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Effect of nitric-oxide-generating system on microcirculatory blood flow in skin of patients with severe Raynaud's syndrome: a randomised trial.

BACKGROUND: Patients with Raynaud's syndrome have abnormal digital vasoconstriction, which may be secondary to impaired synthesis of, or impaired sensitivity to, nitric oxide. We studied the effect on microcirculation of a nitric-oxide-generating system applied topically to the finger and forearm of healthy volunteers and patients with primary Raynaud's syndrome. METHODS: We did a single-blind, randomised, placebo controlled, cross-over study of the microcirculatory response to topical application of a nitric-oxidegenerating gel in 20 patients with severe Raynaud's syndrome, and ten healthy volunteers. We prepared the nitric-oxide-generating system by mixing a solution of KY jelly and sodium nitrite (5% weight/volume), with a solution of KY jelly and ascorbic acid (5% weight/volume). About 0.5 mL of each solution was separately applied to the skin of the forearm (3 cm2), and then mixed with a sterile cotton bud. A similar procedure was done simultaneously on the other arm with KY jelly only (placebo). The procedure was then repeated on the finger pulps. Changes in skin microcirculatory volume and flux were measured bilaterally by infrared photoplethysmography and laser doppler fluxmetry, respectively. FINDINGS: In the forearm, blood flow increased significantly after application of the active gel both in patients with Raynaud's syndrome (microcirculatory volume from mean area under the curve 98 [SE 14] to 1024 [130]; microcirculatory flux from 5060 [462] to 74,800 [3940]) and in healthy controls (volume from 85 [19] to 1020 [60]; flux from 4420 [435] to 84,500 [7000]). In the fingers, although baseline blood flow was lower in patients than in controls, both groups showed increases with application of active gel (volume from 1100 [194] to 3280 [672] and 2380 [441] to 6160 [1160], respectively; flux from 33,400 [4200] to 108,000 [13,600] and 52,000 [8950] to 185,000 [19,500]). Increases in blood flow with placebo gel were not significant. No adverse effects were reported. INTERPRETATION: In primary Raynaud's syndrome, topical application of a nitric-oxide-generating system can stimulate an increase in both microcirculatory volume and flux.

Administration, Topical↗

A placebo-controlled, double-blind study of mesoglycan in the treatment of chronic venous ulcers.

OBJECTIVES: to assess the effect of treatment with mesoglycan, a sulphated polysaccharide compound, on the healing of venous ulcers. Design randomised, placebo-controlled, double-blind, multicentre trial. METHODS: non-diabetic outpatients with chronic venous insufficiency confirmed by duplex ultrasound, normal ankle/arm pressure index and presence of a leg ulcer were eligible. Patients were randomised to mesoglycan, 30 mg/day intramuscularly for 3 weeks followed by 100 mg/day orally, or matching placebo, as an adjunct to compression therapy and topical wound care. Treatment and observation were continued until complete ulcer healing or for 24+/-1 weeks. Time to ulcer healing and healing rates were estimated with the Kaplan-Meier method. RESULTS: One hundred and eighty-three patients were randomised and included in the analysis (92 mesoglycan, 91 placebo). Median ulcer area upon inclusion was 3.6 cm(2)in the mesoglycan group and 3.9 cm(2)in the placebo group. The estimated time to heal 75% of the patients was 90 days on mesoglycan versus 136 days on placebo, while the cumulative rate of healing by the end of observation was 97% versus 82%, respectively. The difference in favour of mesoglycan was statistically significant (p < 0.05, centre-stratified Cox's model). The relative risk of ulcer healing with mesoglycan was 1.48. The rate of adverse events was 7/92 on mesoglycan and 6/91 on placebo. CONCLUSIONS: treatment with mesoglycan in addition to established venous ulcer therapy resulted in a significantly faster and more frequent ulcer healing, and did not raise any safety concerns.

Chronic Disease↗

Efficacy and safety of brimonidine, dorzolamide and latanoprost as adjunctive therapy in primary open angle glaucoma.

A double-blind, randomised, controlled trial was carried out to evaluate the efficacy and safety of brimonidine, dorzolamide and latanoprost as an adjunctive therapy in patients with primary open angle glaucoma (POAG). A total of 200 males and 72 females with POAG uncontrolled with previous glaucoma therapy were randomly allocated to receive topical brimonidine 0.2% b.d. (n = 90), topical dorzolamide 2% b.d. (n=91) or topical latanoprost 0.005% o.d. (n = 91). One year post treatment, the mean percentage reduction in intraocular pressure (IOP) between the three groups was statistically significant (p < 0.0001). In an intergroup comparison of efficacy, there was a statistically significant difference between the brimonidine and dorzolamide groups (p = 0.018) and between the dorzolamide and latanoprost groups (p = 0.76) but the efficacy of brimonidine was not significantly higher than latanoprost in the brimonidine and latanoprost groups (p = 0.002). Patients experiencing mild to severe side-effects were statistically similar in the three groups. On an inter-drug comparison of side-effects, we found no statistically significant difference in the brimonidine and latanoprost groups (p = 0.25); and the brimonidine and dorzolamide groups (p = 0.067), while the number of side-effects with latanoprost was significantly higher in the dorzolamide and latanoprost groups (p<0.003). All three drugs caused a significant reduction in the mean IOP from pretreatment values. The brimonidine group had a higher number of patients experiencing severe side-effects necessitating alteration of therapy.

Administration, Topical↗

Intramedullary nails for extracapsular hip fractures in adults.

BACKGROUND: Intramedullary nails may be used for the surgical fixation of extracapsular hip fractures in adults. They may be inserted from the top (cephalocondylic) or from the bottom (condylocephalic) end of the femur. OBJECTIVES: To compare different types or design modifications of intramedullary nails used in the fixation of extracapsular hip fractures. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group specialised register (September 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 3, 2004), MEDLINE (1966 to September week 1 2004), EMBASE (1988 to 2004 Week 37), the UK National Research Register Issue 2, 2004, several orthopaedic journals, conference proceedings and reference lists of articles. SELECTION CRITERIA: All randomised or quasi-randomised trials comparing different types of intramedullary nails or modifications to the design of intramedullary nails in the treatment of extracapsular hip fractures in adults. DATA COLLECTION AND ANALYSIS: Both authors independently assessed trial quality and extracted data. Additional information was sought from all trialists. MAIN RESULTS: Four studies, involving a total of 834 predominantly female and older patients with mainly unstable trochanteric fractures, were included. All trials compared different designs of cephalocondylic nail. Allocation concealment was likely in one trial, not described in two and not done in the fourth. Two studies, with 674 participants, compared the proximal femoral nail versus the Gamma nail. Blood transfusion was greater for the proximal femoral nail group in one trial, yet blood loss was less in this group in the other trial. Pooled data for re-operation (relative risk 1.08, 95% confidence interval 0.65 to 1.81) and mortality (relative risk 1.24, 95% confidence interval 0.90 to 1.71) showed no statistically significant differences between the two groups. Limited data for long term function also showed no statistically significant differences. The two other studies, with 80 participants each, found respectively no differences between a gliding nail versus a Gamma nail; and a dynamically versus a statically locked intramedullary hip screw. AUTHORS' CONCLUSIONS: The limited evidence from the randomised trials undertaken to date is insufficient to determine if there are important differences in outcome between different designs of intramedullary nails used in the internal fixation of extracapsular hip fractures. Given the evidence of superiority of the sliding hip screw compared with intramedullary nails for extracapsular hip fractures, further studies comparing different designs of intramedullary nails are not a priority. Any new design should be evaluated in a randomised comparison with the sliding hip screw.

Aged↗

Intramedullary nails for extracapsular hip fractures in adults.

BACKGROUND: Intramedullary nails may be used for the surgical fixation of extracapsular hip fractures in adults. They may be inserted from the top (cephalocondylic) or from the bottom (condylocephalic) end of the femur. OBJECTIVES: To compare different types or design modifications of intramedullary nails used in the fixation of extracapsular hip fractures. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (March 2006), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 1, 2006), MEDLINE, EMBASE, the UK National Research Register, several orthopaedic journals, conference proceedings and reference lists of articles. SELECTION CRITERIA: All randomised or quasi-randomised trials comparing different types of intramedullary nails or modifications to the design of intramedullary nails in the treatment of extracapsular hip fractures in adults. DATA COLLECTION AND ANALYSIS: Both authors independently assessed trial quality and extracted data. Additional information was sought from all trialists. MAIN RESULTS: Six studies, involving a total of 1071 predominantly female and older people with mainly unstable trochanteric fractures, were included. Allocation concealment was likely in one trial, not described in three and not done in the other two trials. Four studies, with 910 participants, compared the proximal femoral nail with the Gamma nail. Though there was increased risk of comminution (fragmentation) at the fracture site when inserting a Gamma nail, there was no statistically significant difference in operative fracture of the femur (1/455 versus 5/455; relative risk 0.33, 95% confidence interval 0.07 to 1.63). No notable differences were seen between implants for fracture healing complications, reoperations and other post-operative complications. Pooled data showed no significant difference between implants for mortality (relative risk 1.08, 95% confidence interval 0.82 to 1.41) or function assessment outcomes. One study, with 80 participants, found no differences between a gliding nail versus a standard Gamma nail. Another study, with 81 participants, found no difference between a dynamically versus a statically locked intramedullary hip screw. AUTHORS' CONCLUSIONS: The limited evidence from the randomised trials undertaken to date is insufficient to determine whether there are important differences in outcome between different designs of intramedullary nails used in the internal fixation of extracapsular hip fractures. Given the evidence of superiority of the sliding hip screw compared with intramedullary nails for extracapsular hip fractures, further studies comparing different designs of intramedullary nails are not a priority. Any new design should be evaluated in a randomised comparison with the sliding hip screw.

Aged↗

Is ovarian surgery effective for androgenic symptoms of polycystic ovarian syndrome?

The effectiveness of laparoscopic ovarian drilling for treatment of anovulation in polycystic ovarian syndrome (PCOS) has been proved. The role of ovarian surgery in the treatment of symptoms related to hyperandrogenaemia, such as hirsutism and acne, has been less clear. This review sought to evaluate the effectiveness of ovarian surgery in the treatment of non-infertility symptoms related to PCOS. A systematic literature review was undertaken, by searching the Medline database for the years 1966-2002 inclusive. The search yielded 19 studies recording the outcomes of hirsutism, acne or androgen levels from surgical treatment for women with PCOS: three assessed unilateral oophorectomy; two ovarian wedge resection; and 14 ovarian drilling. There was no consensus of a clear improvement in hirsutism or acne in women undergoing surgery. There was a trend towards a decrease in serum androgen levels in most studies. We conclude that, while there is evidence that ovarian surgery may decrease androgen levels in some women with PCOS, the evidence that this translates into a clear improvement in hirsutism and acne is less clear. Further high quality clinical research, including data from randomisation, would be required to answer this question.

Acne Vulgaris↗

[Therapeutic strategies for patients with tuberculosis].

OBJECTIVES: To determine the effectiveness of strategies used to promote adherence to anti-tuberculosis treatment. SEARCH STRATEGY: MEDLINE 1966-1996 (August), Cochrane Collaboration Trials Registers (October 1996), LILACS 1982-1996 (September); reference lists in articles on adherence, contact with experts in the fields of TB and adherence research. SELECTION CRITERIA: Randomised or pseudo-randomised controlled trials of interventions to promote compliance with curative or preventive chemotherapy for TB, with at least one measure of adherence. DATA COLLECTION AND ANALYSIS: Data on study methods, participants, interventions and outcomes were collected for each study and methodological quality was assessed. Estimates of effect were assessed for categorical outcomes using the Peto odds ratio, with 95% confidence intervals. MAIN RESULTS: Strategies found to be of benefit were reminder cards sent to defaulters, assistance of patients by lay health workers, monetary incentives offered to patients, and increased supervision of TB clinic staff. It is not possible to determine from current trials whether health education by itself leads to better adherence to treatment. Even though directly-observed therapy (DOT) is widely advocated as the most cost-effective means of ensuring completion of TB treatment, no completed trials could be found which confirm or refute this view. CONCLUSIONS: RCT evidence exists that certain strategies improve adherence to anti-tuberculous therapy, and these should be adopted into clinical practice depending on their appropriateness to practice circumstances. Further innovations should be tested to find solutions that will be useful in low income countries. Randomised trials evaluating the independent effects of directly-observed therapy (DOT) are awaited.

Antitubercular Agents↗

Physical methods for preventing deep vein thrombosis in stroke.

BACKGROUND: Deep vein thrombosis (DVT) and resulting pulmonary embolism (PE) are uncommon but important complications of stroke. There is good evidence that anticoagulants can reduce the risk of DVT and PE after stroke, but this benefit is offset by a small but definite risk of serious haemorrhages. Physical methods to prevent DVT and PE (such as compression stockings applied to the legs) are not associated with any bleeding risk and are effective in some categories of medical and surgical patients. We sought to assess their effects in stroke patients. OBJECTIVES: To assess the effectiveness and safety of physical methods of preventing the onset of deep vein thrombosis and fatal or non fatal pulmonary embolism in patients with recent stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched October 2001). In addition we searched the following electronic bibliographic databases: Cochrane Controlled Trials Register (1999, Issue 3), MEDLINE (1966- Jan 2001), EMBASE (1980- Jan 2001) and CINAHL (1982-May 1999). The reference lists of all relevant papers were screened for additional trials. SELECTION CRITERIA: All completed randomised unconfounded trials or controlled clinical trials comparing physical methods in patients allocated to receive physical methods, applied within one week of onset of stroke, with patients allocated to no physical methods. DATA COLLECTION AND ANALYSIS: Two reviewers independently searched for relevant trials and three others independently checked the results. MAIN RESULTS: We identified two small trials which included 123 patients. In one trial of 97 patients, compression stockings were associated with a non significant trend towards a reduction in DVT detected by Doppler ultrasound. In one trial of 26 patients, an intermittent pneumatic compression device was not associated with a significant reduction in DVT detected by 125-I-fibrinogen scanning. Overall, physical methods were not associated with a significant reduction in DVT (Odds ratio 0.59, 95%.CI 0.24-1.48) or death (Odds ratio 5.06, 95% CI 0.96-26.78). REVIEWER'S CONCLUSIONS: There is insufficient evidence from randomised trials to support the routine use of physical methods for preventing DVT in acute stroke.

Bandages↗

Physical methods for preventing deep vein thrombosis in stroke.

BACKGROUND: Deep vein thrombosis (DVT) and resulting pulmonary embolism (PE) are uncommon but important complications of stroke. There is good evidence that anticoagulants can reduce the risk of DVT and PE after stroke, but this benefit is offset by a small but definite risk of serious haemorrhages. Physical methods to prevent DVT and PE (such as compression stockings applied to the legs) are not associated with any bleeding risk and are effective in some categories of medical and surgical patients. We sought to assess their effects in stroke patients. OBJECTIVES: To assess the effectiveness and safety of physical methods of preventing the onset of deep vein thrombosis and fatal or non fatal pulmonary embolism in patients with recent stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (last searched June 2003). In addition we searched the following electronic bibliographic databases: Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2003), MEDLINE (1966 to June 2003), EMBASE (1980 to June 2003) and CINAHL (1982 to June 2003). The reference lists of all relevant papers were screened for additional trials. SELECTION CRITERIA: Unconfounded randomised controlled trials comparing physical methods for the prevention of DVT with control, in which prophylaxis was started within seven days of the onset of stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently searched for relevant trials and three others independently checked the results. MAIN RESULTS: We identified two small trials which included 123 patients. In one trial of 97 patients, compression stockings were associated with a non significant trend towards a reduction in DVT detected by Doppler ultrasound. In one trial of 26 patients, an intermittent pneumatic compression device was not associated with a significant reduction in DVT detected by 125-I-fibrinogen scanning. Overall, physical methods were not associated with a significant reduction in DVT during the treatment period in survivors (Odds ratio (OR) 0.54, 95% Confidence Interval (CI) 0.18 to 1.57) or death (OR 1.54, 95% CI 0.5 to 4.77). REVIEWERS' CONCLUSIONS: There is insufficient evidence from randomised trials to support the routine use of physical methods for preventing DVT in acute stroke.

Bandages↗

Droperidol for acute psychosis.

BACKGROUND: People suffering from acute psychotic illnesses, especially those associated with agitated or violent behaviour, may require urgent pharmacological tranquillisation or sedation. Droperidol, a butyrophenone neuroleptic, has been used for this purpose in several countries. OBJECTIVES: To estimate the effects of droperidol compared to other treatments for controlling disturbed behaviour and reducing psychotic symptoms for people with suspected acute psychotic illnesses. SEARCH STRATEGY: We updated previous searches by searching the Cochrane Schizophrenia Group Register (September 2003). References of all identified studies were searched for further trial citations and authors of trials were contacted. Twenty-one other databases were also searched as part of a broader project and this composite database was searched for this review. This was supplemented by hand searching reference lists and contacting both the pharmacological industry and relevant authors. SELECTION CRITERIA: The review included randomised controlled trials comparing droperidol to any other treatment for people with suspected acute psychotic illnesses, including schizophrenia, schizoaffective disorder, mixed affective disorders, the manic phase of bipolar disorder or a brief psychotic episode. DATA COLLECTION AND ANALYSIS: Relevant studies were selected for inclusion, their quality was assessed and data extracted. Data were excluded when more than 50% of participants were lost to follow up. For binary outcomes, standard estimates of risk ratio (RR) and the corresponding 95% confidence intervals (CI) were calculated. Where possible, weighted number needed to treat or harm statistics (NNT, NNH), and the corresponding 95% confidence intervals (CI), were calculated. MAIN RESULTS: We identified only two relevant trials. One additional study focused on outcomes at 30 days rather than at a few hours. One small (n = 41) randomised trial compared intravenous (iv) droperidol (10 mg) with iv placebo and found that people allocated to droperidol were significantly less likely to need additional injections of another drug, haloperidol, in the first few minutes (n = 41, RR 0.37 CI 0.2 to 0.7, NNT 2 CI 1 to 10) compared to those given placebo. By 90 minutes this difference was still evident but not statistically significant (RR 0.46 CI 0.2 to 1.2). When 5 mg intramuscular (im) droperidol was compared with 5 mg im haloperidol, those given droperidol were also less likely to need additional injections by 30 minutes, than those given haloperidol, but this result was not statistically significant (n = 27, RR 0.45 CI 0.2 to 1.01). One person out of the 16 given haloperidol experienced a mild dystonic reaction (muscle spasms or abnormal contractions), while none of the 11 people allocated to droperidol were reported to have experienced adverse effects. REVIEWERS' CONCLUSIONS: This is an important, and surprisingly under-researched, area. To date, use of droperidol for emergency situations has been justified by experience rather than evidence from well conducted and reported randomised trials, but, as world reserves diminish, droperidol will no longer be a treatment option.

Acute Disease↗

Platinum containing regimens for metastatic breast cancer.

BACKGROUND: Studies have reported high tumour response rates for platinum-containing regimens in the treatment of women with metastatic breast cancer. OBJECTIVES: To identify and review the evidence from randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in the management of women with metastatic breast cancer. SEARCH STRATEGY: The specialised register maintained by the editorial base of the Cochrane Breast Cancer Group was searched on 2nd May 2003 using the codes for "advanced breast cancer", "chemotherapy". Details of the search strategy applied to create the register, and the procedure used to code references, are described in the Cochrane Breast Cancer Group module on The Cochrane Library. SELECTION CRITERIA: Randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in women with metastatic breast cancer. DATA COLLECTION AND ANALYSIS: Studies were assessed for eligibility and quality, and data (from published trials) were extracted by two independent reviewers. Hazard ratios were derived for time-to-event outcomes, where possible, and a fixed effect model was used for meta-analysis. Response rates were analysed as dichotomous variables. Toxicity and quality of life data (not available) were extracted where present. MAIN RESULTS: Thirteen eligible trials were identified, of which 12 had published time-to-event data. The quality of randomisation was generally not described.Data, based on an estimated 987 deaths in 1377 women, was unable to show a statistically significant difference in favour of platinum-containing regimens. The hazard ratio (HR) for overall survival was 1.00 (95% confidence interval (CI) 0.88 to 1.15, p=0.96), with minor heterogeneity. Results were similar when the analysis was limited to trials in women receiving first line chemotherapy. There was no statistically significant difference in favour of platinum-containing regimens for time to progression (overall HR of 1.06 (95% CI 0.95 to 1.19, p=0.31) although there was marked evidence of heterogeneity (p< 0.0001). There was a statistically significant difference in overall response in favour of platinum-containing regimens (OR 1.47; 95% CI 1.23 to 1.76, p=0.0001). However, there was strong statistical evidence of heterogeneity (p < 0.00010) probably reflecting the varying efficacy of the comparator regimens used in the trials. Heterogeneity may also reflect the differences, and difficulties, in assessing response. Women receiving platinum-containing regimens experienced statistically significant greater toxicity levels for leukopenia, hair loss, nausea and vomiting and anaemia compared with those receiving non-platinum regimens. REVIEWERS' CONCLUSIONS: In view of the significant excess toxicity, lack of progression or survival benefit and the availability of less toxic active agents it is difficult to justify the use of platinum-containing regimens, particularly as first line treatment for women with metastatic breast cancer in routine clinical practice. Ongoing trials are examining the possibility of synergy between platins and trastuzamab, a monoclonal antibody treatment. No randomised trials containing oxalplatin were identified for the present review.

Antineoplastic Combined Chemotherapy Protocols↗

Platinum containing regimens for metastatic breast cancer.

BACKGROUND: Studies have reported high tumour response rates for platinum-containing regimens in the treatment of women with metastatic breast cancer. OBJECTIVES: To identify and review the evidence from randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in the management of women with metastatic breast cancer. SEARCH STRATEGY: The specialised register maintained by the editorial base of the Cochrane Breast Cancer Group was searched on 2nd May 2003 using the codes for "advanced breast cancer", "chemotherapy". Details of the search strategy applied to create the register, and the procedure used to code references, are described in the Cochrane Breast Cancer Group module on The Cochrane Library. SELECTION CRITERIA: Randomised trials comparing platinum-containing chemotherapy regimens with regimens not containing platinum in women with metastatic breast cancer. DATA COLLECTION AND ANALYSIS: Studies were assessed for eligibility and quality, and data (from published trials) were extracted by two independent reviewers. Hazard ratios were derived for time-to-event outcomes, where possible, and a fixed effect model was used for meta-analysis. Response rates were analysed as dichotomous variables. Toxicity and quality of life data (not available) were extracted where present. MAIN RESULTS: Thirteen eligible trials were identified, of which 12 had published time-to-event data. The quality of randomisation was generally not described.Data, based on an estimated 987 deaths in 1377 women, was unable to show a statistically significant difference in favour of platinum-containing regimens. The hazard ratio (HR) for overall survival was 1.00 (95% confidence interval (CI) 0.88 to 1.15, p=0.96), with minor heterogeneity. Results were similar when the analysis was limited to trials in women receiving first line chemotherapy. There was no statistically significant difference in favour of platinum-containing regimens for time to progression (overall HR of 1.06 (95% CI 0.95 to 1.19, p=0.31) although there was marked evidence of heterogeneity (p< 0.0001). There was a statistically significant difference in overall response in favour of platinum-containing regimens (OR 1.47; 95% CI 1.23 to 1.76, p=0.0001). However, there was strong statistical evidence of heterogeneity (p < 0.00010) probably reflecting the varying efficacy of the comparator regimens used in the trials. Heterogeneity may also reflect the differences, and difficulties, in assessing response. Women receiving platinum-containing regimens experienced statistically significant greater toxicity levels for leukopenia, hair loss, nausea and vomiting and anaemia compared with those receiving non-platinum regimens. REVIEWERS' CONCLUSIONS: In view of the significant excess toxicity, lack of progression or survival benefit and the availability of less toxic active agents it is difficult to justify the use of platinum-containing regimens, particularly as first line treatment for women with metastatic breast cancer in routine clinical practice. Ongoing trials are examining the possibility of synergy between platins and trastuzamab, a monoclonal antibody treatment. No randomised trials containing oxalplatin were identified for the present review.

Antineoplastic Combined Chemotherapy Protocols↗

Monoaminergic agonists for acute traumatic brain injury.

BACKGROUND: Although there have been considerable gains in understanding the cascade of events that lead to secondary injury after traumatic brain injury (TBI), efforts to translate this understanding into new therapeutic, so-called neuroprotective approaches, have so far proven disappointing. As an alternative, there is growing interest in approaches to enhance brain repair after injury. Animal models suggest that agents enhancing monoaminergic (MA) transmission, particularly amphetamines, promote motor recovery from focal brain injury and it is proposed that this might represent a complementary means of therapeutic intervention in the later post-injury phase. OBJECTIVES: To evaluate the evidence that MAs improve final outcome after TBI. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library, Issue 2, 2005), the Cochrane Injuries Group's Specialised Register (to May 2005), MEDLINE (1966 to May 2005), EMBASE (1980 to May 2005) and the Science Citation Index (1992 to June 2005). We contacted researchers and authors of published and unpublished trials. Searches were updated in May 2005. SELECTION CRITERIA: Randomised controlled trials comparing the use of a MA (together with conventional non-pharmacological rehabilitative therapy) versus conventional non-pharmacological rehabilitative therapy alone. DATA COLLECTION AND ANALYSIS: Two authors independently screened records, extracted data and assessed trial quality. MAIN RESULTS: Although there is a limited clinical literature addressing this topic, none of the studies identified fully met inclusion criteria for this review. AUTHORS' CONCLUSIONS: At present there is insufficient evidence to support the routine use of MAs to promote recovery after TBI.

Acute Disease↗

Drug treatment for myotonia.

BACKGROUND: Abnormal delayed relaxation of skeletal muscles, known as myotonia, can cause disability in myotonic disorders. Sodium channel blockers, tricyclic antidepressive drugs, benzodiazepines, calcium-antagonists, taurine and prednisone may be of use in reducing myotonia. OBJECTIVES: To consider the evidence from randomised controlled trials on the efficacy and tolerability of drug treatment in patients with clinical myotonia due to a myotonic disorder. SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register (April 2004), MEDLINE (January 1966 to December 2003) and EMBASE (January 1980 to December 2003). Grey literature was handsearched and reference lists of identified studies and reviews were examined. Authors, disease experts and manufacturers of anti-myotonic drugs were contacted. SELECTION CRITERIA: We considered all (quasi) randomised trials of participants with myotonia treated with any drug treatment versus no therapy, placebo or any other active drug treatment. The primary outcome measure was:reduced clinical myotonia using two categories: (1) no residual myotonia or improvement of myotonia or (2) No change or worsening of myotonia. Secondary outcome measures were:(1) clinical relaxation time; (2) electromyographic relaxation time; (3) stair test; (4) presence of percussion myotonia; and (5) proportion of adverse events. DATA COLLECTION AND ANALYSIS: Two authors extracted the data independently onto standardised extraction forms and disagreements were resolved by discussion. MAIN RESULTS: Nine randomised controlled trials were found comparing active drug treatment versus placebo or another active drug treatment in patients with myotonia due to a myotonic disorder. Included trials were double-blind or single-blind crossover studies involving a total of 137 patients of which 109 had myotonic dystrophy type 1 and 28 had myotonia congenita. The studies were of poor quality. Therefore, we were not able to analyse the results of all identified studies. Two small crossover studies without a washout period demonstrated a significant effect of imipramine and taurine in myotonic dystrophy. One small crossover study with a washout period demonstrated a significant effect of clomipramine in myotonic dystrophy. Meta-analysis was not possible. AUTHORS' CONCLUSIONS: Due to insufficient good quality data and lack of randomised studies, it is impossible to determine whether drug treatment is safe and effective in the treatment of myotonia. Small single studies give an indication that clomipramine and imipramine have a short-term beneficial effect and that taurine has a long-term beneficial effect on myotonia. Larger, well-designed randomised controlled trials are needed to assess the efficacy and tolerability of drug treatment for myotonia.

Humans↗