Disinvestment in healthcare: an overview of HTA agencies and organizations activities at European level.

BACKGROUND: In an era of a growing economic pressure for all health systems, the interest for "disinvestment" in healthcare increased. In this context, evidence based approaches such as Health Technology Assessment (HTA) are needed both to invest and to disinvest in health technologies. In order to investigate the extent of application of HTA in this field, methodological projects/frameworks, case studies, dissemination initiatives on disinvestment released by HTA agencies and organizations located in Europe were searched. METHODS: In July 2015, the websites of HTA agencies and organizations belonging to the European network for HTA (EUnetHTA) and the International Network of Agencies for HTA (INAHTA) were accessed and searched through the use of the term "disinvestment". Retrieved deliverables were considered eligible if they reported methodological projects/frameworks, case studies and dissemination initiatives focused on disinvestment in healthcare. RESULTS: 62 HTA agencies/organizations were accessed and eight methodological projects/frameworks, one case study and one dissemination initiative were found starting from 2007. With respect to methodological projects/frameworks, two were delivered in Austria, one in Italy, two in Spain and three in U.K. As for the case study and the dissemination initiative, both came from U.K. The majority of deliverables were aimed at making an overview of existing disinvestment approaches and at identifying challenges in their introduction. CONCLUSIONS: Today, in a healthcare context characterized by resource scarcity and increasing service demand, "disinvestment" from low-value services and reinvestment in high-value ones is a key strategy that may be supported by HTA. The lack of evaluation of technologies in use, in particular at the end of their lifecycle, may be due to the scant availability of frameworks and guidelines for identification and assessment of obsolete technologies that was shown by our work. Although several projects were carried out in different countries, most remain constrained to the field of research. Disinvestment is a relatively new concept in HTA that could pose challenges also from a methodological point of view. To tackle these challenges, it is necessary to construct experiences at international level with the aim to develop new methodological approaches to produce and grow evidence on disinvestment policies and practices.

Doppler-guided hemorrhoidal dearterialization with laser (HeLP): a prospective analysis of data from a multicenter trial.

BACKGROUND: Doppler-guided hemorrhoidal laser procedure (HeLP) is a new minimally invasive technique to treat symptomatic hemorrhoids. The aim of this multicenter study was to prospectively assess clinical results and patients' satisfaction in patients treated with HeLP. METHODS: Indications for HeLP included patients with symptomatic hemorrhoids resistant to medical therapy, with low-grade prolapse. Clinical efficacy was evaluated assessing resolution of symptoms and patient satisfaction. Frequency of bleeding and frequency of acute hemorrhoid-related symptoms were given a score of 0 to 4 (where 4 = more than 3 episodes/week) and 0 to 3 (where 3 = more than 5 episodes/year), respectively. Quality of life, pain at rest, and pain with evacuation were scored using a visual analogue scale (VAS) of 0 to 10. Intra- and postoperative complications were recorded. Potential predictive factors for failure were assessed. RESULTS: Two hundred and eighty-four patients (183 males, 101 females) with a mean age of 47.5 years were included in the study. At 6-month follow-up, symptoms had completely resolved in 257/284 (90.5%) and 275/284 (96.8%) patients were satisfied with the results. An analysis of a subgroup of 144 patients followed up for a minimum of 12 months revealed a resolution of symptoms in 130/144 (90.3%) and satisfaction in 139/144 (96.5%). There was a statistically significant improvement of the bleeding score (from 2.4 ± 1.07 to 0.36 ± 0.49; p < 0.0001), acute symptoms score (from 2.03 ± 0.16 to 0.61 ± 0.59; p < 0.0001), quality of life (from 4.63 ± 1.32 to 8.96 ± 1.35; p < 0.0001), pain at rest (from 3.0 ± 2.05 to 1.1 ± 0.99; p < 0.0006), and pain with evacuation (from 4.8 ± 1.22 to 1.7 ± 1.15; p < 0.0001). No significant changes in continence and constipation were observed. Univariate analysis failed to show factors significantly associated with failure. CONCLUSIONS: The HeLP procedure seems to be safe and effective in patients with symptomatic hemorrhoids. It is simple, minimally invasive, and relatively pain free. It can be performed in an ambulatory setting without anesthesia, and it achieves high patient satisfaction. It may, therefore, be considered a "first-line treatment" in all patients without significant hemorrhoidal prolapse in whom medical therapy has failed.

Recurrent use of the Emergency Department in patients with anxiety disorder.

OBJECTIVE: Panic disorder is characterized by the spontaneous and unexpected occurrence of panic attacks. During panic attacks, patients (pts) refer to the Emergency Department (ED). The diagnostic work-up for any panic attack is expensive since symptoms at presentation mimic other diseases such acute coronary syndrome or neurological emergencies. The aim of the present study was to describe a 10 years cohort of pts diagnosed with panic disorder in the ED in terms of ED visit recurrence. METHODS: Case-control study, in a tertiary care, involving pts presenting to the ED and diagnosed with panic attack according to the International Classification of Diseases 9nt Revision (ICD-9). From January 2001 to Dec 2009 were extracted from the electronic clinical database 469 pts and were divided into "recurrent ED visit" (multiple ED access for panic attack) (N=361) and "no recurrent ED visit" (only one ED access for panic attack in 9 years) (N=108). RESULTS: At univariate analysis cases and controls differed for male prevalence (p < 0.01), neurological symptoms at presentation (p = 0.02) and history of other psychiatry disorder (p < 0.01). In multivariate analysis independent predictors were male gender, age under 40 year old, palpitations at presentations, 1 or more cardiovascular risk factors and previous other psychiatry conditions. CONCLUSIONS: Male under 40 years old with palpitations or cardiovascular risk and other psychiatric diseases, have a higher recurrence of panic attacks. General psychiatric evaluation and treatment with benzodiazepine in ED is not useful to prevent recurrences. Identifying those patients at high risk of panic attack and ED visit recurrence might be useful to establish ad-hoc interventions, improve patients' morbidity and save precious resources.

Assessment of baseline characteristics and risk factors among Emergency Department patients presenting with recent onset atrial fibrillation: a retrospective cohort study.

BACKGROUND: The Cardioversion of Atrial Fibrillation in Emergency (CAFE) study was an observational, retrospective, multicenter study focusing on patients with recent onset atrial fibrillation (AF) seen in six different Emergency Departments (ED) of Rome, Italy. AIM: The aim of this study was to present the baseline characteristics and risk factors of the patients enrolled to the CAFE study. MATERIALS AND METHODS: We retrospectively reviewed 3085 eligible patients diagnosed with recent onset AF in any of the EDs between January 2008 and December 2009. Inclusion criteria required documented ICD-9 primary discharge/admission diagnosis of AF in the ED and stable hemodynamic conditions at presentation (systolic blood pressure > 90 mmHg). Exclusion criteria were permanent AF or an ongoing acute coronary syndrome. RESULTS: Median age was 71 years (interquartile ranges, 62-78 years) and 50.8% were men. Palpitations was the most common symptom at ED presentation and was present in 73.5% of the study subjects. Hypertension was the most prevalent comorbidity, affecting 59.3% of the patients evaluated, and the presence of previous episode(s) of AF was also common (52.3%). Regarding home treatment, the drugs most prescribed were antiplatelets (31.2%) and diuretics (25.2%). A CHADS2 score of 0 was found in 814 patients (26.4%), while a CHADS2 score of 1 was reported in 1114 patients (36.1%). Finally, a CHADS2 score ≥ 2 was reported in 1157 patients (37.5%). CONCLUSIONS: The present study represents an important snapshot of demographics, comorbidities, risk factors and anticoagulation management about patients with recent onset AF. Disparities were noted in anticoagulation management, suggesting that this is still a main problem among patients with AF.

Photodynamic chemotherapy in the treatment of superficial mycoses: an evidence-based evaluation.

Photodynamic therapy (PDT) is a constantly evolving treatment modality consisted of a chemical reaction activated by light energy that is used to selectively destroy tissue; it may be considered a particular form of photochemotherapy that uses a photosensitizer, light and oxygen. The combination of the possibility of ablation of lesion with an excellence aesthetic result has allowed the photodynamic therapy an increasing role in the treatment of skin disease, that ranges from skin cancer to cosmetic treatment. Particular attention is paid in the last years to a developing area of research, the antifungal photodynamic therapy. The growing resistance against antifungal drugs has renewed the search for alternative therapies and PDT seems to be a potential candidate. This article provides an extensive review of antifungal photodynamic therapy, its mechanisms and applications in the treatment of superficial mycoses.

A critical review of the efficacy and safety in the use of low-molecular-weight heparin in acute ST-elevation myocardial infarction: a Bayesan approach.

BACKGROUND: ST segment elevation myocardial infarction (STEMI) is an important risk factor of death worldwide. Significant clinical research has been done to assess ideal reperfusion strategies in the setting of STEMI, including the role of the antithrombin agents: unfractionated heparin (UFH) and low molecular weight heparin (LMWH). Given the evidence that LMWH may be safer than UFH in the treatment of other thrombotic disorders, its role in the management of STEMI needs to be more defined. OBJECTIVE: To assess the safety and efficacy of LMWH compared to UFH and/or placebo for the treatment of STEMI. MATERIALS AND METHODS: The Cochrane Library, MedLine and EMABASE databases were searched for randomized controlled trials pertinent to the study objective. Selection criteria included all randomized controlled trials comparing LMWH to either UFH or placebo in the treatment of STEMI through December 2010. Two Authors performed the search independently.After identifying appropriate studies, a random effect model and Bayesian sensitivity analysis were used to combine results from original trials and assess the consistency of results. RESULTS: We identified 13 studies that met the described selection criteria; 8 comparing LMWH to UFH and 5 to placebo in STEMI patients. The combined Odd's ratio was 0.79 with a 95% confidence interval of 0.67-0.94 for all studies and 0.74 (0.54-1.02) for those comparing LMWH to UFH only. A trend toward more frequent hemorrhagic events was identified in the LMWH group (Odd's ratio 1.40) which did not meet statistical significance (95% confidence interval 0.80-2.47). Sensitivity analysis demonstrated clinical benefits of 6% and 12.5% with probabilities of 99% and 95% respectively. CONCLUSION: Compared to placebo or UFH, LMWH is effective as a first line treatment of STEMI patient with no significant increase in major hemorrhagic events.

Cefazolin concentrations in serum during cardiopulmonary bypass surgery.

The objective of the study was to investigate possible changes in cefazolin serum levels induced by cardiopulmonary bypass (CPB). Six cardiac male patients who underwent cardiac surgery requiring CPB took part in the study. Cefazolin 2 g was intravenously infused over 60 min before anesthesia and blood samples were taken at appropriate times after drug administration (0, 0.25, 0.5, 1, 4, 6, 8 h), 2 min before and 5 min after the beginning and 2 min before and 5 min after the end of CPB. Drug serum concentrations were determined by means of a microbiological method. Five minutes after the start of CPB, cefazolin serum levels decreased on average by 46.6% and remained steadily low until 5 min after the end of CPB. Then, they rose on average by 37.3% at 4 h and then declined slowly until the last sampling at 8 h. Cefazolin serum concentrations were low during CPB but remained in a potentially effective range for antimicrobial prophylaxis for this surgery.

Tinea capitis in Campania, Italy: a 9-year retrospective study.

AIM: The present work was carried out to study the prevalence of Tinea capitis (TC) in Campania over a 9-year period and also to delineate the prevalence of the causative fungus responsible and the clinical forms of tinea capitis. METHODS: This retrospective study included all the cases of TC occurring between January 2004 and December 2012 to the Mycology Laboratory at the University of Naples "Federico II" and mycologically confirmed. Samples for potassium hydroxide 20% mounts and fungal cultures were collected. Sabouraud dextrose agar were inoculated with the samples. RESULTS: TC was diagnosed by direct microscopy and culture in 143 patients. TC was found to be most common in the group including patients aged between 1-18 years; 13% of patients were over 18 years old. Non-inflammatory clinical forms were the most common type (80.4%). M. canis was the dermatophyte most frequently isolated (64.1%). Microscopic examination revealed an ectothrix pattern of hair invasion to be more common (72% cases). CONCLUSION: TC was clinical and mycologically diagnosed in 143 patients. It was prevalent in patients aged 1-18 years old; 73.2% of adults affected by TC had possible risk factors and in these patients TC often presented in atypical forms; atypical forms were also observed in children. M. canis was the most common dermatophyte species isolated in children, T. rubrum in adults. We noticed a significant increase of anthropophilic dermatophytes possibly linked to the immigration from African countries. For the diagnosis of TC, mycological examinations are essential.

17beta-estradiol antiinflammatory activity in carrageenan-induced pleurisy.

We have recently demonstrated that 17beta-estradiol (E2) opposes cytokine-dependent increase of inducible nitric oxide synthase (iNOS) activity in rat smooth muscle cells and proposed that this effect might be associated to an antiinflammatory activity of this hormone. In the present study, we examine the E2 effects on a well-known in vivo model of inflammation. We show that, in carrageenan treatment of ovariectomized rats, prior exposure to E2 significantly attenuated inflammatory response as measured by histological examination and exudate production. The effect was visible with a single injection of a physiological dose of E2 1 h before the carrageenan treatment and was blocked by coadministration of the estrogen receptor antagonists ICI 182,780 or tamoxifen. This latter observation suggests that the effect is receptor mediated. The mechanisms by which estradiol has beneficial effects in this model of inflammation are unclear: we show that in hormonally treated rats there is a decrease in polymorphonuclear cells migration as shown by cell counting and myeloperoxidase measurement. In addition, E2 pretreatment opposes carrageneen-induced high lipid peroxidation maintaining malondialdehyde activity at control levels. E2 treatment decreases NO production and the activity of iNOS with consequent diminished nitrite synthesis and nitrosine accumulation. Finally, immunohistochemical analysis for poly (ADP-ribose) synthase revealed a positive staining in lungs from carrageenan-treated rats that was blocked by estradiol treatment. We conclude that E2 attenuates the degree of inflammation and tissue damage associated with carrageenan-induced pleurisy in the rat.

Beneficial effects of n-acetylcysteine on ischaemic brain injury.

1. Nitric oxide (NO), peroxynitrite, formed from NO and superoxide anion, poly (ADP-ribole) synthetase have been implicated as mediators of neuronal damage following focal ischaemia. Here we have investigated the effects of n-acetylcysteine (NAC) treatment in Mongolian gerbils subjected to cerebral ischaemia. 2. Treatment of gerbils with NAC (20 mg kg(-1) 30 min before reperfusion and 1, 2 and 6 h after reperfusion) reduced the formation of post-ischaemic brain oedema, evaluated by water content. 3. NAC also attenuated the increase in the brain levels of malondialdehyde (MDA) and the increase in the hippocampus of myeloperoxidase (MPO) caused by cerebral ischaemia. 4. Positive staining for nitrotyrosine was found in the hippocampus in Mongolian gerbils subjected to cerebral ischaemia. Hippocampus tissue sections from Mongolian gerbils subjected to cerebral ischaemia also showed positive staining for poly (ADP-ribose) synthetase (PARS). The degree of staining for nitrotyrosine and for PARS were markedly reduced in tissue sections obtained from animals that received NAC. 5. NAC treatment increased survival and reduced hyperactivity linked to neurodegeneration induced by cerebral ischaemia and reperfusion. 6. Histological observations of the pyramidal layer of CA1 showed a reduction of neuronal loss in animals that received NAC. 7. These results show that NAC improves brain injury induced by transient cerebral ischaemia.

Sequential cranial MR findings of asymptomatic and neurologically symptomatic HIV+ subjects.

PURPOSE: To compare results of a prospective MR and clinical reevaluation of HIV+ asymptomatic and neurologically symptomatic subjects who had had initially abnormal cranial studies to determine what cranial MR changes occur and how these changes correlate with serial neurologic and neuropsychologic findings. PATIENTS AND METHODS: Thirty-one asymptomatic (n = 20) and neurologically symptomatic (n = 11) subjects seropositive for the human immunodeficiency virus (HIV+) were prospectively reevaluated by cranial magnetic resonance (MR) one to two years following an initially abnormal MR of the brain. RESULTS: All 31 HIV+ subjects with initial abnormal MR had abnormal follow-up scans (showing atrophy and/or white matter lesions). Twenty-seven showed no progression of MR abnormalities (among whom were 18 with minimally abnormal scans who remained asymptomatic with improved or static neuropsychologic performance). Of the four subjects with scan changes (all with clinically suspected HIV encephalopathy), one showed MR, clinical, and neuropsychologic test improvement; the remaining three showed MR (n = 3), neurologic (n = 3), neuropsychologic (n = 1) worsening and autopsy (n = 1) confirmed the presence of HIV-1 containing multinucleated giant cells in the brain. CONCLUSIONS: This study suggests that: 1) Progression of intracranial MR abnormalities due to HIV-1 is seen only in a minority of HIV+ subjects over a 1- to 2-year time period, only in those neurologically symptomatic, and correlates with clinical deterioration. 2) Minor cerebral MR abnormalities seen in HIV+ subjects who remain neurologically asymptomatic do not change over a 1- to 2-year period. 3) Although HIV is known to infect the brain early, it may, nevertheless, not routinely do significant anatomical damage early on in the disease, as based on MR criteria.

Pharmacokinetics, endocrine and antitumour effects of leuprolide depot (TAP-144-SR) in advanced prostatic cancer: a dose-response evaluation.

Twenty-two patients with advanced prostatic cancer and one with benign prostatic hypertrophy were given the GnRH analogue leuprolide in the form of a slow-release depot formulation by subcutaneous injection at doses of 3.75, 7.5, 15 or 30 mg. Following the first dose, drug levels were measured by a double-antibody RIA over an observation period of 5 weeks. Thereafter patients continued long-term subcutaneous treatment at the same dose every 4 weeks. Serum levels of leuprolide showed a rapid increase immediately after injection, reaching a peak proportional to dose within 3 h (range of mean values 13.1-54.5 ng/ml). Subsequently, mean drug levels declined to a plateau proportional to dose (0.49-1.99 ng/ml at 5 weeks). A significant dose-dependent increase in the area under the serum concentration-time curve from zero to 35 days (AUC0-35 days) from 541.7 to 1653.9 ng/ml.h was also noted (p less than 0.01). With all doses there was an initial rise in serum LH and FSH, followed by a rise in testosterone and dihydrotestosterone, then a sharp decrease within 3 weeks. FSH inhibition was achieved in all the 20 evaluable patients and was maintained in 17 of them (85%) over 5 weeks. Fifteen subjects (75%) had marked suppression of LH levels. In 13 of them (65%) this condition continued for the entire observation time. Castration levels of serum testosterone and dihydrotestosterone, however, were maintained in all patients for up to 5 weeks. Two of the 21 evaluable patients (10%) had a complete response; 15 a partial response (71%) and 3 stable disease (14%). No significant differences were observed in relation to dose. Clinical improvement and serum hormonal changes support this as a new and superior method of administration of leuprolide at a dose as low as 3.75 mg.

[Spigelian hernia]. / L'ernia di Spigelio.

The Authors report their experience with the treatment of Spigelian hernia. After addressing the anatomy of the abdominal lateral wall and of etiopathogenic factors responsible for this rare type of hernia, the clinical problems associated with the disease are discussed and the importance of physical examination and instrumental procedures is stressed. The authors then go on to list the possible repair techniques currently available.

[Mechanical intestinal occlusion due to phytobezoars]. / L'occlusione meccanica intestinale da fitobezoario.

The Authors reporting two cases with ileus by phytobezoar in distal jejunum and ileum, respectively, and discuss the pathophysiologic mechanism responsible for the formation of bezoars. They expose the etiological and clinical factors of this uncommon cause of small bowel obstruction and also discuss the surgical technique that consists in the removal of the phytobezoar through enterotomy.

Current drive at plasma densities required for thermonuclear reactors.

Progress in thermonuclear fusion energy research based on deuterium plasmas magnetically confined in toroidal tokamak devices requires the development of efficient current drive methods. Previous experiments have shown that plasma current can be driven effectively by externally launched radio frequency power coupled to lower hybrid plasma waves. However, at the high plasma densities required for fusion power plants, the coupled radio frequency power does not penetrate into the plasma core, possibly because of strong wave interactions with the plasma edge. Here we show experiments performed on FTU (Frascati Tokamak Upgrade) based on theoretical predictions that nonlinear interactions diminish when the peripheral plasma electron temperature is high, allowing significant wave penetration at high density. The results show that the coupled radio frequency power can penetrate into high-density plasmas due to weaker plasma edge effects, thus extending the effective range of lower hybrid current drive towards the domain relevant for fusion reactors.

Relationships between platelet counts, platelet volumes and reticulated platelets in patients with ITP: evidence for significant platelet count inaccuracies with conventional instrument methods.

The platelet count has a primary role in the diagnosis and treatment of idiopathic thrombocytopenic purpura (ITP). This study analysed the accuracy of ITP patient platelet counts determined by Abbott CD-Sapphire (impedance/optical) and Bayer Advia 120 (optical) analyses, compared with a reference immunoplatelet method. Instrument platelet estimates showed broad equivalence in the higher range of observed values, but significant discrepancies against the immunoplatelet count were seen when platelet counts were <10 x 10(9)/l. CD-Sapphire mean platelet volume (MPV) results revealed increased (>12 fl) platelet volumes in eight of eight ITP patients with counts of <20 x 10(9)/l compared with 6/6 and 5/13 patients with platelet counts of 20-50 and >50 x 10(9)/l. In contrast, Bayer Advia MPV values showed no relationship with the platelet count. Increased reticulated platelets were associated with an increasing CD-Sapphire MPV (R(2) = 0.61) and a decreasing platelet count. High (>40%) reticulated platelet values were seen in 9/9 patients with immunoplatelet counts of <20 x 10(9)/l compared with 0/19 patients with platelet counts above 20 x 10(9)/l. There may be a need for caution in the interpretation of platelet counts in ITP patients obtained with conventional instrument methods, and therapeutic decisions should ideally be validated by reference immunoplatelet procedures.