Aseptic preparation of parenteral medicinal products in healthcare establishments in Europe

Парентералните лекарствени продукти с разрешение за употреба не могат да се дават непосредствено на пациентите, т. е. те не са във форма, готова за употреба. Преди да се приложат на пациентите, тези лекарства трябва да се реконституират. Реконституираната форма не се счита нито за фабрично произведен, нито „стандартен` продукт приготвен в аптека. Има други процеси в здравните заведения, свързани с процеса на реконституиране (напр. парентералното хранене), за които националните изисквания на стандартите за осигуряване на качеството за безопасно приготвяне на стерилни продукти са също толкова важни и задължителни. В европейските здравни заведения асептично Преводна то приготвяне на парентерални лекарствени продукти се счита за процес с изключителна важност за безопасността на пациентите, поради това, че грешки при приготвянето на тези лекарства може да доведат до получаване на продукт, който да причини непосредствена вреда на пациента. Асептичното приготвяне на лекарствени продукти се извършва както в болничните аптеки, така и в клиничните зони в лечебните заведения. Комисията от експерти в областта на стандартите за качество и безопасност за фармацевтични практики и фармацевтични грижи (Съвета на Европа, наричана за краткост Експертна комисия), със съдействието на Европейската дирекция по качеството на лекарствата и здравеопазването извършва действия в областта на асептичното приготвяне на лекарства. Работи се съвместно с Европейската асоциация на болничните фармацевти на основание Резолюция CM/Res AP(2011)1 за изискванията за гарантиране на качество и безопасност за лекарствените продукти, приготвени в аптеки за специални нужди на пациентите, приета от Комитета на министрите на 19 януари 2011 г. Резолюцията съдържа някои препоръки и излага перспективата за по-нататъшна работа в областта на реконституирането на парентерални лекарства. Проучване, изпратено до различни европейски страни, показва, че или отсъства регламентиране на реконституирането в Европа, или ако съществува, то е много ограничено. Настоящата статия разглежда рисковете, свързани с лоши практики на реконституиране и извършените и настоящите дейности в областта на европейско ниво. Статията подчертава необходимостта от регламентиране по темата, каквото в момента липсва. Очаква се да се постигне консенсус по документ с указания за реконституиране на европейско ниво.In many cases, parenteral medicines with a marketing authorisation cannot be administered directly to patients, that is, they are not presented in ready-to-administer form. Before administration to patients, these medicines have to be reconstituted. Reconstitution has a special position; it can neither be seen as industrial manufacture nor as ‘regular` pharmacy preparation. There are other processes in healthcare establishments (eg, parenteral nutrition), related to the reconstitution process, where the requirements of national quality assurance standards for the safe preparation of sterile products are equally important and have to be fulfilled. In European healthcare establishments, aseptic preparation of parenteral medicinal products is considered to be a process of crucial importance for patient safety because errors in the preparation of these medicines may lead to a product that can cause immediate damage to patients. Aseptic preparation of medicinal products is carried out in hospital pharmacies as well as in clinical areas in healthcare establishments. The Committee of Experts on Quality and Safety Standards for Pharmaceutical Practices and Pharmaceutical Care (Council of Europe; hereafter: Committee of Experts), supported by the European Directorate for the Quality of Medicines & Healthcare, is undertaking work on the topic of aseptic preparation of medicines. The work is carried out in cooperation with the European Association of Hospital Pharmacists on the basis of a Resolution CM/Res AP(2011)1 on Quality and Safety Assurance requirements for Medicinal Products prepared in Pharmacies for the Special Needs of Patients, which was adopted by the Committee of Ministers on 19 January 2011. The Resolution includes some recommendations and an outlook to further work on reconstitution of parenteral medicines. A survey that was sent to the different European countries demonstrated that there is no or just limited regulation concerning reconstitution in Europe. This article describes the risks associated with poor reconstitution practices and the previous work as well as the ongoing activities concerning reconstitution at the European level. The article emphasises the need for regulation in this area, which is missing at present. It is expected that consensus can be reached on a guidance document for reconstitution at the European level

Results of the c-TRAK TN trial: a clinical trial utilising ctDNA mutation tracking to detect molecular residual disease and trigger intervention in patients with moderate and high-risk early stage triple negative breast cancer

Background: Post-treatment detection of circulating tumour DNA (ctDNA) in early-stage triple negative breast cancer (TNBC) patients predicts high risk of relapse. c-TRAK-TN assessed the utility of prospective ctDNA surveillance in TNBC and the activity of pembrolizumab in patients with ctDNA detected (ctDNA+). Patients and methods: c-TRAK-TN, a multi-centre phase II trial, with integrated prospective ctDNA surveillance by digital PCR, enrolled patients with early-stage TNBC and residual disease following neoadjuvant chemotherapy, or, stage II/III with adjuvant chemotherapy. ctDNA surveillance comprised three monthly blood sampling to 12 months (18 months if samples were missed due to COVID), and ctDNA+ patients were randomised 2:1; intervention:observation. ctDNA results were blinded unless patients were allocated to intervention, when staging scans were done and those free of recurrence were offered pembrolizumab. A protocol amendment (16/09/2020) closed the observation group; all subsequent ctDNA+ patients were allocated to intervention. Co-primary endpoints were i) ctDNA detection rate ii) sustained ctDNA clearance rate on pembrolizumab (NCT03145961). Results: 208 patients registered between 30/01/18 - 06/12/19, 185 had tumour sequenced, 171 (92·4%) had trackable mutations, and 161 entered ctDNA surveillance. Rate of ctDNA detection by 12 months was 27·3% (44/161,95%CI:20·6-34·9). Seven patients relapsed without prior ctDNA detection. 45 patients entered the therapeutic component (intervention n=31; observation n=14; 1 observation patient was re-allocated to intervention following protocol amendment). Of patients allocated intervention, 72% (23/32) had metastases on staging at time of ctDNA+, and 4 patients declined pembrolizumab. Of the five patients who commenced pembrolizumab, none achieved sustained ctDNA clearance. Conclusion: c-TRAK-TN is the first prospective study to assess whether ctDNA assays have clinical utility in guiding therapy in TNBC. Patients had a high rate of metastatic disease on ctDNA detection. Findings have implications for future trial design, emphasising the importance of commencing ctDNA testing early, with more sensitive and/or frequent ctDNA testing regimes

May measurement month 2018: an analysis of blood pressure screening results from United Arab Emirates.

Hypertension is one of the most important modifiable risk factors for cardiovascular disease and death even in high-income countries. According to the PURE Study, globally only half of hypertensives are aware and less than a fifth controlled. May Measurement Month (MMM) is a global campaign to raise awareness and screen for high blood pressure (BP) in lieu of formal screening. United Arab Emirates (UAE) has taken part in MMM since its inception and here data from MMM18 are reported. Trained volunteers from 54 sites screened 31 316 individuals from all the Emirates of UAE using convenience sampling. Blood pressure measurement, the definition of hypertension, and statistical analysis followed the standard MMM protocol. The mean age was 36.8 ± 11.4 years and 18 411(59%) were male. Participants of Arab descent were 11 829 (38%) and 11 569 (37%) were South Asian. Mean body mass index was 26.8 ± 5.29 kg/m2. Of those screened, 7 917 (25%) had never had a BP recorded, while 16 892 (54%) had recorded BP in the previous year. After imputation, 6 243 (20%) had hypertension. Of those participants, only 2 540 (41%) were aware and 2 331 (37%) were on antihypertensive medication, of which 61% were controlled. Of all hypertensives, only 23% were controlled. May Measurement Month in UAE expanded significantly compared to 2017. A quarter had never had BP measured and awareness of hypertension low (41%). This opportunistic screening method found a substantial number of adults with untreated or inadequately treated hypertension

May Measurement Month 2019: an analysis of blood pressure screening results from Brazil

The aim of this study is to describe the results of the May Month Measurement (MMM) campaign implemented in Brazil, in 2019. Questionnaire data were collected and three measures of blood pressure (BP) were performed. The sample consisted of 13 476 individuals, 58.2% were white, 60.8% were women. The average age was 46.3 (18.6) years. Of all 13 476 participants, 6858 (50.9%) had hypertension defined as a systolic BP ≥140 mmHg or a diastolic BP ≥90 mmHg or being on anti-hypertensive medication. Of those with hypertension, 68.8% were aware of their diagnosis, 65.3% were on antihypertensive medication, and 36.1% had controlled BP (<140/90 mmHg). In addition, of 4479 participants on anti-hypertensive medication, 55.2% had controlled BP. The use of anti-hypertensive medication was associated with higher systolic (P < 0.001) and diastolic BP (P < 0.001) and having diabetes with higher systolic BP (P < 0.001). Previous hypertension in pregnancy was associated with higher systolic (P = 0.038) and diastolic BP (P = 0.003), and smoking was associated with higher systolic BP (P < 0.001). Lastly, obese and overweight individuals showed significantly higher systolic (P < 0.001) and diastolic (P < 0.001) BP. The Brazilian MMM19 data demonstrate that strategies to increase awareness of hypertension and a better control of the risk factors are still needed

May measurement month 2018: an analysis of blood pressure screening in Libya.

Elevated blood pressure (BP) is an important public health concern and leads to several adverse cardiovascular outcomes. In the stepwise survey done in Libya by the Libyan Cardiac Society and National Centre for Disease Control in 2009, the percentage of hypertension was 40.6%. To raise awareness of high BP and to highlight the size of the problem and the need for screening. A cross-sectional opportunistic study included men and women aged ≥18 years. Blood pressure was measured three times and a questionnaire was completed. Hypertension was defined as BP ≥140/90 mmHg based on the mean of the 2nd and 3rd readings, or on antihypertensive treatment. Among 7279 participants, the mean age was 44.3 ± 14.8 years, 57.8% male, 2567 (35.3%) of the participants had hypertension of whom 63.4% were aware of having hypertension, 55.8% on medication, and of those on medication 50.9% had controlled BP. This survey identified a high proportion of individuals with high BP, which highlights the need for a more strategic approach to fighting hypertension

May measurement month 2018: an analysis of blood pressure screening results from Republic of the Congo.

To determine the proportion with hypertension among opportunistic screenees in the Republic of the Congo. This cross-sectional study was conducted in Republic of the Congo in May 2018. This screening was done in urban and rural areas that included Brazzaville, Pointe-Noire, District of Ngoyo, and District of Nkayi. The study protocol was provided by the International Society of Hypertension, and local ethical clearance was obtained. The data were processed by the May Measurement Month global project team. In total, 6169 people were screened, 2418 of which were female (39.2%). Most of the people screened were from 18 to 29 years old (n = 4184, 67.8%). The proportion of hypertension found was 22.2% (n = 1371). Among the hypertensive patients, 40.2% were aware of their hypertension, but only 493 (36.0%) were on antihypertensive treatment, and only 16.0% were controlled. The frequency of diabetes was 2.2% (n = 135), 2.3% (n = 139) had a previous stroke, and overweight and obesity were present in 15.4% (n = 952) and 7.3% (n = 449), respectively. Hypertension is frequent in the Republic of the Congo, and levels of awareness, treatment and control are low. Actions are needed to increase access of all to a correct diagnosis and treatment of hypertension to achieve universal health coverage