Assessing decisional conflict and challenges in decision-making among perinatal women using or considering using antidepressants during pregnancy-a mixed-methods study.

This study aims to investigate decisional conflict and elucidate challenges in decision-making among perinatal women using or considering using antidepressant (AD) during pregnancy. A sequential, mixed-methods study was employed among pregnant and postnatal women in Norway who had been offered ADs in the last 5 years. Quantitative data were obtained through an electronic questionnaire. Decisional conflict in pregnancy was assessed using the Decisional Conflict Scale (DCS) defined as either low (< 25) or moderate-high ( ≥ 25) (evaluated retrospectively for postnatal women). Logistic regression was used to identify factors associated with moderate-high decisional conflict. Qualitative data were collected through focus groups with pregnant and postnatal women, and an inductive approach was used for data analysis. Among 174 pregnant and 102 postnatal women, 67.8% and 69.6%, respectively, reported moderate-high decisional conflict during pregnancy. Unsatisfactory doctor-patient relationship was associated with greater likelihood of having moderate-high decisional conflict in pregnancy, both in pregnant (aOR = 1.20, 95% CI: 1.00-1.44) and postnatal women (aOR = 1.40, 95% CI: 1.08-1.82). Reported barriers to decision-making regarding AD use in pregnancy encompassed five DCS subscales: uninformed knowledge following contradictory research and unfamiliarity with authorised resources, unclear values due to emotional blunting and fear associated with AD use, inadequate support, uncertainty in decisions and ineffective decisions due to difficulty in finding personalised treatment, and diverging recommendations by the healthcare providers (HCPs). The quality of the interaction with the HCP plays a crucial role in managing decisional conflict and supporting informed decisions in the management of perinatal mental illness. This study highlights the need for increased provision of clear, evidence-based information by HCPs to facilitate shared decision-making and create personalised treatments for perinatal women considering AD use during pregnancy.

Institutional barriers and enablers to implementing and complying with internationally accepted quality standards in the local pharmaceutical industry of Pakistan: a qualitative study.

Complying with good manufacturing practices (GMP) and ensuring a quality system is integral to production and supply of quality medicines and achieving universal health coverage. This study focus on the local production of medicines in Pakistan, a lower middle-income country that has observed considerable growth in the number of pharmaceutical companies over the past two decades. Against this background, we investigated: (1) How is quality assurance (QA) and GMP compliance understood and acted upon by local pharmaceutical manufacturers?; (2) What are the institutional barriers and enablers for QA and GMP compliance in the local pharmaceutical sector from the perspective of key stakeholders?; and (3) What are the institutional barriers and enablers for strengthening local regulatory capacity to improve QA in the industry in the long term? We used a qualitative study design involving 22 interviews of the drug regulatory bodies (n = 9), academia (n = 3) and local manufacturers (n = 10), identifying key themes in data by thematic analysis. Document analysis was used to collect additional information and supplement the interview data. We identified that manufacturing facilities operated under different GMP standards and interpretations, pointing towards an absence of harmonization in quality standards across the industry. Views diverged about the status of GMP compliance, with interviewees from academia presenting a more critical view compared with regulators who promoted a more positive story. Among the barriers explaining why companies struggled with quality standards, the lack of a mindset promoting quality and safety among profit-oriented manufacturers was prominent. At the federal level, DRAP's establishment represented an institutional improvement aiming to promote QA through inspections and guidance. While some positive measures to promote quality have been observed, the need for DRAP to strengthen its technical and regulatory capacity, enhance its engagement in international collaboration and learning, and improve transparency and accountability were highlighted. Overall, since the challenges in Pakistan are shared with other low- and middle-income countries with local production, there is a need to commit to international collaborative mechanisms, such as those lead by WHO, on this issue.

Characterisation of non-warfarin-associated bleeding events reported to the Norwegian spontaneous reporting system.

OBJECTIVE: The aim of the study was to analyse non-warfarin-associated bleeding adverse drug events reported to the Norwegian spontaneous reporting system, with characterisation of the bleeding locations, outcome and drug interactions. In addition, concordance in assessments between reporters and evaluators, trend shifts in reporting, and detection of potentially new adverse drug interaction signals were studied. METHODS: Data on bleeding events reported between 1 January 2003 and 31 December 2005 were retrieved from the Norwegian spontaneous reporting system database. RESULTS: Of 327 case reports of non-warfarin-associated bleeding events, 270 reports (82.6 %) were characterised as serious and 69 (21.1 %) had a fatal outcome. One hundred and eighty-seven bleeds (57.5 %) were gastrointestinal, 57 (17.4 %) were cerebral, and 81 (24.8 %) were from other bleeding sites. The bleeding sites differed with respect to the patient's age, drug use, diagnoses and outcomes. Of drugs associated with bleeding, nonsteroidal anti-inflammatory drugs (NSAIDs)/COX-2 inhibitors (145 reports) and acetylsalicylic acid (128 reports) were most frequently used. Only fibrinolytics were associated with increased mortality. There was a 67.4 % correlation between reporters and evaluators in assessment of drugs associated with bleeding (P < 0.001), with considerable variation in concordance between drug groups. CONCLUSION: Non-warfarin-associated bleeding events are associated with substantial mortality. Old age, cerebral bleeds, number of drugs used, and use of fibrinolytics are all independently associated with increased mortality. The recognition of the bleeding risk of commonly used drugs such as acetylsalicylic acid and heparins may be insufficient among prescribers.

Warfarin-associated bleeding events and concomitant use of potentially interacting medicines reported to the Norwegian spontaneous reporting system.

AIMS: To study warfarin associated bleeding events reported to the Norwegian spontaneous reporting system and evaluate the differences in assessment of potentially interacting medicines between reporters and evaluators. METHODS: Data on bleeding events on warfarin were retrieved from the Norwegian spontaneous reporting system database. Key measurements were time to bleeding, use of concomitant medications and the evaluation done by reporters. RESULTS: In 289 case reports a total of 1261 medicines (median 4.0 per patient, range 1-17) was used. The evaluators (authors of this article) identified 546 medicines including warfarin (median 2.0 per patient, range 1-7) that could possibly cause bleeding alone or in combination. Reporters assessed 349 medicines (median 1.0 per patient, range 1-4) as suspect. Evaluators identified 156 pharmacokinetic and 101 pharmacodynamic interactions, compared with 19 pharmacokinetic and 56 pharmacodynamic interactions reported as suspected by the reporters. Time to bleeding was stated in 224 reports. Among the early bleeding events, the reports on warfarin without interacting medicines showed the highest INR (international normalized ratio). Heparin was used in 17/21 reported bleeding events during the first week on warfarin. Among the late bleeding events, reports with pharmacokinetic interacting medicines had the highest INR. CONCLUSIONS: Concomitant use of potentially interacting medicines was involved in the majority of the warfarin-associated bleeding events reported to the Norwegian spontaneous reporting system. Reporters assessed mostly warfarin as the only contributor to bleeding. In particular, pharmacokinetically interacting medicines were not suspected as contributing to bleeding.

Venlafaxine and asthma.

A 54-year-old man of Asian origin with major depression developed an asthma-like reaction during venlafaxine treatment. Two weeks after therapy was initiated, he experienced gradually worsening dry cough at night and periodically dyspnea during the daytime. After 5 weeks, clinical examination revealed marked signs of pulmonary obstruction and the forced expiratory volume (FEV1) was assessed to only 32% of the expected value. The venlafaxine medication was gradually decreased and eventually discontinued 9 weeks after its initiation, resulting in a successive improvement of the patient's respiratory complaints.