Expert guidance on target product profile development for AMR diagnostic tests.

Diagnostics are widely considered crucial in the fight against antimicrobial resistance (AMR), which is expected to kill 10 million people annually by 2030. Nevertheless, there remains a substantial gap between the need for AMR diagnostics versus their development and implementation. To help address this problem, target product profiles (TPP) have been developed to focus developers' attention on the key aspects of AMR diagnostic tests. However, during discussion between a multisectoral working group of 51 international experts from industry, academia and healthcare, it was noted that specific AMR-related TPPs could be extended by incorporating the interdependencies between the key characteristics associated with the development of such TPPs. Subsequently, the working group identified 46 characteristics associated with six main categories (ie, Intended Use, Diagnostic Question, Test Description, Assay Protocol, Performance and Commercial). The interdependencies of these characteristics were then identified and mapped against each other to generate new insights for use by stakeholders. Specifically, it may not be possible for diagnostics developers to achieve all of the recommendations in every category of a TPP and this publication indicates how prioritising specific TPP characteristics during diagnostics development may influence (or not) a range of other TPP characteristics associated with the diagnostic. The use of such guidance, in conjunction with specific TPPs, could lead to more efficient AMR diagnostics development.

Treatment options for secondary osteonecrosis of the knee.

Knee osteonecrosis is a debilitating progressive degenerative disease characterized by subchondral bone ischemia. It can lead to localized necrosis, tissue death, and progressive joint destruction. For this reason, it is essential to diagnose and treat this disease early to avoid subchondral collapse, chondral damage, and end-stage osteoarthritis, where the only solution is total knee arthroplasty. Three types of knee osteonecrosis have been documented in the literature: spontaneous or primitive, secondary, and post arthroscopy. Spontaneous osteonecrosis is the most common type studied in the literature. Secondary osteonecrosis of the knee is a rare disease and, unlike the spontaneous one, involves patients younger than 50 years. It presents a particular set of pathological, clinical, imaging, and progression features. The management of secondary osteonecrosis is determined by the stage of the disorder, the clinical manifestation, the size and location of the lesions, whether the involvement is unilateral or bilateral, the patient's age, level of activity, general health, and life expectancy. This review aims to present the recent evidence on treatment options for secondary osteonecrosis of the knee, including conservative treatment, joint preserving surgery, and knee replacement.

Arthroscopic anterior cruciate ligament reconstruction in a patient with multiple hereditary exostoses.

Background Multiple hereditary exostoses (MHE) also known as Multiple Osteochondromas is a rare benign bone tumour disease, characterized by multiple osteocartilaginous masses. The knee is one of the most affected sites. Anterior cruciate ligament (ACL) surgery is the most common and generally most successful surgical knee procedure; however, the association between MHE and ACL reconstruction is very rare and may represent a challenging procedure because of the anatomical anomaly related to presence of multiple masses around the knee. Here, we present a case report of ACL reconstruction in a patient affected by multiple exostoses. Case report The patient was a 30-year-old woman affected by MHE, with an ACL tear arising after knee trauma. As the patient complained of pain, swelling and the knee "giving way", she successfully underwent arthroscopic-assisted ACL reconstruction using quadrupled hamstring tendon grafts, with femoral suspension and double tibial fixations. Conclusion Symptomatic ACL tears in a patient affected by MHE should be considered for arthroscopic reconstruction, which requires that particular attention be paid to tendons harvesting, tunnel placement and the choice of graft fixation system, given the presence of multiple masses around the knee.

ARTHROPLASTY IN ALKAPTONURIC OCHRONOSIS.

Ochronotic degenerative arthropathy occurs in patients with alkaptonuria. Alkaptonuria disorder is an extremely rare disease characterized by black pigmentation of various tissues (e.g., cartilage and connective tissue). Ochronotic arthropathy is a disabling disease that primarily affects the large joints. Like other metabolic diseases that involve the musculoskeletal system, care must be taken with regard to the quality of the affected bones, tendons and ligaments, and therefore the stability and survival of joint prosthesis. The following is a report of a 66-year-old man affected by several musculoskeletal manifestations of alkaptonuria with severe joints disruption, who was successfully treated with total left hip and total right knee replacements. Surgical, anesthesiological and postoperative management of these patients may require more vigilance due to the associated comorbidities of this disorder.

The successful uptake and sustainability of rapid infectious disease and antimicrobial resistance point-of-care testing requires a complex 'mix-and-match' implementation package.

The emergence and spread of antimicrobial resistance is one of the major global issues currently threatening the health and wealth of nations, with effective guidelines and intervention strategies urgently required. Such guidelines and interventions should ideally be targeted at individuals, communities, and nations, requiring international coordination for maximum effect. In this respect, the European Joint Programming Initiative on Antimicrobial Resistance Transnational Working Group 'Antimicrobial Resistance - Rapid Diagnostic Tests' (JPIAMR AMR-RDT) is proposing to consider a 'mix-and-match' package for the implementation of point-of-care testing (PoCT), which is described in this publication. The working group was established with the remit of identifying barriers and solutions to the development and implementation of rapid infectious disease PoCT for combatting the global spread of antimicrobial resistance. It constitutes a multi-sectoral collaboration between medical, technological, and industrial opinion leaders involved in in vitro diagnostics development, medical microbiology, and clinical infectious diseases. The mix-and-match implementation package is designed to encourage the implementation of rapid infectious disease and antimicrobial resistance PoCT in transnational medical environments for use in the fight against increasing antimicrobial resistance.

Two-Stage Revision Total Knee Arthroplasty for Suspected Periprosthetic Joint Infection and Metal and Bone Cement Hypersensitivity.

Hypersensitivity to implant components and periprosthetic joint infection should be detected before all revision arthroplasty, as misdiagnosis can lead to replacement loosening and the need for further revision procedures. We describe the case of a 69-year-old woman presenting a history of a painful cemented total knee replacement. Postoperative investigations showed loosening of X-ray components, suspected periprosthetic joint infection, and patch test hypersensitivity to nickel sulfate and methyl methacrylate. Two months later, a more specific patch test indicated non-allergy to the solid scratch of one bone cement. The patient underwent a two-stage revision with prosthesis removal and the temporary application of a specific cement spacer followed by the successful reimplantation of a cemented revision prosthesis. All candidates for the revision arthroplasty procedure must be investigated for hypersensitivity to metal and bone cement in order to avoid complications related to prosthesis intolerance and the need for further revision surgery; in the presence of hypersensitivity to bone cement and periprosthetic joint infection with a two-stage revision indication, the patient must be submitted to further patch tests with scratches of solid bone cement.

Diagnosis of smear-negative tuberculosis is greatly improved by Xpert MTB/RIF.

BACKGROUND: Diagnosis of pulmonary (PTB) and extra-pulmonary tuberculosis (EPTB) in smear-negative patients can be difficult. We assessed retrospectively the performance of Xpert MTB/RIF system (Xpert, Cepheid) in diagnosing smear-negative tuberculosis (TB), which represents the most common form of TB in a low incidence setting. METHODS: Performance of Xpert was compared to acid-fast microscopic examination using Ziehl-Neelsen (ZN) stain in patients with culture-confirmed TB. RESULTS: 386 Mycobacterium tuberculosis (MTB) culture-positive samples were detected out of 5170 specimens tested with smear microscopy, Xpert and culture: 323 were both culture- and Xpert-positive, and 63 culture-positive only. Of these, 234 (60.6%) were smear-negative. In addition Xpert detected 40 probable TB cases, based on clinical findings, which were culture-negative. Compared to culture, Xpert showed an overall sensitivity of 83.7% and a specificity of 99.1%; sensitivity was higher for respiratory samples (86.5%) than for non-respiratory samples (76.8%). Xpert sensitivity for smear-negative culture-confirmed TB was 73.1% and was not influenced by TB localization. As sensitivity of microscopy alone was poor (39.4%), Xpert improved both diagnosis of pulmonary TB (Δ = 36.5%) and extra-pulmonary TB (Δ = 63.4%). CONCLUSIONS: Xpert MTB/RIF is a sensitive method for rapid diagnosis of TB compared to the conventional ZN staining. Xpert can serve as a sensitive and time-saving diagnostic method for microbiological diagnosis of smear-negative TB in countries with a low TB prevalence.

PubMed search filters for the study of putative outdoor air pollution determinants of disease.

OBJECTIVES: Several PubMed search filters have been developed in contexts other than environmental. We aimed at identifying efficient PubMed search filters for the study of environmental determinants of diseases related to outdoor air pollution. METHODS: We compiled a list of Medical Subject Headings (MeSH) and non-MeSH terms seeming pertinent to outdoor air pollutants exposure as determinants of diseases in the general population. We estimated proportions of potentially pertinent articles to formulate two filters (one 'more specific', one 'more sensitive'). Their overall performance was evaluated as compared with our gold standard derived from systematic reviews on diseases potentially related to outdoor air pollution. We tested these filters in the study of three diseases potentially associated with outdoor air pollution and calculated the number of needed to read (NNR) abstracts to identify one potentially pertinent article in the context of these diseases. Last searches were run in January 2016. RESULTS: The 'more specific' filter was based on the combination of terms that yielded a threshold of potentially pertinent articles ≥40%. The 'more sensitive' filter was based on the combination of all search terms under study. When compared with the gold standard, the 'more specific' filter reported the highest specificity (67.4%; with a sensitivity of 82.5%), while the 'more sensitive' one reported the highest sensitivity (98.5%; with a specificity of 47.9%). The NNR to find one potentially pertinent article was 1.9 for the 'more specific' filter and 3.3 for the 'more sensitive' one. CONCLUSIONS: The proposed search filters could help healthcare professionals investigate environmental determinants of medical conditions that could be potentially related to outdoor air pollution.

Influenza vaccination coverage among medical residents: an Italian multicenter survey.

Although influenza vaccination is recognized to be safe and effective, recent studies have confirmed that immunization coverage among health care workers remain generally low, especially among medical residents (MRs). Aim of the present multicenter study was to investigate attitudes and determinants associated with acceptance of influenza vaccination among Italian MRs. A survey was performed in 2012 on MRs attending post-graduate schools of 18 Italian Universities. Each participant was interviewed via an anonymous, self-administered, web-based questionnaire including questions on attitudes regarding influenza vaccination. A total of 2506 MRs were recruited in the survey and 299 (11.9%) of these stated they had accepted influenza vaccination in 2011-2012 season. Vaccinated MRs were older (P = 0.006), working in clinical settings (P = 0.048), and vaccinated in the 2 previous seasons (P<0.001 in both seasons). Moreover, MRs who had recommended influenza vaccination to their patients were significantly more compliant with influenza vaccination uptake in 2011-2012 season (P<0.001). "To avoid spreading influenza among patients" was recognized as the main reason for accepting vaccination by less than 15% of vaccinated MRs. Italian MRs seem to have a very low compliance with influenza vaccination and they seem to accept influenza vaccination as a habit that is unrelated to professional and ethical responsibility. Otherwise, residents who refuse vaccination in the previous seasons usually maintain their behaviors. Promoting correct attitudes and good practice in order to improve the influenza immunization rates of MRs could represent a decisive goal for increasing immunization coverage among health care workers of the future.

Impact of meningococcal C conjugate vaccination campaign in Emilia-Romagna, Italy.

The incidence of reported meningococcal disease in Italy is among the lowest in Europe. The trend of the disease was increasing up to 2005 and then declined after the gradual introduction of a universal Men C vaccination program in 17/21 Italian regions. Since 2006, in Emilia-Romagna region vaccination against Neisseria meningitidis serogroup C was actively offered free of charge in a single dose to the age groups 12-15 months and 14-15 years, in addition to people with defined epidemiological risk. Our aim was to measure the impact of vaccination on the incidence of meningococcal disease caused by different serogroups among the population of Emilia Romagna Region, Northern Italy (approximately 4.5 million inhabitants) subdivided by age. Using surveillance data, we computed the incidence rates of Neisseria meninigitidis related invasive disease per 100.000 inhabitants for the years 2000 to 2012. In addition, the percentage change in incidence and the mortality rates were calculated. Results indicate a 70.1% decrease in the incidence of meningococcus C-related invasive disease after the introduction of MenC universal vaccination. No case of serogroup C related infection was observed since 2006 in children aged 1-4 years. These findings suggest that the single-dose vaccination strategy against serogroup C N.meningitidis targeted to the age groups 12-15 months and 14-15 years was effective in the Emilia-Romagna population. However, the occurrence of two cases of meningiditis in a 5-month child and in a 9-years child suggests caution and careful consideration in surveillance for the next years.

[The Breast Unit in the European and national policy documents: similarities and differences]. / La Breast Unit nei documenti di indirizzo europei e nazionali: analogie e differenze.

Aim of this study is to assess differences and similarities in official European and Italian Ministry of Health policy documents referring to the subject "Breast Unit". The T-Lab software package for textual analysis was used to analyze the documents. This instrument permits the identification of the most frequent used words and the semantic network associated with "Breast Unit". Results show that the European document gives more emphasis to the concept of "integrated care", delivered by a multi-professional team that meets the clinical, psychological and informational needs of the patient. The Italian document gives more prominence to themes related to the clinical content of the interventions and managerial aspects through the use of clinical guidelines.

PubMed search strings for the study of agricultural workers' diseases.

BACKGROUND: Several optimized search strategies have been developed in Medicine, and more recently in Occupational Medicine. The aim of this study was to identify efficient PubMed search strategies to retrieve articles regarding putative occupational determinants of agricultural workers' diseases. METHODS: We selected the Medical Subjects Heading (MeSH) term agricultural workers' diseases and six MeSH terms describing farm work (agriculture, agrochemicals NOT pesticides, animal husbandry, pesticides, rural health, rural population) alongside 61 other promising terms. We estimated proportions of articles containing potentially pertinent information regarding occupational etiology to formulate two search strategies (one "more specific," one "more sensitive"). We applied these strategies to retrieve information on the possible occupational etiology among agricultural workers of kidney cancer, knee osteoarthritis, and multiple sclerosis. We evaluated the number of needed to read (NNR) abstracts to identify one potentially pertinent article in the context of these pathologies. RESULTS: The "more specific" search string was based on the combination of terms that yielded the highest proportion (40%) of potentially pertinent abstracts. The "more sensitive" string was based on use of broader search fields and additional coverage provided by other search terms under study. Using the "more specific" string, the NNR to find one potentially pertinent article were: 1.1 for kidney cancer; 1.4 for knee osteoarthritis; 1.2 for multiple sclerosis. Using the sensitive strategy, the NNR were 1.4, 3.6, and 6.3, respectively. CONCLUSION: The proposed strings could help health care professionals explore putative occupational etiology for agricultural workers' diseases (even if not generally thought to be work related).

Socio-economic factors associated with infant mortality in Italy: an ecological study.

INTRODUCTION: One issue that continues to attract the attention of public health researchers is the possible relationship in high-income countries between income, income inequality and infant mortality (IM). The aim of this study was to assess the associations between IM and major socio-economic determinants in Italy. METHODS: Associations between infant mortality rates in the 20 Italian regions (2006-2008) and the Gini index of income inequality, mean household income, percentage of women with at least 8 years of education, and percentage of unemployed aged 15-64 years were assessed using Pearson correlation coefficients. Univariate linear regression and multiple stepwise linear regression analyses were performed to determine the magnitude and direction of the effect of the four socio-economic variables on IM. RESULTS: The Gini index and the total unemployment rate showed a positive strong correlation with IM (r = 0.70; p < 0.001 and r = 0.84; p < 0.001 respectively), mean household income showed a strong negative correlation (r = -0.78; p < 0.001), while female educational attainment presented a weak negative correlation (r = -0.45; p < 0.05). Using a multiple stepwise linear regression model, only unemployment rate was independently associated with IM (b = 0.15, p < 0.001). CONCLUSIONS: In Italy, a high-income country where health care is universally available, variations in IM were strongly associated with relative and absolute income and unemployment rate. These results suggest that in Italy IM is not only related to income distribution, as demonstrated for other developed countries, but also to economic factors such as absolute income and unemployment. In order to reduce IM and the existing inequalities, the challenge for Italian decision makers is to promote economic growth and enhance employment levels.

Omega 3 polyunsaturated fatty acids supplementation and blood pressure levels in hypertriglyceridemic patients with untreated normal-high blood pressure and with or without metabolic syndrome: a retrospective study.

Recent evidence suggests that at least a part of the polyunsaturated fatty acids (PUFAs) heart protective effect is mediated by a relatively small but significant decrease in blood pressure level. We retrospectively evaluated the long-term effect of a PUFA supplementation on the blood pressure level of 111 hypertriglyceridemic subjects with untreated normal-high blood pressure that were prescribed a 2 grams PUFA supplementation in order to improve their plasma lipid pattern. After 12 months of treatment, systolic blood pressure (SBP) meanly decreased by 2.7 +/- 2.5 mmHg (p = 0.001) and diastolic blood pressure (DBP) by 1.3 +/- 3.3 mmHg (p < 0.001), while basal heart rate decreased by 4.0 +/- 4.4 bpm (p < 0.001). Both SBP and DBP reduction were significantly related to the baseline SBP (p < 0.001) and DBP (p < 0.001), respectively. Diastolic blood pressure change was also inversely related to the patient's age (p = 0.004). No significant difference was perceived in the metabolic syndrome subgroup. In our retrospective study, highly purified omega-3 PUFA long-term supplementation is associated with a significant reduction in SBP, DBP, Pulse pressure (PP), and basal heart rate in hypertriglyceridemic patients with normal-high blood pressure. No significant difference was perceived in the metabolic syndrome subgroup. The main determinants of the PUFA anti-hypertensive effect appear to be the basal blood pressure level and age.

Effect of a sequential training programme on inflammatory, prothrombotic and vascular remodelling biomarkers in hypertensive overweight patients with or without metabolic syndrome.

BACKGROUND: It is not known whether serum level of vascular remodelling parameters, such as matrix metalloproteinases could be modulated by physical activity and whether the eventual change could be influenced by metabolic syndrome (MS) diagnosis. DESIGN: Open, intervention study to evaluate the effects of a sequential physical activity training on inflammatory, prothrombotic and vascular remodelling biomarkers in overweight patients with and without MS. METHODS: We enrolled 80 overweight patients (mean age: 62.9+/-8.3 years; male : female = 36 : 44) with newly diagnosed hypertension, with or without MS. After 3 months of American Heart Association step 2 diet, they followed a sequential training programme including 56 days of added three metabolic equivalent tasks/week and 56 days of six metabolic equivalent tasks/week. RESULTS: All patients experienced a significant decrease in body mass index, waist circumference and blood pressure after both the training phases. High-density lipoprotein-cholesterolemia, triglycerides, and glycaemia significantly improved only after the intensive training phase compared with the baseline in MS patients. Prothrombotic parameters improved irrespectively from the MS diagnosis. High-sensitivity C-reactive protein P level significantly decreased towards baseline and towards the previous phase, after exercise intensification, but only in MS patients. The plasma level of matrix metalloproteinase 2 and 9, and their activated forms improved significantly when compared with the baseline both after the first and the second training period, independently from the MS diagnosis. CONCLUSION: Diagnosis of MS is a determinant of changes in metabolic and inflammatory biomarkers, but not of the prothrombotic and vascular remodelling ones in a sample of overweight hypertensive patients.

Effects of AT1 receptor and beta1 receptor blocking on blood pressure, peripheral hemodynamic and lipid profile in statin-treated hypertensive hypercholesterolemic patients.

Recent evidences suggest a relationship between angiotensin 1 (AT1) receptor gene expression and low density lipoprotein cholesterol (LDL-C) plasma level. We enrolled 16 untreated hypertensive hypercholesterolemic patients (57.4 +/- 7 years old) in a randomized, single-blind, cross-over design. All the patients were allocated to treatment with simvastatin 20 mg/day for 2 weeks, then randomly assigned to telmisartan (40-80 mg/day) or bisoprolol (5-10 mg/day). After 4 weeks the antihypertensive drugs have been withdrawn for a wash-out period of 2 weeks when they were treated with simvastatin alone, then they have been allocated to the alternative antihypertensive treatment for four additional weeks. We measured: systolic (SBP) and diastolic BP (DBP), 24-h mean BP (MBP), Baseline and post-ischemia forearm blood flow (FBF) and vascular resistance (FVR), and Lipid profile. After 2 weeks of treatment with Simvastatin, baseline and post-ischemic FBF increased (both P < 0.05), while baseline and post-ischemic FVR decreased (both P < 0.05). Standing DBP and MBP were reduced more after treatment with telmisartan than with bisoprolol (P < 0.05). Basal and post-ischemic FBF were significantly increased (P < 0.05 and P < 0.005, respectively) and basal and post-ischemic FVR significantly decreased (both P < 0.005) only after treatment with telmisartan, as well as plasma triglycerides (TG) (P < 0.05). From this preliminary study carried out on hypercholesterolemic hypertensive patients it appears that the association of telmisartan and simvastatin (but not of bisoprolol and simvastatin) could exert positive effects on a large quantity of vascular functionality parameters, just after a short treatment.