Patient Individualized Therapy – From Patient Education to Molecular Biomarkers

Für diese Arbeit wurden zwei verschiedenen Projekte zum Thema personalisierte Medizin durchgeführt. Bei dem ersten Projekt handelte es sich um eine klinische Studie, die die Langzeiteffekte einer komplexen Schulung für Patienten mit oraler Antikoagulation untersuchte. An der cluster-randomisierten Studie nahmen 367 Patienten in 22 allgemeinmedizinischen Praxen teil. Die komplexe Intervention bestand aus einem Video, einer Broschüre und einer individuellen Schulung mithilfe einer medizinischen Fachangestellten. Die Kontrollgruppe erhielt lediglich die Broschüre. Primäre Endpunkte waren der Wissenszuwachs nach sechs Monaten, gemessen mithilfe eines selbstentwickelten Fragebogens, und die Stabilisierung der INR. Nach sechs Monaten wussten die Patienten in der Interventionsgruppe signifikant mehr als vor der Schulung, während Patienten in der Kontrollgruppe keinen signifikanten Wissensunterschied zeigten. Das komplexe Schulungsprogramm verbessert das Wissen, das für eine sichere und effektive Therapie der Patienten mit oralen Antikoagulantien notwendig ist, deutlich. Im zweiten Projekt wurde der Einfluss von genetischen Polymorphismen auf die Aufnahme von Antidepressiva in der Leber analysiert. Fast 10% der kaukasischen Bevölkerung besitzen aufgrund von genetischen Polymorphismen kein aktives OCT1. Es wurde analysiert, ob es sich bei Venlafaxine und O?Desmethylvenlafaxin um Substrate von OCT1 handelt und ob bekannte und häufig auftretende OCT1-Varianten einen Einfluss auf die Aufnahme haben. HEK293-Zellen, die entweder OCT1 oder eine bekannte genetischen OCT1-Funktionsverlustvarianten Arg61Cys überexprimieren, wurden verwendet. Die Aufnahme von Venlafaxin veränderte sich in den OCT1-überexprimierenden Zellen nicht im Vergleich zu den Kontrollzellen. Bei O?Desmethylvenlafaxin führten die OCT1-überexprimierenden Zellen zu einem 1,96-fachen Anstieg in der Aufnahme. Die Funktionsverlustvarianten führten zu keiner Aufnahme von O?Desmethylvenlafaxin.The aim of this work was to analyze two different projects concerning personalized medicine. The first project was a clinical study designed to assess and evaluate the long-term effects of a complex nurse-based patient education program for patients receiving oral anticoagulants. The study population consisted of 367 patients in 22 general practices recruited to a cluster randomized trial. The education consisted of a video, a brochure and individual training by a nurse while the control group received a brochure only. Primary endpoints were changes in knowledge after six months measured by a self-developed questionnaire and stabilization of the INR. After six months the patients randomized to the intervention group knew significantly more than before the education program, while patients randomized to the control group had no significant changes in level of knowledge. In the second project the effects of genetic polymorphisms on antidepressant transport in the liver were analyzed. Close to 10% of Caucasians are lacking active OCT1 due to loss-of-function polymorphisms. Venlafaxine and O?desmethylvenlafaxine were analyzed to determine whether they are substrates of OCT1, and whether common loss-of-function OCT1 polymorphisms may affect the uptake of venlafaxine and O?desmethylvenlafaxine. HEK293 cells overexpressing OCT1 and common OCT1 variants carrying the loss-of-function polymorphisms were used. Venlafaxine uptake in HEK293 cells did not change after OCT1 overexpression. In contrast, O?desmethylvenlafaxine uptake increased 1.96-fold in OCT1-overexpressing HEK 293 cells. The increase of O?desmethylvenlafaxine uptake was reversed by the the common loss-of-function polymorphisms

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Barriers to Timely Seeking of Breast Cancer Care Among Palestinian Women: A Cross-Sectional Study

PURPOSEExamining the association of breast cancer (BC) symptom awareness with time to help seeking and exploring barriers to timely presentation may enhance the effectiveness of BC awareness campaigns and early detection efforts. This study aimed to assess the anticipated time for seeking medical advice when experiencing a potential BC symptom among women in Palestine and to identify their barriers to early presentation.MATERIALS AND METHODSA convenience sampling method was used to recruit adult women from hospitals, primary health care facilities, and public areas across 11 governorates in Palestine. A translated-into-Arabic version of the validated BC Awareness Measure was used. The questionnaire consisted of three sections: sociodemographic information, recognition of 13 BC symptoms and reporting time for seeking medical advice, and barriers to early presentation.RESULTSA total of 5,257 questionnaires were included. The proportion of participants who would seek medical advice immediately varied on the basis of the nature of BC symptoms. For symptoms related to the breast, the proportion ranged from 25.7% for redness of the breast skin to 53.5% for a lump or thickening in the breast. For symptoms related to the nipple, the proportion ranged from 30.7% for nipple rash to 48.0% for discharge or bleeding from the nipple. Exhibiting good BC symptom awareness was associated with a higher likelihood of seeking medical advice within a week for all BC symptoms. Emotional barriers were the most frequently reported barriers. There was no association between increasing levels of BC awareness and reporting fewer or more barriers.CONCLUSIONThe nature of BC symptoms had an impact on help-seeking behaviors. Participants with good BC symptom awareness were more likely to seek medical advice earlier

Myths and common misbeliefs about cervical cancer causation among Palestinian women: a national cross-sectional study

Acknowledgements: The authors would like to thank all participants who took part into the study.Abstract Background Cervical cancer (CC) myths and beliefs can negatively impact women's preventive behaviors, including vaccination against human papillomavirus and having regular screening tests. This study aimed to examine awareness of Palestinian women about myths related to CC causation and investigated factors associated with good awareness. Methods A national cross-sectional study was conducted to recruit adult Palestinian women from hospitals, primary healthcare facilities, and public areas in 11 Palestinian governorates. A translated-into-Arabic version of the Cancer Awareness Measure-Mythical Causes Scale was used to collect data. Awareness level was determined based on the number of CC myths around CC causation recognized to be incorrect: poor (0–4), fair (5–9), and good (10–13). Results A total of 7058 questionnaires were included. Myths unrelated to food were more commonly recognized as incorrect compared to those related to food. The most recognized food-unrelated myth was ‘having a physical trauma’ (n = 3714, 52.6%), whereas the least recognized was ‘using mobile phones’ (n = 2238, 31.7%). The most recognized food-related myth was ‘drinking from plastic bottles’ (n = 2708, 38.4%), whereas the least recognized was ‘eating food containing additives’ (n = 1118, 15.8%). Only 575 participants (8.1%) displayed good awareness and promptly recognized at least 10 out of 13 myths around CC causation as incorrect. Factors associated with lower likelihood of displaying good awareness of myths around CC causation included living in the West Bank and Jerusalem, being married, widowed or divorced, knowing someone with cancer, and visiting hospitals or primary healthcare centers. Conclusions A very small proportion of Palestinian women recognized 10 or more myths around CC causes as incorrect. Initiatives addressing CC myths are needed in the Palestinian community. </jats:sec

The poorly membrane permeable antipsychotic drugs amisulpride and sulpiride are substrates of the organic cation transporters from the SLC22 family.

Variations in influx transport at the blood-brain barrier might affect the concentration of psychotropic drugs at their site of action and as a consequence might alter therapy response. Furthermore, influx transporters in organs such as the gut, liver and kidney may influence absorption, distribution, and elimination. Here, we analyzed 30 commonly used psychotropic drugs using a parallel artificial membrane permeability assay. Amisulpride and sulpiride showed the lowest membrane permeability (P e -6 cm/s) and will require influx transport to penetrate the blood-brain barrier and other physiological barriers. We then studied the uptake of amisulpride and sulpiride by the organic cation transporters of the SLC22 family OCT1, OCT2, OCT3, OCTN1, and OCTN2 Amisulpride was found to be transported by all five transporters studied. In contrast, sulpiride was only transported by OCT1 and OCT2. OCT1 showed the highest transport ability both for amisulpride (CLint = 1.9 ml/min/mg protein) and sulpiride (CLint = 4.2 ml/min/mg protein) and polymorphisms in OCT1 significantly reduced the uptake of both drugs. Furthermore, we observed carrier-mediated uptake that was inhibitable by known OCT inhibitors in the immortalized human brain microvascular endothelial cell line hCMEC/D3. In conclusion, this study demonstrates that amisulpride and sulpiride are substrates of organic cation transporters of the SLC22 family. SLC22 transporters may play an important role in the distribution of amisulpride and sulpiride, including their ability to penetrate the blood-brain barrier