing symptoms than either of the topical preparations. Adverse events, mostly mild or moderate in severity, were reported by 7 (14.6%) of 48 patients who had received oral metronidazole and 4 (7.8%) of 51 women who used AVC suppositories. There were no adverse events reported by the 50 women who used clotrimazole vaginal tablets. CONCLUSIONS: Oral metronidazole was more effective in eradicating T. vaginalis than clotrimazole vaginal tablets or AVC vaginal suppositories. All three regimens reduced symptoms; oral metronidazole was more effective in reducing symptoms than either topical preparation.

A review of loratadine in the treatment of patients with allergic bronchial asthma.

Patients with seasonal or allergic bronchial asthma experience an immediate allergic response caused by allergen-specific immunoglobulin E-mediated histamine release. The release of histamine and other chemical mediators may trigger airway hyperresponsiveness and exaggerated bronchoconstriction, characteristic features of allergic bronchial asthma. Traditional antihistamines have demonstrated only moderate activity of short duration against this disease. In contrast, loratadine, a potent, nonsedating, histamine-1-receptor antagonist with activity in seasonal and perennial allergic rhinitis, has demonstrated effective control of asthma symptoms, improved pulmonary function, and long duration of action in patients with allergic bronchial asthma. This review summarizes preclinical evidence for the antiallergic activity of loratadine and the results of clinical studies with oral loratadine in patients with allergic bronchial asthma.

Comparative study of SCH 434 and CTM-D in the treatment of seasonal allergic rhinitis.

The efficacy and safety of an extended-release combination of loratadine plus pseudoephedrine sulfate (SCH 434) was compared with that of a tablet containing chlorpheniramine maleate plus pseudoephedrine sulfate (CTM-D) in 131 patients with symptomatic seasonal allergic rhinitis. Patients were randomly assigned to receive either SCH 434 (loratadine 5 mg and pseudoephedrine sulfate 120 mg) or CTM-D (chlorpheniramine maleate 12 mg and pseudoephedrine sulfate 120 mg) twice daily for 2 weeks. Evaluations were made after 3, 7, and 14 days of treatment. Demographics (age, race, sex, and duration of seasonal allergic rhinitis) and baseline total symptom scores were comparable between groups. Both combination products were effective in relieving the symptoms of allergic rhinitis. Improvement in total symptom scores was 54% on day 3 and 65% on day 14 in the SCH 434 group versus 57% on day 3 and 64% on day 14 in the CTM-D group. Individual symptom scores (nasal discharge, stuffiness, nasal itching, sneezing, and ocular symptoms) responded similarly. A smaller proportion of patients in the SCH 434 group reported side effects, especially dry mouth (7% vs 19%, P = 0.07), fatigue (6% vs 25%, P < 0.01), and sedation (7% vs 22%, P < 0.03). In conclusion, the combination of loratadine plus pseudoephedrine sulfate was equally as effective as a classic antihistamine (chlorpheniramine maleate) plus pseudoephedrine sulfate but had a lower incidence of side effects.

Loratadine. A review of recent findings in pharmacology, pharmacokinetics, efficacy, and safety, with a look at its use in combination with pseudoephedrine.

Antihistamines are considered first-line therapy for the relief of symptoms from allergic rhinitis and chronic urticaria. The newer, second-generation, nonsedating antihistamines reduce the central nervous system and anticholinergic side effects commonly found with previous drugs. The availability of H1-receptor antagonists that produce therapeutic effects without causing unwanted CNS effects fulfills an important practical need, since these drugs are clearly preferable in patients who drive or operate heavy machinery, or who are involved in activities requiring full alertness. Physicians and patients alike are pleased with the efficacy and safety the second-generation antihistamines bring to the treatment of allergy symptoms. Loratadine is an especially effective second-generation H1-receptor antagonist and is comparable to many of the other second-generation antihistamines. Loratadine may be particularly advantageous because of its low dose and the convenience of once-daily dosing. A more subtle advantage, loratadine's antiallergic properties, may warrant its use for specific treatment situations as future research clarifies the nature of the inflammatory response and the mechanisms of action antiallergic antagonists have in this regard.

Relative efficacy and safety of loratadine, hydroxyzine, and placebo in chronic idiopathic urticaria.

The efficacy and safety of a new non-sedating antihistamine, loratadine (Clarityn, CAS 79794-75-5) 10 mg q.d., was compared to the classical antihistamine, hydroxyzine 25 mg t.i.d. and placebo in a 4-week (optional 12 week) randomized, double-blind, multi-center study in 203 patients with chronic idiopathic urticaria. Efficacy evaluations included weekly physician and patient assessments of pruritus, overall disease condition, and therapeutic response to treatment. Loratadine and hydroxyzine were significantly more effective than placebo and clinically comparable to each other as measured by all efficacy evaluations at each visit. Loratadine was safe and well tolerated with sedation and dry mouth similar to placebo and significantly less than hydroxyzine.

Evaluation of a new aminoglycoside antibiotic in the treatment of infections in neonates, infants, and children.

A total of 804 pediatric patients (572 neonates and 232 infants and children) with suspected or documented serious infections were enrolled in a multicenter open study of netilmicin, a new semisynthetic aminoglycoside. All patients were evaluable for safety; 161 (20%) had bacteriologically documented infections and were thus evaluable for efficacy. Clinical success was seen in 94.4% (169/179) and bacteriological success in 91.1% (163/179) of sites; clinical success was seen in 94% (205/218) and bacteriological success was seen in 90.3% (196/217) of organisms. No significant adverse renal function changes were seen, and only one instance of an eighth nerve problem, probably related to netilmicin therapy, was encountered.

Multicenter comparative evaluation of netilmicin and gentamicin in adult patients. Efficacy and safety.

Netilmicin and gentamicin were compared in a multicenter clinical trial in 12 study locations. The two aminoglycosides were randomly assigned to hospitalized adult patients with systemic infections, and were administered by i.m. injection or slow i.v. infusion in divided doses generally calculated to deliver either 4-6.5 mg/kg per day of netilmicin, or 3-5 mg/kg per day of gentamicin. Lower dosages were given to patients with impaired renal function. Data from 210 patients receiving netilmicin and 212 receiving gentamicin were analyzed for efficacy. Favorable bacteriologic responses occurred in 95.5% (255/267) of the netilmicin-treated sites and in 90.1% (247/274) of the gentamicin-treated sites (p = 0.05). Netilmicin eliminated or reduced 95.6% (283/296) of all pathogens isolated from all infection sites compared with 89.5% (289/323) for gentamicin (p = 0.012). Favorable clinical responses were observed in 94.2% (275/292) of the netilmicin-treated patients and 89.5% (289/323) of the gentamicin-treated patients. Data from 377 netilmicin-treated patients and 378 gentamicin-treated patients were analyzed for safety. Evidence of nephrotoxicity probably related to treatment was observed in 8 of the netilmicin-treated patients and 14 of the gentamicin-treated patients. Audiometrically documented hearing loss probably related to treatment was observed in one gentamicin-treated patient. In one netilmicin-treated patient there were transient auditory and vestibular effects. Local tolerance to parenteral administration of the two drugs was excellent.

Safety and toleration of oxymetazoline ophthalmic solution.

Two studies were carried out in volunteers without any abnormal ocular conditions to assess the effects and safety of an ophthalmic preparation of oxymetazoline (0.025%). In the first study in which oxymetazoline was compared with placebo and phenylephrine, the results of infra-red electronic pupillography showed that oxymetazoline in therapeutic doses had no effect on pupil size or near point recession. The second study, which was a double-blind forced choice comparison of two different formulations against placebo and 1% naphazoline, showed from assessments of the degree of ocular discomfort and hyperaemia that oxymetazoline was well tolerated and the subjects preferred oxymetazoline in a boric acid rather than in a phosphate solution.

A double-blind, multi-centre controlled trial of 0.25% oxymetazoline ophthalmic solution in patients with allergic and non-infectious conjunctivitis.

Oxymetazoline (0.025%) ophthalmic solution, 2 drops 4-times daily, was compared with a placebo in the treatment of allergic and non-infectious conjunctivitis. In this 1 week, double-blind, multi-centre study, oxymetazoline proved significantly superior to the placebo (p < 0.001) in providing rapid and sustained clearing of inflamed conjunctiva. Overall, 84% of allergic patients treated with oxymetzoline were improved compared to 58% on placebo. Patients with non-infectious conjunctivitis exhibited a high degree of improvement (94%) compared to placebo (51%).

Effectiveness of antihistamines in the symptomatic management of the common cold.

A multicentric trial compared the effect of chlorpheniramine maleate with a placebo on the signs and symptoms of the common cold. Two hundred seventy-one patients were domiciled for 48 hours and evaluated during this period and for four days afterwards. Evaluations by both patients and physicians showed that chlorpheniramine maleate was superior to placebo in lessening the degree of symptoms of the common cold. Statistically significant differences were found both on the first day and as late as the seventh day. Significant differences and trends were shown in such measures as total objective score, physicians' evaluation of symptoms. The overall incidence of side effects other than drowsiness did not differ between the treatment groups.

Oxymetazoline in the treatment of allergic and non-infectious conjunctivitis.

In a double-blind study of 141 patients, 0.025% oxymetazoline ophthalmic solution was compared with its vehicle in the treatment of allergic and non-infectious conjunctivitis. There was a marked difference in response at the first evaluation. By the tenth day (second evaluation) the total improvement in hyperaemia was 95% for oxymetazoline compared to 54% for the placebo. Oxymetazoline's decongestant effect in the eye matches its effect as a nasal vasoconstrictor.