Direct-to-consumer genetic testing in Slovenia: availability,ethical dilemmas and legislation

Introduction

Over the last few years, many private companies are advertising direct-to-consumer genetic testing (DTC GT), mostly with no or only minor clinical utility and validity of tests and without genetic counselling. International professional community does not approve provision of DTC GT and situation in some EU countries has been analysed already. The aim of our study was to analyse current situation in the field of DTC GT in Slovenia and related legal and ethical issues.

Materials and methods

Information was retrieved through internet search, performed independently by two authors, structured according to individual private company and the types of offered genetic testing.

Results

Five private companies and three Health Insurance Companies offer DTC GT and it is provided without genetic counselling. Available tests include testing for breast cancer, tests with other health-related information (complex diseases, drug responses) and other tests (nutrigenetic, ancestry, paternity). National legislation is currently being developed and Council of Experts in Medical Genetics has issued an opinion about Genetic Testing and Commercialization of Genetic Tests in Slovenia.

Conclusions

Despite the fact that Slovenia has signed the Additional protocol to the convention on human rights and biomedicine, concerning genetic testing for health purposes, DTC GT in Slovenia is present and against all international recommendations. There is lack of or no medical supervision, clinical validity and utility of tests and inappropriate genetic testing of minors is available. There is urgent need for regulation of ethical, legal, and social aspects. National legislation on DTC GT is being prepared.Key words: Direct-to-consumer genetic testing, DTC, ethics in genetics, legislation     

Croatian survey on critical results reporting

Introduction

Poor harmonization of critical results management is present in various laboratories and countries, including Croatia. We aimed to investigate procedures used in critical results reporting in Croatian medical biochemistry laboratories (MBLs).

Materials and methods

An anonymous questionnaire, consisting of 24 questions/statements, related to critical results reporting procedures, was send to managers of MBLs in Croatia. Participants were asked to declare the frequency of performing procedures and degree of agreement with statements about critical values reporting using a Likert scale. Total score and mean scores for corresponding separate statements divided according to health care setting were calculated and compared.

Results

Responses from 111 Croatian laboratories (48%) were analyzed. General practice laboratories (GPLs) more often re-analyzed the sample before reporting the critical result in comparison with the hospital laboratories (HLs) (score: 4.86 (4.75-4.96) vs. 4.49 (4.25-4.72); P = 0.001) and more often reported the critical value exclusively to the responsible physician compared to HLs (4.46 (4.29-4.64) vs. 3.76 (3.48-4.03), P < 0.001). High total score (4.69 (4.56-4.82)) was observed for selection of the critical results list issued by the Croatian Chamber of Medical Biochemistry (CCMB) indicating a high harmonization level for this aspect of critical result management. Low total scores were observed for the statements regarding data recording and documentation of critical result notification.

Conclusions

Differences in practices about critical results reporting between HLs and GPLs were found. The homogeneity of least favorable responses detected for data recording and documentation of critical results notification reflects the lack of specific national recommendations.Key words: critical results, laboratory testing, quality indicators, survey, post-analytical phase     

Hemolysis from a nurses’ standpoint – survey from four Croatian hospitals

Introduction

Hemolysis can occur during sample collection, handling and transport. It is more frequent when the non-laboratory staff performs sampling. The aim of this study was to assess nurses’ knowledge on the causes of hemolysis and consequential impact on the laboratory tests results. Additionally, the differences in knowledge, related to work experience, professional degree and previous education about hemolysis were explored.

Materials and methods

An anonymus survey, containing 11 questions on demographics, causes of hemolysis, its impact on biochemical parameters and nurses’ attitude towards additional education in preanalytics, was conducted in four Croatian hospitals. The answers were compared by Chi-squared and Fischer exact test.

Results

In total, 562 survey results were collected. Majority of nurses declared familiarity with the term “hemolysis” (99.6%). There were 77% of correct answers regarding questions about the causes of hemolysis, but only 50% when it comes to questions about interference in biochemical tests. The percentage of correct answers about causes was significantly lower (P = 0.029) among more experienced nurses, and higher (P = 0.027) in those with higher professional degree, while influence of previous education was not significant. Also, higher percentage of correct answers about interferences was encountered in nurses with longer work experience (P = 0.039). More than 70% of nurses declared that additional education about preanalytical factors would be beneficial.

Conclusion

Croatian nurses are familiar with the definition of hemolysis, but a lack of knowledge about causes and influence on laboratory test results is evident. Nurses are eager to improve their knowledge in this field of preanalytical phase.Key words: hemolysis, nurses, survey, preanalytical phase     

How compliant are technicians with universal safety measures in medical laboratories in Croatia? – A pilot study

Introduction

This pilot study aimed to investigate the use of personal protective equipment (PPE) and compliance to the code of conduct (rules defined in institutional, governmental and professional guidelines) among laboratory technicians in Croatian medical laboratories. In addition, we explored the differences in compliance between participants of different age groups, laboratory ownership and accreditation status.

Materials and methods

An anonymous and voluntary survey with 15 questions was conducted among Croatian medical laboratory technicians (N = 217). The questions were divided into two groups: demographic characteristics and the use of PPE. The questions of the second part were graded according to the Likert scale (1-4) and an overall score, shown as median and range (min-max), was calculated for each participant. Differences between the overall scores were tested for each group of participants.

Results

The majority of participants always wear protective clothes at work, 38.7% of them always wear gloves in daily routine, more than 30.0% consume food and almost half of them drink beverages at workplace. A significantly lower overall score was found for participants working in public compared to private laboratories (36 (16-40) vs. 40 (31-40), P < 0.001). There were no statistically significant differences in overall scores for participants of different age groups (P = 0.456) and laboratory accreditation status (P = 0.081).

Conclusion

A considerable percentage of laboratory technicians in Croatian medical laboratories do not comply with safety measures. Lack of compliance is observed in all personnel regardless laboratory accreditation and participants’ age. However, those working in private laboratories adhere more to the code of conduct.Key words: survey, compliance, laboratory technician, universal safety measures, total quality management, clinical laboratory services     

Low level of adherence to instructions for 24-hour urine collection among hospital outpatients

Introduction:

We hypothesized that patients are poorly informed about proper procedure for 24-hour urine specimen collection and its relevance in determination of biochemical analytes, despite availability of leaflets and webpage with instruction for collection. The aim of this survey was to question outpatients how well are they informed about procedure of 24-hour urine specimen collection.

Materials and methods:

The survey with 10 questions was done in outpatient laboratory of University Department of Chemistry, Medical School University Hospital Sestre Milosrdnice, Zagreb, Croatia. The study included 59 patients with collected 24-hour urine sample who have consented to participate in the survey.

Results:

Out of 59 participants, most of them (0.97) were older than 40 years. Internet was not recognized as a source of information (1/59). Almost one third of the patients have changed their drinking habits to collect more urine volume. Although most of the patients (0.60) were aware that the bottle of water is the best choice for the container, almost half of them were collected urine samples in the plastic soft drink bottle. Laboratory staff and physicians often have given information about proper collection procedure, but that information was insufficient.

Conclusions:

Patients are usually not aware of importance of proper preanalytical procedure for collecting urine specimen and how improper collection could affect results of requested tests. Education of outpatients, general practitioners and laboratory staff is needed in order to improve sample quality and trueness of results.     

Do Croatian open access journals support ethical research? Content analysis of instructions to authors

Introduction

The aim of our study was to investigate the extent to which Instructions to authors of the Croatian open access (OA) journals are addressing ethical issues. Do biomedical journals differ from the journals from other disciplines in that respect? Our hypothesis was that biomedical journals maintain much higher publication ethics standards.

Materials and methods

This study looked at 197 Croatian OA journals Instructions to authors to address the following groups of ethical issues: general terms; guidelines and recommendations; research approval and registration; funding and conflict of interest; peer review; redundant publications, misconduct and retraction; copyright; timeliness; authorship; and data accessibility. We further compared a subset of 159 non-biomedical journals with a subset of 38 biomedical journals. Content analysis was used to discern the ethical issues representation in the instructions to authors.

Results

The groups of biomedical and non-biomedical journals were similar in terms of originality (χ² = 2.183, P = 0.140), peer review process (χ² = 0.296, P = 0.586), patent/grant statement (χ² = 2.184, P = 0.141), and timeliness of publication (χ² = 0.369, P = 0.544). We identified significant differences among categories including ethical issues typical for the field of biomedicine, like patients (χ² = 47.111, P < 0.001), and use of experimental animals (χ² = 42.543, P < 0.001). Biomedical journals also rely on international editorial guidelines formulated by relevant professional organizations heavily, compared with non-biomedical journals (χ² = 42.666, P < 0.001).

Conclusion

Low representation or absence of some key ethical issues in author guidelines calls for more attention to the structure and the content of Instructions to authors in Croatian OA journals.Key words: instructions to authors, publication ethics, publication standards, open access, OA, research integrity     

Are patients well informed about the fasting requirements for laboratory blood testing?

Introduction:

Proper preparation of the individual is a key prerequisite for ensuring the quality of laboratory testing. Our hypothesis was that many outpatients are not sufficiently familiar with the correct way of preparing for the laboratory tests, for which the individual needs to be at fasting. This study aimed to investigate: i) whether patients are aware of how they need to prepare properly for laboratory tests; ii) the way in which users are informed about how to prepare for laboratory testing; and iii) whether users arrive to the laboratory for phlebotomy properly prepared.

Materials and methods:

An anonymous questionnaire was conducted on 150 outpatients older than 18 years, during February 2013. The response rate was 11%. All patients were interviewed by the laboratory staff. Patients were informed about detail of the questionnaire and agreed to participate in the survey.

Results:

Out of the total number subjects, 39% were fully aware of the proper definition of the fasting, whereas even 46% subjects replied that the last meal has to be taken the day before and the exact time that must pass after the last meal to blood sampling is not important. Furthermore, 52% subjects did not receive any information about how they need to prepare themselves properly for blood testing. Only 60% of them came properly prepared for the laboratory blood testing.

Conclusions:

Substantial proportion of patients do not come properly prepared for laboratory testing. We conclude that patients are not well informed about the fasting requirements for laboratory blood testing. Moreover, requesting physician is the preferred source of information from which patients learn how to prepare themselves for phlebotomy.     

Confidence level in venipuncture and knowledge on causes of in vitro hemolysis among healthcare professionals

Introduction

This study aimed to assess confidence level of healthcare professionals in venipuncture and their knowledge on the possible causes of in vitro hemolysis.

Materials and methods

A sample of 94 healthcare professionals (nurses and laboratory technicians) participated in this survey study. A four-section questionnaire was used as a research instrument comprising general information for research participants, knowledge on possible causes of in vitro hemolysis due to type of material used and venipuncture technique and specimen handling, as well as assessment of healthcare professionals’ confidence level in their own ability to perform first and last venipuncture.

Results

The average score on the knowledge test was higher in nurses’ than in laboratory technicians (8.11 ± 1.7, and 7.4 ± 1.5, respectively). The difference in average scores was statistically significant (P = 0.035) and Cohen’s d in the range of 0.4 indicates that there is a moderate difference on the knowledge test among the health care workers. Only 11/94 of healthcare professionals recognized that blood sample collection from cannula and evacuated tube is method which contributes most to the occurrence of in vitro hemolysis, whereas most risk factors affecting occurrence of in vitro hemolysis during venipuncture were recognized. There were no significant differences in mean score on the knowledge test in relation to the confidence level in venipuncture (P = 0.551).

Conclusion

Confidence level at last venipuncture among both profiles of healthcare staff was very high, but they showed insufficient knowledge about possible factors affecting hemolysis due to materials used in venipuncture compared with factors due to venipuncture technique and handling of blood sample.Key words: hemolysis, patient safety, phlebotomy, medical staff, questionnaire, preanalytical phase     

Accidental digitoxin intoxication: an interplay between laboratory and clinical medicine

Introduction:

Two Italian adults arrived at the Emergency Department referring diarrhea, nausea and vomiting for 4 days; weakness, fatigue and visual hallucinations were also complained of. Patients reported the ingestion of some leaves of a plant, which they supposed to be “donkey ears”, a week before. Physical examination showed hypotension and bradycardia and ECG examination disclosed sinus rhythm and repolarization abnormalities (scooping of the ST-T complex) in both patients and a 2:1 AV block in the man.

Materials and methods:

Digoxin concentration was evaluated twice for each patient (at the admission and after 4 hours) by the automated immunoassay system ADVIA Centaur^®. Digitoxin concentration was evaluated by liquid chromatography-mass spectrometry (LC-MS/MS).

Results:

Despite clinical picture was suggestive of digitalis intoxication, digoxin levels were undetectable. Due to the more severe clinical picture, the male patient was treated with anti-digoxin antibodies (Digifab^®) achieving a good clinical improvement and remission of the AV block within two hours. Initial diagnosis was confirmed by LC-MS/MS showing high digitoxin concentrations, but digoxin was undetectable. Patients remained stable and 48 hours later were discharged from the hospital.

Conclusion:

Whereas digoxin determination frequently relies on monoclonal antibodies which do not cross-react to digitoxin, polyclonal antibodies constituting Digifab^® recognize a large spectrum of cardiac glycosides, including digitoxin. This report emphasizes the primary role of the clinical approach to patients in the emergency setting and how an active communication and a continuous sharing of professional experiences between Laboratory and Clinicians ensure an early and correct diagnosis.     

Correlation between mean platelet volume and B-type natriuretic peptide concentration in emergency patients with heart failure

Background

In heart failure patients, mean platelet volume (MPV) may reflect increased platelet activation or increased numbers of large, hyper-aggregable platelets. B-type natriuretic peptide (BNP) concentration in blood is a sensitive and specific marker of heart failure, correlating with the severity and prognosis of illness, in patients presenting with acute dyspnea to the emergency department. This study evaluated the correlation between BNP concentration and MPV.

Material and methods

Data were collected from 319 patients admitted to the emergency department of a cardiology hospital from January–July 2014. EDTA blood samples drawn at admission were analyzed using automated hematology system, and BNP concentration was measured using a fluorescence immunoassay.

Results

The study included 190 patients with and 129 without acute heart failure (AHF). These groups had BNP concentration of 200-5000 ng/L and 5-98 ng/L, respectively. MPV levels were significantly higher in the AHF group (P < 0.001). BNP concentrations were positively correlated with MPV (r = 0.41, P < 0.001) and neutrophil / lymphocyte ratio (r = 0.38, P < 0.001).

Conclusion

Increased MPV values correlate with BNP concentration, an indicator of HF severity and clinical status, in patients with AHF admitted to the emergency department.Key words: natriuretic peptide, brain; heart failure; platelet; mean platelet volume     

Effect of sample type,centrifugation and storage conditions on vitamin D concentration

Introduction:

Studies about vitamin D [25(OH)D] stability in plasma are limited and preanalytical variables such as tube type may affect results. We aimed to evaluate effect of storage conditions, sample type and some preanalytical variables on vitamin D concentration.

Materials and methods:

Blood samples from 15 healthy subjects were centrifuged at different temperatures and stored under different conditions. Serum and plasma 25(OH)D difference, effect of centrifugation temperature and common storage conditions were investigated.

Results:

There was no difference between serum and plasma vitamin D concentration. Centrifugation temperature had no impact on vitamin D concentration. 25(OH)D is stable under common storage conditions: 4 hours at room temperature, 24 hours at 2–8 °C, 7 days at −20 °C, 3 months at −80 °C.

Conclusion:

Vitamin D does not require any special storage conditions and refrigeration. Both serum and plasma can be used for measurement.     

Larger differences in utilization of rarely requested tests in primary care in Spain

Introduction

The study was performed to compare and analyze the inter-departmental variability in the request of rarely requested laboratory tests in primary care, as opposed to other more common and highly requested tests.

Materials and methods

Data from production statistics for the year 2012 from 76 Spanish laboratories was used. The number of antinuclear antibodies, antistreptolysin O, creatinine, cyclic citrullinated peptide antibodies, deaminated peptide gliadine IgA antibodies, glucose, protein electrophoresis, rheumatoid factor, transglutaminase IgA antibodies, urinalysis and uric acid tests requested was collected. The number of test requests per 1000 inhabitants was calculated. In order to explore the variability the coefficient of quartile dispersion was calculated.

Results

The smallest variation was seen for creatinine, glucose, uric acid and urinalysis; the most requested tests. The tests that were least requested showed the greatest variability.

Conclusion

Our study shows through a very simplified approach, in a population close to twenty million inhabitants, how in primary care, the variability in the request of laboratory tests is inversely proportional to the request rate.Key words: primary care, laboratory proficiency testing, clinical laboratory services, test requesting, preanalytical phase     

Validation of a laboratory and hospital information system in a medical laboratory accredited according to ISO 15189

Introduction

The aim of the study was to present a protocol for laboratory information system (LIS) and hospital information system (HIS) validation at the Institute of Clinical Chemistry and Laboratory Medicine of the Merkur University Hospital, Zagreb, Croatia.

Materials and methods:

Validity of data traceability was checked by entering all test requests for virtual patient into HIS/LIS and printing corresponding barcoded labels that provided laboratory analyzers with the information on requested tests. The original printouts of the test results from laboratory analyzer(s) were compared with the data obtained from LIS and entered into the provided template. Transfer of data from LIS to HIS was examined by requesting all tests in HIS and creating real data in a finding generated in LIS. Data obtained from LIS and HIS were entered into a corresponding template. The main outcome measure was the accuracy of transfer obtained from laboratory analyzers and results transferred from LIS and HIS expressed as percentage (%).

Results:

The accuracy of data transfer from laboratory analyzers to LIS was 99.5% and of that from LIS to HIS 100%.

Conclusion:

We presented our established validation protocol for laboratory information system and demonstrated that a system meets its intended purpose.     

Nonalcoholic fatty liver disease associated with impairment of kidney function in nondiabetes population

Background

Nonalcoholic fatty liver disease (NAFLD) is associated with the increased burden of kidney. However, there is still no large population study to explore the potential relationship between NAFLD and mild kidney function damage (MKFD) after adjusted for confounding factors. This study is to test the hypothesis that NAFLD is associated with MKFD under controlling the effects of confounding factors.

Materials and methods:

Levels of serum fasting glucose, creatinine, cholesterol, triglyceride, alanine aminotransferase and aspartate aminotransferase were analyzed from 1412 Chinese Han adults. Questionnaire and physical examination were performed to explore the potential association of NAFLD with kidney function.

Results:

NAFLD was associated with impairment of kidney function. Multivariate-adjusted odds ratio illustrated that, compared to subjects with normal liver, NAFLD subjects had a significantly higher risk of MKFD with or without adjusted for blood glucose and other covariates (P = 0.041). Further results from multi-interaction analysis demonstrated that the underlying mechanisms linked NAFLD with impaired kidney function may be that they share common risk factors and similar pathological processes.

Conclusions:

The most striking finding of this study is that NAFLD is negatively associated with kidney function, in nondiabetic population. NAFLD and MKFD may share similar risk factors and/or pathological processes.     

Cardiac indexes, cardiac damage biomarkers and energy expenditure in professional cyclists during the Giro d'Italia 3-weeks stage race

Introduction

The study of cardiac response to strenuous and continuous exercise is crucial to understanding the physiology of endurance. N-terminal proB-type natriuretic peptide (NT-proBNP) is a potential marker for monitoring myocardial wall stress, and troponins (TnT and TnI) are widely used in the diagnosis of cardiac ischemia and infarction. Strenuous exercise may generate transitory ischemia, myocardial stress, and diastolic left ventricular dysfunction, inducing the increased production of both these biomarkers. We measured changes in NT-proBNP and TnT in elite cyclists during a 3-week stage race, a model of strenuous exercise.

Materials and methods:

The study population was 9 professional cyclists participating in the 2011 Giro d’Italia. Pre-analytical and analytical phases scrupulously followed official recommendations. Anthropometric data, net energy expenditure and cardiac indexes (rate, diastolic and systolic blood pressure) were recorded. Blood samples were drawn pre-race (day −1) and at days 12 and 22; NT-proBNP and highly sensitive-troponin (Hs-TnT) concentrations were assayed and corrected for plasma volume changes.

Results:

Body-mass index decreased and energy expenditure increased by 52% during the race. NT-proBNP concentrations increased [day −1: 23.52 ng/L (9.67–34.33); day 12: 63.46 ng/L (22.15–93.31); P = 0.039; day 22: 89.26 ng/L (34.66–129.78) vs. day −1; P < 0.001] and correlated with heart rate (r = −0.51; P = 0.006), systolic pressure (r = 0.39; P = 0.046) and energy expenditure (r = 0.70; P < 0.001). TnT concentrations did not vary, but a widened TnT amplitude distribution was observed.

Conclusions:

Increases in NT-proBNP correlated with higher energy expenditure over a 3-week cycling stage race, possibly indicating myocardial stress.     

Avoidance to wipe alcohol before venipuncture is not a source of spurious hemolysis

Background

It is still uncertain whether or not avoidance to let disinfectant alcohol dry at the site of venipuncture is a source of spurious hemolysis when drawing venous blood.

Methods:

In a consecutive series of 52 outpatients referred for routine laboratory testing, venous blood was drawn by direct venipuncture with (odd group) or without (pair group) wiping 70% isopropyl alcohol at the site of venipuncture. A 3.5 mL evacuated tube with clot activator and gel separator was drawn from a vein of the upper limb, serum was immediately separated with standard centrifugation and tested for potassium, lactate dehydrogenase (LD), aspartate aminotransferase (AST) and hemolysis index (HI) on Roche Cobas.

Results:

No specimen was discarded for unsatisfactory venipuncture. No differences for age and gender were observed between groups. As regards the four parameters investigated, no significant differences could be observed between patients in whom blood was drawn with or without letting the alcohol dry. It is also noteworthy that no sample in both groups exceeded the conventional sample rejection threshold of cell-free hemoglobin.

Conclusions:

The results of our prospective, randomized study attest that failure to wipe alcohol at the site of venipuncture should not be considered as a potential source of spurious hemolysis when drawing blood.     

Education and communication is the key for the successful management of vitamin D test requesting

Introduction

Pre-preanalytical and post-postanalytical phases are steps where the laboratory professional may play a crucial role. Measuring the serum circulating 25 hydroxyvitamin D level (25(OH)D) is recommended to evaluate vitamin D status in patients at risk for vitamin D deficiency while 1,25 hydroxyvitamin D (1,25(OH)₂D) is only recommended to monitor several particular conditions (chronic kidney disease, hereditary phosphate-losing disorders, and some other) clearly defined by the current clinical guidelines of Endocrine Society.
Our research hypothesis was that through education and communication through comments in the Laboratory Information System (LIS), we could improve appropriateness in the request vitamin D tests.

Materials and methods

A retrospective observational cross-sectional study was conducted from January 2005 to December 2014. Each 1,25(OH)₂D request was reviewed individually by a member of the laboratory staff. Starting in November 2011, each inappropriate 1,25(OH)₂D request was registered in LIS and 25(OH)D was measured instead of 1,25(OH)₂D. We counted the overall number of 1,25(OH)₂D requests and the number of inappropriate requests which then were marked with a comment.

Results

The request of 25(OH)D increased along years. However, 1,25(OH)₂D requests increased until 2012 when demand began to diminish.

Conclusions

Education and communication through comments in the LIS, corrected the inappropriate request of 1,25(OH)₂D and promoted the use of 25(OH)D to study vitamin D deficiency.Key words: clinical laboratory services, utilization, vitamin D, communication, education     

Comparison of blood ethanol stabilities in different storage periods

Introduction

Measurements of blood ethanol concentrations must be accurate and reliable. The most important factors affecting blood ethanol stability are temperature and storage time. In this study, we aimed to compare ethanol stability in plasma samples at -20 °C for the different storage periods.

Materials and methods

Blood samples were collected from intoxicated drivers (N = 80) and initial plasma ethanol concentrations were measured immediately. Plasma samples were then stored at -20 °C and re-assessed after 2, 3, 4, or 5 months of storage. Differences between the initial and stored ethanol concentrations in each group (N = 20) were analyzed using Wilcoxon matched-pairs test. The deviation from the initial concentration was calculated and compared with Clinical Laboratory Improvement Amendments (CLIA’88) Proficiency Testing Limits. Relationships between the initial concentrations and deviations from initial concentrations were analyzed by Spearman’s correlation analysis. For all statistical tests, differences with P values of less than 0.05 were considered statistically significant.

Results

Statistically significant differences were observed between the initial and poststorage ethanol concentrations in the overall sample group (P < 0.001). However, for the individual storage duration groups, analytically significant decreases were observed only for samples stored for 5 months, deviations from the initial concentrations exceeded the allowable total error (TEa). Ethanol decreases in the other groups did not exceed the TEa.

Conclusion

According to our results, plasma ethanol samples can be kept at -20 °C for up to 3-4 months until re-analysis. However, each laboratory should also establish its own work-flow rules and criterion for reliable ethanol measurement in forensic cases.Key words: preanalytical phase, ethanol, stability, storage temperature