Epidemiological and Financial Aspects of the Use of Non-Steroidal Anti-Inflammatory Analgesics

Abstract The availability of many new nonsteroidal anti-inflammatory drugs (NSAIDs) has increased the total consumption during the past 20 years. The cost of different NSAID brands varies considerably probably reflecting increased research and development costs rather than a true therapeutic benefit for the patient. The current therapeutic problem in the treatment of musculoskeletal conditons with NSAIDs is to make a balanced analysis between benefits, risks, and costs. Assessment of risks and benefits should focus on the large subgroup (about 40%) of elderly NSAID users over 60 years who clearly stand at increased risk of NSAID-induced gastrointestinal complications. In the treatment of osteoarthritis more trials are needed to compare NSAIDs with plain analgesics (e.g. paracetamol).     

Cardioventilator effects of TRH in anaesthetized rats: role of the brain stem

Cardioventilator responses were studied in anaesthetized rats after injections of TRH into either the lateral (i.c.v. lat) or the fourth (i.c.v. IV) cerebral ventricles. TRH induced a more rapid hypertensive effect i.c.v. IV than i.c.v. lat. Blocking of the cerebral aqueduct abolished the hypertensive and tachypnoeic effects of TRH i.c.v. lat but not those of TRH i.c.v. IV. It is concluded that TRH increased blood pressure and ventilation rate via brain stem structures close to the fourth ventricle.     

Copy number alterations and neoplasia‐specific mutations in MELK,PDCD1LG2, TLN1, and PAX5 at 9p in different neoplasias

Genetic alterations affecting 9p are commonly present in many cancer types and many cancer‐related genes are located in this chromosomal region. We sequenced all of the genes located in a 32Mb region of 9p by targeted next generation sequencing (NGS) in 96 patients with different cancer types, including acute lymphoblastic leukemia, bone malignant fibrous histiocytoma/undifferentiated pleomorphic sarcoma, fibrosarcoma, Ewing's sarcoma, and lung carcinoma. Copy number alterations (CNA), and mutations were studied from the NGS data. We detected a deletion at the CDKN2A locus as being the most frequent genetic alteration in all cancer types. In addition to this locus, NGS also identified other small regions of copy number loss and gain. However, different cancer types did not reveal any statistically significant differences with regard to CNA frequency or type. Of the 191 genes within the target region, two novel recurrent mutations were found in the MELK and PDCD1LG2 genes. The most commonly mutated gene in sarcomas was TLN1 (8%) and PAX5 in ALL (9%). Mutations in PAX5, and RUSC2, were seen exclusively in ALL patients and those in KIAA1432, CA9, TLN1, and MELK only in sarcomas (MFH, FS, EFT). Thus using targeted NGS of the 9p region, in addition to commonly deleted CDKN2A locus, we were able to identify a number of small deletions and gains, as well as novel recurrent mutations in different cancer types. © 2014 Wiley Periodicals, Inc.     

Redefining the prognostic likelihood of chronic lymphocytic leukaemia patients with borderline percentage of immunoglobulin variable heavy chain region mutations

In chronic lymphocytic leukaemia (CLL), caution is warranted regarding the clinical implications of immunoglobulin variable heavy chain region (IGHV) rearrangements with a ‘borderline’ (BL) percentage of mutations (i.e. 97–97·9% IGHV identity). We analysed the IGHV mutational status in 759 untreated CLL patients (cohort 1). BL-CLL (n = 36, 5%) showed a time to first treatment (TFT) similar to that of M-CLL (n = 338) and significantly longer than that of UM-CLL (n = 385), despite the enrichment in subset #2 cases. In fact, CLLs belonging to subset #2 (n = 15/759, 2%) were significantly more frequent among BL-CLLs (n = 5/36, 14%), with a brief TFT. TFT of BL-CLL remained comparable to that of M-CLL also considering the 327 CLL patients evaluated at diagnosis. These findings were then validated in an independent cohort 2 of 759 newly diagnosed CLL patients (BL-CLL: n = 11, 1·4%) and in all newly diagnosed patients from cohorts 1 and 2 (n = 1 086, 84% stage A; BL-CLL: n = 47, 4·3%). BL-CLL at diagnosis showed a biological profile comparable to that of M-CLL with a low frequency of unfavourable prognostic markers, except for a significant enrichment in subset #2. Our data suggest that the prognosis of BL-CLL is good and similar to that of M-CLL, with the exception of subset #2 cases.     

Failure of hand disinfection with frequent hand washing: a need for prolonged field studies

In a prolonged field trial a 4% chlorhexidine digluconate detergent scrub (Hibiscrub^R), that had earlier proved to be an effective hand disinfectant, was studied in hospital wards. Finger tips were found to harbour more bacteria than the hand dorsum and the samples collected from them yielded more information on the bacteriological and dermatological effects of hand disinfectants in practice.     

Antibiotic lock with vancomycin and urokinase can successfully treat colonized central venous catheters in pediatric cancer patients

We used an antibiotic lock technique with vancomycin in combination with urokinase in 10 consecutive eligible children with Gram-positive catheter-related bacteremia persisting after appropriate intravenous antibiotics. Treatment was successful in sterilizing all colonized central venous catheters, avoiding device removal and delay of further chemotherapy. The antibiotic lock technique may represent a safe and effective therapeutic option in patients with selected, uncomplicated catheter-related bacteremias resistant to systemic antimicrobial therapy, particularly when maintaining a venous access is mandatory.     

Totally extraperitoneal endoscopic (TEP) treatment of sportsman's hernia

Sportsman's hernia is a term used to describe a weakness or disruption of is a term used to describe the musculotendinous part of the posterior inguinal wall, which causes persistent groin pain in athletes. A video-assisted placement of extraperitoneal synthetic mesh to support the damaged area may heal this injury. Forty-one male athletes at an elite level (mean age 27 +/- 7.1 years) with chronic groin pain, which was resistant to conservative therapy, were referred to surgery by sports clinics or club doctors. The majority of the patients were soccer (58%) or ice hockey players (27%) at a professional level. A 10 x 15 cm polypropylene mesh was placed into the preperitoneal space using a totally extraperitoneal video-assisted technique. The severity of pain, and the time to return to sports, were determined after 1 month and after the mean follow-up of 4 years. On operation, no macroscopic abnormality was found in 24 patients (58%), obvious musculotendinous tear was present in 10 patients, and muscle asymmetry was present in 7 patients. All except 2 patients (95%) returned to their sport activities after 1 month of convalescence. No immediate or long-term complications were associated with the operation. The placement of a retropubic mesh was safe and a mini-invasive method to repair sportsman's hernia and chronic groin pain of athletes.     

Pattern of cardiovascular anomalies associated with esophageal atresia: support for a caudal pharyngeal arch neurocristopathy

Patients with cephalic neurocristopathy (an abnormality of neural crest differentiation) present a striking pattern of associated cardiovascular anomalies (CVA). Therefore, to support the hypothesis that esophageal atresia (EA) may be related to a defective contribution from the cephalic neural crest, we studied the pattern of CVA associated with EA. Medical records of 99 patients with isolated EA, 101 with isolated anorectal malformations (ARM) and 15 with both EA and ARM, consecutively admitted to our unit, were reviewed. The prevalence and pattern of CVA associated with isolated EA or isolated ARM were compared on the assumption that the cranial or caudal location of a major malformation is related to a different regional patterning of associated anomalies. The prevalence of CVA was 39% in patients with isolated EA and 7% in those with isolated ARM (p < 0.01). Neural crest-related CVA (aortic arch anomalies, conotruncal defects, and superior vena cava malformations) accounted for 72% of all CVA in patients with isolated EA versus 14% in those with isolated ARM (p < 0.02). In patients with isolated EA, anomalies of the fourth and sixth aortic arch derivatives accounted for 75% of all neural crest related CVA. The present pattern of CVA in infants with EA supports the concept that EA may be related to an abnormal contribution from caudal portion of cephalic neural crest.     

Living related conjunctival limbal allograft for the treatment of stem cell deficiency

PURPOSE: To evaluate the outcomes of living related conjunctival limbal allograft transplantation for the treatment of stem cell deficiency. DESIGN: Retrospective, noncomparative case series. PARTICIPANTS: Nine living related donors, eight recipients (10 eyes) with Stevens-Johnson syndrome (3 eyes), ectodermal dysplasia (3 eyes), chemical injury (2 eyes), ocular cicatricial pemphigoid (1 eye), and atopic keratoconjunctivitis (n = 1). INTERVENTION: Four clock hours of limbal conjunctival tissue from the best matched human leukocyte antigen (HLA) relative donor were transplanted to the recipient eye superiorly and inferiorly after conjunctival peritomy and removal of conjunctival pannus. Systemic cyclosporine was administered to all recipients. MAIN OUTCOME MEASURES: Restoration of corneal epithelium, reduction of vascularity and conjunctivalization, improved comfort, improved corneal clarity, and visual improvement. RESULTS: Mean follow-up period was 26.2 months. Two highly inflamed eyes failed to initially epithelialize. The remainder all survived with restoration of corneal epithelium and reduction of vascularization. Corneal opacification was reduced (four of eight eyes) and visual improvement was achieved in seven eyes. All five eyes with pain had an improvement in symptoms. Allograft rejection occurred in two eyes (25%), and both were treated successfully. Both eyes had two class I HLA mismatches, and both had an underlying diagnosis of Stevens-Johnson syndrome. One eye developed a recurrent epithelial defect and perforated, requiring a penetrating keratoplasty that remained clear with an intact epithelial surface. The two initial failures also perforated and required penetrating keratoplasties that failed. None of the donor eyes had any complications. CONCLUSIONS: Restoration of the ocular surface by HLA-matched conjunctival limbal allograft transplantation can be accomplished in selected recipients. Systemic cyclosporine, even at low doses, is useful in ensuring long-term survival.