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Randomized Controlled Trial (RCT) is a power tool to assess causality. The use of RTCs among sociologists is limited by common constraints, for example the ethical issues and the non-manipulability of several individual characteristics (i.e. social origins, education, gender, etc.). Moreover, limited use is due also to the lack of knowledge and misunderstanding about how RCTs can generate robust causal inference. In this essay we confront these topics, moving from a recent Italian book about experiments (Rago, 2018). Focusing on several objections to the internal and external validity of RCTs, we show a small amount of the large body of methodological solutions provided by consolidated international literature in the field. In doing so, we try to eliminate the most common misunderstandings related to RCTs. We also argue that a larger use of RCTs may be useful for sociology, thanks to the possibility to integrate rigorous causal estimates with our deeper knowledge of mechanisms underlying social phenomena.

Nel precedente articolo pubblicato su questa rivista, abbiamo analizzato la struttura di un RCT nelle sezioni del titolo, dell'abstract, l'introduzione, gli obiettivi o ipotesi, i metodi, il disegno, i pazienti, il setting, gli interventi, gli outcome, la dimensione del campione, la randomizzazione e i metodi statistici. In questo secondo articolo chiuderemo l'analisi di un reporting di RCT nella sezione dei Risultati: la flow chart del flusso dei pazienti, le date e il periodo di reclutamento, le caratteristiche demografiche e cliniche, i risultati per gli outcome, i risultati per gli effetti indesiderati e avversi. Nella sezione Discussione: i limiti di un trial, la generalizzabilità dei risultati, il confronto dei risultati, la registrazione del trial e infine il finanziamento di un trial. (nursing)

Introduzione. Questo lavoro è il primo di due articoli che affronteranno la problematica fondamentale dell'utilizzo corretto della metodologia RCT nella ricerca in Italia nel campo nefrologico e dialitico. Il gold standard per misurare l'efficacia di un intervento assistenziale e sanitario è rappresentato dal trial controllato randomizzato. Numerosi RCT presentano ancora oggi però diversi gap metodologici, evidenziati a livello della qualità del reporting del trial. Obiettivo. Mostrare una Linea Guida per il reporting di un trial, utile per gli Autori per una strutturazione e conduzione corrette e rigorose del trial e per i lettori per avere gli strumenti metodologici per una lettura critica di qualsiasi RCT. Strumenti e Metodi. Il reporting è lo strumento metodologico standard per garantire la rigorosità di un RCT. La metodologia utilizzata è quella di analizzare in maniera sintetica, ma completa, le fasi fondamentali che compongono un reporting che un trial deve rispettare. Risultati. Il rispetto di una Linea Guida del reporting di un RCT mostra risultati non ambigui, chiari, non manipolati o distorti, prodotti da una metodologia corretta e rigorosa in ogni fase del RCT, permettendo una comprensione corretta dei risultati e la loro possibile generalizzazione. Conclusioni. Gli Autori dovrebbero usare sistematicamente le Linee Guida standard per la produzione di RCT, rispettandone ogni indicazione, per garantire un'utile ed efficace progressione della conoscenza scientifica nonché l'eticità e la serietà della ricerca. (nursing)

The objective of this prospective parallel randomized single-blind study was to assess that a cycle of mud-bath therapy (MBT) provides any benefits over usual treatment in patients with bilateral knee osteoarthritis (OA). Patients with symptomatic primary bilateral knee OA, according to ACR criteria, were included in the study and randomized to one of two groups: one group received a cycle of MBT at spa center of Chianciano Terme (Italy) in addition to the usual treatment, and one group continued their regular care routine alone. Clinical assessments were performed 7�days before enrollment (screening visit), at the time of enrollment (basal time), after 2�weeks, and after 3, 6, 9, and 12�months after the beginning of the study. All assessments were conducted by two researchers blinded to treatment allocation. The primary efficacy outcomes were the global pain score evaluated by Visual Analog Scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscore for physical function (W-TPFS). Of the 235 patients screened, 103 met the inclusion criteria: 53 patients were included in the MBT group and 50 in the control group. In the group of patients treated with MBT, we observed a statistically significant (p�

Background: Enhanced reduction of multinodular goiter (MNG) can be achieved by stimulation with recombinant human thyrotropin (rhTSH) before radioiodine ( 131I) therapy. The objective was to compare the long-term efficacy and safety of two low doses of modified release rhTSH (MRrhTSH) in combination with 131I therapy. Methods: In this phase II, single-blinded, placebo-controlled study, 95 patients (57.2±9.6 years old, 85% women, 83% Caucasians) with MNG (median size 96.0mL; range 31.9-242.2mL) were randomized to receive placebo (n=32), 0.01mg MRrhTSH (n=30), or 0.03mg MRrhTSH (n=33) 24 hours before a calculated 131I activity. Thyroid volume (TV) and smallest cross-sectional area of trachea (SCAT) were measured (by computed tomography scan) at baseline, six months, and 36 months. Thyroid function and quality of life (QoL) was evaluated at three-month and yearly intervals respectively. Results: At six months, TV reduction was enhanced in the 0.03mg MRrhTSH group (32.9% vs. 23.1% in the placebo group; p=0.03) but not in the 0.01mg MRrhTSH group. At 36 months, the mean percent TV reduction from baseline was 44±12.7% (SD) in the placebo group, 41±21.0% in the 0.01mg MRrhTSH group, and 53±18.6% in the 0.03mg MRrhTSH group, with no statistically significant differences among the groups, p=0.105. In the 0.03mg MRrhTSH group, the subset of patients with basal 131I uptake 131I, enhanced MNG reduction could not be demonstrated with MRrhTSH doses ≤0.03mg, indicating that the lower threshold for efficacy is around this level.

La tecnica buttonhole (BT) è un'alternativa alle tecniche standard per l'incannulamento della fistola artero-venosa (AVF). Non è certo se i vantaggi della BT siano superiori ai rischi ad essa associati. Al fine di analizzare la letteratura recente, abbiamo cercato su PubMed le voci “randomized controlled study on buttonhole” e “review of buttonhole cannulation” negli anni tra il Gennaio 2011 e il Novembre 2013. Abbiamo identificato tre studi randomizzati e tre recensioni. Uno studio randomizzato ha mostrato una migliore sopravvivenza delle FAV (100% vs 82%), meno interventi (19% vs 39%) e una minore crescita degli aneurismi preesistenti (23% vs 67%) nel gruppo BT. Un secondo studio ha mostrato un maggior numero di infezioni ed ematomi e una maggiore percezione del dolore nel gruppo BT. Nel terzo studio, non ci sono state differenze nella percezione del dolore e nel tempo di sanguinamento tra il gruppo BT e il gruppo di controllo e sono stati rilevati un maggior numero di ematomi nel gruppo di controllo e un maggior numero di infezioni locali e sepsi nel gruppo BT. Le tre review non hanno mostrato risultati certi riguardo agli end point della BT (percezione del dolore, formazione di aneurismi, tempo di sanguinamento), confermando l'aumentato rischio di infezioni locali e sistemiche. Sulla base di questa analisi, si può concludere che la BT produce un aumento del rischio di infezioni locali e sistemiche senza benefici definiti. Studi recenti suggeriscono di riservare la BT a casi selezionati (vasi particolarmente profondi o tratti troppo brevi). Non si può escludere che ulteriori studi randomizzati e controllati possano produrre un diverso giudizio sulla BT.

The range of osteoporosis treatments is increasingly large and, like any disease, the pharmacological management of patients should involve a risk/benefit evaluation to attain the greatest reduction in risk of fracture with the lowest incidence of adverse events. The aim of this review is to critically appraise the literature about the safety issues of the main pharmacological treatments of osteoporosis. This document is the result of a consensus of experts based on a systematic review of regulatory documents, randomized controlled trials, metaanalyses, pharmacovigilance surveys and case series related to possible adverse drug reactions to osteoporosis treatment with calcium and vitamin D supplements, bisphosphonates, strontium ranelate, selective estrogen receptor modulators, denosumab, and teriparatide. As expected, randomized controlled trials showed only the most common adverse events due to the samples size and the short observation time. Case series and observational studies are able to provide data about uncommon side effects, but in some cases a sure cause-effect relationship needs still to be confirmed. Consistently with methodological limitations, the newer drugs have a tolerance profile that has not been fully explored yet. Osteoporosis treatments showed an overall good tolerance profile with rare serious adverse events that, however, must be well known by the clinician who prescribes these drugs. The concern about possible adverse events should be weighed against the reduction of morbidity and mortality associated with a significant fracture risk reduction.

In this paper we deal with the difficulties posed by the placebo effect in the appraisal of hypotheses concerning the efficacy of treatments in medicine. We suggest that what we call the ‘efficacy hypotheses’ can be viewed as a special kind of causal statistical hypotheses, and that the principles governing their test and possible acceptance are provided by an appropriate statistical version of the principles of eliminative induction put forward by John Stuart Mill.

Background: Recombinant human TSH (rhTSH) can be used to enhance (131)I therapy for shrinkage of multinodular goiter (MG). Objective, Design, and Setting: The objective of the study was to compare the efficacy and safety of 0.01 and 0.03 mg modified-release (MR) rhTSH as an adjuvant to (131)I therapy, vs. (131)I alone, in a randomized, placebo-controlled, international, multicenter study. Patients and Intervention: Ninety-five patients (57.2 ± 9.6 yr old, 85% females, 83% Caucasians) with MG (median size 96.0, range 31.9-242.2 ml) were randomized to receive placebo (group A, n = 32), MRrhTSH 0.01 mg (group B, n = 30), or MRrhTSH 0.03 mg (group C, n = 33) 24 h before a calculated activity of (131)I. Main Outcome Measures: The primary end point was a change in thyroid volume (by computerized tomography scan, at 6 months). Secondary end points were the smallest cross-sectional area of the trachea; thyroid function tests; Thyroid Quality of Life Questionnaire; electrocardiogram; and hyperthyroid symptom scale. Results: Thyroid volume decreased significantly in all groups. The reduction was comparable in groups A and B (23.1 ± 8.8 and 23.3 ± 16.5%, respectively; P = 0.95). In group C, the reduction (32.9 ± 20.7%) was more pronounced than in groups A (P = 0.03) and B. The smallest cross-sectional area of the trachea increased in all groups: 3.8 ± 2.9% in A, 4.8 ± 3.3% in B, and 10.2 ± 33.2% in C, with no significant difference among the groups. Goiter-related symptoms were effectively reduced and there were no major safety concerns. Conclusion: In this dose-selection study, 0.03 mg MRrhTSH was the most efficacious dose as an adjuvant to (131)I therapy of MG. It was well tolerated and significantly augmented the effect of (131)I therapy in the short term. Larger studies with long-term follow-up are warranted.

Insulin analogues are increasingly used in patients with type 2 diabetes. We performed a systematic review of randomized controlled trials (RCTs) to assess the role of insulin analogues to reach different hemoglobin A1c (HbA1c) targets (from 6.5% to 8%) in type 2 diabetic patients.RCTs involving insulin regimens (basal, prandial, biphasic, and basal-bolus) with insulin analogues in type 2 diabetes were identified through electronic searches (MEDLINE, EMBASE, CINAHL, and The Cochrane Library) through August 2010. We included any study arm of RCTs if they were at least 12 weeks in duration, and reported HbA1c as an outcome and the proportion of diabetic patients reaching the HbA1c target of7%. The proportion of patients with HbA1c6.5%,7.0%,7.5%, and8.0% was estimated using mean and standard deviation of HbA1c at the end of treatment.We identified 53 RCTs, with 92 arms, and 32,689 patients. The proportion of patients at target was highest with the basal-bolus regimen, and ranged from 27.8% (95% CI, 22.2-34%) for the HbA1c target6.5% to 88% (CI 83-92%) for the HbA1c target8%. Biphasic insulin regimen ranked second at any HbA1c target, while prandial and basal regimens alternated across different HbA1c targets.At any HbA1c target, basal-bolus insulin regimens with insulin analogues obtained the best results, which may be useful for detailing the best treatment effect in individual patients.

Purpose The purpose of this study was to investigate and compare, in a randomized and controlled clinical trial, the use of ultrasound bone surgery devices and the use of rotary instruments in lower third molar extractions. Materials and Methods We selected 26 patients (12 women and 14 men) for this study; the mean age was 31.2 years (range, 24-45 years). A randomized clinical trial was planned. Patients in the control group received treatment with the conventional rotary instruments; patients in the test group received treatment with the ultrasound bone surgery tools. Twenty-six third molars were allocated to the test and control groups according to a computer-generated randomization list. All the surgical procedures were performed by the same surgeon. Pain, trismus, cheek swelling, and number of analgesics taken were evaluated at baseline (before surgery) and at the first-, third-, fifth-, and seventh-day visits. Results Pain levels (evaluated on a visual analog scale) were higher in the control group when compared with the ultrasonic group; however, no statistically significant differences were found. On the contrary, the number of analgesics taken in the test group was significantly lower when compared with the control group. The occurrence of trismus was significantly higher in the control group when compared with the test group. The clinical values of cheek swelling were higher in the rotary group when compared with the ultrasound group at the fifth-day visit. Conclusion This study showed that the use of ultrasound bone surgery for third molar extraction significantly reduced the occurrence of postsurgical trismus, the occurrence of swelling, and the number of analgesics taken after surgery.

Background Congenital toxoplasmosis is considered a rare but potentially severe infection. Prenatal education about congenital toxoplasmosis could be the most efficient and least harmful intervention, yet its effectiveness is uncertain. Objectives To assess the effects of prenatal education for preventing congenital toxoplasmosis. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 May 2015), and reference lists of relevant papers, reviews and websites. Selection criteria Randomized and quasi-randomized controlled trials of all types of prenatal education on toxoplasmosis infection during pregnancy. Cluster-randomized trials were eligible for inclusion. Data collection and analysis Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Main results Two cluster-randomized controlled trials (RCTs) (involving a total of 5455 women) met the inclusion criteria. The two included trials measured the effectiveness of the intervention in different ways, which meant that meta-analysis of the results was not possible. The overall quality of the two studies, as assessed using the GRADE approach, was low, with high risk of detection and attrition bias in both included trials. One trial (432 women enrolled) conducted in Canada was judged of low methodological quality. This trial did not report on any of the review's pre-specified primary outcomes and the secondary outcomes reported results only as P values. Moreover, losses to follow-up were high (34%, 147 out of 432 women initially enrolled). The authors concluded that prenatal education can effectively change pregnant women's behavior as it increased pet, personal and food hygiene. The second trial conducted in France was also judged of low methodological quality. Losses to follow-up were also high (44.5%, 2233 out of 5023 women initially enrolled) and differential (40% in the intervention group and 52% in the control group). The authors concluded that prenatal education for congenital toxoplasmoses has a significant effect on improving women's knowledge, whereas it has no effect on changing women's behavior. In this trial 17/3949 pregnant women seroconverted for toxoplasmosis: 13/2591 (0.5%) in the intervention group and 4/1358 (0.3%) in the control group. The rate of seroconversion detected during the study did not differ between groups (risk ratio (RR) 1.70, 95% confidence interval (CI) 0.56 to 5.21; participants = 3949; studies = one, low quality evidence). The number of events was too small to reach conclusions about the effect of prenatal education on seroconversion rate during pregnancy. No other randomized trials on the effect of prenatal education on congenital toxoplasmosis rate, or toxoplasmosis seroconversion rate during pregnancy were detected. Authors' conclusions Even though primary prevention of congenital toxoplasmosis is considered a desirable intervention, given the lack of related risks compared to secondary and tertiary prevention, its effectiveness has not been adequately evaluated. There is very little evidence from RCTs that prenatal education is effective in reducing congenital toxoplasmosis even though evidence from observational studies suggests it is. Given the lack of good evidence supporting prenatal education for congenital toxoplasmosis prevention, further RCTs are needed to confirm any potential benefits and to further quantify the impact of different sets of educational intervention.

This randomized controlled clinical trial was designed to compare the clinical outcomes of guided tissue regeneration with calcium sulfate graft and membrane (CS) versus guided tissue regeneration with collagen membrane (CM) or open flap debridement (OFD) only in terms of clinical attachment gain in periodontal intrabony defects.Fifty-one systemically healthy, non-smoking subjects affected by moderate to severe chronic periodontitis were recruited. The subjects had one deep intrabony defect with a probing depth (PD)or =6 mm and were randomly divided into three equal groups (17 subjects per group). Subjects were surgically treated with OFD (OFD group), OFD with CS (CS group), or OFD and CM (CM group). One year after surgical treatment, a complete clinical examination and a surgical reentry were performed. The pre- and post-therapy clinical parameters, including PD, clinical attachment level (CAL), gingival recession (GR), and intrasurgical parameters (defect bone level [DBL]), were compared.After 1 year, the clinical and intrasurgical parameters showed statistically significant changes from baseline within each group for all of the evaluated parameters (PD and CAL, P0.001; GR and DBL, P0.05). Differences (PD, CAL, and DBL, P0.001; GR, P0.05) were also seen across the three groups. The CM and CS groups had significantly smaller PD, CAL, and DBL values than subjects treated with only OFD. Groups treated with regenerative techniques had a significantly greater PD reduction and CAL and DBL gain compared to the OFD group. No significant differences were seen between CM and CS. Conversely, the CM group showed a significantly greater GR increase compared to OFD and CS.Both regenerative treatments produced additional clinical benefits over OFD alone. Moreover, the use of CS may minimize post-surgical recession.

During the past several years Carotid ultrasound has assumed an even greater role in the diagnosis of carotid stenosis and has been adopted as the first line preoperative test. It is advisable that each ultrasound laboratory should undertake regular validated comparisons between Duplex and angiography before systematic Duplex practice, especially when new machines or technologists arrive. Unfortunately, there is no general consensus on what constitutes the exact gold-standard for Duplex evaluation. This has been evidenced by the survey described in the article of Walker and Naylor published in this number of EJVES. 1 The Authors sent a questionnaire to assess which Duplex criteria were most commonly used to define carotid stenosis among members of the Society of Vascular Technology of Great Britain and Ireland: astonishingly, the majority of technologists did not know which measurements method was used in their unit. Furthermore, despite both the above countries were the largest contributors to ECST, most of the responders were using criteria that were more consistent with a NASCET than an ECSTclassification. In the face of redefinition of indications for carotid revascularization, the attempt to identify which Duplex criteria are mostly employed should be appreciated and the use of a questionnaire is a valuable tool. The paper of Walker and Naylor confirms the value that Audits and, to a larger extent, well conducted Registries may have in providing useful information. The most important messages provided by the above paper can be summarized as follows: (1) Despite several papers published shortly after the NASCETand ECSTresults questioned the safety of performing CEAwithout diagnostic angiography, 2 other studies, including the survey of Walker and Naylor, 1 have shown that the use of ultrasound as the sole imaging techniques to establish the indication for CEA has worldwide replaced the utilization of other more expensive and risky technologies without detriment for patients outcome. This practice, in the attempt to decrease invasiveness and complications of carotid revascularization, has occurred in face of lack of evidence-based data supporting this switching of technologies. The issue may be even more important in the perspective of comparing CEA with carotid stenting (CAS), if and when, after the necessary randomized trials, CAS will be confirmed as an alternative or even substitute for CEA.

Descrizione delle caratteristiche degli studi di trattamento al fine della loro valutazione critica.

The notable success of stapled prolapsectomy in recent years led us to compare this technique with Milligan-Morgan hemorrhoidectomy in terms of the results obtained both in the immediate postoperative period and in the long term.We performed conventional hemorrhoidectomy on 50 randomly selected patients and operated on a further 50 using the stapler technique. The patients were monitored over the immediate postoperative period (e.g., type of anesthesia, mean duration of operation, mean hospitalization time, analgesic administration, time before returning to work) and over a long-term follow-up period of 48 months (later complications such as prolapse relapse, bleeding, stenosis, incontinence).The stapled group experienced significantly less pain (mean number of analgesic tablets 2.60 vs. 15.9) and returned to normal activity sooner (8.04 vs. 16.9 days), as reported by other authors. In the long-term follow-up at 48 months, stapled hemorrhoidectomy was found to control prolapse, discharge, and bleeding, with no stenosis or significant incontinence, in 94% of cases.Our conclusions confirm the excellent advantages of stapled hemorrhoidectomy which allows the rapid recovery of patients and also promises the complete resolution of hemorrhoidal prolapse in the long term.

Orphan drugs definition should be related to prevalence criteria. In Europe the prevalence criterion is 5/10.000. These drugs are called “orphans” because the pharmaceutical industry has little interest under normal market conditions in developing and marketing products intended for only a small number of patients. For this reason governments have emphasized the need for economic incentives to encourage drug companies to develop and market orphan drugs. Aim of this study is the analysis of the contributing factors involved in the price definition of orphan drugs in Italy, focusing on the case of DepoCyte®, a new orphan drug recently approved by the European Medicines Agency. DepoCyte® is a slow-release formulation of cytarabine designed for intrathecal administration in the treatment of neoplastic meningitis due to metastatic cancers. It maintains cytotoxic concentrations of free cytarabine in the cerebrospinal fluid for more than 14 days following a single injection. In two randomized clinical trials DepoCyte® was compared to standard formulation of cytarabine, showing a better time to neurologic progression and survival trend in favor of DepoCyte®, associated with an improved mean change about quality of life in Karnofsky performance score. The innovative technology and the efficacy of DepoCyte® allow to frame some interesting pharmacoeconomical consequences: the results of the present work showed that DepoCyte® is more expensive but also more effective than standard formulation, and the new formulation-correlated improvement in the patients’ quality of life seems to justify the difference between the costs of the two alternatives.