[Updated report on STOPP-START criteria in Primary Care]. / Evaluación de la actualización de los criterios STOPP-START en atención primaria.

INTRODUCTION: The aim of this study is to determine the rate of potentially inappropriate prescriptions (PIP) in people older than 64 years of age in Avilés, Asturias, Spain. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted in six Health Care Centres. A sample of 400 people was selected, obtained by a random sampling proportional to the population registered in each Health Centre. A review was made of the computerised clinical records, and the STOPP-START (version 2014 with 114 items) criteria were applied to evaluate the PIP. RESULTS: The study contained 378 (95.5%) patients with a mean age of 75.4 (SD: 7.4) and of which 57.7% were women. Almost all (94.2%: 95% CI; 91.7-96.7) met some PIP criteria. Taking only the STOPP criteria into consideration, 52.4% (95%CI: 47.2-57.6) met at least one breach, and in the START criteria a 90.5% (95%CI; 87.4-93.6), which was reduced to 40.5% (95%CI; 36.4-45.6) if criteria on vaccination were removed. In the STOPP criteria, the most frequent PIP was taking benzodiazepines followed by the use of medication without indications based on the evidence; in the START, the criteria was the anti-pneumococcus vaccination, and the lack of taking vitamin D supplements and calcium in osteoporosis. CONCLUSIONS: There were high levels of PIP, very superior to the previous version, especially for the START criteria. There is a high level of PIP related to the use of benzodiazepines and the use of medication without any clinic evidence. The STOPP-START criteria are useful in Primary Care to assess the PIP.

Screening of antifungal activity of 12 essential oils against eight pathogenic fungi of vegetables and mushroom.

The antifungal properties of 12 Eos, that is, Syzygium aromaticum, Pelargonium graveolens, Lavandula angustifolia, Cupresus sempervirens, Mentha piperita, Santolina chamaecyparissus, Citrus sinensis, Pogostemon patchouli, Thymus mastichina, Thymus vulgaris, Eucalyptus globulus and Rosmarinus officinalis, were screened. The influence of five doses of each EOs was tested against Botrytis cinerea, Sclerotinia sclerotiorum, Fusarium oxysporum, Phytophthora parasitica, Pythium aphanidermatum, Alternaria brassicae, Cladobotryum mycophilum and Trichoderma aggressivum f.sp. europaeum using disc-diffusion method. The mycelial growth inhibition and ED50 were calculated. The chemical analysis of the EOs was analysed using gas chromatography-mass spectroscopy. A total of 58 compounds were identified in the 12 EOs. All essential oils (EOs) analysed showed antifungal activity against the test pathogens in the range of 5·32-100%. The inhibitory effect of oils showed dose-dependent activity on the tested fungus. Based on the ED50 values, clove, rose geranium, peppermint and patchouli were the most effective. This study warrants further research into the practical use of EOs for the control of important myco- and phytopathogens in intensive horticulture. SIGNIFICANCE AND IMPACT OF THE STUDY: Due to the serious damage caused by fungal pathogens of vegetables and mushrooms, it is necessary to search for integrated strategies of disease control. This study provides relevant information about the effects of 12 essential oils (EOs) against eight pathogens of agricultural interest, included mycopathogens with emphasis on the possible future application of the EOs as alternative antifungal agents.

Osteonecrosis of the jaw (ONJ) and atypical femoral fracture (AFF) in an osteoporotic patient chronically treated with bisphosphonates.

The aim of the study is to report the rare association of two complications of long-term treatment of osteoporosis with bisphosphonates in the same Caucasian elderly patient. A female patient of Italian descent, age 87 years, consulted in February 2013. She had a history of osteoporosis and had taken alendronate weekly for 7 years (1999-2006). Due to low back pain, an orthopedist had indicated i.v. zoledronic acid, 5 mg/year for 3 years (2006-2008). She received occasional supplements of ergocalciferol. In 2009, she suffered a fall and sustained a subtrochanteric fracture of the left femur. She was operated on and recovered uneventfully. In 2012, she consulted a dentist due to loose teeth. She underwent the removal of a molar and was given a denture. She had discomfort when using the prosthesis, and developed an ulceration in the gum of the mandible, which exposed the bone and did not heal for 2 months. After radiologic studies, the diagnosis was osteonecrosis of the jaw. She improved after surgical debridement and local and systemic antibiotics. In early 2013, laboratory tests were normal except for a slight elevation of serum PTH and CTX-I. Calcitriol 0.25 mcg/day was prescribed; after 3 months serum calcium, phosphate, PTH, and CTX-I showed no variation. Two years later, she experienced acute low back pain after a fall; MRI showed recent crushing of D12, and chronic deformities of D11 and L1. Bone densitometry of her right hip (DXA) showed a T-score of -2.3 at the femoral neck. An X-ray film of the right femur showed diffuse thickening of both cortices. She was treated with nasal calcitonin and analgesics. After the back pain subsided, she was treated with s.c. denosumab. Although the association of ONJ and AFF was known in cancer patients treated with high doses of bisphosphonates, it is very rare in patients with osteoporosis receiving these drugs at usual doses. Only three cases have been reported, all in oriental women. This appears to be the first reported case in a Caucasian woman.

Adapted ice cream as a nutritional supplement in cancer patients: impact on quality of life and nutritional status

AIMS: The aim of this study was to assess the impact of adapted ice cream as a dietary supplement on the quality of life (QLQ) of malnourished patients with cancer. MATERIAL AND METHODS: We present an exploratory prospective observational study comparing two patterns of nutrition in cancer patients admitted during the study period who presented malnutrition disorders: adapted ice cream (Group I: 39 patients) and nutritional supplements (Group II: 31 patients). Patients were selected from two different hospitals from the same Oncologic Institute. QLQ was evaluated with the Hospital Anxiety and Depression Scale (HADS) and QLQ of the European Organization for Research and Treatment of Cancer (EORTC QLQ C30). Nutrition was determined by the PG-SGA test. RESULTS: HADS showed significant differences in anxiety (p = 0.023) and depression (p = 0.011) at the end of the study only in Group I. QLQ-C30 revealed statistically significant differences in baseline measures of global dimension between the two groups (Group I: 40.64-56.36 CI; Group II: 25.70-43.11 CI; p = 0.017). Differences were also present in the social dimension (Group I: 77.42-93.51 CI; Group II: 55.85-82.85 CI; p = 0.039). Statistically significant differences were observed between the two groups at the end of the study in the global scale: Group I had 49.36-63.88 CI and Group II had 33.05-51.88 CI (p = 0.016), and in the fatigue scale: Group I had 36.19-53.83 CI and Group II had mean = 65.87, 52.50-79.23 CI (p = 0.007). CONCLUSIONS: The administration of ice cream could cover, in part, the social aspect of food and improve QLQ in malnourished cancer patients. These results are encouraging and deserve further confirmation (AU)

Tolerance and short-term effect of a cluster schedule with pollen-extracts quantified in mass-units.

We performed a prospective, multicenter study to assess the tolerance and possible short-term effects of allergen vaccines administered according to a cluster schedule in the months immediately preceding the onset of the pollen season. The study was carried out in eight centers and included 191 patients (children and adults) with allergic respiratory disease due to sensitization to olive tree and/or grass pollen. Of these, 34 patients acted as controls and the remaining patients received immunotherapy administered in the initiation phase according to a cluster schedule of eight doses injected on four visits. After 3 months of treatment, significant differences were found between the two groups in medication consumption (antihistamines in drops and oral formulations: p = 0.045 and p = 0.001, respectively; short-acting beta2-agonist treatments: p = 0.004) and respiratory symptoms (wheezing and coughing: p = 0.035 and 0.014, respectively). The cytokine profile (interleukin [IL]-4, 5, 10 and 2, interferon [IFN-gamma], and tumor necrosis factor [TNF-alpha]) was determined before the start of treatment and at the end of follow-up (4-5 months). Levels of IL-4, 5 and 10 (Th2 profile) decreased while those of IL-2, IFN-gamma, and TNF-alpha (Th1 profile) decreased. These differences were more marked in the active group than in the control group but were not statistically significant. No severe adverse effects were recorded. This study shows that the schedule tested had an acceptable tolerance profile and produced significant changes in symptom and medication scores after a few months of treatment. A double-blind, placebo-controlled study is needed to confirm these results.

Tolerance and short-term effect of a cluster schedule with pollen-extracts quantified in mass-units

We performed a prospective, multicenter study to assess the tolerance and possible short-term effects of allergen vaccines administered according to a cluster schedule in the months immediately preceding the onset of the pollen season. The study was carried out in eight centers and included 191 patients (children and adults) with allergic respiratory disease due to sensitization to olive tree and/or grass pollen. Of these, 34 patients acted as controls and the remaining patients received immunotherapy administered in the initiation phase according to a cluster schedule of eight doses injected on four visits. After 3 months of treatment, significant differences were found between the two groups in medication consumption (antihistamines in drops and oral formulations: p = 0.045 and p = 0.001, respectively; short-acting β2-agonist treatments: p = 0.004) and respiratory symptoms (wheezing and coughing: p = 0.035 and 0.014, respectively). The cytokine profile (interleukin [IL]-4, 5, 10 and 2, interferon [IFN-γ], and tumor necrosis factor [TNF-α]) was determined before the start of treatment and at the end of follow-up (4-5 months). Levels of IL-4, 5 and 10 (Th2 profile) decreased while those of IL-2, IFN-γ, and TNF-α (Th1 profile) decreased. These differences were more marked in the active group than in the control group but were not statistically significant. No severe adverse effects were recorded. This study shows that the schedule tested had an acceptable tolerance profile and produced significant changes in symptom and medication scores after a few months of treatment. A double-blind, placebo-controlled study is needed to confirm these results (AU)

Se ha llevado a cabo un estudio prospectivo y multicéntrico con el objetivo de valorar la tolerancia y posible efecto a corto plazo de las vacunas alergénicas administradas bajo pauta cluster en los meses inmediatamente anteriores al inicio de la estación polínica. El estudio se realizó en 8 centros, incluyéndose un total de 191 pacientes (niños y adultos) con enfermedad alérgica respiratoria por sensibilización a polen de olivo y/o gramíneas. De ellos, 34 actuaron como controles y a los pacientes restantes se les administró inmunoterapia bajo una pauta cluster, en la fase de iniciación, de 8 dosis administradas en 4 visitas. Tras 3 meses de tratamiento, se registraron diferencias significativas entre ambos grupos en el consumo de medicación (antihistamínicos en colirio y orales -p = 0,045 y p = 0,001 respectivamente- y ß2 de corta duración -p = 0,004-) así como en síntomas pulmonares (sibilancias y tos -p = 0,035 y 0,014 respectivamente-). Por otro lado, se determinó el perfil de citocinas (IL-4, 5, 10 y 2, IFN-gamma y TNF-a) de forma previa al inicio del tratamiento y al finalizar el seguimiento (4-5 meses). Se observaron descensos en los niveles de IL-4, 5 y 10 (perfil TH2) y aumento en los valores de IL-2, IFN-gamma y TNF-a (perfil TH1), más marcados en el grupo activo que en el control, sin alcanzar significación estadística. No se registraron efectos adversos severos. Por tanto, podemos observar que la pauta ensayada mostró un adecuado perfil de tolerancia, y tras pocos meses de tratamiento se registraron cambios significativos en la puntuación de síntomas y medicación, siendo necesaria la realización de un estudio con un diseño doble ciego frente a placebo para confirmar los resultados obtenidos (AU)

Homocysteine levels in polymyalgia rheumatica and giant cell arteritis: influence of corticosteroid therapy.

OBJECTIVES: It has been suggested that patients with giant cell arteritis (GCA) may share a common pathway with atherosclerosis. Furthermore, patients with GCA and polymyalgia rheumatica (PMR), in addition to advanced age, are treated for prolonged periods of time with corticosteroids, a factor that can also accelerate atherosclerosis. Hyperhomocysteinaemia is considered an independent risk factor for atherosclerosis, and might play a role in ischaemic manifestations that occur with a variable frequency during the course of GCA. The purposes of the present study were: (i). to analyse the plasma levels of homocysteine in patients with GCA and PMR, (ii). to determine the influence of corticosteroid therapy on the homocysteine levels and (iii). to analyse if the levels of homocysteine may predict the development of ischaemic complications in patients with GCA. METHODS: Plasma homocysteine concentration was measured in 56 patients with active PMR/GCA (17 GCA and 39 isolated PMR) before steroid treatment and 23 healthy age-matched volunteers were used as controls. The total plasma homocysteine level was quantified using a fluorescent polarization immunoassay. RESULTS: Homocysteine concentrations were higher in PMR and GCA patients than age-matched controls (P < 0.05). Patients with GCA had slightly higher levels of plasma homocysteine than those with isolated PMR (13.6+/-4.3 vs 12.7+/-3.1 micromol/l, P=0.6). In 30 of these patients (12 GCA and 18 PMR) a second measurement of homocysteine concentration was done when they were in clinical remission with steroid treatment. The post-treatment levels of homocysteine were significantly increased in GCA rather than in PMR patients. In 13 patients with homocysteine levels above the normal upper limit of our laboratory, therapy with folic acid and/or vitamin B12 was started. After 3 months of vitamin supplements, the homocysteine concentration significantly decreased from 19.2+/-3.1 to 13.6+/-3.2 micromol/l (P=0.001). Such decrease was less marked in the PMR than in GCA patients. Ten out of the 17 patients with GCA had ischaemic manifestations of the disease. The levels of homocysteine were slightly higher in GCA patients with ischaemia than in those without ischaemic manifestations, although the difference did not reach statistical significance (15+/-4.9 vs 11.6+/-1.9 micromol/l, P=0.46). CONCLUSIONS: Patients with active PMR and GCA had elevated plasma concentrations of homocysteine. Corticosteroid therapy significantly increased such levels, especially in GCA patients. Treatment with supplements of folic acid and/or vitamin B12 reduced the homocysteine concentrations. These data support the hypothesis that patients with GCA (and to a lesser extend PMR patients) may share a common pathway with atherosclerosis and suggest a new atherogenic mechanism of corticosteroids.

Tolerance of a cluster schedule on the treatment of seasonal allergic respiratory disease with pollen extracts quantified in mass units.

In order to evaluate the tolerance of a cluster schedule on specific immunotherapy (SIT), 306 patients were included in a multicenter study. The patients were suffering from rhinoconjunctivitis with/without asthma, caused by sensitization to olive and/or grass pollen. SIT was administered subcutaneously according to a cluster schedule in which the maintenance dose is reached after four visits (3 weeks). The extracts were biologically standardized with major allergens quantified in mass units. Local reactions appeared in 7.2% of the patients and 1.3% of the doses. Systemic reactions (SR) were recorded in 1.2% of the doses administered to 9.5% of the patients. No anaphylactic shock was registered, and all the SR responded fully and rapidly to treatment. There was no difference in SR according to diagnosis or allergen extract used. The majority of SR occurred with the administration of vial of higher concentration (Vial 2: 7 SR (22%), Vial 3: 32 SR (78%), p < 0.05). Of the 32 SR recorded with Vial 3, 13 (41%) were immediate, with no existing association between dose administered and appearance of SR. However, of the 18 delayed SR (56%), 14 occurred after the administration of the first two doses of Vial 3 and four occurred after administration of the second two doses (78% vs 22%, p < 0.05). On the other hand, this regime realized an important saving in cost and time compared to the conventional schedule (1581 fewer doses and 2754 fewer visits were necessary to reach the optimal dose). Considering all these factors, the clinical profile of the proposed regime may be qualified as good. However, future studies are necessary in order to better adjust the schedule to avoid the delayed SR that occurred after the administration of the first two doses of Vial 3.

Fas and Fas ligand expression in Alzheimer's disease.

The Fas/Fas ligand (L) signaling system has been implicated in the control of cell death and cell survival of T and B lymphocytes and in a variety of cell types under particular pathological conditions. In the present study we examined the expression of Fas and Fas-L, by Western blotting and immunohistochemistry, in the human frontal cortex and hippocampus of individuals with advanced Alzheimer's disease (AD) and age-matched controls. Expression levels of Fas and Fas-L, as seen in Western blots, are preserved in the frontal cortex but decreased in the hippocampus in AD when compared with age-matched controls. Yet Fas and Fas-L immunoreactivity is found in remaining AD neurons in the frontal cortex and hippocampus. Moreover, Fas and Fas-L are expressed equally in tangle-bearing and non-tangle-bearing neurons, as revealed with double-labeling immunohistochemistry to Fas or Fas-L and tau or phosphorylated neurofilament epitopes. Dystrophic neurites of senile plaques are not stained with Fas and Fas-L antibodies. A moderate increase in Fas and a strong increase in Fas-L immunoreactivity occur in reactive astrocytes in AD. Yet there is no relationship between Fas or Fas-L expression and increased nuclear DNA vulnerability as revealed with double-labeling immunohistochemstry and in situ end-labeling of nuclear DNA fragmentation. Although the Fas/Fas-L system may have some effect in the control of reactive astrocytosis in AD, the present results show no evidence that Fas/Fas-L signals participate in specific processes of the disease, including neurofibrillary degeneration, dystrophic neurite formation, and cell death.