Topical insulin in wound healing: a randomised, double-blind, placebo-controlled trial

Two studies were carried out to assess the relative roles of insulin and zinc in the acceleration of wound healing. In the first study, six diabetic and five non-diabetic human volunteers had two uniform cuts created, one on each forearm. One forearm wound was treated with topical regular insulin (Iletin-II) and the other with normal saline four times a day until healed. Treatment was double-blind and forearms were assigned randomly. The wounds treated with insulin healed 2.4 +/- 0.8 days faster than the wounds treated with saline (P < 0.001 by paired t-test). Zinc is used to crystallise insulin. When wounds are treated with insulin, they are therefore also being treated with zinc. If insulin accelerates wound healing, it is not clear if the increase in the rate of healing would be due to insulin (a known growth factor), the zinc it contains, or a combination of the two. The second study used a randomised, double-blind, placebo-controlled design to compare the efficacy of insulin with that of a solution containing the same amount of zinc in accelerating the healing of standardised wounds in rats and humans. Although these pilot investigations did not have the power to define the relative roles of insulin and zinc with accuracy, the results suggest that zinc does play a role in the wound healing process. It is concluded that topical insulin accelerates wound healing in humans. More importantly, however, this study describes a method of creating uniform wounds in humans acceptable to an institutional review board, thus solving one of the major impediments to the scientific evaluation of human wound healing.     

A prospective, randomized clinical trial of wound debridement versus conservative wound care in soft-tissue injury from civilian gunshot wounds

While clear-cut evidence exists documenting the extensive tissue destruction from blast and cavitation in high-velocity projectile injury and that wounds from projectiles of all velocities can be contaminated by bacteria potentially leading to infection, less is known about the tissue effects of lower-velocity projectile injury from gunshot wounds seen in the civilian sector. Despite this, traditional recommendations have supported debridement, admission, and aggressive wound care in these patients. This study will determine the effect of two methods of wound care on the outcome of soft-tissue gunshot wounds. Patients who had suffered a gunshot wound and were transported to the Trauma Center at the University of Florida Health Science Center postinjury were considered eligible for this study. All patients with torso injury, skeletal injury, neurovascular injury, or vascular proximity were excluded. Patients were then randomized to two treatment regimens based on a previously determined scheme. All wound care, follow-up, and healing evaluations were performed by the same individual. A total of 163 patients met the study criteria and they were randomized to the two treatment regimens: 89 patients, debridement and wound care; 74 patients, wound care alone. Each group was similar in age, sex, time to treatment, and caliber/velocity. Patients available for follow-up were similar in each group. Four patients in the wound-debridement group and two patients in the conservative wound-care group developed superficial infections. All infections responded to prompt local therapy. This study supports the conservative treatment of soft-tissue injury from low-velocity gunshot wounds.     

Desmopressin in the treatment of nocturia: a double-blind, placebo-controlled study

OBJECTIVES: To investigate efficacy, safety, and impact on quality of sleep of desmopressin in the treatment of nocturia. METHODS: Adults aged > or =18 yr with nocturia (> or =2 voids/night) received desmopressin tablets (0.1, 0.2, or 0.4 mg) during a 3-wk dose-titration period. Patients should show sufficient response during the dose-titration period (> or =20% reduction in nocturnal diuresis) and a return of nocturnal diuresis to > or =80% of baseline levels during washout. Eligible patients then entered a 3-wk double-blind treatment period and received either desmopressin or placebo. RESULTS: 127 patients were randomised to either desmopressin (n=61) or placebo (n=66). Twenty (33%) desmopressin-treated patients compared with seven (11%) placebo-treated patients showed a clinical response, defined as a > or =50% reduction in the number of nocturnal voids compared with baseline (p=0.0014). Compared with placebo, desmopressin resulted in a significant reduction in the mean number of nocturnal voids (39% reduction with desmopressin vs. 15% with placebo; absolute difference -0.84, p<0.0001) and duration of the first sleep period (prolonged by 108 min with desmopressin vs. 41 min with placebo; p<0.0001). Quality of sleep was also improved with desmopressin versus placebo (statistically significant for one of the two parameters evaluated). Adverse events were mainly mild. CONCLUSIONS: Oral desmopressin tablets provide an effective and well-tolerated treatment for nocturia. Compared with placebo, nocturnal voiding frequency is reduced, duration of the first sleep period is increased, and sleep quality may be improved.     

Vitamin E therapy in IgA nephropathy: a double-blind,placebo-controlled study

IgA nephropathy is the world's most common primary glomerulonephropathy. Recent evidence in a rat model implicated excessive production of oxygen-free radicals in the pathogenesis and suggested that vitamin E-treatment ameliorated progression. We studied this antioxidant therapy on the glomerular filtration rate (GFR), proteinuria and hematuria in biopsy-proven IgA nephropathy in children. The duration of treatment or placebo was 2 years, with vitamin E treatment consisting of 400 IU/day in children weighing <30 kg, and twice that dose for those >30 kg. We measured GFR at entry, midpoint and exit. At baseline and at 4-month intervals after randomization, urinary protein/creatinine ratios and urinalysis were examined. The mixed model procedure with log transformation was used in data analysis to test treatment difference as well as the potential time effect. Fifty-five patients were randomized and 38 completed at least 1 year of follow-up. At entry, the clinical characteristics were not different between the treatment and placebo groups. There was a trend toward better preservation of GFR in vitamin E-treated versus placebo patients, 127±50 vs. 112±31 ml/min/1.73 m², respectively (P=0.09). The urinary protein/creatinine ratio was significantly lower in the vitamin E-treated group vs. placebo; 0.24±0.38 vs. 0.61±1.37 (P<0.013). However, there was no difference in the prevalence of hematuria between the groups. Vitamin E treatment in our study patients was associated with significantly lower proteinuria, but no effect on hematuria. While there was a trend toward stabilization of GFR in the vitamin E-treated patients, long-term treatment and follow-up are needed to determine whether antioxidant therapy is associated with preservation of renal function in IgA nephropathy.     

Palliation of painful bone metastases from prostate cancer using sodium etidronate: results of a randomized, prospective, double-blind, placebo-controlled study

Sodium etidronate is a diphosphonate compound that inhibits bone resorption and mineralization. The drug has been reported to be highly effective for the palliation of painful bone metastasis from prostatic cancer. Fifty-seven patients were entered into a randomized, prospective, double-blind, placebo-controlled study of sodium etidronate. All patients had hormone refractory metastatic prostatic cancer and bone pain requiring analgesics. No difference was seen in the symptomatic response rate or analgesic requirement between patients treated with sodium etidronate and placebo. With the dose scheme used in this study sodium etidronate was ineffective for palliation of bone pain from prostatic cancer.     

Melatonin vs. midazolam premedication in children: a double-blind, placebo-controlled study

BACKGROUND AND OBJECTIVE: Unlike midazolam, melatonin premedication is not associated with cognitive impairment in adults despite its anxiolytic properties. The use of melatonin as a premedicant in children has not been reported. This randomized, double-blind, placebo-controlled study compared the perioperative effects of different doses of melatonin and midazolam in children. METHODS: Seven groups of children (n = 15 in each) were randomly assigned to receive one of the following premedicants. Midazolam 0.1, 0.25 or 0.5 mg kg(-1) orally, melatonin 0.1, 0.25 or 0.5 mg kg(-1) orally each mixed in 15 mg kg(-1) acetaminophen, or placebo only (15 mg kg(-1) acetaminophen). Anxiety and temperament were evaluated before and after administration of the study drug, on separation from parents and on the introduction of the anaesthesia mask. At week 2 postoperatively, the behaviour of the children was measured by the Post Hospitalization Behaviour Questionnaire. RESULTS: Melatonin or midazolam each in doses of 0.25 or 0.5 mg kg(-1) were equally effective as premedicants in alleviating separation anxiety and anxiety associated with the introduction of the anaesthesia mask. A trend was noted for midazolam to prolong recovery times as the dosage increased. The use of melatonin was associated with a lower incidence (P = 0.049) of excitement at 10 min postoperatively, and a lower incidence (P = 0.046) of sleep disturbance at week 2 postoperatively than that observed with midazolam and control groups. No postoperative excitement was noted in the melatonin groups at 20, 30 and 45 min. DISCUSSION: Melatonin was not only as effective as midazolam in alleviating preoperative anxiety in children, but it was also associated with a tendency towards faster recovery, lower incidence of excitement postoperatively and a lower incidence of sleep disturbance at week 2 postoperatively.     

Salvage of sildenafil failures with cabergoline: a randomized, double-blind, placebo-controlled study

To evaluate the safety and efficacy of cabergoline in men with erectile dysfunction (ED) who did not respond to sildenafil. Four hundred two sildenafil nonresponders aged from 21 to 59 years were included in the study. Patients were randomly divided into group 1, those who received 0.5-1 mg cabergoline weekly for 6 months and group 2, who received placebo for the same period. They underwent preliminary assessment, including medical and sexual history, self-administered International Index of Erectile Function (IIEF) and intravaginal ejaculatory latency time (IVELT) evaluation. Standard biochemistry and hematological laboratory tests, and measurement of serum testosterone and prolactin levels were also carried out. When indicated, other tests were used to establish the diagnosis of vasculogenic and neurogenic ED, including penile color duplex Doppler ultrasonography, pudendal nerve conduction test and impaired sensory-evoked potentials studies. The efficacy of two treatments was assessed every 2 weeks during treatment, at the end of the study, using responses to IIEF, IVELT evaluation, mean intercourse satisfaction domain, mean weekly coitus episodes and adverse drug effects. The trial was completed by 370 (92%) men. Positive clinical results were seen in 31.2% of patients in the cabergoline group compared with 7.1% of patients in the placebo group (P=0.04). The mean weekly intercourse episodes increased from pretreatment values of 1.4 and 1.2 to 2.2 and 1.4, for cabergoline and placebo, respectively (P=0.04). Baseline mean intercourse satisfaction domain values of IIEF 10 and 11 reached to 15 and 10 at 6-month treatment in groups 1 and 2, respectively (P=0.04). The IVELT after cabergoline and placebo gradually increased from 98 and 101 s to approximately 242 and 116 s, respectively (P=0.001). More drug-related adverse effects occurred in cabergoline group and 12 (5.9%) had to discontinue treatment (P=0.001). Cabergoline is moderately effective salvage therapy for sildenafil nonresponse. Further studies with different dosages and treatment regimens are necessary to draw final conclusions on the efficacy of this drug in ED.     

Pregabalin reduces post-operative pain after mastectomy: a double-blind, randomized, placebo-controlled study

Background: Pregabalin is used for the treatment of neuropathic pain and has shown analgesic efficacy in post‐operative pain. The aim of this randomized, double‐blinded, placebo‐controlled trial (Clinical Trials.gov ID NCT00938548) was to investigate the efficacy and safety of pregabalin for reducing post‐operative pain in patients after mastectomy. Methods: Eighty‐four women scheduled for elective mastectomy were randomly assigned to groups that received either pregabalin (75 mg) or placebo, 1 h before surgery and 12 h after the initial dose. Assessments of pain [verbal numerical rating scale (VNRS), at rest and with arm abduction] and side effects were performed at 1, 6, 24 and 48 h post‐operatively. After discharge from the hospital, pain was assessed by telephone interview at post‐operative 1 week and 1 month. Results: VNRS scores for pain at rest were lower in the pregabalin group (n=42) than the placebo group (n=42) at 1, 24 and 48 h post‐operatively (P<0.05). VNRS scores for pain with arm abduction were lower in the pregabalin group (n=42) than the placebo group (n=42) at 1 and 24 h, and 1 week post‐operatively (P<0.05). Incidences of side effects such as nausea and vomiting, headache, dizziness and blurred vision were similar in both groups. Conclusion: Perioperative administration of pregabalin for a single day (75 mg twice daily) was easy, safe and effective in reducing post‐operative pain in patients undergoing mastectomy.     

Intravenous lidocaine suppresses fentanyl-induced coughing: a double-blind, prospective, randomized placebo-controlled study

IV lidocaine is effective in suppressing the cough reflex of tracheal intubation, extubation, bronchography, bronchoscopy, and laryngoscopy. We investigated this effect of lidocaine on fentanyl-induced cough in 502 patients of ASA physical status I and II scheduled for elective surgery. The patients were assigned to 2 equal groups to receive either lidocaine 1.5 mg/kg or placebo (0.9% saline) over 5 s 1 min before the administration of fentanyl 3 mug/kg in a randomized and double-blind fashion. Coughs were classified as coughing and graded as mild (1-2), moderate (3-4), or severe (5 or more). The results of the study suggest that IV lidocaine 1.5 mg/kg, when administered 1 min before fentanyl, is significantly effective in suppressing fentanyl-induced cough compared to placebo (0.9% saline) (218 versus 165 patients) (P < 0.002) but without affecting the severity of cough (P > 0.05).     

Gabapentin in postamputation phantom limb pain: a randomized,double-blind,placebo-controlled,cross-over study

BACKGROUND AND OBJECTIVES: Severe phantom limb pain after surgical amputation affects 50% to 67% of patients and is difficult to treat. Gabapentin is effective in several syndromes of neuropathic pain. Therefore, we evaluated its analgesic efficacy in phantom limb pain. METHODS: Patients attending a multidisciplinary pain clinic with phantom limb pain were enrolled into this randomized, double-blind, placebo-controlled, cross-over study. Other anticonvulsant therapy was discontinued. Each treatment was 6 weeks separated by a 1-week washout period. Codeine/paracetamol was allowed as rescue analgesia. The daily dose of gabapentin was titrated in increments of 300 mg to 2400 mg or the maximum tolerated dose. Patients were assessed at weekly intervals. The primary outcome measure was visual analog scale (VAS) pain intensity difference (PID) compared with baseline at the end of each treatment. Secondary measures were indices of sleep interference, depression (Hospital Anxiety and Depression [HAD] scale), and activities of daily living (Bartel Index). RESULTS: Nineteen eligible patients (mean age, 56 years; range, 24 to 68 years; 16 men) were randomized, of whom 14 completed both arms of the study. Both placebo and gabapentin treatments resulted in reduced VAS scores compared with baseline. PID was significantly greater than placebo for gabapentin therapy at the end of the treatment (3.2 +/- 2.1 v 1.6 +/- 0.7, P =.03). There were no significant differences between placebo and gabapentin therapy in terms of the number of tablets of rescue medication required, sleep interference, HAD scale, or Bartel Index. The medication was well tolerated with few reports of adverse effects. CONCLUSIONS: After 6 weeks, gabapentin monotherapy was better than placebo in relieving postamputation phantom limb pain. There were no significant differences in mood, sleep interference, or activities of daily living, but a type II error cannot be excluded for these variables.     

Subarachnoid sufentanil for early postoperative pain management in orthopedic patients: a placebo-controlled, double-blind study using spinal microcatheters

BACKGROUND: Continuous spinal anesthesia is frequently used for intraoperative anesthesia but rarely for postoperative pain management. Because even small doses of local anesthetics can be associated with motor deficits, subarachnoid opioid injection may be an alternative. METHODS: Eighty patients randomly received a subarachnoid injection of 10 microg sufentanil, 5 mg bupivacaine, 2.5 microg sufentanil plus 2.5 mg bupivacaine, or saline through 28-gauge spinal microcatheters for early postoperative pain relief after major lower-limb surgery (n = 20 in each group). Hemodynamic and respiratory parameters, pain scores, and motor function were monitored, and sufentanil concentrations in plasma and cerebrospinal fluid were measured. Ten additional patients received up to three repetitive injections of 10 microg sufentanil over 24 h. RESULTS: All drugs provided excellent pain relief within 15 min after injection, lasting 128 +/- 61 min with sufentanil, 146 +/- 74 min with bupivacaine, and 167 +/- 78 min with the mixture. Patients receiving bupivacaine showed the highest cephalad extension of sensory block (median, T6) and the most intense motor block, whereas patients given only sufentanil had no motor deficit. The duration of analgesia was shorter after subsequent sufentanil injection (100-115 min) than after the first injection (198 +/- 70 min). Six of 50 patients with sufentanil experienced a short episode of respiratory depression within 30 min after the first injection. Cerebrospinal fluid concentrations of sufentanil peaked at 5 min after injection (183 +/- 167 ng/ml) but were at the level of detection in the plasma. CONCLUSIONS: Sufentanil injected through microspinal catheters provided profound pain relief without impairing motor function when compared with bupivacaine. However, close monitoring remains mandatory in this setting.     

Reduction of blood loss using high-dose aprotinin in major orthopaedic surgery: a prospective,double-blind,randomised and placebo-controlled study

We have investigated in a prospective,randomised placebo-controlled study the effect of high-dose aprotinin on blood loss in patients admitted for major surgery (revision arthroplasty of the hip or knee, or for resection of a soft-tissue sarcoma). The mean intraoperative blood loss was reduced from 1957 ml in the control group to 736 ml in the aprotinin group (p = 0.002). The mean requirement for intraoperative homologous blood transfusion in the aprotinin group was 1.4 units (95% CI 0.2 to 2.7) and 3.1 units (95% CI 1.7 to 4.6) in the control group (p = 0.033). The mean length of hospital stay was reduced from 27.8 days in the control group to 17.6 days in the aprotinin group which was not statistically significant. The intraoperative use of aprotinin in major orthopaedic operations significantly reduced blood loss and the required amount of packed cells. It may result in in the length of hospital stay and costs.     

Tranexamic acid in off-pump coronary surgery: a preliminary, randomized, double-blind, placebo-controlled study

BACKGROUND: We evaluated the hemostatic effects of tranexamic acid, a synthetic antifibrinolytic drug, in patients undergoing beating-heart coronary surgery. METHODS: Forty consecutive patients were in a double-blind manner, prospectively randomized into two groups: 20 patients received tranexamic acid (bolus of 1 g before skin incision, followed by continuous infusion of 400 mg/hr during surgery), and 20 patients received saline. As primary outcomes, bleeding and allogeneic transfusions were considered. D-dimer and fibrinogen plasma levels were also evaluated to monitor the activation of fibrinolysis. Major postoperative thrombotic events, as a potential consequence of antifibrinolytic treatment, were recorded. RESULTS: The treatment group had significantly lower postoperative bleeding (median [25th to 75th percentiles]: 400 mL [337 to 490 mL] vs 650 ml [550 to 862 mL], p < 0.0001), lower need for allogeneic blood products (1,200 vs 5,300 mL, p < 0.001), and lower postoperative D-dimer plasma levels. No postoperative thrombotic complications were observed in either group. CONCLUSIONS: In this initial series of patients undergoing off-pump coronary surgery, tranexamic acid appears to be effective in reducing postoperative bleeding and the need for allogeneic blood products.     

Effect of cilostazol in patients with intermittent claudication: a randomized, double-blind, placebo-controlled study

A multicenter, double-blind, randomized, placebo-controlled, parallel study was conducted to compare the efficacy and safety of cilostazol 100 mg and 50 mg, both administered twice daily, with that of placebo in patients with moderately severe intermittent claudication (IC) secondary to peripheral arterial disease.A total of 394 subjects 40 years of age or older with chronic, stable, symptomatic IC received cilostazol 100 mg twice daily, 50 mg twice daily, or placebo for 24 weeks. Subjects receiving cilostazol 100 mg twice daily experienced a 21% net improvement in maximal walking distance (MWD)compared with placebo subjects (p = 0.0003) and a 22% net improvement in distance walked to the onset of symptoms (PFWD) (p = 0.0015). Subjects who received cilostazol 50 mg twice daily also benefited from therapy, but not to a statistically significant degree (7% and 11% improvement in MWD and PFWD, respectively). Quality-of-life and functional status assessments corroborated these objective results. Cilostazol, in particular 100 mg twice daily, significantly improves symptoms in patients with IC.     

Maggot debridement therapy of infected ulcers: patient and wound factors influencing outcome - a study on 101 patients with 117 wounds

INTRODUCTION

It has been known for centuries that maggots are potent debriding agents capable of removing necrotic tissue and slough. In January 2004, the US Food and Drug Administration decided to regulate maggot debridement therapy (MDT). As it is still not clear which wounds are likely or unlikely to benefit from MDT, we performed a prospective study to gain more insight in patient and wound characteristics influencing outcome.

PATIENTS AND METHODS

In the period between August 2002 and December 2005, patients with infected wounds with signs of gangrenous or necrotic tissue who seemed suited for MDT were enrolled in the present study. In total, 101 patients with 117 ulcers were treated. Most wounds were worst-case scenarios, in which maggot therapy was a treatment of last resort.

RESULTS

In total, 72 patients (71%) were classified as ASA III or IV. In total, 78 of 116 wounds (67%) had a successful outcome. These wounds healed completely (n = 60), healed almost completely (n = 12) or were clean at least (n = 6) at last follow-up. These results seem to be in line with those in the literature. All wounds with a traumatic origin (n = 24) healed completely. All wounds with septic arthritis (n = 13), however, failed to heal and led in half of these cases to a major amputation. According to a multivariate analysis, chronic limb ischaemia (odds ratio [OR], 7.5), the depth of the wound (OR, 14.0), and older age (≥ 60 years; OR, 7.3) negatively influenced outcome. Outcome was not influenced by gender, obesity, diabetes mellitus, smoking, ASAclassification, location of the wound, wound size or wound duration.

CONCLUSIONS

Some patient characteristics (i.e. gender, obesity, smoking behaviour, presence of diabetes mellitus and ASA-classification at presentation) and some wound characteristics (i.e. location of the wound, wound duration and size) do not seem to contra-indicate eligibility for MDT. However, older patients and patients with chronic limb ischaemia or deep wounds are less likely to benefit from MDT. Septic arthritis does not seem to be a good indication for MDT.