102,439 research outputs found
Tapentadol in the management of cancer pain: current evidence and future perspectives
No full textHans G Kress,1 Flaminia Coluzzi2 1Department of Special Anesthesia and Pain Medicine, Medical University, Vienna General Hospital, Vienna, Austria; 2Department of Medical and Surgical Sciences and Biotechnologies, Unit of Anesthesia, Intensive Care and Pain Medicine, Sapienza University of Rome, Polo Pontino, Latina, Italy Abstract: Thanks to the progress in early diagnosis and treatment of cancer, the life expectancy of cancer patients has now increased. Patients are, therefore, more likely to experience their individual cancer pain as a chronic pain. As a consequence, long-term treatment of cancer-related pain and oncological therapy-related pain are a major need for all patients and a challenge to all healthcare professionals. Tapentadol is a centrally acting analgesic drug characterized by two synergistic mechanisms of action, since it acts at the µ-opioid receptor (MOR) and inhibits noradrenalin re-uptake (NRI). Therefore, tapentadol has been considered the first of a new class of drugs, MOR-NRI. Tapentadol has been tested in different populations of cancer patients (opioid-naive and -pretreated), such as those with pain of mixed etiology, patients with pain from hematological malignancies and patients experiencing pain conditions due to anticancer treatment. According to available evidence, tapentadol prolonged release was well tolerated and effective in cancer pain patients. In randomized, double-blind and active-controlled trials it proved non-inferior to standard opioids like morphine or oxycodone in the management of moderate-to-severe cancer pain, both in opioid-naive and in opioid-pretreated patients. The good analgesic efficacy may be partly due to the action of tapentadol on neuropathic pain components. Together with the low rate of gastrointestinal adverse effects and the overall favorable safety profile, tapentadol can be considered a good option in cancer pain patients, who can suffer frequently from nausea, vomiting, constipation or other events that further reduce their quality of life. Keywords: cancer pain, tapentadol, neuropathic pai
Diffuse and Localized Functional Dysconnectivity in Schizophrenia: a Bootstrapped Top-Down Approach
No full textSchizophrenia (SZ) is a brain disorder leading to detached mind's normally
integrated processes. Hence, the exploration of the symptoms in relation to
functional connectivity (FC) had great relevance in the field. FC can be
investigated on different levels, going from global features to single edges
between regions, revealing diffuse and localized dysconnection patterns. In
this context, SZ is characterized by a diverse global integration with reduced
connectivity in specific areas of the Default Mode Network (DMN). However, the
assessment of FC presents various sources of uncertainty. This study proposes a
multi-level approach for more robust group-comparison. FC between 74 AAL brain
areas of 15 healthy controls (HC) and 12 SZ subjects were used. Multi-level
analyses and graph topological indexes evaluation were carried out by the
previously published SPIDER-NET tool. Robustness was augmented by bootstrapped
(BOOT) data and the stability was evaluated by removing one (RST1) or two
subjects (RST2). The DMN subgraph was evaluated, toegether with overall local
indexes and connection weights to enhance common activations/deactivations. At
a global level, expected trends were found. The robustness assessment tests
highlighted more stable results for BOOT compared to the direct data testing.
Conversely, significant results were found in the analysis at lower levels. The
DMN highlighted reduced connectivity and strength as well as increased
deactivation in the SZ group. At local level, 13 areas were found to be
significantly different (), highlighting a greater divergence in the
frontal lobe. These results were confirmed analyzing the negative edges,
suggesting inverted connectivity between prefronto-temporal areas. In
conclusion, multi-level analysis supported by BOOT is highly recommended,
especially when diffuse and localized dysconnections must be investigated in
limited samples.Comment: 28 pages, 8 figure
ANEMIA EMOLITICA AUTOIMMUNE E GRAVIDANZA
No full textANEMIA EMOLITICA AUTOIMMUNE
E GRAVIDANZA
Coluzzi S.(1), Giovannetti G.(1), La Rocca U.(1), Neri A.(1), Santilio I.(1), Girelli G.(1), Arista M.C.(1)
(1)UOC Immunoematologia e Medicina Trasfusionale, Azienda Ospedaliero-Universitaria Policlinico Umberto I, Roma
Premessa. La malattia emolitica autoimmune (MEA) è una condizione acquisita rara causata da anticorpi (Ac) rivolti verso antigeni self eritrocitari. La presenza di autoimmunizzazione eritrocitaria pre-esistente o l'insorgenza durante la gravidanza sono oggetto di attento monitoraggio immunoematologico, in particolare nei casi in cui l'autoAc sia di classe IgG, pertanto in grado di superare la barriera placentare e potenzialmente causare sensibilizzazione degli eritrociti fetali.
Metodi. Sono state revisionate le schede del workup immunoematologico di donne in gravidanza pervenute in un anno nel nostro ambulatorio per il monitoraggio finalizzato alla prevenzione della malattia emolitica feto-neonatale (MEFN); nella maggior parte dei casi si trattava di donne con ricerca Ac risultata positiva presso altri laboratori. In accordo con quanto previsto dalle Raccomandazioni SIMTI-SIGO, è stata effettuata una determinazione del fenotipo ABO/Rh/K nel I trimestre di gravidanza, confermata a 28 settimane di gestazione, e la ricerca di Ac eritrocitari irregolari. In caso di risultato positivo, lo studio includeva: test dell'antiglobulina diretto (TAD), caratterizzazione della classe Ig dell'autoAc ed identificazione di eventuali alloAC, titolazione Ac(auto/ alloAc), come parte del check-up finalizzato all'inquadramento di un'eventuale insorgenza di MEFN e nell'eventualità di una richiesta trasfusionale nella madre e/o nel figlio. Il monitoraggio immunoematologico è stato condotto, in relazione ai risultati ottenuti, secondo quanto previsto dalle Raccomandazioni. Risultati. Nel corso di un anno sono stati effettuati 375 studi immunoematologici in 124 donne in gravidanza. Di queste, in 10 lo studio dava esito negativo, in 3 era evidenziata interferenza dovuta ad Ac verso mezzi potenzianti/conservanti dei pannelli eritrocitari, mentre in 111 lo studio risultava positivo per la presenza di auto o alloAc; in 10/111 pazienti (9%) veniva diagnosticata una MEA (8 da Ac di tipo caldo IgG, 1 di tipo freddo IgM, 1 di tipo misto IgG+IgM). In4/10 pazienti si associavano alloAc (4 casi anti-Wra, 1 anti-Wra+anti-E (titolo1), 1 anti-C (indosabile); il titolo dell'autoAc IgG era<16 in tutti i casi. In 3/10 neonati da madri con autoimmunizzazione eritrocitaria, il TAD alla nascita era risultato positivo, di tipo IgG, e si eluiva l'Ac privo di specificità convenzionali, di provenienza materna; nessuno dei tre neonati con TAD positivo aveva presentato anemia e/o iperbilirubinemia alla nascita e al controllo a 1 mese.
Conclusioni Nella nostra esperienza il riscontro di autoAc materni non ha comportato alcuna conseguenza nel feto/ neonato; tuttavia in tutti i casi il titolo degli autoAc era modesto, anche nei casi in cui era stato necessario instaurare terapia steroidea nella madre a causa della significatività clinica dell'autoAc. Seppur anche in letteratura sia riportata una bassa percentuale di neonati con segni di emolisi causati da autoAc materni, cionondimeno è raccomandato un atteggiamento di attenta sorveglianza, al fine di instaurare un pronto trattamento nella madre, soprattutto nei casi in cui si associ un più ampio disordine dell'immunità, e per evidenziare alloAc che, eventualmente presenti e più pericolosi per il feto, potrebbero essere mascherati dall'autoAc
APPLICAZIONE DI LINEE GUIDA AZIENDALI PER L'IMPIEGO DELL'ALBUMINA UMANA: IMPATTO SUI CONSUMI
No full textXXXVIII CONVEGNO NAZIONALE DI STUDI DI MEDICINA TRASFUSIONALE 8.02 ALTRI – EVIDENCE BASED MEDICINE E DIFINIZIONE DI LINEE GUIDA
ABS396 APPLICAZIONE DI LINEE GUIDA AZIENDALI PER L’IMPIEGO DELL’ALBUMINA UMANA: IMPATTO SUI CONSUMI
De Nicolò M.C.(1), Coluzzi S.(1), Tomei G.(1), Carmini D.(1), Pasqualetti D.(1), Screnci M.(1), Merli M.(2), Girelli G.(1)
(1) SIMT, Az.Pol.Umberto I Univ. “La Sapienza”, Roma; (2) Gastroenterologia, Az.Pol.Umberto I, Univ.”La Sapienza”, Roma
Introduzione
In Italia, come in Europa, non è stata raggiunta l’autosufficienza del plasma per la produzione di plasmaderivati tra cui l’albumina; è pertanto necessario un uso razionale e appropriato per evitare di depauperare scorte già insufficienti. L’uso appropriato di emocomponenti e di emoderivati è uno dei compiti istituzionali dei Servizi di Medicina Trasfusionale.
Metodi
Nel 2006 presso la nostra Azienda abbiamo richiesto l’istituzione di una commissione, da noi coordinata, per la messa a punto di Linee Guida (LG) per migliorare l’appropriatezza d’uso dell’albumina. I componenti del gruppo di lavoro sono stati nominati dalla Direzione Sanitaria con il coinvolgimento dei reparti maggiori utilizzatori di albumina. Per la stesura delle LG si è tenuto conto della revisione della letteratura, delle LG internazionali e di quelle SIMTI. Le LG elaborate e validate e la nuova modulistica per la richiesta sono state diffuse da Dicembre 2006 in ambito aziendale per via cartacea e attraverso la rete intranet. Le richieste vengono evase dalla Farmacia previa autorizzazione del SIMT. Al fine di verificare il corretto impiego delle LG e l’impatto sul consumo aziendale, abbiamo confrontato i consumi di albumina prima e dopo l’applicazione delle LG.
Risultati
Vedi Tabella.
Conclusioni
L’applicazione delle LG ha comportato nel 2007 una riduzione del consumo di albumina del 27%, pari a 5779 flaconi. Considerando il costo unitario di 35.64 € per flacone, il risparmio per la nostra Azienda è stato di 205.963 €. 6.027 flaconi, pari al 38.6% dei consumi totali del 2007, è coperto da soli 5 Reparti (Rianimazione, Trapianti d’Organo, Cardiochirurgia, Gastroenterologia e Chirurgia d’Urgenza) su una parte dei quali è sicuramente possibile un intervento di miglioramento dell’impiego. Da una prima analisi dei consumi è emerso che la riduzione nel 2007 è senza dubbio dovuta ad un migliore utilizzo legato all’introduzione delle LG; tuttavia dall’analisi delle singole richieste emerge che è possibile un ulteriore ottimizzazione dell’impiego attraverso un audit con i reparti coinvolti
Common Clinical Practice for Opioid-Induced Constipation: A Physician Survey
No full textFlaminia Coluzzi,1,2 Domenico Alvaro,3 Augusto Tommaso Caraceni,4 Walter Gianni,5 Franco Marinangeli,6 Giuseppe Massazza,7 Carmine Pinto,8 Giustino Varrassi,9 Fabio Lugoboni10 1Department of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, LT, Italy; 2Anesthesiology, Intensive Care, and Pain Medicine Unit, Sant’Andrea University Hospital, Rome, RM, Italy; 3Department of Translational and Precision Medicine, Gastroenterology Division, Sapienza University of Rome, Rome, RM, Italy; 4Palliative Care, Pain Therapy, and Rehabilitation Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, MI, Italy; 5Department of Internal Medicine and Geriatric Medicine, University Hospital Policlinico Umberto I, Rome, RM, Italy; 6Department of Anesthesiology, Pain Medicine, and Palliative care, University of L’Aquila, L’Aquila, AQ, Italy; 7Division of Physical Medicine and Rehabilitation, Department of Surgical Sciences, University of Turin and “Città della Salute e della Scienza” University Hospital, Torino, TO, Italy; 8Medical Oncology Unit, Clinical Cancer Center, AUSL-IRCCS of Reggio Emilia, Reggio Emilia, RE, Italy; 9Fondazione Paolo Procacci, Rome, RM, Italy; 10Department of Medicine, Addiction Unit, University Hospital of Verona, Verona, VR, ItalyCorrespondence: Flaminia ColuzziDepartment of Medical and Surgical Sciences and Biotechnologies, Sapienza University of Rome, Polo Pontino, Latina, Corso della Repubblica 79, Latina, LT, 04100, ItalyTel +39 06 33775673Email [email protected]: Opioid-induced constipation (OIC) remains an important clinical obstacle despite the availability of several guidelines and pharmacological options for its management. Here, we surveyed common practices and perceptions about OIC among physicians who prescribe opioids in Italy.Methods: The online survey included 26 questions about OIC. Responses were analyzed descriptively and aggregated by physician specialty.Results: A total of 501 physicians completed the survey. Most respondents (67%) did not feel adequately educated about OIC despite general consensus regarding interest in the topic. Overall, 62– 75% of physicians regularly evaluated intestinal function or OIC symptoms in patients receiving opioid therapy. The most common method for assessment was patient diary; few physicians used a validated instrument such as the Rome IV criteria. Psychiatrists and addiction specialists showed the lowest interest and poorest practices. Most respondents (78%) preferred macrogol prophylaxis followed by macrogol plus another laxative for first-line treatment of OIC symptoms. Peripheral-acting mu opioid receptor antagonists (PAMORAs) were not widely used among physicians; 61% had never prescribed a PAMORA for OIC.Conclusion: Our findings reveal important differences in clinical practice for OIC across physician specialties. Additional formative efforts are necessary to improve awareness about best practices in OIC.Keywords: chronic pain, opioid, opioid-induced constipation, peripherally acting mu opioid receptor antagonis
The challenge of perioperative pain management in opioid-tolerant patients
No full textFlaminia Coluzzi,1 Francesca Bifulco,2 Arturo Cuomo,2 Mario Dauri,3 Claudio Leonardi,4 Rita Maria Melotti,5 Silvia Natoli,3 Patrizia Romualdi,6 Gennaro Savoia,7 Antonio Corcione8 1Department of Medical and Surgical Sciences and Biotechnologies, Unit of Anaesthesia, Intensive Care and Pain Medicine, Sapienza University of Rome, Polo Pontino, Latina, 2National Cancer Institute “G Pascale” Foundation, Unit of Anaesthesia, Intensive Care and Pain Medicine, Naples, 3Department of Clinical Science and Translational Medicine, Tor Vergata University of Rome, 4Addiction Disease Department, Local Health Unit (ASL) Rome 2, Rome, 5Department of Medical and Surgical Sciences, 6Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna, Bologna, 7Department Anesthesia, Fatebenefratelli Hospital, Naples, 8Unit of Anaesthesia and Intensive Care, Dei Colli Hospital, V. Monaldi, Naples, Italy Abstract: The increasing number of opioid users among chronic pain patients, and opioid abusers among the general population, makes perioperative pain management challenging for health care professionals. Anesthesiologists, surgeons, and nurses should be familiar with some pharmacological phenomena which are typical of opioid users and abusers, such as tolerance, physical dependence, hyperalgesia, and addiction. Inadequate pain management is very common in these patients, due to common prejudices and fears. The target of preoperative evaluation is to identify comorbidities and risk factors and recognize signs and symptoms of opioid abuse and opioid withdrawal. Clinicians are encouraged to plan perioperative pain medications and to refer these patients to psychiatrists and addiction specialists for their evaluation. The aim of this review was to give practical suggestions for perioperative management of surgical opioid-tolerant patients, together with schemes of opioid conversion for chronic pain patients assuming oral or transdermal opioids, and patients under maintenance programs with methadone, buprenorphine, or naltrexone. Keywords: opioids, postoperative pain, addiction, abusers, buprenorphine, methadone 
A look inside the association codeine-paracetamol: clinical pharmacology supports analgesic efficacy
No full textAcute and chronic pain often requires a multimodal approach. Combination therapy reduces the number of individual daily administrations and improves patient's compliance with the prescribed analgesic treatment. Despite the association codeine/paracetamol is one of the most widely used central analgesic, the exact mechanism of action, particularly of paracetamol, is still object of pharmacological research. Recent findings showed that paracetamol may act through cerebral cyclo-oxygenase, descending opioidergic inhibitory pathways, serotonin pathway, and the endocannabinoid system; while codeine activity seems to related not only to its conversion to morphine, as previously known, but also by itself and through its metabolites, such as norcodeine (NORC) and codeine-6-glucuronide (C-6-G). The addition of codeine to paracetamol significantly improves the analgesic action and reduces the number needed to treat (NNT) from 5 to 2.3-3.1. Recent warnings about the risk of its metabolism related to CYP450 and its genetic variability in general population should be mainly considered when the association is used in paediatric patients undergoing tonsillectomy and/or adenoidectomy procedures for obstructive sleep apnoea syndrome (OSAS). In adults, the association codeine/paracetamol has been shown to be effective and safe in different settings: acute pain, trauma patients, and chronic nociceptive pain
The pyrethroid knock-down resistance gene in the Anopheles gambiae complex in Mali and further indication of incipient speciation within An. gambiae s.s.
No full textIn Mali the Anopheles gambiae complex consists of An. arabiensis and Mopti, Savanna and Bamako chromosomal forms of An. gambiae s.s. Previous chromosomal data suggests a complete reproductive isolation among these forms. Sequence analysis of rDNA regions led to the characterization of two molecular forms of An. gambiae, named M-form and S-form, which in Mali correspond to Mopti and to Savanna/Bamako, respectively, while it has failed so far to show any molecular difference between Savanna and Bamako. The population structure of An. gambiae s.l. was analysed in three villages in the Bamako and Sikasso areas of Mali and the frequency of pyrethroid resistance of the knock-down resistance (kdr) type was calculated. The results show that the kdr allele is associated only with the Savanna form populations and absent in sympatric and synchronous populations of Bamako, Mopti and An. arabiensis. This is the first molecular indication of barriers to gene flow between the Bamako and Savanna chromosomal forms. Moreover, analyses of specimens collected in the Bamako area in 1987 show that the kdr allele was already present in the Savanna population at that time, and that the frequency of this allele has gradually increased since then
Incipient speciation in the malaria mosquito Anopheles gambiae s.s.: Sequence analysis of intron I of the voltage-gated sodium channel gene
No full textIncipient speciation processes within Anopheles gambiae s.s. have been revealed by polytene chromosome analysis (Coluzzi et al., 1985, Boll Zool 52: 45-63) and, more recently, by sequence analysis of different rDNA regions (della Torre et al., 2001 Insect Mol Biol, 10: 9-18; Gentile et al., 2001, Insect Moi Biol, 10: 25-32). The latter has shown the existence in West Africa of two non-panmictic molecular forms, Sand M, which in the northern part of their range of distribution coincide with chromosomal forms Savanna/Bamako and Mopti, respectively. Recently, Chandre et al. (1999, Parassitologia 41: 319-322) found that in the voltage-gated sodium channel gene, the point-mutation associated with kdr (knock-down resistance), which confers resistance to pyrethroids and DDT, shows a non-homogeneous distribution in the two molecular forms. Further, preliminary sequence analysis of the intron I upstream the kdr mutation showed two nucleotide differences respectively associated with Sand M forms (Weill et al., 2000, Insect Mol Biol, 9: 451-455). We sequenced 535 bp of intron I in more than 100 specimens from 10 West African countries from Senegal to Angola. Specimens had been previously karyotyped, assigned to a chromosomal form, identified as molecular form S or M and characterized for the presence of the kdr allele. At position 702 a T and a C were consistently associated with Sand M form, respectively. At position 896 a C was fixed in all S samples analysed, while M samples showed either a fixed C Iike S samples or an A/C polymorphism, depending on the geographical origin of the samples. In S samples in which the kdr allele is present, no difference among kds/kds, kds/kdr and kdr/kdr genotypes was recorded at both sites. Kds/kdr specimens were found in a single M sample from Benin and resulted T/C heterozygotes at sites 702: this supports the hypothesis that the kdr and the intron alleles have been transferred from S to M through introgression Weill et al. (op. cit.). Microsatellite studies carried out on Sand M forms have revealed virtually no differentiation between chromosome arms except for the 2R (Lanzara et al. 1998, Proc. NatI. Acad. Sci., USA 95:14260-14265; Taylor et al. 2001, Genetics 157:743-750) and a single microsatellite closely Iinked to the rDNA region (Wang et al. 2001, Prac. Nat. Acad. Sci. USA 98: 1 0769-1 0774). The mutation at position 702 represents the first marker in an intron DNA region that consistently correlates over a wide geographic range with the rDNA markers used to define An. gambiae molecular forms. Interestingly, the voltage-gated sodium channel gene maps on Div. 20C, on the left arm of the chromosome 2 (Ranson et al., 2000, Insect Mol Biol, 9: 491-497), a chromosomal region associated neither with rDNA (X chromosome), nor with inversions (2R) used to define the chromosomal forms
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