The combined effect of surgeon and hospital volume on health outcomes: a systematic review.

OBJECTIVES: To explore the interaction between surgeon volumes (SVs) and hospital volumes (HVs) on health outcomes. MATERIALS AND METHODS: We searched MEDLINE, Embase, CINAHL, Web of Science as of May 2017. We included studies investigating the interaction between high or low SVs operating in high or low HVs. Review process follows the PRISMA guidelines. We assessed the methodological quality of the included studies using validated critical appraisal checklists. RESULTS: Sixteen studies were included. Due to the heterogeneity of studies, it was not possible to perform a quantitative analysis. Heath outcome are worse when high SV operating in low HV vs high HV, for the majority of the conditions (colorectal cancer, cystectomy, liver resection, mitral valve surgery, pancreatico-duodenectomy). Results for low SV are better when operating in high HV vs low HV for patients undergoing pancreatic-duodenectomy for mortality, 30 days complications and length of stay. Results for low SV are worse vs high SV when operating in high HV for most considered conditions. Results were in favour of higher SV vs low SV when operating in low HV for digital replantation success after injuries, 30 days mortality and complications after pancreatic-duodenectomy. CONCLUSIONS: The available evidence is limited. It is necessary to increase the monitoring of the association between surgeons volumes and hospitals volumes in which they operate, to ensure fairness and accuracy of care for better health outcomes.

Conjugation of a TLR7 agonist and antigen enhances protection in the S. pneumoniae murine infection model.

Next generation vaccine adjuvants include Toll like receptor agonists, which are mostly extracted from microorganisms, but synthetic small molecule TLR agonists have also been identified. However, their delivery systems have not been optimized for effective administration in conjunction with antigens. Here, we describe a novel approach in which a small molecule TLR agonist was directly conjugated to antigen to ensure effective co-delivery. We describe the conjugation of a recombinant protective antigen from Streptococcus pneumoniae linked to a TLR7 agonist. Following thorough characterization to ensure no aggregation, the conjugate was evaluated in a murine infection model. Results showed that the conjugate extended the animals' survival after lethal challenge with S. pneumoniae. Comparable results were obtained with a dose 10-fold lower than that of the native unconjugated antigen. Notably, the animals immunized with the same dose of unconjugated TLR7 agonist and antigen showed no adjuvant effect. The increased immunogenicity was likely a consequence of the co-localization of TLR7 agonist and antigen by chemical binding and was more effective than simple co-administration. This approach can be adopted to increase potency of a broad variety of antigens and reduce the dose of antigen required to induce protective immunity.

[Hand management in recessive dystrophic bullous epydermolysis]. / Il trattamento della mano nel paziente affetto da epidermolisi bollosa distrofica recessiva.

PURPOSE: Recessive distrofic epidermolysis bullosa creates severe hand deformities with disabling functional limitations. Hand surgeon should perform surgery when deformity inibits function, in order to restore the pinch. MATERIALS AND METHOD: We present our experience on 44 patients and 58 operated hands, with the following schema: hand degloving, grafting of the first web and intraoperative dynamic splinting. RESULTS: In 30 patient with an 8 years follow up, 25 had had good or excellent results, and the 5 remaining shows early recurrence. CONCLUSION: Association of a correct surgical approach and adequate intra and post-operative rehabilitation improve hand function and a slow down inevitable recurrence.

Maintenance agonist treatments for opiate dependent pregnant women.

BACKGROUND: The prevalence of opiate use among pregnant women ranges from 1% to 2% to as much as 21%. Heroin crosses the placenta and pregnant opiate dependent women experience a six fold increase in maternal obstetric complications such as low birth weight, toxaemia, 3rd trimester bleeding, malpresentation, puerperal morbidity, fetal distress and meconium aspiration. Neonatal complications include narcotic withdrawal, postnatal growth deficiency, microcephaly, neurobehavioral problems, increased neonatal mortality and a 74-fold increase in sudden infant death syndrome. OBJECTIVES: To assess the effectiveness of any maintenance treatment alone or in combination with psychosocial intervention compared to no intervention, other pharmacological intervention or psychosocial interventions on child health status, neonatal mortality, retaining pregnant women in treatment, and reducing use of substances SEARCH STRATEGY: We searched Cochrane Drugs and Alcohol Group' Register of Trials (June 2007), PubMed (1966 - June 2007), CINAHL (1982- June 2007), reference lists of relevant papers, sources of ongoing trials, conference proceedings, National focal points for drug research. Authors of included studies and experts in the field were contacted. SELECTION CRITERIA: Randomised controlled trials enrolling opiate dependent pregnant women DATA COLLECTION AND ANALYSIS: The authors assessed independently the studies for inclusion and methodological quality. Doubts were solved by discussion. MAIN RESULTS: We found three trials with 96 pregnant women. Two compared methadone with buprenorphine and one methadone with oral slow morphine. For the women there was no difference in drop out rate RR 1.00 (95% CI 0.41 to 2.44) and use of primary substance RR 2.50 (95% CI 0.11 to 54.87) between methadone and buprenorphine, whereas oral slow morphine seemed superior to methadone in abstaining women from the use of heroin RR 2.40 (95% CI 1.00 to 5.77)For the newborns in one trial buprenorphine performed better than methadone for birth weight WMD -530 gr (95% CI -662 to -397), this result is not confirmed in the other trial. For the APGAR score both studies didn't find significant difference . No differences for NAS measures used. Comparing methadone with oral slow morphine no differences for birth weight and mean duration of NAS. The APGAR score wasn't considered. AUTHORS' CONCLUSIONS: We didn't find any significant difference between the drugs compared both for mother and for child outcomes; the trials retrieved were too few and the sample size too small to make firm conclusion about the superiority of one treatment over another. There is an urgent need of big randomized controlled trials.

Anticonvulsants for cocaine dependence.

BACKGROUND: Cocaine dependence is a major public health problem that is characterized by recidivism and a host of medical and psychosocial complications. Although effective pharmacotherapy is available for alcohol and heroin dependence none exists currently for cocaine dependence despite two decades of clinical trials primarily involving antidepressant, anti convulsivant and dopaminergic medications. There has been extensive consideration of optimal pharmacological approaches to the treatment of cocaine dependence with consideration of both dopamine antagonists and agonists. Anticonvulsants have been candidates for the treatment of addiction based on the hypothesis that seizure kindling-like mechanisms contribute to addiction. OBJECTIVES: To evaluate the efficacy and the acceptability of anticonvulsants for cocaine dependence SEARCH STRATEGY: We searched the Cochrane Drugs and Alcohol Groups specialised register (issue 4, 2007), MEDLINE (1966 - march 2007), EMBASE (1988 - march 2007), CINAHL (1982- to march 2007) SELECTION CRITERIA: All randomised controlled trials and controlled clinical trials which focus on the use of anticonvulsants medication for cocaine dependence DATA COLLECTION AND ANALYSIS: Two authors independently evaluated the papers, extracted data, rated methodological quality MAIN RESULTS: Fifteen studies (1066 participants) met the inclusion criteria for this review: the anticonvulsants drugs studied were carbamazepine, gabapentin, lamotrigine, phenytoin, tiagabine, topiramate, valproate. No significant differences were found for any of the efficacy measures comparing any anticonvulsants with placebo. Placebo was found to be superior to gabapentin in diminishing the number of dropouts, two studies, 81 participants, Relative Risk (RR) 3.56 (95% CI 1.07 to 11.82) and superior to phenythoin for side effects, two studies, 56 participants RR 2.12 (95% CI 1.08 to 4.17). All the other single comparisons are not statistically significant. AUTHORS' CONCLUSIONS: Although caution is needed when assessing results from a limited number of small clinical trials at present there is no current evidence supporting the clinical use of anticonvulsants medications in the treatment of cocaine dependence. Aiming to answer the urgent demand of clinicians, patients, families, and the community as a whole for an adequate treatment for cocaine dependence, we need to improve the primary research in the field of addictions in order to make the best possible use out of a single study and to investigate the efficacy of other pharmacological agent.

Oral naltrexone maintenance treatment for opioid dependence.

BACKGROUND: Research on the clinical application of oral naltrexone agrees on several things. From a pharmacological perspective, naltrexone works. From an applied perspective, however, this medication is not used since the medication compliance and the retention rates are very poor. OBJECTIVES: To evaluate the effects of naltrexone maintenance treatment versus placebo or other treatments in preventing relapse in opioid addicts after detoxification. SEARCH STRATEGY: We searched the Cochrane Drugs and Alcohol Group Register of Trials (January 2005), Cochrane Central Register of Controlled Trials (CENTRAL - The Cochrane Library Issue 1, 2005), MEDLINE (1973-first year of naltrexone use in humans- January 2005), EMBASE (1974- January 2005), PsycINFO (OVID-January 1985 to January 2004). We inspected reference lists of relevant articles and we contacted pharmaceutical producers of naltrexone, authors and other Cochrane review groups. SELECTION CRITERIA: All randomised and controlled clinical trials which focus on the use of naltrexone maintenance treatment versus placebo, or other treatments to reach sustained abstinence from opiate drugs DATA COLLECTION AND ANALYSIS: Three reviewers independently assessed studies for inclusion and extracted data. One reviewer carried out the qualitative assessments of the methodology of eligible studies using validated checklists. MAIN RESULTS: Ten studies, 696 participants, met the criteria for inclusion in this review. Only two studies described an adequate allocation concealment. The results show that naltrexone maintenance therapy alone or associated with psychosocial therapy is more efficacious that placebo alone or associated with psychosocial therapy in limiting the use of heroin during the treatment (RR 0,72 95% confidence interval 0.58 to 0.90). If we consider only the studies comparing naltrexone with placebo, the difference do not reach the statistical significancy, RR 0.79 (95%CI 0.59 to 1.06). With respect to the number of participants re incarcerated during the study period, the naltrexone associated with psychosocial therapy is more effective than the psychosocial treatment alone; RR 0.50 (95%CI 0.27 to 0.91). No statistically significant benefit was shown in terms of retention in treatment, side effects or relapse results at follow-up for any of the considered comparisons. AUTHORS' CONCLUSIONS: Unfortunately the studies did not provide an objective evaluation of naltrexone treatment in the field of opioid dependence. The conclusions are also limited due to the heterogeneity of the trials both in the interventions and in the assessment of outcomes.

Psychosocial combined with agonist maintenance treatments versus agonist maintenance treatments alone for treatment of opioid dependence.

BACKGROUND: Methadone maintenance at proper doses is effective in retaining patients in treatment and suppressing heroin use. Questions remain regarding the efficacy of the psychosocial services that are offered by most maintenance programs. OBJECTIVES: To evaluate the effectiveness of any psychosocial plus any agonist maintenance treatment versus any agonist treatment alone in retaining patients in treatment, reducing the use of substances and improving health and social status. SEARCH STRATEGY: We searched the Cochrane Central Register of Trials (CENTRAL) issue 3, 2003; MEDLINE 1966-2003; EMBASE 1980-2003; PsycINFO 1985-2003; relevant web sites; scan of reference list of relevant articles. There were no language or publication restrictions. SELECTION CRITERIA: RCTs which focus on any psychosocial plus any agonist compared to any agonist maintenance intervention for opiate dependence. People aged less than 18 and pregnant women were excluded. Psychosocial in combination with antagonist maintenance treatment are excluded too. DATA COLLECTION AND ANALYSIS: The trials were independently assessed for inclusion and methodological quality by the reviewers. Data were extracted independently and double checked. MAIN RESULTS: The searching process resulted in the identification of 77 different studies: 12 studies met the inclusion criteria. These studies considered 8 different psychosocial interventions and 1 pharmacological treatment: Methadone Maintenance (MMT). The results show additional benefit in adding any psychosocial treatment to standard methadone maintenance treatment in relation to the use of heroin during the treatment RR 0.69 (95% CI 0.53-0.91); no statistically significant additional benefit was shown in terms of retention in treatment RR 0.94 (95% CI 0.85-1.02); and results at follow-up RR 0.90 (95% CI 0.76-1.07). REVIEWERS' CONCLUSIONS: The present evidence suggests that adding any psychosocial support to Standard MMT significantly improves the non-use of heroin during treatment. Retention in treatment and results at follow-up are also improved, although this findings did not achieve statistical significance. Insufficient evidence is available on other possible relevant outcomes such as Psychiatric symptoms/psychological distress, Quality of life. Limitations to this review are imposed by the heterogeneity of the trials both in the interventions and the assessment of outcomes. Results of studies were sometimes in disagreement and because of lack of detailed information no meta analysis could be performed to analyse the results related to the outcomes more often reported as positive results in the single studies. Duration of the studies was also too short to analyse other relevant outcomes such as mortality. In order to study the possible added value of any psychosocial treatment over an already effective treatment such as standard MMT, only big multi-site studies could be considered which define experimental interventions and outcomes in the most standardized way as possible.

Psychosocial and pharmacological treatments versus pharmacological treatments for opioid detoxification.

BACKGROUND: Different pharmacological approaches aimed at opioid detoxification are effective. Nevertheless a majority of patients relapse to heroin use, and relapses are a substantial problem in the rehabilitation of dependent heroin users. Some studies have suggested that the sorts of symptoms which are most distressing to addicts during detoxification are psychological symptoms rather than physiological symptoms associated with the withdrawal syndrome. OBJECTIVES: To evaluate the effectiveness of any psychosocial plus any pharmacological interventions versus any pharmacological alone for opioid detoxification, in helping patients to complete the treatment, reduce the use of substances and improve health and social status. SEARCH STRATEGY: We searched the Cochrane Central Register of Trials (CENTRAL) issue 3, 2003; MEDLINE 1966-2003; EMBASE 1980-2003; PsycINFO 1985-2003; relevant web sites; scan of reference list of relevant articles. There were no language or publication restrictions. SELECTION CRITERIA: Randomised controlled trials which focus on any psychosocial associated with any pharmacological intervention aimed at opioid detoxification. People less than 18 years of age and pregnant women were excluded. DATA COLLECTION AND ANALYSIS: The trials were independently assessed for inclusion and methodological quality by three reviewers. Data were extracted independently and double checked. MAIN RESULTS: The searching process resulted in the identification of 77 different studies: 8 studies met inclusion criteria. These studies considered 5 different psychosocial interventions and 2 substitution detoxification treatments: Methadone and Buprenorphine. The results show promising benefit from adding any psychosocial treatment to any substitution detoxification treatment in terms of completion of treatment RR 1.68 (95% CI 1.11-2.55), results at follow-up RR 2.43 (95% CI 1.61-3.66), and compliance RR 0.48 (95% CI 0.38-0.59). In respect of the use of heroin during the treatment, the differences were not statistically significant but favoured the combined treatments. REVIEWERS' CONCLUSIONS: Psychosocial treatments offered in addition to pharmacological detoxification treatments are effective in terms of completion of treatment, results at follow-up and compliance. Although a treatment, like detoxification, that exclusively attenuates the severity of opiate withdrawal symptoms can be at best partially effective for a chronic relapsing disorder like opiate dependence, this type of treatment is an essential step prior to longer-term drug-free treatment and it is desirable to develop adjunct psychosocial approaches that might make detoxification more effective. Limitations to this review are imposed by the heterogeneity of the assessment of outcomes. Because of lack of detailed information no meta analysis could be performed to analyse the results related to several outcomes.

Barkas effect for antiproton stopping in H2.

We report the stopping power of molecular hydrogen for antiprotons of kinetic energy above the maximum (approximately 100 keV) with the purpose of comparing with the proton one. Our result is consistent with a positive difference in antiproton-proton stopping powers above approximately 250 keV and with a maximum difference between the stopping powers of 21%+/-3% at around 600 keV.