Ana Jerončić

Ethical aspects of human biobanks: a systematic review

Aim To systematically assess the existing literature on ethical aspects of human biobanks. Method We searched the Web of Science and PubMed databases to find studies addressing ethical problems in biobanks with no limits set (study design, study population, time period, or language of publication). All identified articles published until November 2010 were included. We analyzed the type of published articles, journals publishing them, involvement of countries/institutions, year of publication, and citations received, and qualitatively assessed every article in order to identify ethical issues addressed by the majority of published research on human biobanking. Results Hundred and fifty four studies satisfied our review criteria. The studies mainly came from highly developed countries and were all published in the last two decades, with over half of them published in 2009 or 2010. They most commonly discussed the informed consent, privacy and identifiability, return of results to participants, importance of public trust, involvement of children, commercialization, the role of ethics boards, international data exchange, ownership of samples, and benefit sharing. Conclusions The focus on ethical aspects is strongly present through the whole biobanking research field. Although there is a consensus on the old and most typical ethical issues, with further development of the field and increasingly complex structure of human biobanks, these issues will likely continue to arise and accumulate, hence requiring constant re-appraisal and continuing discussion.

Neurophysiologic markers in laryngeal muscles indicate functional anatomy of laryngeal primary motor cortex and premotor cortex in the caudal opercular part of inferior frontal gyrus

OBJECTIVE The aim of this study was to identify neurophysiologic markers generated by primary motor and premotor cortex for laryngeal muscles, recorded from laryngeal muscle. METHODS Ten right-handed healthy subjects underwent navigated transcranial magnetic stimulation (nTMS) and 18 patients underwent direct cortical stimulation (DCS) over the left hemisphere, while recording neurophysiologic markers, short latency response (SLR) and long latency response (LLR) from cricothyroid muscle. Both healthy subjects and patients were engaged in the visual object-naming task. In healthy subjects, the stimulation was time-locked at 10-300 ms after picture presentation while in the patients it was at zero time. RESULTS The latency of SLR in healthy subjects was 12.66 ± 1.09 ms and in patients 12.67 ± 1.23 ms. The latency of LLR in healthy subjects was 58.5 ± 5.9 ms, while in patients 54.25 ± 3.69 ms. SLR elicited by the stimulation of M1 for laryngeal muscles corresponded to induced dysarthria, while LLR elicited by stimulation of the premotor cortex in the caudal opercular part of inferior frontal gyrus, recorded from laryngeal muscle, corresponded to speech arrest in patients and speech arrest and/or language disturbances in healthy subjects. CONCLUSION In both groups, SLR indicated location of M1 for laryngeal muscles, and LLR location of premotor cortex in the caudal opercular part of inferior frontal gyrus, recorded from laryngeal muscle, while stimulation of these areas in the dominant hemisphere induced transient speech disruptions. SIGNIFICANCE Described methodology can be used in preoperative mapping, and it is expected to facilitate surgical planning and intraoperative mapping, preserving these areas from injuries.

Sex-specific association of anthropometric measures of body composition with arterial stiffness in a healthy population

Summary Background Anthropometric measures of body composition and arterial stiffness are commonly used as indicators of cardiovascular risk. Little is known, however, about the association of the anthropometric measures with arterial stiffness, especially in a healthy, generally non-obese population. Material/Methods In a sample of 352 healthy subjects (200 premenopausal women), 3 arterial stiffness indices were analyzed (pulse wave velocity, augmentation index and central systolic blood pressure) in relation to 5 anthropometric measures of body composition (body mass index – BMI, body fat percentage by skinfold measurements –%BF, waist circumference – WC, waist-hip ratio – WHpR, and waist-height ratio – WHtR). Data were analyzed using correlation and regression analyses, with adjustment for the following confounders: age, blood pressures, height, heart rate, blood lipids and smoking. Results Most correlations between anthropometric measures and arterial stiffness indices were significant and positive in both sex groups (r=0.14–0.40, P<0.05). After adjustment for confounding effects, BMI, WC and WHtR remained significant (but inverse) predictors of arterial stiffness (β from −0.06 to −0.16; P<0.05) in the females, while in the males BMI was the only measure inversely predicting arterial stiffness (β from −0.09 to −0.13; P<0.05). Conclusions Measures of body composition are weak and inverse predictors of arterial stiffness and their influence is sex-dependent. BMI, WC and WHtR were key predictors of arterial stiffness in the females, while BMI was the principal predictor in the males. The associations of anthropometric measures with arterial stiffness are strongly and differently confounded by various factors that have to be taken into account when explaining results of similar studies.

Does unilateral laparoscopic diathermy adjusted to ovarian volume increase the chances of ovulation in women with polycystic ovary syndrome

STUDY QUESTION Does unilateral volume-adjusted laparoscopic diathermy increase the chances of ovulation in women with polycystic ovary syndrome (PCOS)? SUMMARY ANSWER Although unilateral laparoscopic ovarian drilling (ULOD) using adjusted thermal doses was more efficient than bilateral laparoscopic ovarian drilling (BLOD) using fixed doses, the chances of ovulation were improved in patients irrespective of the technique used. WHAT IS KNOWN ALREADY The adjustment of the thermal dose to ovarian volume in BLOD increases ovulation and pregnancy rates compared with fixed-dose treatment, but BLOD causes the formation of adhesions, particularly on the left ovary, and increases the risk of damage to ovarian tissue. In contrast, ULOD with a fixed thermal dose minimizes the risk of ovarian tissue damage, and can increase the activity in both right and left ovaries, although this varies in humans and in other species. STUDY DESIGN, SIZE, DURATION This prospective, longitudinal, study, between September 2009 and January 2013, included 96 infertile women with PCOS who were unresponsive to clomiphene citrate treatment and had underwent either ULOD or BLOD. After surgery, the groups were followed up for 6 months to assess ovulatory response. PARTICIPANTS/MATERIALS, SETTING, METHODS Patients were assigned to two groups; one group underwent laparoscopic ovarian drilling of the right ovary alone, while both ovaries were treated in the second group. The ULOD group (n = 49) received thermal doses adjusted to the volume of the right ovary (60 J/cm³). The BLOD group (n = 47) received fixed doses of 600 J per ovary, regardless of its volume. The two treatment groups were matched by the number of participants, age and baseline parameters. MAIN RESULTS AND THE ROLE OF CHANCE The ovulation rate during the first menstrual cycle after LOD was significantly higher in the ULOD group than in the BLOD group [73 versus 49%; absolute risk reduction (ARR), -0.25; 95% confidence interval (CI), -0.44 to -0.03; P = 0.014]. Treatment with ULOD on the right ovary significantly increased the chances of ovulation in patients with a larger right ovary compared with those who had a smaller right ovary (100 versus 36%; ARR, -0.64; 95% CI, -0.84 to -0.37; P = 0.004). Interestingly, the chances of ovulation were also significantly higher in patients in the BLOD group who had a larger right ovary compared with those who had a smaller right ovary (88 versus 33%; ARR, -0.55; 95% CI, -0.73 to -0.28; P = 0.002). The pregnancy rate was also significantly higher in patients with a larger right ovary compared with those with a smaller right ovary, regardless of the treatment group. LIMITATIONS, REASONS FOR CAUTION The 6-month follow-up was too short to demonstrate any long-term differences in the ovulation rates. Future research should therefore extend the follow-up beyond 6 months. Another limitation is that ULOD was used to treat only the right ovary. Future studies should investigate whether ULOD treatment of the larger ovary, whether left or right, would significantly increase the ovulation rate. WIDER IMPLICATIONS OF THE FINDINGS This study represents an advance in the determination of the optimal laparoscopic treatment for women with PCOS, as it was shown that improved results can be achieved using less thermal energy in volume-adjusted ULOD.

No health research without education for research--experience from an integrated course in undergraduate medical curriculum.

13 (Honey and Mumford Learning Styles and Myers–Briggs Type Indicator – MBTI). The reflector learning style was the most preferred and pragmatist, the least preferred learning style in both groups and the personality-type SFEJ was the commonest MBTI bestfit type amongst both groups. The poor performers were similar to the satisfactory performers in Learning Styles and Personality profiles (p4 0.05). Contrary to our hypothesis, the findings showed that learning style preference and personality profile were not related to clinical under-performance. There are limitations to our study with a single-point estimate of clinical performance in one centre. However, our study did not show any differences in Learning Style preferences and Personality profiles in poorly and satisfactorily performing medical students in an early clinical assessment. It might be that poorly performing clinical students are best identified using a composite measure of clinical performance, either cross-sectional or longitudinal, which would allow further investigation of the underlying causes and evidencebased targeted remediation.

Why do you think you should be the author on this manuscript? Analysis of open-ended responses of authors in a general medical journal

BackgroundTo assess how authors would describe their contribution to the submitted manuscript without reference to or requirement to satisfy authorship criteria of the International Committee of Medical Journal Editors (ICMJE), we analyzed responses of authors to an open-ended question “Why do you think you should be the author on this manuscript?”.MethodsResponses of authors (n=1425) who submitted their manuscripts (n=345) to the Croatian Medical Journal, an international general medical journal, from March 2009 until July 2010 were transcribed and matched to ICMJE criteria. Statements that could not be matched were separately categorized. Responses according to the number of authors or their byline position on the manuscript were analyzed using Mann–Whitney U test and Moses test of extreme reactions.ResultsThe number of authors per manuscript ranged from 1 to 26 (median=4, IQR=3-6), with the median of 2 contributions per author (IQR=2-3). Authors’ responses could be matched to the ICMJE criteria in 1116 (87.0%) cases. Among these, only 15.6% clearly declared contributions from all 3 ICMJE criteria; however, if signing of the authorship form was taken as the fulfillment of the third ICMJE criterion, overall fraction of deserving authorship was 54.2%. Non-ICMJE contributions were declared by 98 (7.6%) authors whose other contributions could be matched to ICMJE criteria, and by 116 (13.0%) authors whose contributions could not be matched to ICMJE criteria. The most frequently reported non-ICMJE contribution was literature review. Authors on manuscripts with more than 8 authors declared more contributions than those on manuscript with 8 or fewer authors: median 2, IQR 1–4, vs. median 2, IQR 1–3, respectively (Mann Whitney U test, p=0.001; Moses Test of Extreme Reactions, p<0.001). Almost a third of single authors (n=9; 31.0%) reported contributions that could not be matched to any ICMJE criterion.ConclusionsIn cases of multi-author collaborative efforts but not in manuscripts with fewer authors open-ended authorship declaration without instructions on ICMJE criteria elicited responses from authors that were similar to responses when ICMJE criteria were explicitly required. Current authorship criteria and the practice of contribution declaration should be revised in order to capture deserving authorship in biomedical research.

A complex pattern of agreement between oscillometric and tonometric measurement of arterial stiffness in a population-based sample

Objective: Arterial stiffness can be estimated by several noninvasive methods. In a large population-based sample we performed an agreement analysis of the set of arterial stiffness indices (ASIs) measured by tonometric (SphygmoCor) and oscillometric (Arteriograph) techniques. Methods: Central augmentation index (cAIx) and peripheral augmentation index (pAIx), as well as central SBP (cSBP) were measured in 1012 participants from a population-based study. Data were analyzed using Bland–Altman agreement analysis, multivariate adaptive regression splines and Fishers linear discriminant analysis. Results: In contrast to high initial correlation between two devices (r = 0.87 for pAIx, 0.88 for cAIx and 0.95 for cSBP), plotting against each other the values of measured ASIs revealed their uneven distribution and grouping into three distinctive clusters of participants. The strongest cluster discriminators were age and DBP (cluster 1: age <40, DBP 70.42 ± 7.41; cluster 2: age >40, DBP 77.36 ± 10.16; cluster 3: age >60, DBP 82.56 ± 9.48). Bland–Altman analysis of clusters showed complex differences in agreement pattern for cAIx and pAIx. For cAIx SphygmoCor gives lower readings, especially in cluster 1, whereas for pAIx Arteriograph gives lower readings in cluster 1 and higher readings in clusters 2 and 3. The agreement for pAIx was better in younger participants and the same for cAIx in older participants. Conclusion: ASIs obtained by SphygmoCor and Arteriograph cannot be interchangeably used as they seem to be differently influenced by predictors of arterial stiffness, predominantly by age. Different pattern of pAIx and cAIx agreement across clusters demonstrates importance of distinguishing cAIx and pAIx. Homogeneity of the study population for age should be considered when interpreting results of the studies investigating ASI.

Anti-Müllerian hormone, testosterone and free androgen index following the dose-adjusted unilateral diathermy in women with polycystic ovary syndrome

OBJECTIVE The aim of this study was to investigate changes of anti-Müllerian hormone, testosterone and free androgen index after two diathermy methods. We have also aimed at evaluating prognostic value of these parameters for an ovulatory response. STUDY DESIGN This prospective, comparative study included ninety-six women with polycystic ovary syndrome unresponsive to clomiphene citrate. Patients were assigned to two groups; the first group underwent unilateral laparoscopic ovarian drilling with thermal doses adjusted to ovarian volume: median of 720J (IQR), while the second group underwent bilateral drilling with fixed doses of 1200J. Anti-Müllerian hormone (AMH), testosterone (T), free androgen index (FAI)and luteinizing hormone (LH) were measured at baseline, at 1st and 6th month of follow up. RESULTS AMH, T and LH levels significantly decreased (P<0.001, P≤0.024, P<0.001) after diathermy in both responders and nonresponders from either treatment group. On contrary, FAI levels (P<0.001) significantly changed only in responders, irrespective of the treatment. In 1st and 6th month of follow up median levels of AMH, T and FAI among responders from different treatment groups were equivalent, whereas the responders in bilateral group had higher LH levels in the 1st month of follow up (P=0.003). Nonresponders differed between treatment groups only in AMH level which was decreased in unilateral group throughout the follow up (P≤0.021). The baseline value of T (semi-standardized coefficient, β=-0.28) and value of T in the 1st month (β=-0.72) after the diathermy were significant and consistent indicator of the response to therapy within 6months and the ovulation response in the 1st month. CONCLUSIONS The value of T is the strongest and consistent indicator of ovulatory response after diathermy. CLINICAL TRIAL REGISTRATION www.ClinicalTrials.gov , NCT01833949.

Who would students ask for help in academic cheating? Cross-sectional study of medical students in Croatia

BackgroundAcademic cheating does not happen as an isolated action of an individual but is most often a collaborative practice. As there are few studies that looked at who are collaborators in cheating, we investigated medical students’ readiness to engage others in academic dishonest behaviours.MethodsIn a cross-sectional survey study in Zagreb, Croatia, 592 medical students from the first, 3rd and 6th (final) study year anonymously answered a survey of readiness to ask family, friends, colleagues or strangers for help in 4 different forms of academic cheating or for 2 personal material favours. Stepwise multiple linear regression models (MLR) were used to evaluate potential factors influencing propensity for engaging others in these two types of behaviour.ResultsMany students would ask another person for help in academic cheating, from 88.8% to 26.9% depending on a cheating behaviour. Students would most often ask a family member or friend for help in academic cheating. The same “helpers” were identified for non-academic related behaviour – asking for personal material favours. More respondents, however, would include three or four persons for asking help in academic cheating than for routine material favours. Score on material favours survey was the strongest positive predictor of readiness for asking help in academic cheating (stepwise MLR model; beta = 0.308, P < 0.0001) followed by extrinsic motivation (compensation) and male gender, whereas intrinsic motivation, year of study and grade point average were weak negative predictors.ConclusionsOur study indicates that medical students are willing to engage more than one person in either close or distant relationships in academic cheating. In order to develop effective preventive measures to deter cheating at medical academic institutions, factors surrounding students’ preference towards academic cheating rather than routine favours should be further investigated.

A Comparison of Endoloop Ligatures and Nonabsorbable Polymeric Clips for the Closure of the Appendicular Stump During Laparoscopic Appendectomy in Children

BACKGROUND The aim of this prospective trial was to evaluate the clinical outcomes of nonabsorbable polymeric clips in laparoscopic appendix stump closure in children by comparing the endoloop ligature. PATIENTS AND METHODS From June 2011 to June 2016, 277 children who underwent laparoscopic appendectomy were included in the study. The patients were divided into two groups based on the technique used for appendiceal stump closure: there were 101 patients in the polymeric clips group and 176 in the endoloop group. The risk of intraoperative and postoperative complications was investigated for two different techniques to close the appendiceal stump. RESULTS Among the 277 patients who underwent laparoscopic appendectomy, no intraoperative complications and 17 (6.1%) postoperative complications were recorded. There were no significant differences between the groups with respect to the postoperative complications (P = .546). The median length of the operation was 10 minutes shorter when the polymeric clips were used (P < .001). The median hospital stay was also shorter in the polymeric clips group (P = .008). Costs of polymeric clip were significantly lower (€ 17.64) compared to endoloop (€ 34.16). CONCLUSIONS Closure of the appendix stump with polymeric nonabsorbable clips in laparoscopic appendectomy reduces operative time and may be a cost-effective and simpler alternative to widely used endoloops.