Evidence for external beam radiotherapy in mediastinal Hodgkin and non-Hodgkin lymphoma - systematic review.

INTRODUCTION AND OBJECTIVE: Proton beam therapy (PBT) provides the opportunity for a more localized delivery of high energy protons and may reduce the damage to healthy tissues and vital organs. The aim of this review was to assess the effects of proton therapy for patients diagnosed with Hodgkin or non-Hodgkin lymphoma treated with mediastinal irradiation. REVIEW METHODS: A systematic search of EMBASE, MEDLINE via OVID and Cochrane Library was conducted in May 2022 according to PRISMA guidelines to identify relevant data on the efficacy and toxicity of proton beam therapy for patients diagnosed with Hodgkin or non-Hodgkin lymphoma. BRIEF DESCRIPTION OF THE STATE OF KNOWLEDGE: Of 566 screened abstracts (430 after de-duplication) 11 studies with a total of 529 patients were included. All studies were case series published between 2011-2021. Median range of follow-up time was 15-63.6 months. The overall survival (OS) for 2 years varied from 91% - 98% for 5 of the included studies. Three of the included studies had favourable outcomes with 2-year progression-free survival (PFS) ranging from 73% - 94%. Skin reaction, oesophagitis and fatigue were found to be the most common grade 1 and grade 2 toxicities. No acute or late grade 4 and higher toxicities/adverse events were observed. SUMMARY: There are data indicating that PBT may to be an effective treatment against mediastinal Hodgkin and non-Hodgkin lymphoma. Because all the studies were case series, the authors of this review have little confidence in the evidence. There remains a need for well-designed randomized controlled trials to inform about the optimal approach to proton irradiation in HL and NHL.

Predictors of Recovery Following Lumbar Microdiscectomy for Sciatica: A Systematic Review and Meta-Analysis of Observational Studies.

Chronic post-surgical pain is reported by up to 40% of patients after lumbar microdiscectomy for sciatica, a complaint associated with disability and loss of productivity. We conducted a systematic review of observational studies to explore factors associated with persistent leg pain and impairments after microdiscectomy for sciatica. We searched eligible studies in MEDLINE, Embase, and CINAHL that explored, in an adjusted model, predictors of persistent leg pain, physical impairment, or failure to return to work after microdiscectomy for sciatica. When possible, we pooled estimates of association using random-effects models using the Grading of Recommendations Assessment, Development, and Evaluation approach. Moderate-certainty evidence showed that the female sex probably has a small association with persistent post-surgical leg pain (odds ratio (OR) = 1.15, 95% confidence interval (CI) = 0.63 to 2.08; absolute risk increase (ARI) = 1.8%, 95% CI = -4.7% to 11.3%), large association with failure to return to work (OR = 2.79, 95% CI = 1.27 to 6.17; ARI = 10.6%, 95% CI = 1.8% to 25.2%), and older age is probably associated with greater postoperative disability (ß = 1.47 points on the 100-point Oswestry Disability Index for every 10-year increase from age (>/=18 years), 95% CI = -4.14 to 7.28). Among factors that were not possible to pool, two factors showed promise for future study, namely, legal representation and preoperative opioid use, which showed large associations with worse outcomes after surgery. The moderate-certainty evidence showed female sex is probably associated with persistent leg pain and failure to return to work and that older age is probably associated with greater post-surgical impairment after a microdiscectomy. Future research should explore the association between legal representation and preoperative opioid use with persistent pain and impairment after microdiscectomy for sciatica.

Predictors of Higher Quality of Systematic Reviews Addressing Nutrition and Cancer Prevention.

Systematic reviews/meta-analyses (SR/MAs) are considered a reliable source of information in healthcare. We aimed to explore the association of several characteristics of SR/MAs addressing nutrition in cancer prevention and their quality/risk of bias (using assessments from AMSTAR-2 and ROBIS tools). The analysis included 101 SR/MAs identified in a systematic survey. Associations of each specified characteristic (e.g., information about the protocol, publication year, reported use of GRADE, or other methods for assessing overall certainty of evidence) with the number of AMSTAR-2 not met ('No' responses) and the number of ROBIS items met ('Probably Yes' or "Yes' responses) were examined. Poisson regression was used to identify predictors of the number of 'No' answers (indicating lower quality) for all AMSTAR-2 items and the number of 'Yes' or 'Probably Yes' answers (indicating higher quality/lower concern for bias) for all ROBIS items. Logistic regression was used to identify variables associated with at least one domain assessed as 'low concern for bias' in the ROBIS tool. In multivariable analysis, SR/MAs not reporting use of any quality/risk of bias assessment instrument for primary studies were associated with a higher number of 'No' answers for all AMSTAR-2 items (incidence rate ratio (IRR) 1.26, 95% confidence interval (CI) 1.09-1.45), and a lower number of 'Yes' or 'Probably Yes' answers for all ROBIS items (IRR 0.76, 95% CI 0.66-0.87). Providing information about the protocol and search for unpublished studies was associated with a lower number of 'No' answers (IRR 0.73, 95% CI 0.56-0.97 and IRR 0.75, 95% CI 0.59-0.95, respectively) and a higher number of 'Yes' or 'Probably Yes' answers (IRR 1.43, 95% CI 1.17-1.74 and IRR 1.28, 95% CI 1.07-1.52, respectively). Not using at least one quality/risk of bias assessment tool for primary studies within an SR/MA was associated with lower odds that a study would be assessed as 'low concern for bias' in at least one ROBIS domain (odds ratio 0.061, 95% CI 0.007-0.527). Adherence to methodological standards in the development of SR/MAs was associated with a higher overall quality of SR/MAs addressing nutrition for cancer prevention.

Are systematic reviews addressing nutrition for cancer prevention trustworthy? A systematic survey of quality and risk of bias.

CONTEXT: The last 30 years have yielded a vast number of systematic reviews and/or meta-analyses addressing the link between nutrition and cancer risk. OBJECTIVE: The aim of this survey was to assess overall quality and potential for risk of bias in systematic reviews and meta-analyses (SRMAs) that examined the role of nutrition in cancer prevention. DATA SOURCES: MEDLINE, Embase, and the Cochrane Library databases were searched (last search performed November 2018). STUDY SELECTION: Studies identified as SRMAs that investigated a nutritional or dietary intervention or exposure for cancer prevention in the general population or in people at risk of cancer and in which primary studies had a comparison group were eligible for inclusion. Screening, data extraction, and quality assessment were conducted independently by 2 reviewers. DATA EXTRACTION: Altogether, 101 studies were randomly selected for analysis. The methodological quality and risk of bias were evaluated using the AMSTAR-2 and ROBIS tools, respectively. RESULTS: Most SRMAs included observational studies. Less than 10% of SRMAs reported a study protocol, and only 51% of SRMAs assessed the risk of bias in primary studies. Most studies conducted subgroup analyses, but only a few reported tests of interaction or specified subgroups of interest a priori. Overall, according to AMSTAR-2, only 1% of SRMAs were of high quality, while 97% were of critically low quality. Only 3% had a low risk of bias, according to ROBIS. CONCLUSIONS: This systematic survey revealed substantial limitations with respect to quality and risk of bias of SRMAs. SRMAs examining nutrition and cancer prevention cannot be considered trustworthy, and results should be interpreted with caution. Peer reviewers as well as users of SRMAs should be advised to use the AMSTAR-2 and/or ROBIS instruments to help to determine the overall quality and risk of bias of SRMAs. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD42019121116.

Similarities, reliability and gaps in assessing the quality of conduct of systematic reviews using AMSTAR-2 and ROBIS: systematic survey of nutrition reviews.

BACKGROUND: AMSTAR-2 ('A Measurement Tool to Assess Systematic Reviews, version 2') and ROBIS ('Risk of Bias in Systematic Reviews') are independent instruments used to assess the quality of conduct of systematic reviews/meta-analyses (SR/MAs). The degree of overlap in methodological constructs together with the reliability and any methodological gaps have not been systematically assessed and summarized in the field of nutrition. METHODS: We performed a systematic survey of MEDLINE, EMBASE, and the Cochrane Library for SR/MAs published between January 2010 and November 2018 that examined the effects of any nutritional intervention/exposure for cancer prevention. We followed a systematic review approach including two independent reviewers at each step of the process. For AMSTAR-2 (16 items) and ROBIS (21 items), we assessed the similarities, the inter-rater reliability (IRR) and any methodological limitations of the instruments. Our protocol for the survey was registered in PROSPERO (CRD42019121116). RESULTS: We found 4 similar domain constructs based on 11 comparisons from a total of 12 AMSTAR-2 and 14 ROBIS items. Ten comparisons were considered fully overlapping. Based on Gwet's agreement coefficients, six comparisons provided almost perfect (> 0.8), three substantial (> 0.6), and one a moderate level of agreement (> 0.4). While there is considerable overlap in constructs, AMSTAR-2 uniquely addresses explaining the selection of study designs for inclusion, reporting on excluded studies with justification, sources of funding of primary studies, and reviewers' conflict of interest. By contrast, ROBIS uniquely addresses appropriateness and restrictions within eligibility criteria, reducing risk of error in risk of bias (RoB) assessments, completeness of data extracted for analyses, the inclusion of all necessary studies for analyses, and adherence to predefined analysis plan. CONCLUSIONS: Among the questions on AMSTAR-2 and ROBIS, 70.3% (26/37 items) address the same or similar methodological constructs. While the IRR of these constructs was moderate to perfect, there are unique methodological constructs that each instrument independently addresses. Notably, both instruments do not address the reporting of absolute estimates of effect or the overall certainty of the evidence, items that are crucial for users' wishing to interpret the importance of SR/MA results.

Anti-cytokine targeted therapies for ANCA-associated vasculitis.

BACKGROUND: Anti-neutrophilic cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) are a group of rare auto-inflammatory diseases that affects mainly small vessels. AAV includes: granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). Anti-cytokine targeted therapy uses biological agents capable of specifically targeting and neutralising cytokine mediators of the inflammatory response. OBJECTIVES: To assess the benefits and harms of anti-cytokine targeted therapy for adults with AAV. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (2019, Issue 7), MEDLINE and Embase up to 16 August 2019. We also examined reference lists of articles, clinical trial registries, websites of regulatory agencies and contacted manufacturers. SELECTION CRITERIA: Randomised controlled trials (RCTs) or controlled clinical trials of targeted anti-cytokine therapy in adults (18 years or older) with AAV compared with placebo, standard therapy or another modality and anti-cytokine therapy of different type or dose. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included four RCTs with a total of 440 participants (mean age 48 to 56 years). We analysed the studies in three groups: 1) mepolizumab (300 mg; three separate injections every four weeks for 52 weeks) versus placebo in participants with relapsing or refractory EGPA; 2) belimumab (10 mg/kg on days 0, 14, 28 and every 28 days thereafter until 12 months after the last participant was randomised) or etanercept (25 mg twice a week) with standard therapy (median 25 months) versus placebo with standard therapy (median 19 months) in participants with GPA/MPA; and 3) infliximab (3 mg/kg on days 1 and 14, before the response assessment on day 42) versus rituximab (0.375g/m2 on days 1, 8, 15 and 22) in participants with refractory GPA for up to 12 months. None of the studies were assessed as low risk of bias in all domains: one study did not report randomisation or blinding methods clearly. Three studies were at high risk and one study was at unclear risk of bias for selective outcome reporting. One trial with 136 participants with relapsing or refractory EGPA compared mepolizumab with placebo during 52 weeks of follow-up and observed one death in the mepolizumab group (1/68, 1.5%) and none in the placebo group (0/68, 0%) (Peto odds ratio (OR) 7.39, 95% confidence interval (CI) 0.15 to 372.38; low-certainty evidence). Low-certainty evidence suggests that more participants in the mepolizumab group had ≥ 24 weeks of accrued remission over 52 weeks compared to placebo (27.9% versus 2.9%; risk ratio (RR) 9.5, 95% CI 2.30 to 39.21), and durable remission within the first 24 weeks sustained until week 52 (19.1% mepolizumab versus 1.5% placebo; RR 13.0, 95% CI 1.75 to 96.63; number needed to treat for an additional beneficial outcome (NNTB) 6, 95% Cl 4 to 13). Mepolizumab probably decreases risk of relapse (55.8% versus 82.4%; RR 0.68, 95% CI 0.53 to 0.86; NNTB 4, 95% CI 3 to 9; moderate-certainty evidence). There was low-certainty evidence regarding similar frequency of adverse events (AEs): total AEs (96.9% versus 94.1%; RR 1.03, 95% CI 0.96 to 1.11), serious AEs (17.7% versus 26.5%; RR 0.67, 95% CI 0.35 to 1.28) and withdrawals due to AEs (2.9% versus 1.5%; RR 2.00, 95% CI 0.19 to 21.54). Disease flares were not measured. Based on two trials with different follow-up periods (mean of 27 months for etanercept study; up to four years for belimumab study) including people with GPA (n = 263) and a small group of participants with MPA (n = 22) analysed together, we found low-certainty evidence suggesting that adding an active drug (etanercept or belimumab) to standard therapy does not increase or reduce mortality (3.4% versus 1.4%; Peto OR 2.45, 95% CI 0.55 to 10.97). Etanercept may have little or no effect on remission (92.3% versus 89.5%; RR 0.97, 95% CI 0.89 to 1.07), durable remission (70% versus 75.3%; RR 0.93, 95% CI 0.77 to 1.11; low-certainty evidence) and disease flares (56% versus 57.1%; RR 0.98, 95% CI 0.76 to 1.27; moderate-certainty evidence). Low-certainty evidence suggests that belimumab does not increase or reduce major relapse (1.9% versus 0%; RR 2.94, 95% CI 0.12 to 70.67) or any AE (92.5% versus 82.7%; RR 1.12, 95% CI 0.97 to 1.29). Low-certainty evidence suggests a similar frequency of serious or severe AEs (47.6% versus 47.6%; RR 1.00, 95% CI 0.80 to 1.27), but more frequent withdrawals due to AEs in the active drug group (11.2%) compared to the placebo group (4.2%), RR 2.66, 95% CI 1.07 to 6.59). One trial involving 17 participants with refractory GPA compared infliximab versus rituximab added to steroids and cytotoxic agents for 12 months. One participant died in each group (Peto OR 0.88, 95% CI, 0.05 to 15.51; 11% versus 12.5%). We have very low-certainty evidence for remission (22% versus 50%, RR 0.44, 95% Cl 0.11 to 1.81) and durable remission (11% versus 50%, RR 0.22, 95% CI 0.03 to 1.60), any severe AE (22.3% versus 12.5%; RR 1.78, 95% CI 0.2 to 16.1) and withdrawals due to AEs (0% versus 0%; RR 2.70, 95% CI 0.13 to 58.24). Disease flare/relapse and the frequency of any AE were not reported. AUTHORS' CONCLUSIONS: We found four studies but concerns about risk of bias and small sample sizes preclude firm conclusions. We found moderate-certainty evidence that in patients with relapsing or refractory EGPA, mepolizumab compared to placebo probably decreases disease relapse and low-certainty evidence that mepolizumab may increase the probability of accruing at least 24 weeks of disease remission. There were similar frequencies of total and serious AEs in both groups, but the study was too small to reliably assess these outcomes. Mepolizumab may result in little to no difference in mortality. However, there were very few events. In participants with GPA (and a small subgroup of participants with MPA), etanercept or belimumab may increase the probability of withdrawal due to AEs and may have little to no impact on serious AEs. Etanercept may have little or no impact on durable remission and probably does not reduce disease flare.

Clinical development success rates and social value of pediatric Phase 1 trials in oncology.

OBJECTIVES: Drug development trials must fulfill social value requirement but no estimates of value provided by pediatric Phase 1 trials in oncology exist. These trials involve a particularly vulnerable population. Our objective was to assess of surrogates of social value of Phase 1 trials performed in pediatric oncology: rates of approval of tested interventions, transition to further phases of testing and citation in subsequent primary research reports. METHODS: We performed an analysis on a subset of eligible trials included in a previous meta-analysis. That study systematically searched EMBASE and PubMed for small sample size, non-randomized, dose escalation pediatric cancer Phase 1 studies of any malignancy, assessing chemotherapy and/or targeted therapy and looked at risk and benefit. The current analysis assessed all studies in that review published between January 1st 2004 and December 31st 2013 for predictors of social value. This time range allowed for at least five years of subsequent development activity. Sources of data included FDA and EMA medicine databases (for approval), ClinicalTrials.gov and EU Clinical Trials Register (for transition) and Google Scholar (for citation). RESULTS: One hundred thirty-nine trials enrolling 3814 patients met the eligibility criteria. Seven trials (5%) led to drugs being registered for pediatric use in therapy of cancer. Fifty-two (37%) transitioned to later phases of pediatric oncology trials according to ClinicalTrials.gov and/or EU Register. Over 90% of trials were cited by at least one subsequent primary research report or systematic review. Most of the citations were preclinical studies. CONCLUSIONS: Our analysis shows that treatments tested in pediatric Phase 1 trials in oncology have low rates of regulatory approval. However, a large proportion of Phase 1 trials inform further testing and development of tested interventions.

Correction: Offline Digital Education for Postregistration Health Professions: Systematic Review and Meta-Analysis by the Digital Health Education Collaboration.

[This corrects the article DOI: 10.2196/12968.].

Legionella sp. in water systems in public teaching and education facilities in Malopolskie voivodeship in 2016

INTRODUCTION: Bacteria Legionella sp. found in water distribution systems, especially warm, transferred to water spray devices for aerators and showers in the form of aerosols infected with them become a threat to the human inhaler. OBJECTIVE: Assessment of colonization of the water supply network with Legionella bacteria in teaching and education facilities in Malopolska in 2016 year. MATERIAL AND METHODS: The results of water samples taken from plumbing installations were analyzed in teaching and education facilities by employees of the State Sanitary Inspection of the Lesser Poland Voivodeship. RESULTS: The results of 366 testing hot water samples in 111 teaching and education centers in Malopolska have shown that in 123 testing samples (33,6%) in 48 centers (43,2%) the water sample was colonized with Legionella sp. and the water quality did not meet the requirements of the current ordinance of the Minister of Health. CONCLUSIONS: It is justified to periodically monitor the presence of Legionella sp. in water supply installations in teaching and education centers and taking action to reduce the colonization of these bacteria.

Offline Digital Education for Postregistration Health Professions: Systematic Review and Meta-Analysis by the Digital Health Education Collaboration.

BACKGROUND: The shortage and disproportionate distribution of health care workers worldwide is further aggravated by the inadequacy of training programs, difficulties in implementing conventional curricula, deficiencies in learning infrastructure, or a lack of essential equipment. Offline digital education has the potential to improve the quality of health professions education. OBJECTIVE: The primary objective of this systematic review was to evaluate the effectiveness of offline digital education compared with various controls in improving learners' knowledge, skills, attitudes, satisfaction, and patient-related outcomes. The secondary objectives were (1) to assess the cost-effectiveness of the interventions and (2) to assess adverse effects of the interventions on patients and learners. METHODS: We searched 7 electronic databases and 2 trial registries for randomized controlled trials published between January 1990 and August 2017. We used Cochrane systematic review methods. RESULTS: A total of 27 trials involving 4618 individuals were included in this systematic review. Meta-analyses found that compared with no intervention, offline digital education (CD-ROM) may increase knowledge in nurses (standardized mean difference [SMD]=1.88; 95% CI 1.14 to 2.62; participants=300; studies=3; I2=80%; low certainty evidence). A meta-analysis of 2 studies found that compared with no intervention, the effects of offline digital education (computer-assisted training [CAT]) on nurses and physical therapists' knowledge were uncertain (SMD 0.55; 95% CI -0.39 to 1.50; participants=64; I2=71%; very low certainty evidence). A meta-analysis of 2 studies found that compared with traditional learning, a PowerPoint presentation may improve the knowledge of patient care personnel and pharmacists (SMD 0.76; 95% CI 0.29 to 1.23; participants=167; I2=54%; low certainty evidence). A meta-analysis of 4 studies found that compared with traditional training, the effects of computer-assisted training on skills in community (mental health) therapists, nurses, and pharmacists were uncertain (SMD 0.45; 95% CI -0.35 to 1.25; participants=229; I2=88%; very low certainty evidence). A meta-analysis of 4 studies found that compared with traditional training, offline digital education may have little effect or no difference on satisfaction scores in nurses and mental health therapists (SMD -0.07; 95% CI -0.42 to 0.28, participants=232; I2=41%; low certainty evidence). A total of 2 studies found that offline digital education may have little or no effect on patient-centered outcomes when compared with blended learning. For skills and attitudes, the results were mixed and inconclusive. None of the studies reported adverse or unintended effects of the interventions. Only 1 study reported costs of interventions. The risk of bias was predominantly unclear and the certainty of the evidence ranged from low to very low. CONCLUSIONS: There is some evidence to support the effectiveness of offline digital education in improving learners' knowledge and insufficient quality and quantity evidence for the other outcomes. Future high-quality studies are needed to increase generalizability and inform use of this modality of education.

Risk and surrogate benefit for pediatric Phase I trials in oncology: A systematic review with meta-analysis.

BACKGROUND: Pediatric Phase I cancer trials are critical for establishing the safety and dosing of anti-cancer treatments in children. Their implementation, however, must contend with the rarity of many pediatric cancers and limits on allowable risk in minors. The aim of this study is to describe the risk and benefit for pediatric cancer Phase I trials. METHODS AND FINDINGS: Our protocol was prospectively registered in PROSPERO (CRD42015015961). We systematically searched Embase and PubMed for solid and hematological malignancy Phase I pediatric trials published between 1 January 2004 and 1 March 2015. We included pediatric cancer Phase I studies, defined as "small sample size, non­randomized, dose escalation studies that defined the recommended dose for subsequent study of a new drug in each schedule tested." We measured risk using grade 3, 4, and 5 (fatal) drug-related adverse events (AEs) and benefit using objective response rates. When possible, data were meta-analyzed. We identified 170 studies meeting our eligibility criteria, accounting for 4,604 patients. The pooled overall objective response rate was 10.29% (95% CI 8.33% to 12.25%), and was lower in solid tumors, 3.17% (95% CI 2.62% to 3.72%), compared with hematological malignancies, 27.90% (95% CI 20.53% to 35.27%); p < 0.001. The overall fatal (grade 5) AE rate was 2.09% (95% CI 1.45% to 2.72%). Across the 4,604 evaluated patients, there were 4,675 grade 3 and 4 drug-related AEs, with an average grade 3/4 AE rate per person equal to 1.32. Our study had the following limitations: trials included in our review were heterogeneous (to minimize heterogeneity, we separated types of therapy and cancer types), and we relied on published data only and encountered challenges with the quality of reporting. CONCLUSIONS: Our meta-analysis suggests that, on the whole, AE and response rates in pediatric Phase I trials are similar to those in adult Phase I trials. Our findings provide an empirical basis for the refinement and review of pediatric Phase I trials, and for communication about their risk and benefit.

Vortioxetine: A review of the pharmacology and clinical profile of the novel antidepressant.

The aim of this paper was to review the up-to-date evidence base on pharmacology and clinical properties of vortioxetine. Vortioxetine is a novel antidepressant, approved by the US Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD). Because vortioxetine exhibits both an antidepressant and anxiolytic effect, it may be effective in treating both depressive and anxiety disorders, such as generalized anxiety disorder (GAD). Based on its pharmacodynamics profile and preclinical studies, it is believe that the drug's clinical action is mediated mainly by selective blockade of serotonin reuptake (by inhibiting the serotonin transporter [SERT]) and direct modulation of 5-HT receptors activity (such as 5-HT3, 5-HT7, 5-HT1D and 5-HT1B). In patients with MDD the recommended doses range is 5-20mg/day. Vortioxetine was shown to be more effective than placebo both in MDD and GAD. In terms of side effects, nausea, vomiting, diarrhea, and dry mouth were most commonly observed in individuals receiving vortioxetine. In direct comparison to duloxetine, vortioxetine is found to have a smaller efficacy but had a lower risk of developing the common antidepressant-induced adverse effects.

Clinical guidelines development process in Poland

Clinical practice guidelines are set of recommendations for cliniciansa bout the care of patients. The aim of clinical practice guidelines is to support clinical decision-making, rationalize diagnostic and therapeutic procedures and provide high-quality healthcare. Development of clinical practice guidelines should be a systematic process based on evidence based medicine (EBM). However, as practice shows, they are not always reliable and are not developed according to the recommended world-wide methodology. The purpose of this article is to provide an outline of the clinical guidelines development process and to present international instruments for guidance development, evaluation and adaptation

The Cochrane collaboration ­ the role in the evolution of evidence-based medicine and development of cooperation in Poland

Evidence-based medicine (EBM) is an approach to decision making on the basis of the reliable and up to date best evidence. EBM is regarded as the gold standard all over the world. Cochrane Collaboration is one of the institutions, which promote EBM among physicians, policy makers and other health care workers. Cochrane Collaboration is international non-profit organization bringing together people from all over the world, the aim of which is to create and disseminate reliable scientific information. The Cochrane Collaboration develops and publishes systematic reviews on medical and diagnostic procedures. The article presents the history of the Cochrane Collaboration, the Cochrane Library and the first Cochrane Branch in Poland. Cochrane Branch in Poland is hosted by the Systematic Reviews Centre created in 2015 within the Faculty of Medicine at the Jagiellonian University Medical College in Krakow. The authors presented the activities of the Cochrane Collaboration, the scope of activities of Polish Branch and briefly principles for the development of Cochrane systematic reviews.

Limited responsiveness related to the minimal important difference of patient-reported outcomes in rare diseases.

OBJECTIVES: To explore the responsiveness of patient-reported outcomes (PROs) in interventional studies involving patients with rare lysosomal storage diseases (LSDs). STUDY DESIGN AND SETTING: We searched eight databases for experimental and nonexperimental studies. Pairs of trained reviewers independently screened articles and subsequently extracted data from the eligible studies. Among studies with 10 or more patients using a valid PRO, we assessed the responsiveness of PROs based on a reanalysis of the data using minimal important difference estimates. Our analyses focused on statistically significant within-group differences in PROs for observational studies or the statistically significant between-group differences in PRO scores for controlled studies. RESULTS: Of 2,679 unique records, 62 interventional studies addressing patients with Fabry (55%), Gaucher (19%), Pompe (16%), and mucopolysaccharidoses (11%) proved eligible. The most frequently used PROs were the Short-Form-36 (25 studies), Brief Pain Inventory (20 studies), EuroQoL-5D (9 studies), and the Fatigue Severity Scale (6 studies). Observational studies suggest that PROs sometimes detect significant within-group changes when present. Randomized trials raise questions regarding the responsiveness of PROs to small differences between groups. CONCLUSIONS: Most studies have relied on generic PROs to evaluate quality of life and symptoms in patients with rare LSDs. PROs appear more responsive in observational studies than randomized trials.

Production lost due to cervical cancer in Poland in 2012.

BACKGROUND: Poland has one of the highest cervical cancer mortality rates in Europe. It is related to the problem of late diagnosis and low attendance rate in screening programs. The objective of the study has been to assess the annual production loss due to the cervical cancer morbidity and mortality in Poland in 2012. The outcomes have been to provide comprehensive information on cervical cancer's influence on population's ability to work and its overall economic burden for the society. The study has also provided the methodological framework for disease-related production losses in Polish settings. MATERIAL AND METHODS: The human capital method was used. The production losses were calculated in both monetary and quantitative terms (working days lost) due to 4 following reasons: 1) temporary disability to work, 2) permanent disability, 3) informal care, and 4) mortality. RESULTS: Cervical cancer resulted in approx. 702 964 working days lost in 2012 due to absence at work for both patients and care givers and a total number of 957 678 working days lost due to patients' mortality. The total value of production lost was assessed at 111.4 million euros. More than 66% of this value was attributed to women's mortality. CONCLUSIONS: The calculation of production lost due to cervical cancer burden provides strong evidence to support adequate health promotion and disease prevention actions. Actions promoting cervical cancer screening should be intensified including workplace health promotion activities. Med Pr 2016;67(3):289-299.

The Lyme disease as the increasing health problem in Malopolskie voivodeship compared with Poland in 1998-2014 / Borelioza jako narastajacy problem zdrowotny w województwie malopolskim na tle Polski w latach 1998-2014

OBJECTIVE: Lyme disease is one of the most known tick borne diseases in Poland caused by spirochetes of the genus Borrelia burgdorferi. Most cases of Lyme disease are diagnosed in the northeastern Poland and the south of Poland, in Slaskie, Malopolskie, Podkarpackie voivodeship. The aim of the study was to evaluate epidemiological data of Lyme disease in Malopolskie voivodeship and other voivodeships in Poland and frequency analysis of the Lyme disease as an occupational disease. METHODS: The authors analyzed prevalence from 1998 to 2014. Incidence of the Lyme disease was evaluated through review data from "Choroby zakazne i zatrucia" Bulletin and Lyme disease as an occupational disease obtained data from the Nofer Institute of Occupational Medicine in Lódz. RESULTS: It is estimated that the number of Lyme disease cases in Poland increased 18 times between 1998 and 2014 year (2,0 to 36 per 100,000 population), in the same period it was over 35 times of sudden rise in Lyme disease incidence in Malopolskie voivodeship. In years 2005-2014 the number of cases of Lyme disease as an occupational disease fluctuated with a slight upward trend both in Poland and Malopolskie voivoideship. CONCLUSIONs: In Poland number of reported cases is systematically increasing. Podlaskie and Warminsko- Mazurskie voivodeships are areas of high prevalence. Exponential increase in the number of cases is observed in southern Poland, especially in Malopolskie voivodeship from 2013.

Alert microorganisms isolated from patients hospitalized in Malopolskie province in 2010-2012.

OBJECTIVE: Healthcare centers undertake supervisory activities to control health care-associated infections (HCAIs) by elaborating procedures, identifying alert microorganisms and analyzing data collected. The aim of the study was to analyze the prevalence of alert microorganisms in hospital wards in 2010-2012. MATERIAL AND METHODS: Legislation which is in force since several years introduced the principles of health care-associated infections control and reporting system. Analysis was based on annual reports on alert microorganisms provided by 19 District Sanitary and Epidemiological Stations from Malopolskie province. The data discuss positive tests results for alert microorganisms in patients who stayed in hospitals supervised by the Sanitary and Epidemiological Stations. RESULTS: Compared to 2010-2011, the number of tests per hospital bed in 2012 was lower, amounting to 24 (2010 - 44, 2011 - 34). Of these tests, the majority was performed in the following wards: transplantology (2010 - 339, 2011 - 354, 2012 - 330), burn care (2010 - 354, 2011 - 148, 2012 - 113) and ICUs for adults (2010 - 155, 2011 - 157, 2012 - 140). In 2010-2012, an increase in the number of positive test results for extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL+) and Clostridium difficile as well as slight decrease in the number of positive test results for other alert microorganisms were noted. The highest number of microorganisms was identified in neonatal and neonatal pathology (Enterobacteriaceae ESBL+); pediatric and infectious diseases (Rotavirus); infectious diseases (Rotavirus, C.difficile); burn care (Acinetobacter baumanii, Pseudomonas sp.) and ophthalmic and hemodialysis wards (MRSA). CONCLUSION: Irrespective of a decrease in the number of tests per hospital bed in 2012, a high number of positive test results for alert microorganisms was observed. It suggests the necessity for wider application of collected data as to improve monitoring of infections and reduce resulting threats.