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Does post-withdrawal cue exposure improve outcome in opiate addiction? A controlled trial.

A controlled trial studied whether cue exposure prevented relapse in opiate addiction. Subjects were randomly allocated to one of two inpatient treatment settings: a drug dependence unit with a special 10 week program and 4 weeks in a behavioural/general treatment unit without such a program. In each setting, following drug-withdrawal, subjects had either cue exposure for at least six sessions over 3 weeks, or a control condition. Subjects were followed up twice, at about 6 weeks and 6 months post-treatment. 186 subjects were randomly allocated; 69 were assessed post-detoxification, and of these 43 completed cue exposure or control treatments. Cue exposure and control subjects did not differ in cue reactivity. This was evaluated post-treatment for cue exposure subjects and at a comparable time point for controls. All groups showed a significant decrement in cue-elicited craving, withdrawal responses and negative mood. Cue exposure and control subjects did not differ at either of the two follow up interviews.

Adult↗

Acute intervention studies in patients with myocardial infarction using atenolol, propranolol, oxprenolol and disopyramide phosphate.

The value of beta-blockade and of disopyramide phosphate in the immediate treatment of patients with suspected acute myocardial infarction was assessed in two placebo controlled trials. In the first study 388 patients with suspected acute myocardial infarction were randomly allocated to treatment with propranolol, atenolol, or placebo, and when analysed on an initial intention to treat basis there was no significant difference between the three groups in respect of the mortality at one year. In addition, there was no evidence to suggest that either atenolol, or propranolol reduced the incidence of 'serious' ventricular arrhythmias in the coronary care unit. In the second study 473 patients with suspected acute myocardial infarction were randomly allocated to treatment with oxprenolol, disopyramide phosphate, or placebo. Again no significant differences were seen with respect to the mortality at six weeks. There was, however, a significantly increased incidence of heart failure in the group which received disopyramide phosphate. Patients who received this drug also showed a reduced number of dysrhythmic episodes on 24-hour ECG recordings, but this trend did not achieve statistical significance. These results suggest that none of the three beta-blockers tested nor disopyramide phosphate is likely to reduce the mortality from acute myocardial infarction when given prophylactically, although disopyramide phosphate does reduce the incidence of 'serious' ventriicular arrhythmias.

Adrenergic beta-Antagonists↗

Long-term functional outcome after early surgery compared with laser and medicine in open-angle glaucoma.

PURPOSE: This randomly allocated prospective clinical study was designed to assess the relative efficacy of laser trabeculoplasty, medical therapy, and trabeculectomy used as the primary treatment in open-angle glaucoma, with particular regard to the level of intraocular pressure control and the amount of visual field decay. No patient had received any antiglaucoma treatment before entry into the trial. METHODS: One hundred sixty-eight patients were entered into the trial and randomly allocated into one of the three treatment groups--laser, medicine, or surgery. Follow-up was for a minimum of 5 years. The patients were monitored in the standard way, including intraocular pressure estimations and visual field tests (initially using the Friedmann analyzer and later including Humphrey automated perimetry). RESULTS: Despite similar initial composition of the three treatment groups, primary surgery resulted in the lowest mean intraocular pressures. The perimeter Friedmann visual fields were shown to have deteriorated in patients in the medicine-treated group and to a lesser extent in patients in the laser-treated group, but not in patients in the surgery-treated group. Multivariate linear regression analysis showed that the difference in field changes between laser and surgical treatments could be explained entirely by the difference between the intraocular pressure values at 6 months between the two groups. The same was not true for the medicine-treated group. CONCLUSION: Primary trabeculectomy appears to have the desired effect in preserving visual function in patients with high-tension glaucoma. This may be related to laser treatment might be expected to have the same effect.

Aged↗

Efficacy of dose-intensified MEC (methotrexate, epirubicin and cisplatin) chemotherapy for advanced urothelial carcinoma: a prospective randomized trial comparing MEC and M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin). Japanese Urothelial Cancer Research Group.

BACKGROUND: To evaluate the antitumor activity in patients with T3b, T4 or metastatic urothelial carcinoma treated with MEC or M-VAC chemotherapy, by performing a multi-center randomized prospective study. METHODS: From 1991 to 1995, 89 patients with T3b, T4 or metastatic urothelial carcinoma were randomly allocated to a methotrexate, epirubicin and cisplatin chemotherapy group (arm 1: S-MEC therapy; n = 29), a dose-intensified MEC therapy combined with G-CSF group (arm 2: I-MEC therapy; n = 30) or a methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy (arm 3: M-VAC therapy; n = 30). At the registration center, the patients were stratified into previously untreated patients and patients with recurrence after radical operation and then randomly allocated to the treatment groups. In each arm, two or more courses of chemotherapy (4-week cycles) were performed. RESULTS: Of the 88 eligible patients, four treated with S-MEC therapy and two treated with I-MEC therapy showed CR. The response rates (CR + PR) were 52% (15/29) with S-MEC therapy, 76% (22/29) with I-MEC therapy and 47% (14/30) with M-VAC therapy. The response rate with I-MEC therapy was significantly higher than that with M-VAC therapy (P = 0.02). Although the incidence of leukopenia was low with I-MEC therapy, the incidence of thrombocytopenia was high with this therapy. CONCLUSION: MEC therapy used in this study is promising in terms of the antitumor effects.

Adult↗

Intraperitoneal catheter outcomes in a phase III trial of intravenous versus intraperitoneal chemotherapy in optimal stage III ovarian and primary peritoneal cancer: a Gynecologic Oncology Group Study.

OBJECTIVES: To evaluate reasons for discontinuing intraperitoneal (IP) chemotherapy, and to compare characteristics of patients who did versus did not successfully complete six cycles of IP chemotherapy. METHODS: In a phase III trial, women with optimal stage III ovarian or peritoneal carcinoma were randomly allocated to receive IP therapy (paclitaxel 135 mg/m(2) intravenously (IV) over 24 h, cisplatin 100 mg/m(2) IP day 2, paclitaxel 60 mg/m(2) IP day 8) every 21 days for six cycles. Patients unable to receive IP therapy were treated with the alternate (IV) regimen. Variables compared included surgical procedures prior to enrollment, timing of IP catheter insertion, and primary and contributing reasons for discontinuing IP therapy. RESULTS: Among 205 eligible patients randomly allocated to the IP arm, 119 (58%) did not complete six cycles of IP therapy. Forty (34%) patients discontinued IP therapy primarily due to catheter complications and 34 (29%) discontinued for unrelated reasons. Hysterectomy, appendectomy, small bowel resection, and ileocecal resection were not associated with failure to complete six cycles. IP therapy was not initiated in 16% of patients who did versus 5% of those who did not have a left colon or rectosigmoid colon resection (P = 0.015). There was no association between timing of catheter insertion and failure to complete IP therapy. CONCLUSIONS: In this multi-institutional setting, it was difficult to deliver six cycles of IP therapy without complications. There appears to be an association between rectosigmoid colon resection and the inability to initiate IP therapy. Catheter choice, timing of insertion, and how surgical treatment of ovarian cancer influences the successful completion of intraperitoneal chemotherapy require further study.

Antineoplastic Combined Chemotherapy Protocols↗

Laparoscopic staging and subsequent palliation in patients with peripancreatic carcinoma.

OBJECTIVE: To test the hypothesis that laparoscopic staging improves outcome in patients with peripancreatic carcinoma compared to standard radiology staging. SUMMARY BACKGROUND DATA: Diagnostic laparoscopy of peripancreatic malignancies has been reported to improve assessment of tumor stage and to prevent unnecessary exploratory laparotomies in 10% to 76% of patients. METHODS: Laparoscopy and laparoscopic ultrasound were performed in 297 consecutive patients with peripancreatic carcinoma scheduled for surgery after radiologic staging. Patients with pathology-proven unresectable tumors were randomly allocated to either surgical or endoscopic palliation. All others underwent laparotomy. RESULTS: Laparoscopic staging detected biopsy-proven unresectable disease in 39 patients (13%). At laparotomy, unresectable disease was found in another 72 patients, leading to a detection rate for laparoscopic staging of 35%. In total, 145 of the 197 patients classified as having "possibly resectable" disease after laparoscopic staging underwent resection (74%). Average survival in the group of 14 patients with biopsy-proven unresectable tumors randomly allocated to endoscopic palliation was 116 days, with a mean hospital-free survival of 94 days. The corresponding figures were 192 days and 164 days in the 13 patients allocated to surgical palliation. CONCLUSIONS: Because of the limited detection rate for unresectable metastatic disease and the likely absence of a large gain after switching from surgical to endoscopic palliation, laparoscopic staging should not be performed routinely in patients with peripancreatic carcinoma.

Aged↗

The OMENS trial: opportunistic evaluation of musculo-skeletal physician care among orthopaedic outpatients unlikely to require surgery.

STUDY OBJECTIVE: For orthopaedic outpatients judged as unlikely to require surgery, how does the cost-effectiveness of treatment from a musculo-skeletal medicine physician compare with that of a conventional orthopaedic surgeon-led service? DESIGN: Partially randomised, pragmatic trial comparing management from a single musculo-skeletal medicine physician with orthopaedic surgeon-led management, with the timing and nature of treatments at the discretion of individual clinicians. Main outcomes were: change in patient reported health (SF-36 and EuroQol), and marginal health service costs. SETTING: Outpatient department of an Edinburgh orthopaedic hospital. SUBJECTS: One thousand three hundred and twenty six people; aged over 18, referred to and later attending the outpatient department with a 'non-surgical' musculo-skeletal condition, who provided baseline information. Eight hundred and twenty nine were randomly allocated to management by either the musculo-skeletal medicine physician (medical group) or a conventional orthopaedic surgeon-led service (surgical group); 497 were assigned to the treatment groups according to their general practitioner's preference. RESULTS: There are aspects of the study design concerning statistical power, potential selection bias and generalisability, which mean that any results must be treated with caution. Although there was no statistically significant difference in health gain between the randomly allocated groups (with similar findings in the non-randomised medical and surgical groups), the patient groups were heterogeneous and the confidence intervals did not rule out clinically important differences. The medical group received more outpatient treatment, 20% vs. 10% (difference 95% CI 5% to 15%) with a higher rate of physiotherapy referral, 45% vs. 30% (15%, 9% to 22%). The surgical group received more inpatient surgical care 6% vs. 17% (-11%, -15% to -7%). Mean healthcare costs in the medical group were 179 Pounds per patient compared with 287 Pounds in the surgical group (-108 Pounds, -25 Pounds to -191 Pounds). CONCLUSIONS: Interpretation should take into account the practical difficulties and circumstances of the study. Although no differences in health gain were found between these two management policies for 'non-surgical' orthopaedic outpatients, the trial was less statistically powerful than planned and the confidence intervals included clinically important differences. Differences in treatment emphasis gave estimated costs savings to the Health Service of 108 Pounds per patient treated by the musculo-skeletal medicine service.

Adult↗

Allogeneic bone marrow transplantation in adult acute lymphoblastic leukemia in first complete remission: a comparative study. French Group of Therapy of Adult Acute Lymphoblastic Leukemia.

PURPOSE: Optimal postremission therapy remains controversial in adult patients with acute lymphoblastic leukemia (ALL). In a large multicentric trial (LALA87), we compared allogeneic bone marrow transplantation (BMT) with other postremission therapies (chemotherapy or autologous transplantation) using the result of the human leukocyte antigen (HLA) typing as a random allocation. PATIENTS AND METHODS: Patient eligibility requirements were as follows: (1) inclusion in LALA87 trial, (2) complete response to induction or salvage therapy, (3) age 15 to 40 years, and (4) at least one potential sibling donor. Patients with an HLA-identical sibling were assigned to the BMT group, while patients without a sibling donor constituted the control group. Allogeneic transplantation was scheduled for patients in the BMT group; in the control group, patients were randomly allocated to receive chemotherapy or autologous transplantation. RESULTS: Of 284 eligible points, 257 entered the study: 116 were allocated to the BMT group and 141 to the control group. The 5-year survival rates were not statistically significantly different between the two groups. When only patients with high-risk ALL were considered (those with [1] Philadelphia chromosome [Ph1] ALL, [2] null or undifferentiated ALL, or [3] c-ALL with either age greater than 35 years or WBC count > 30 x 10(9)/L or time to achieve complete remission > 4 weeks), overall survival (P = .03) and disease-free-survival (P = .01) were better for the BMT group compared with the control group (5-year overall survival rates, 44% v 20%; 5-year disease-free survival rates, 39% v 14%). CONCLUSION: Allogeneic transplantation does not improve survival in patients with standard-risk ALL and should be recommended only for patients with adverse prognostic factors.

Adolescent↗

Perception of quality of life before and after disclosure of trial results: a report from the Program on the Surgical Control of the Hyperlipidemias (POSCH).

The Program on the Surgical Control of the Hyperlipidemias (POSCH) was a randomized controlled clinical trial designed to ascertain whether cholesterol lowering induced by the partial ileal bypass operation would favorably affect overall mortality and the mortality and morbidity due to coronary heart disease. The trial results provided strong clinical and coronary arteriographic support for the beneficial effects of lipid modification for the reduction of atherosclerosis progression. At the same time, the surgery-assigned group experienced diarrhea and an increased incidence of kidney stones and gallstones compared to the control-assigned group. Identical quality of life determinations were performed in the POSCH study population shortly before disclosure of the trial results to the patients and shortly thereafter. The purpose of this dual assessment was to evaluate the effect of knowledge of outcomes on the patients' subjective evaluation of quality of life. The primary instrument utilized for analysis of the perception of quality of life in POSCH was the McMasters Health Index Questionnaire (MHIQ). In addition, four study-specific questions were asked of the trial patients. The results for the MHIQ before disclosure of trial results showed a difference (p = 0.07) favoring the control-assigned group (diet-treated), for the social function index of the MHIQ. After disclosure of the trial results, the difference was larger (p < 0.05). For the four study-specific questions, all differences favored the control-assigned group (p < 0.01) before and after disclosure of the trial results, with the exception of satisfaction with randomization allocation in the surgery-assigned group (p = 0.08). The intragroup MHIQ indices before and after disclosure of the trial results showed no suggestive significant differences, except in the surgery-assigned group, in which there was an improvement in the emotional function index after disclosure of the trial results (p = 0.03). The intragroup responses to the study-specific questions before and after disclosure of the trial results again showed no significant differences, except in the surgery-assigned group, in which there was an improvement in patient satisfaction with randomization allocation after disclosure of the trial results (p = 0.04).(ABSTRACT TRUNCATED AT 400 WORDS)

Attitude to Health↗

The healing properties of Promogran in venous leg ulcers.

OBJECTIVE: To evaluate the healing rate of venous leg ulcers treated with Promogran. METHOD: Patients with stagnating venous leg ulcers were recruited. Target wounds were > or = 2 cm but < or = 10 cm in any one dimension. Subjects were randomly allocated to receive either Promogran or a non-adherent dressing (Adaptic) with a secondary dressing of gauze followed by short-stress compression (Biflex). Weekly wound assessments occurred over 12 weeks and dressings were changed twice weekly by the investigator and/or nurse team. Planimetry tracings and photographs were blindly reviewed and assessed by two independent investigators. An intent-to-treat analysis was performed. RESULTS: Seventy-three patients were included. Thirty-seven were randomly allocated Promogran and 36 Adaptic. Twenty-nine patients completed the 12-week follow-up visit, 25 healed before week 12 and 19 stopped follow-up before week 12 for reasons unrelated to healing. Significantly more patients in the Adaptic group than in the Promogran group switched to another dressing (22.2% versus 5.4%; p = 0.035). Eleven venous leg ulcers healed in the control group (31%) and 15 in the Promogran group (41%) (p = 0.373). Overall, 15 venous leg ulcers healed or improved in the control group (42%) and 23 in the Promogran group (62%) (p = 0.079). Surface area decreased, on average, by 36.5 +/- 11.4% (median decrease: 44.6%) in the Adaptic group and by 54.4 +/- 10.9% (median decrease: 82.4%) in the Promogran group (p < 0.001). A < or = 20% surface area reduction was observed in 15 patients in the Adaptic group and in seven in the Promogran group (42% versus 19%; p = 0.034). No severe local adverse events were noted in either group, although poor tolerability caused a dressing switch in five patients in the control group and three in the Promogran group. Dressing acceptability was good or excellent in more than 60% of subjects in both groups. CONCLUSION: The results suggest that Promogran may accelerate healing in venous leg ulcers and was well tolerated compared with the current standard of care.

Adult↗

Maintenance therapy after quadruple induction therapy in HIV-1 infected individuals: Amsterdam Duration of Antiretroviral Medication (ADAM) study.

BACKGROUND: Highly active antiretroviral therapy (HAART) has led to health benefits for patients infected with HIV-1. However, long-term use of multidrug regimens is difficult to sustain. Simplifying antiretroviral treatment regimens would increase patients' adherence and minimise toxicity. We investigated the feasibility of a strategy of induction therapy followed by maintenance therapy with HAART in a randomised open-label study. METHODS: From March, 1997, we enrolled patients infected with HIV-1 with at least 200 CD4 cells/microL, at least 1000 HIV-1 RNA copies/mL in plasma, and no previous exposure to antiretroviral drugs. After 26 weeks of induction therapy (stavudine, lamivudine, saquinavir, and nelfinavir) patients were randomly allocated maintenance therapy (either stavudine and nelfinavir or saquinivir and nelfinavir) or prolonged induction therapy (if the plasma HIV-1 RNA concentration at weeks 24 and 25 was <50 copies/mL). FINDINGS: In February, 1998, we discontinued randomisation after an interim analysis. 62 patients had been enrolled. 39 (91%) of the 43 patients who were followed up for at least 26 weeks had an undetectable plasma HIV-1 RNA concentration at week 16. At week 26, 31 patients were randomly allocated treatment. Of these patients 25 had a total follow-up of at least 36 weeks. At week 36, a higher proportion of patients on maintenance therapy (nine [64%] of 14) had a detectable HIV-1 RNA than patients on prolonged induction therapy (one [9%] of 11, p=0.01). The initial virion-clearance rate during induction therapy was higher in five patients on maintenance therapy with a sustained undetectable plasma HIV-1 RNA concentration than in nine patients with recurrence of a detectable plasma HIV-1 RNA concentration at week 36 (0.35 vs 0.19 per day, respectively; p=0.0008). INTERPRETATION: The induction regimen provided a rapid suppression of viral replication to below 50 copies/mL. However, suppression was not sustained in a considerable number of patients who went onto maintenance therapy. It is currently inadvisable to continue attempts at moving from induction to maintenance therapy in day-to-day practice.

Adult↗

[The different meanings of the word stratification].

In clinical research, stratification has three different meanings. In its first meaning, it describes the natural distribution of patients into subgroups, for instance patients may be stratified by stage. In its second meaning, stratification controls the random allocation of the treatments in a clinical trial, for instance the randomisation can be stratified on stage. Lastly, in its third meaning, stratification of a trial analysis consists into taking into account patients' characteristics in the analysis. This three meanings will be illustrated with a basic example.

Humans↗

Reducing diazepam prescribing for illicit drug users: a randomised control study.

Illicit drug users undergoing mandatory reductions in prescribed diazepam were randomly allocated to one of two methods of delivering psychological support to help reduce their prescription: a) an enhanced intervention consisting of skills training and reinforcement, and b) a limited intervention where patients initially received skills training and thereafter only advice. Outcome measures at baseline and six-months consisted of daily diazepam dose; reported illicit drug use; Severity of Dependence Scale; Hospital Anxiety and Depression Scale (HADS); Pittsburgh Sleep Quality Index. Fifty-three of 119 eligible patients agreed to be randomly allocated to the interventions. Those in the enhanced intervention reduced their daily dose of prescribed diazepam from a mean of 27.8 mgs to 19.9 mgs at six months (5.3% per month) compared with 29.8 mgs to 17.6 mgs at six months (7.5%) among those in the limited intervention group. However, there was no statistically significant difference in the reduction rate between the intervention groups. Approximately 75% of patients in each group suspended their reduction programme. The enhanced intervention group reported a statistically and clinically greater reduction in the mean HADS depression score (10.6 at baseline and 7.7 at follow-up), compared with a rise from 8.9 to 11.2 in the limited intervention group. In conclusion, it is possible to reduce prescribed diazepam among illicit drug users but not at the rate of 10% per month set by the study. The difficulties of working with this population necessitate a flexible and possibly long-term approach to reducing prescribed benzodiazepines.

Adult↗

Effect of feeding level pre- and post-puberty and body weight at first calving on growth, milk production, and fertility in grazing dairy cows.

The effect of feeding to achieve differential growth rates in Holstein-Friesian (HF; n = 259) and Jersey (n = 430) heifers on time to puberty and first lactation milk production was investigated in a 3 x 2 factorial design. Holstein-Friesian and Jersey calves were reared to achieve a BW of 100 and 80 kg, respectively, at 100 d. At target weight, all calves were randomly allocated to one of 3 feeding treatments to achieve different growth rates. Holstein-Friesian and Jersey calves were fed fresh pasture to achieve average daily growth rates of 0.77, 0.53, or 0.37 kg of BW/d (HF) and 0.61, 0.48, or 0.30 kg of BW/d (Jersey), respectively. Period 1 (prepubertal) was imposed until HF and Jersey treatment groups averaged 200 and 165 kg of BW, respectively. Following period 1, HF and Jersey calves from each treatment group were randomly allocated to one of 2 feeding treatments to achieve average daily growth rates of 0.69 or 0.49 kg of BW/d (HF) and 0.58 and 0.43 kg of BW/d (Jersey), respectively. Period 2 (postpubertal) was imposed until 22 mo, when heifers were returned to their farms of origin. Body weight, body condition score, height, heart girth circumference (HGC), milk production, and fertility-related data were collected until the end of the third lactation. Time to reach puberty was negatively associated with level of feeding, and heifers attained puberty at the same BW (251 +/- 25.4 and 180 +/- 24.0 kg for HF and Jersey heifers, respectively). Heifers on high feed allowances during periods 1 and 2 were heavier, taller, and had greater HGC than their slower grown counterparts until 39 mo of age when height and HGC measurements stopped. Body weight differences remained until 51 mo, when measurements ceased. High feed allowance during period 1 (prepubertal) did not affect milk production during the first 2 lactations, but did reduce milk production in lactation 3. It is possible that the expected negative effect of accelerated pre-pubertal growth was masked by greater calving BW, as BW-corrected milk yield declined in both breeds with increasing prepubertal feed allowance. Growth rate during period 2 was positively correlated with first lactation milk production. Milk yield increased 7% in first lactation heifers on the high feed allowance, which resulted in higher growth rate during period 2. Milk production during subsequent lactations was not affected. Results suggest that accelerated prepubertal growth may reduce mammary development in grazing dairy cows, but this does not affect milk production in early lactations because of superior size. Body weight at calving and postpubertal growth rate management are important in first lactation milk production, but do not affect milk production in subsequent lactations.

Animals↗

Extubation from low-rate intermittent positive airways pressure versus extubation after a trial of endotracheal continuous positive airways pressure in intubated preterm infants.

BACKGROUND: Failure of extubation and subsequent reintubation may result in additional stress and trauma to the premature infant. Testing infants about to be extubated with a period of endotracheal CPAP has been suggested as a method of demonstrating readiness for extubation. However, this process has been criticized as increasing the neonate's work of breathing and perhaps increasing the likelihood of extubation failure. OBJECTIVES: In premature infants having their endotracheal tube removed, is direct extubation from low rate intermittent positive pressure ventilation (IPPV) more successful than that following a period of endotracheal continuous positive airway pressure (CPAP)? SEARCH STRATEGY: The standard search strategy of the Neonatal Review Group as outlined in the Cochrane Library was used. This included searches of the Oxford Database of Perinatal Trials, Cochrane Controlled Trials Register, MEDLINE, previous reviews including cross references, abstracts, conferences, symposia proceedings, expert informants and journal hand searching mainly in the English language. SELECTION CRITERIA: All trials using random or quasi-random allocation of premature infants to endotracheal CPAP or direct extubation following a period of IPPV were included. DATA COLLECTION AND ANALYSIS: Data were extracted using standard methods of the Cochrane Collaboration and its Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author and synthesis of data using relative risk. MAIN RESULTS: Direct extubation from low rate ventilation is associated with a trend to increased chance of successful extubation when compared to extubation after a period of endotracheal CPAP, RR 0.45 (0.19,1.07), RD -0.103 (-0.200,-0.006), NNT 10 (5,167). When only truly randomized trials are considered, this result becomes both statistically significant and clinically important, RR 0.10 (0.01,0.78), RD -0.201 (-0.319,-0.083), NNT 5 (3, 12). Similar differences are seen for the secondary outcome, apnea. REVIEWER'S CONCLUSIONS: Preterm infants no longer requiring endotracheal intubation and IPPV should be directly extubated without a trial of ETT CPAP.

Humans↗

Prevention of oral mucositis or oral candidiasis for patients with cancer receiving chemotherapy (excluding head and neck cancer).

BACKGROUND: Treatment of cancer with chemotherapy is becoming increasingly more effective but is associated with short and long-term side effects. Oral side effects remain a major source of illness despite the use of a variety of agents to prevent them. OBJECTIVES: To evaluate the effectiveness of oral (and topical) prophylactic agents for oral mucositis and oral candidiasis in patients with cancer (excluding head and neck cancer), compared with placebo or no treatment. SEARCH STRATEGY: Computerised MEDLINE, EMBASE, CINAHL, CANCERLIT, the Cochrane Controlled Trials Register and the Cochrane Oral Health Group Specialist Register search up to July 1999. Reference lists from relevant articles were scanned and the authors of eligible studies were contacted to identify trials and obtain additional information. SELECTION CRITERIA: Studies were selected if they met the following criteria: design - random or quasi-random allocation of participants; participants - anyone with cancer receiving chemotherapy (excluding head and neck cancer); interventions - prophylactic agents prescribed to reduce oral conditions arising from cancer or its treatment; outcomes - mucositis and oral candidiasis. DATA COLLECTION AND ANALYSIS: Information regarding methods, participants, interventions and outcome measures and results were independently extracted, in duplicate, by two reviewers (JC & HW). Specialist advice was sought to categorise interventions. Authors were contacted for details of randomisation and withdrawals and a quality assessment was carried out using the Jadad criteria (Jadad 1998). The Cochrane Oral Health Group statistical guidelines were followed and relative risk values calculated using random effects models where significant heterogeneity was detected (P < 0.1). MAIN RESULTS: Thirty-eight reports of trials were initially included. Two were duplicate reports and nine were excluded as there was no useable information. Of the 27 useable studies 14 had data for mucositis comprising 945 randomised patients and 15 included data for oral candidiasis with 1164 randomised patients. Of the eight prophylactic agents used for mucositis only one, ice chips, was effective (Relative risk 0.57, 95% CI 0.43 to 0.77, chi-square for heterogeneity = 0.26 (df = 1), p = 0.61). The NNT to prevent one extra case of mucositis over the baseline incidence using ice chips was 4 (95%CI: 3 to 7). The NNT for when the baseline incidence of mucositis in the population ranges from 50% to 80% are 5 to 4 respectively. There is evidence that antifungal agents which are partially or fully absorbed from the gastrointestinal tract prevent oral candidiasis and that the partially absorbed agents may be more effective than the fully absorbed agents. The RR for partially absorbed agents was 0.13 (95% CI 0.06 to 0.27, chi-square for heterogeneity = 5.3 (df = 3), P = 0. 15). The NNT to prevent one extra case of oral candidiasis over the baseline incidence using partially absorbed drugs was 3 (95% CI: 3 to 5). The NNT for when the baseline incidence of oral candidiasis in the population ranges from 30% to 70% are 4 to 2 respectively. The general reporting of RCT's was poor however the median Jadad score was acceptable and improved further when the authors provided additional information. The sensitivity analysis confirmed the findings for oral candidiasis. REVIEWER'S CONCLUSIONS: There is some evidence that ice chips prevent mucositis. None of the other prophylactic agents included in this review prevented mucositis. There is evidence that prophylactic use of antifungal agents which are absorbed or partially absorbed from the gastrointestinal tract reduce the clinical signs of oral candidiasis, and the partially absorbed drugs may be more effective. Future trials in this area should address the link between oral and general health including outcomes relevant to the patient. Collaboration between medical and dental teams is indicated.

Administration, Oral↗

Amoxicillin concentrations in nasal secretions of patients with acute uncomplicated sinusitis and in paranasal sinus mucosa of patients with chronic sinusitis.

In this prospective randomized clinical study a total of 59 patients of both sexes (above 18 years of age) were enrolled. Thirty patients with acute sinusitis were randomly allocated to two treatment groups, one group receiving 1000 mg amoxicillin every 12 h for 10 days and the other group receiving 500 mg amoxicillin every 8 h for 10 days. The median concentration of amoxicillin in nasal secretions was 2.34 micrograms/ml in the 12-h administration group and 1.95 micrograms/ml in the 8-h administration group. Median bioavailability of antibiotic at 8-24 h did not show any statistical differences between the two treatment schemes [probability (Z) = 0.2]. Twenty-nine patients with chronic sinusitis were then randomly allocated to three groups, with patients receiving 1000 mg amoxicillin at 12, 8 or 6 h before nasal and/or sinus surgery was carried out. The mean amoxicillin concentrations in mucosal tissues removed intraoperatively ranged from 0.69 to 0.99 microgram/g samples. Statistical evaluation by analysis of variance did not show any statistically significant differences among the three treatment groups [probability (F) = 0.1705]. In all cases of acute and chronic sinusitis, amoxicillin concentrations exceeded minimum inhibitory concentration values for pathogens common in sinusitis. Our results indicate that 1000 mg amoxicillin administered twice daily produces tissue concentrations high enough to be clinically effective in patients with either acute or chronic sinusitis.

Acute Disease↗

Use of hypertonic saline-dextran solution to resuscitate hypovolemic calves with diarrhea.

OBJECTIVE: To determine effectiveness of a new and practical method for fluid resuscitation of dehydrated diarrheic calves. DESIGN: Animals randomly allocated to 4 groups with appropriate controls. ANIMALS: 16 healthy male dairy calves, 3 to 6 days old. PROCEDURE: After instrumentation and recording baseline data, diarrhea and hypovolemia were induced by administering milk replacer (33 ml/kg of body weight) and isotonic sucrose solution (2 g of sucrose in 19.5 ml of water/kg, PO) every 8 hours, and furosemide (2 mg/kg, IM) every 4 to 8 hours. Administration of milk replacer and furosemide was discontinued when calves became 6% dehydrated. Calves were then randomly allocated as: control (no treatment); hypertonic saline-dextran (HSD) solution (4 ml/kg, 2,400 mOsm/L NaCl in 6% dextran-70, administered once over 4 minutes, IV); isotonic alkalinizing oral electrolyte solution (55 ml/kg, PO, q 8 h); and HSD-oral electrolyte solution (combination of HSD and oral treatments). Calves were monitored for 24 hours after treatment. RESULTS: Significant changes included moderate dehydration (8% body weight), marked lethargy, decreased cardiac output and plasma volume, and increased blood lactate concentration, hematocrit, and serum concentrations of albumin, creatinine, sodium, and phosphate. Control calves continued to be lethargic and dehydrated, with significant increases in hematocrit and serum creatinine concentration. Increase in cardiac output and plasma volume was transient in the HSD group and waned by 2 to 8 hours after treatment. Oral electrolyte fluid administration caused slow and sustained increase in cardiac output and plasma volume, and decrease in heart rate, blood lactate concentration, and hematocrit. Combined administration of HSD-oral electrolyte solution caused immediate and sustained increase in cardiac output and plasma volume, and decrease in heart rate, blood lactate concentration, and hematocrit. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment of hypovolemic diarrheic calves with IV HSD and oral electrolyte solution is superior to administration of either solution alone.

Animals↗