The comparative efficacy of intravenous cefotaxime and trimethoprim/sulfamethoxazole in preventing infection after neurosurgery: a prospective, randomized study. Brisbane Neurosurgical Infection Group

The objective of the investigation was to determine the comparative efficacy of cefotaxime versus trimethoprim-sulfamethoxazole in the prophylaxis of patients undergoing neurosurgical procedures. In this prospective randomized open study, 780 adult patients undergoing elective craniotomy, shunt surgery or stereotactic surgery were randomized to receive preoperative cefotaxime (1 g) or trimethoprim-sulfamethoxazole (160 mg trimethoprim, 800 mg sulfamethoxazole) as prophylaxis: 613 patients were available for analysis, of whom 315 received cefotaxime and 298 received trimethoprim-sulfamethoxazole. Forty-two patients (6.9%) experienced 49 postoperative infections, with no significant difference between treatment groups. The most common infections unrelated to neurosurgery were urinary tract infections (17 cases) and pneumonia (seven cases). Fifteen neurosurgical infections occurred, comprising 11 wound infections, two shunt infections and two cerebral abscesses. Neurosurgical infection rates were similar in the cefotaxime group (2.5%) and the trimethoprim-sulfamethoxazole group (2.3%). We concluded cefotaxime and trimethoprim-sulfamethoxazole administered as single dose prior to neurosurgery are equally effective in controlling neurosurgical infection and postoperative infection at remote sites.     

Prospective randomized, double-blind comparative study of dexamethasone, ondansetron, and ondansetron plus dexamethasone as prophylactic antiemetic therapy in patients undergoing day-case gynaecological surgery

Dexamethasone alone and in combination with selective 5-hydroxytryptaminereceptor antagonists is of benefit in the prophylaxis of post-operativenausea and vomiting. In this study, the effectiveness of sucha combination in comparison to either drug alone is investigatedin day case gynaecological surgery. A total of 177 patientswere randomized to three treatment groups: dexamethasone 8 mg,ondansetron 4 mg, and dexamethasone 8 mg plus ondansetron 4mg. The only significant difference between groups was seenin the first 3 h when failure of prophylaxis was more frequentin patients who had received dexamethasone alone (P=0.0085;Fisher’s exact probability test). Confidence intervalanalysis indicates a modest treatment effect for the combinationand the decision whether to perform a larger study depends uponwhether such an effect is clinically relevant. Br J Anaesth 2001; 87: 588–92     

Prospective assessment of the efficacy of single dose versus traditional 3‐day antimicrobial prophylaxis in 12‐core transrectal prostate biopsy

Objectives: To prospectively evaluate the efficacy of single dose antibiotic prophylaxis in 12‐core transrectal ultrasonography (TRUS) guided prostate biopsy. Methods: A total of 400 patients who underwent prostate biopsy with TRUS guidance were included. The patients were prospectively randomized in three groups regarding antibiotic prophylaxis. The first group (139 patients) received a single gram of intramuscular ceftriaxone, while the second group (131 patients) had a 3‐day course of oral ciprofloxacin. The third group (130 patients) had single oral 500 mg of ciprofloxacin. All patients had urine cultures prior to biopsy and on the second day after biopsy. Results: The study groups were compared in terms of the results of urine cultures and clinical parameters. Overall, only seven patients (1.8% of the cases) had positive urine cultures with no difference between these three groups. Additionally, no significant difference was observed regarding morbidity rates in all groups. Only eight patients (2%) developed major complications requiring hospitalization. There was no increase in the rate of infectious complications when the biopsy core numbers were increased up to 12. Conclusions: The current study suggests that a single oral dose of antimicrobial prophylaxis is reasonable in TRUS prostate biopsy even in the case of 12‐core sampling.     

A single center, randomized, comparative, prospective clinical study to determine the efficacy of the VelaSmooth system versus the Triactive system for the treatment of cellulite

BACKGROUND AND OBJECTIVES: One area of cosmetic concern for women of all races is the unsightly appearance of cellulite in the buttocks area and lower extremities. Two modern technological advances claim to improve cellulite and provide reproducible results, TriActive and VelaSmooth. The TriActive laser is intended to reduce the appearance of cellulite through the combination of low-energy diode laser, contact cooling, suction, and massage. The VelaSmooth is based on a combination of two different ranges of electromagnetic energy: infrared light and radio frequency (RF) combined with mechanical manipulation of the skin. This single center study was designed to evaluate the efficacy of the VelaSmooth versus TriActive in the reduction of the appearance of cellulite. STUDY DESIGN/MATERIALS AND METHODS: Twenty female patients were treated twice a week for 6 weeks with the randomization of TriActive on one side and VelaSmooth on the other side. Patients were evaluated with photographs and circumferential thigh measurements before treatment and after the final treatment. RESULTS: Although there was improvement in the reduction of cellulite for each device individually, there was no significant difference between VelaSmooth or TriActive devices in the following categories: reduction of thigh circumference, photographic evaluation, and perceived change in before and after photographic grading. There was a statistically significant increase in the incidence of post-treatment bruising with the VelaSmooth compared to TriActive. CONCLUSIONS: In conclusion, both the TriActive and VelaSmooth provide improvement of cellulite. When comparing differences in efficacy, the average mean percent change calculated was roughly the same for both treatments and showed no statistical difference.     

腹腔镜与开腹肝切除术治疗肝细胞癌临床疗效的真实世界比较研究

背景与目的：目前,腹腔镜肝切除术治疗肝细胞癌(HCC)的适应证已逐渐趋同于开腹肝切除术,腹腔镜肝切除术的可行性、安全性、有效性也逐步得到证实。但在手术方式的选择上外科医师往往存在选择偏倚,故腹腔镜和开腹肝切除术的选择也有待在不同的人群和医学中心仔细评估,且时至今日,仍有学者对腹腔镜肝切除术的不良肿瘤学结局心存疑虑。因此,本研究分析比较腹腔镜与开腹肝切除术治疗HCC的临床疗效。方法：回顾性分析2016年1月1日—2020年12月31日在中南大学湘雅医院517例因HCC施行肝切除术的患者临床资料。其中,196例行腹腔镜肝切除术(腹腔镜组),321例行开腹肝切除术(开腹手术组)。分析比较两组患者一般资料、围手术期情况及随访指标。结果：一般资料中,腹腔镜组与开腹手术组患者的肿瘤分期、肿瘤直径、术前白蛋白水平及肝切除部位方面的差异有统计学意义(均P<0.05),其余差异无统计学意义(均P>0.05)。围手术期指标中,腹腔镜组的中位术中出血量(200.00 mL vs. 300.00 mL)、术后中位住院时间(6 d vs. 8 d)、术后肝功能恢复、术后并发症发生率(6.63%vs....     

Intraoperative ketorolac dose of 15 mg versus the standard 30 mg on early postoperative pain after spine surgery: A randomized,blinded, non-inferiority trial

Study objectiveThe primary aim of this study is to show the non-inferiority of 15 mg intraoperative dose of ketorolac as compared to the standard 30 mg ketorolac by looking at the visual analog scale pain (VAS) scores 4 h after an adult spine surgery.DesignThe study design is a prospective randomized non-inferiority clinical trial looking at non-inferiority of intraoperative 15 mg ketorolac from the standard 30 mg dose.SettingQuaternary care center.Patients50 adult (18–65 years of age) undergoing lumbar decompression spine surgery.InterventionsGroup A received a single intraoperative dose of 15 mg ketorolac at the end of surgery and group B received single intraoperative dose of 30 mg ketorolac.MeasurementsThe primary outcome was the visual analog scale (VAS) pain scores 4 h after an adult spine surgery. Secondary measures were morphine usage in the first 8 and 24 h postoperatively, numeric rating scores (NRS) up to 24 h, sedation, nausea, vomiting, respiratory depression, pruritus and bleeding complications.Main resultsIntention to treat analysis showed a mean increase in 4 h VAS pain score of 7.9 mm (95% CI: − 4.5 mm to 20.4 mm) in patients administered 15 mg ketorolac. This difference was neither statistically (P = 0.207) nor clinically significant (< 18 mm on VAS scale). A similar increase in the 15 mg group was noted through a per protocol analysis, 6.9 mm (95% CI: − 6.6 mm to 20.5 mm, P = 0.307) greater in the 15 mg group. Non-inferiority of 15 mg was not confirmed. No significant difference was found in secondary endpoints.ConclusionsKetorolac 30 mg intravenous was not superior to 15 mg intravenous for post-operative pain management after spine surgery. However, 15 mg failed to meet the pre-specified criteria for non-inferiority to the 30 mg dose.     

The pharmacokinetics and analgesic efficacy of larger dose rectal acetaminophen (40 mg/kg) in adults: a double-blinded, randomized study

Analgesic acetaminophen plasma concentrations are not known. We investigated in a randomized, double-blinded study the pharmacokinetics and analgesic efficacy of small- (AS; 20 mg. kg(-1)) and larger- (AL; 40 mg/kg) dose rectal acetaminophen and compared it with the combination (C) of rectal diclofenac (100 mg) and acetaminophen (20 mg/kg) in 65 women undergoing hysterectomy. Suppositories were administered after the induction of a standardized general anesthesia. Pain (measured by using a 10-cm visual analog scale) and morphine consumption (patient-controlled analgesia) were repeatedly assessed for 24 h. Acetaminophen plasma concentrations were measured by using a fluorescence polarization immunoassay. Antipyretic plasma concentrations (10-20 mg/L) after 40 mg/kg acetaminophen were not associated with improved analgesia or decreased opioid requirements; 20 mg/kg acetaminophen produced subtherapeutic plasma levels (<10 mg/L). Maximal plasma concentrations of 17.2 and 10.4 mg/L (P < 0.01, analysis of variance) were achieved after 4.2 and 3.6 h for the AL and AS groups, respectively. The only difference in clinical outcome was lower visual analog scale scores after acetaminophen/diclofenac (C 2.0 versus AS 3.2 and AL 3.4) 4 h after the induction (P < 0.05, analysis of variance). Acetaminophen pharmacokinetics in adults were similar to those observed in children. Analgesic plasma concentrations are likely to be higher than antipyretic plasma levels, which were only attained after twice the recommended rectal dose was administered. Analgesic plasma concentrations have yet to be determined but may be higher than those associated with antipyresis. IMPLICATIONS: Acetaminophen pharmacokinetics were comparable in adults and children. Plasma concentrations known to reduce fever did not produce better pain relief and were only achieved after twice the conventional dose was administered. Analgesic plasma concentrations have yet to be determined but may be higher than those associated with antipyresis.     

Prospective longitudinal comparative study of early health-related quality-of-life outcomes in patients undergoing surgical treatment for localized prostate cancer: a short-term evaluation of five approaches from a single institution

BACKGROUND AND PURPOSE: Quality of life (QoL) issues are a vital concern for the majority of patients seeking therapeutic intervention once they are found to have prostate cancer. A prospective longitudinal comparison using validated QoL instruments is a valuable technique to evaluate outcome differences. We evaluated the short-term QoL changes from baseline of five surgical approaches for localized prostate carcinoma delivered at a single institution. PATIENTS AND METHODS: A prospective longitudinal survey of 719 patients with newly diagnosed prostate cancer was initiated in 2001. The surgical procedures performed during this time period were open radical prostatectomy (ORP), laparoscopic radical prostatectomy (LRP), da Vinci robotic prostatectomy (dVP), (103)Pd brachytherapy ((103)Pd), and prostate cryoablation (PCryo). An Institutional Review Board-approved questionnaire comprised of validated QoL instruments (UCLA Prostate Cancer Index and American Urological Association Symptom Index [SI]) was mailed to enrolled patients prior to their selected surgery and again at 1, 3, 6, 9, 12, 18, 24, and 36 months after therapy. A percent of baseline score calculation including data from all five treatment cohorts for follow-up months 1, 3, and 6 was compared within groups. Group I consisted of patients undergoing ORP, LRP, or dVP. Group II consisted of patients undergoing (103)Pd or PCryo. RESULTS: Between January 2000 and April 2005, 498 patients (69%) were enrolled who completed the baseline questionnaire and at least one follow-up survey at 1, 3, or 6 months. The mean patient age at ORP, LRP, dVP, (103)Pd, and PCryo was 59, 61, 60, 67, and 72 years, respectively. Within Group I, early recovery of sexual function (at 3 months) appeared to occur sooner after dVP (35% return to baseline [RTB]) than ORP (24% RTB) and LRP (21% RTB) (P = 0.03). No other significant differences were noted, and trends toward improvement were seen in all groups. Within Group II, PCryo (18% RTB) had a more negative impact on sexual function at 3 months than did 103Pd (63% RTB) (P = 0.007), although a significant difference in baseline sexual function was also noted (P = 0.001). Early urinary function (at 1 month) was better after (103)Pd (82% RTB) than PCryo (72%) (P = 0.05), but this difference was lost at 6 months. In addition, the irritative and obstructive symptoms evaluated by the AUA SI were significantly worse (P = 0.003) at 3 months after (103)Pd than after PCryo. CONCLUSIONS: Different surgical approaches for the treatment of localized prostate cancer affect the shortterm QoL results in different ways. Urinary, sexual, and bowel function and bother are affected to a similar degree by ORP, LRP, and dVP. In an older population, the tissue destruction resulting from PCryo appears to relieve obstructive and irritative urinary symptoms but at the sacrifice of sexual function compared with (103)Pd.     

Basiliximab: a comparative study between the use of the recommended two doses versus a single dose in living donor kidney transplantation

Basiliximab (Simulect) is a high-affinity chimeric and humanized monoclonal antibody, directed against the alpha chain of human interleukin-2 receptor (CD25). The administration of two doses (20 mg intravenously per dose), one given 2 hours before transplantation and the second on day 4 posttransplant, provides suppression of the interleukin-2 receptor for up to 45 days, reducing the rate of acute rejection in kidney transplantation. This study was designed to compare the efficacy of a single dose of Simulect to the recommended two doses. The other objective was the reduction of the costs related to the standard two dose protocol. Fifty-two patients were included: group I (32 patients) received two doses of Simulect; group II (20 patients) received one dose. There were 39 living related donors and 13 living unrelated. All patients were followed for 1 year. Maintenance immunosuppression consisted of tacrolimus or cyclosporine, mycophenolate mofetil, and steroids. The diagnosis of rejection was made clinically. All episodes were treated with intravenous steroids. The incidence of rejection was similar in both groups; there was no graft loss to rejection. There were two deaths in group I, and one death in group II, yielding graft and patient actual survival rates at 1 year of 93% and 95%, respectively. These results suggest that Simulect is equally effective when administered in two doses or in a single dose in kidney transplantation. The reduction of cost by giving a single dose is significant, especially in developing countries without national health insurance.     

The efficacy and safety of degarelix: a 12‐month,comparative, randomized,open‐label,parallel‐group phase III study in patients with prostate cancer

OBJECTIVE

To evaluate the efficacy and safety of degarelix, a new gonadotrophin‐releasing hormone (GnRH) antagonist (blocker), vs leuprolide for achieving and maintaining testosterone suppression in a 1‐year phase III trial involving patients with prostate cancer.

PATIENTS AND METHODS

In all, 610 patients with adenocarcinoma of the prostate (any stage; median age 72 years; median testosterone 3.93 ng/mL, median prostate‐specific antigen, PSA, level 19.0 ng/mL) were randomized and received study treatment. Androgen‐deprivation therapy was indicated (neoadjuvant hormonal treatment was excluded) according to the investigator’s assessment. Three dosing regimens were evaluated: a starting dose of 240 mg of degarelix subcutaneous (s.c.) for 1 month, followed by s.c. maintenance doses of 80 mg or 160 mg monthly, or intramuscular (i.m.) leuprolide doses of 7.5 mg monthly. Therapy was maintained for the 12‐month study. Both the intent‐to‐treat (ITT) and per protocol populations were analysed.

RESULTS

The primary endpoint of the trial was suppression of testosterone to ≤0.5 ng/mL at all monthly measurements from day 28 to day 364, thus defining the treatment response. This was achieved by 97.2%, 98.3% and 96.4% of patients in the degarelix 240/80 mg, degarelix 240/160 mg and leuprolide groups, respectively (ITT population). At 3 days after starting treatment, testosterone levels were ≤0.5 ng/mL in 96.1% and 95.5% of patients in the degarelix 240/80 mg and 240/160 mg groups, respectively, and in none in the leuprolide group. The median PSA levels at 14 and 28 days were significantly lower in the degarelix groups than in the leuprolide group (P < 0.001). The hormonal side‐effect profiles of the three treatment groups were similar to previously reported effects for androgen‐deprivation therapy. The s.c. degarelix injection was associated with a higher rate of injection‐site reactions than with the i.m. leuprolide injection (40% vs <1%; P < 0.001, respectively). There were additional differences between the degarelix and leuprolide groups for urinary tract infections (3% vs 9%. P < 0.01, respectively), arthralgia (4% vs 9%, P < 0.05, respectively) and chills (4% vs 0%, P < 0.01, respectively). There were no systemic allergic reactions.

CONCLUSIONS

Degarelix was not inferior to leuprolide at maintaining low testosterone levels over a 1‐year treatment period. Degarelix induced testosterone and PSA suppression significantly faster than leuprolide; PSA suppression was also maintained throughout the study. Degarelix represents an effective therapy for inducing and maintaining androgen deprivation for up to 1 year in patients with prostate cancer, and has a different mechanism of action from traditional GnRH agonists. Its immediate onset of action achieves a more rapid suppression of testosterone and PSA than leuprolide. Furthermore, there is no need for antiandrogen supplements to prevent the possibility of clinical ‘flare’.     

Aceclofenac–tizanidine in the treatment of acute low back pain: a double-blind, double-dummy, randomized, multicentric, comparative study against aceclofenac alone

Tizanidine and aceclofenac individually have shown efficacy in the treatment of low back pain. The efficacy and tolerability of the combination have not yet been established. The objective of the study was to evaluate the efficacy and safety of aceclofenac-tizanidine fixed dose combination against aceclofenac alone in patients with acute low back pain. This double-blind, double-dummy, randomized, comparative, multicentric, parallel group study enrolled 197 patients of either sex in the age range of 18–70 years with acute low back pain. The patients were randomized to receive either aceclofenac (100 mg)–tizanidine (2 mg) b.i.d or aceclofenac (100 mg) alone b.i.d for 7 days. The primary efficacy outcomes were pain intensity (on movement, at rest and at night; on VAS scale) and pain relief (on a 5-point verbal rating scale). The secondary efficacy outcomes measures included functional impairment (modified Schober’s test and lateral body bending test) and patient’s and investigator’s global efficacy assessment. aceclofenac–tizanidine was significantly superior to aceclofenac for pain intensity (on movement, at rest and at night; P < 0.05) and pain relief (P = 0.00) on days 3 and 7. There was significant increase in spinal flexion in both the groups from baseline on days 3 and 7 with significant difference in favour of the combination group (P < 0.05). There were significantly more number of patients with excellent to good response for the aceclofenac–tizanidine treatment as compared to aceclofenac alone (P = 0.00). Both the treatments were well tolerated. In this study, aceclofenac–tizanidine combination was more effective than aceclofenac alone and had a favourable safety profile in the treatment of acute low back pain.     

Platelet function following administration of a novel formulation of intravenous diclofenac sodium versus active comparators: a randomized, single dose, crossover study in healthy male volunteers

Study ObjectiveTo assess platelet function and safety following single-dose administration of a novel formulation of intravenous (IV) diclofenac sodium (Dyloject) 37.5 mg versus oral diclofenac 50 mg, IV ketorolac 30 mg, and oral acetylsalicylic acid (ASA) 325 mg.DesignOpen-label, randomized, single-dose, 4-treatment crossover study.SettingClinical research unit.Patients30 healthy, ASA physical status I adult men.InterventionsSubjects were randomized to one of 6 treatment sequences that included 4 single-dose treatments. Study drug administration occurred on Days 1, 3, 5, and 7.MeasurementsPlatelet count, closure time as measured by platelet function analyzer (PFA-100), prothrombin time (PT), activated partial thromboplastin time (aPTT), and plasma concentrations of the study drugs were obtained over 24 hours after each treatment. The primary endpoint was the area under the curve for PFA collagen-epinephrine (CEPI) closure time difference from 0-6 hours post-drug administration (AUC_0-6h). Secondary endpoints included the maximum change from baseline in PFA CEPI closure time.Main ResultsAUC_0-6h (mean ± SD) for CEPI closure time difference was significantly smaller after IV diclofenac 37.5 mg (249 ± 216 sec.hrs) than after ketorolac [and ASA (950 ± 287 sec.hrs and 834 ± 237 sec.hrs, respectively); P ≤ 0.0001 for both] but not after the oral diclofenac control (286 ± 265 sec.hrs; P = 0.40). Similarly, the maximum change from baseline in PFA CEPI closure time was lower after IV diclofenac than after ketorolac or ASA across all time intervals examined. There were no significant changes in PT or aPTT at any time point with any treatment. There was a low frequency of adverse events.ConclusionsAcetylsalicylic acid and ketorolac both substantially disrupted platelet function in contrast to IV diclofenac 37.5 mg or oral diclofenac 50 mg control. Diclofenac, with its balanced COX-1 and COX-2 inhibitory profile, may pose less risk of postoperative bleeding than nonsteroidal antiinflammatory drugs (NSAIDs) such as ketorolac and ASA, which predominantly inhibit COX-1.     

Effect of prophylactic treatment with intravesical epirubicin on recurrence of superficial bladder cancer--The 6th Trial of the Japanese Urological Cancer Research Group (JUCRG): a randomized trial of intravesical epirubicin at dose of 20mg/40ml, 30mg/40ml, 40mg/40ml

OBJECTIVES: We compared the prophylactic efficacy and safety of epirubicin (EPI) in primary superficial bladder cancer. METHODS: The major inclusion criteria were primary superficial bladder tumour (Ta, T1, G1, G2) and new cases of primary multiple tumours, or recurrent cases. The major exclusion criteria were Tis or G3 tumours. Group A received 17 doses of EPI 20mg/40ml over a period of 12 months for a total dose of 340mg. In contrast, Group B received 12 doses of EPI 30mg/40ml over a period of 7 months, while Group C received 9 doses of EPI 40mg/40ml over a period of 4 months, both for a total dose of 360mg. This study enrolled a total of 622 patients diagnosed as having primary superficial bladder cancer during the period from June 1994 through November 1996 at the 118 institutions. Follow-up of the patients was conducted through October 1999. RESULTS: The relationship between the EPI concentration and the recurrence-free rate was evaluated by Tarone's test, and it was found that the recurrence-free rate became significantly higher as the drug concentration increased (p=0.0375). In the safety evaluation, with regard to adverse drug reactions, pollakiuria and pain on urination occurred at significantly higher incidences as the concentration of the EPI solution increased. CONCLUSIONS: The greatest effect of intravesical instillation of EPI after TUR-BT was shown by the regimen using the highest concentration of the drug solution which was administered during a short period of time.     

Evaluation of the efficacy and safety of once-a-day dosing of tadalafil 5mg and 10mg in the treatment of erectile dysfunction: results of a multicenter, randomized, double-blind, placebo-controlled trial

BACKGROUND: Erectile dysfunction (ED) is a chronic disease; however, therapy is currently administered as needed with oral phosphodiesterase 5 (PDE5) inhibitors like tadalafil. Because the 17.5-h half-life of tadalafil enables therapeutic plasma levels to be sustained with daily administration, tadalafil is a good candidate for once daily dosing therapy. METHODS: This multicenter, randomized, double-blind, placebo-controlled, parallel-group, 12-week study enrolled 268 men 1:2:2 to placebo, tadalafil 5mg, and tadalafil 10mg taken once daily. Primary efficacy measures included changes in the International Index of Erectile Function Erectile Function domain (IIEF EF), Sexual Encounter Profile diary Questions 2 (SEP2: successful penetration), and 3 (SEP3: successful completion of intercourse), and tolerability. Secondary measures included percentage of patients at endpoint who reported improved erectile function (EF), and percentage who reported "no ED" (IIEF EF score 26-30). RESULTS: For patients who took placebo, tadalafil 5mg, and tadalafil 10mg, changes from baseline to endpoint were, respectively, 0.9, 9.7, and 9.4 for IIEF EF; 11.2, 36.5, and 39.4 for SEP2; and 13.2, 45.5, and 50.1 for SEP3. At endpoint, 28.3%, 84.5%, and 84.6% reported improved erections, and 8.3%, 51.5%, and 50.5% reported "no ED," respectively. All comparisons between tadalafil and placebo were significant (p<0.001). Adverse events that occurred in at least 5% of patients were dyspepsia, headache, back pain, upper abdominal pain, and myalgia; nine patients (3.4%) discontinued because of adverse events. CONCLUSIONS: Once-a-day tadalafil 5mg or 10mg was well tolerated and significantly improved EF in men with ED.