Co-prescribing of opioids and benzodiazepines/Z-drugs associated with all-cause mortality-A population-based longitudinal study in primary care with weak opioids most commonly prescribed.

Introduction: The risk of mortality associated with the co-prescribing of benzodiazepines and opioids has been explored in a number of papers mainly focusing on strong opioids. The mortality risk associated with the use of weak opioids has not been dealt with to a similar extent. Objective: To assess the mortality risk in primary care patients with consistent 3-year co-prescribing of benzodiazepine/Z-drugs (benzodiazepine receptor modulators) and mainly weak opioids (codeine, tramadol). Methods: Of 221,804 patients contacting the primary healthcare centres, 124,436 were selected for further analysis, 88,832 participants fulfilled the inclusion criteria, aged 10-69 years and were divided into four groups with neither any use of benzodiazepines/Z-drugs nor opioids as Group 1, 3 years' use of opioids and no/minimal benzodiazepines/Z-drugs as Group 2, with benzodiazepines/Z-drugs and no/minimal opioids as Group 3, and finally both benzodiazepines/Z-drugs and opioids as Group 4. Hazard ratios were calculated with the no-drug group as a reference, using Cox proportional hazards regression model adjusted for age, sex, number of chronic conditions and cancer patients excluded (n = 87,314). Results: Hazard ratios for mortality increased both in Group 3 where it was 2.66 (95% CI 2.25-3.09) and in Group 4 where it was 5.12 (95% CI 4.25-6.17), with increased dose and higher number of chronic conditions. In Group 4 an opioid dose-dependent increase in mortality among persons using >1000 DDDs benzodiazepines/Z-drugs was observed when those on less than ≤300 DDDs of opioids with HR 4.94 (95% CI 3.54-6.88) were compared to those on >300 DDDs with HR 7.61/95% CI 6.08-9.55). This increase in mortality was not observed among patients on <1000 DDDs of benzodiazepines/Z-drugs. Conclusion: The study supports evidence suggesting that mortality increases in a dose-dependent manner in patients co-prescribed benzodiazepines/Z-drugs and weak opioids (codeine, tramadol). An association between the number of chronic conditions and a rise in mortality was found. Long-term use of these drugs should preferably be avoided. Non-pharmacological therapy should be seriously considered instead of long-term use of benzodiazepines/Z-drugs, and deprescribing implemented for chronic users of these drugs when possible.

The Role of Anger in Motivating Leadership.

As doctors, we see every working day the pervasive effects of different forms of structural violence and discrimination that undermine the hopes and aspirations of those on the losing side. This leads to powerlessness, fear and anger. Anger is not only forward facing but also directed toward, systems, institutions, governments-rather than individuals. At its best it is a protest against the status quo. We point out that leadership is one of the core values of our professionalism. In the light of what we see and hear, we have a responsibility to use the anger that this engenders within us to speak truth to power: this speaking is leadership. Our message is: feel the fear and the anger, use it to change the world, and enfold leadership in hope and the pursuit of justice.

How primary healthcare in Iceland swiftly changed its strategy in response to the COVID-19 pandemic.

OBJECTIVE: To describe how the primary healthcare (PHC) in Iceland changed its strategy to handle the COVID-19 pandemic. DESIGN: Descriptive observational study. SETTING: Reykjavik, the capital of Iceland. POPULATION: The Reykjavik area has a total of 233 000 inhabitants. MAIN OUTCOME MEASURES: The number and the mode of consultations carried out. Drug prescriptions and changes in the 10 most common diagnoses made in PHC. Laboratory tests including COVID-19 tests. Average numbers in March and April 2020 compared with the same months in 2018 and 2019. RESULTS: Pragmatic strategies and new tasks were rapidly applied to the clinical work to meet the foreseen healthcare needs caused by the pandemic. The number of daytime consultations increased by 35% or from 780 to 1051/1000 inhabitants (p<0.001) during the study period. Telephone and web-based consultations increased by 127% (p<0.001). The same tendency was observed in out-of-hours services. The number of consultations in maternity and well-child care decreased only by 4% (p=0.003). Changes were seen in the 10 most common diagnoses. Most noteworthy, apart from a high number of COVID-19 suspected disease, was that immunisation, depression, hypothyroidism and lumbago were not among the top 10 diagnoses during the epidemic period. The number of drug prescriptions increased by 10.3% (from 494 to 545 per 1000 inhabitants, p<0.001). The number of prescriptions from telephone and web-based consultations rose by 55.6%. No changes were observed in antibiotics prescriptions. CONCLUSIONS: As the first point of contact in the COVID-19 pandemic, the PHC in Iceland managed to change its strategy swiftly while preserving traditional maternity and well-child care, indicating a very solid PHC with substantial flexibility in its organisation.

Complex issues in general practice - a prevalence study. / Komplekse problemstillinger i allmennpraksis ­ en prevalensstudie.

BACKGROUND: The contract GP scheme in Norway has been a success, but the scheme's sustainability has been weakened. In summer 2017, the so-called Trønder rebellion arose among GPs who wished to analyse the situation. In order to obtain a better understanding of their total daily workload, all GPs in Norway were invited to record all their activity on a typical day in their practices. This included 22 pre-defined, currently relevant issues that form the basis of this article. MATERIAL AND METHOD: In 2018, all of Norway's 4 784 registered GPs received a web-based questionnaire survey. Altogether 1 032 doctors responded to the survey. The dataset elucidates more than 20 000 consultations throughout the country and more than 44 000 issues. RESULTS: On average, the GPs carried out 20 consultations addressing 43 different issues on a typical day in their practices. There were small differences between men and women doctors. Multimorbidity was a factor in 29 % of the consultations, mental disorders in 22 % and stress and life strains in 18 %. The GPs felt that they had a key role in providing support or life coaching in 15 % of the consultations. INTERPRETATION: The study documents that complex and demanding issues are a frequent occurrence. The GPs play a key role in the treatment of multimorbid patients, prevention of disease and detection and follow-up of cancer. The study underscores the importance of broad-based knowledge and fundamental continuity in the doctor-patient relationship.

Association between prescription of hypnotics/anxiolytics and mortality in multimorbid and non-multimorbid patients: a longitudinal cohort study in primary care.

OBJECTIVES: To assess the risk of mortality in primary care patients, multimorbid (≥2 chronic conditions) or not, prescribed hypnotics/anxiolytics. DESIGN: A longitudinal cohort study SETTING: Primary healthcare in the Reykjavik area. PARTICIPANTS: 114 084 individuals (aged 10-79 years, average 38.5, SD 18.4) contacting general practitioners during 2009-2012 (mortality follow-up to 31 December 2016). Of those, the reference group comprised 58 560 persons who were neither multimorbid nor had redeemed prescriptions for hypnotics/anxiolytics. Participants (16 108) redeeming prescriptions for hypnotics/anxiolytics on a regular basis for 3 consecutive years were considered as consistent, long-term users. They were subdivided into low-dose (1-300 defined daily doses (DDD)/3 years), medium-dose (301-1095 DDDs/3 years) and high-dose users (>1095 DDDs/3 years). All six groups taking these drugs were compared with the reference group. MAIN OUTCOME MEASURES: All-cause mortality. RESULTS: HRs were calculated with the no multimorbidity-no drug group as a reference, using Cox proportional hazards regression model adjusting for age, sex and the number of chronic conditions (n=111 767), patients with cancer excluded. During follow-up, 516 358 person-years in total, 1926 persons died. Mean follow-up was 1685 days (4.6 years), range 1-1826 days (5.0 years). For all multimorbid patients who took no drugs the HR was 1.14 (95% CI 1.00 to 1.30) compared with those without multimorbidity. HRs in the non-multimorbid participants varied from 1.49 to 3.35 (95% CI ranging from 1.03 to 4.11) with increasing doses of hypnotics/anxiolytics, and correspondingly from 1.55 to 3.52 (1.18 to 4.29) in multimorbid patients. CONCLUSIONS: Mortality increased in a dose-dependent manner among both multimorbid and non-multimorbid patients taking hypnotics/anxiolytics. This increase was clearly associated with prescribing of these drugs. Their use should be limited to the recommended period of 2-4 up to 6 weeks; long-term use may incur increased risk and should be re-examined.

Use of pregnancy ultrasound before the 19th week scan: an analytical study based on the Icelandic Childbirth and Health Cohort.

BACKGROUND AND AIM: Use of ultrasound scans early in pregnancy is increasing, but we have limited knowledge about the actual prevalence, associated decision-making and impact on expectant women/couples in a general population. The aim of this study was to document the use of, and experiences related to, foetal scanning before the recommended 19th week scan among pregnant women in Iceland. POPULATION AND METHODS: The data come from the Icelandic Childbirth and Health Cohort Study 2009-11. A total of 1111 women attending prenatal care at primary care health centres answered questionnaires before mid-pregnancy and after birth, including questions about the number of scanning procedures during pregnancy. These might include consumer-initiated 'pregnancy confirmation scans,' scans for clinical reasons, and screening for foetal anomalies in week 11-14 which is optional in Iceland. The questionnaires also addressed parental decision-making associated with the 11-14 week screening, perception of the pre-screening information, reasons for attending or declining, and whether/how early foetal screening affected the women's concerns related to the unborn child. RESULTS: A total of 95% of the women reported some kind of foetal ultrasound scanning before the 19th week scan, and 64% reported two or more scans in this period. 78% of the women chose to participate in screening for foetal anomalies in week 11-14. Decision-making in relation to this screening was mainly informed by sources outside the healthcare system, and many women characterized participation as 'self-evident'. Most women felt they got sufficient information about the scope of screening, whilst information regarding potential downsides and risks was frequently perceived as insufficient. Most women who chose the 11-14 week screening reported a reassuring or neutral effect, whilst 10% of the women reported that it increased their concerns related to their unborn child. CONCLUSIONS: Ultrasound scans in the first half of pregnancy are in high use in Iceland and have apparently become part of a broader pregnancy culture, encompassing both high- and low-risk pregnancies. Whether this is a favourable development or to some extent represents unwarranted medicalization, can be debated. More balanced information might be provided prior to early screening for foetal anomalies.

Does 'existential unease' predict adult multimorbidity? Analytical cohort study on embodiment based on the Norwegian HUNT population.

OBJECTIVES: Multimorbidity is prevalent, and knowledge regarding its aetiology is limited. The general pathogenic impact of adverse life experiences, comprising a wide-ranging typology, is well documented and coherent with the concept allostatic overload (the long-term impact of stress on human physiology) and the notion embodiment (the conversion of sociocultural and environmental influences into physiological characteristics). Less is known about the medical relevance of subtle distress or unease. The study aim was to prospectively explore the associations between existential unease (coined as a meta-term for the included items) and multimorbidity. SETTING: Our data are derived from an unselected Norwegian population, the Nord-Trøndelag Health Study, phases 2 (1995-1997) and 3 (2006-2008), with a mean of 11 years follow-up. PARTICIPANTS: The analysis includes 20 365 individuals aged 20-59 years who participated in both phases and was classified without multimorbidity (with 0-1 disease) at baseline. METHODS: From HUNT2, we selected 11 items indicating 'unease' in the realms of self-esteem, well-being, sense of coherence and social relationships. Poisson regressions were used to generate relative risk (RR) of developing multimorbidity, according to the respondents' ease/unease profile. RESULTS: A total of 6277 (30.8%) participants developed multimorbidity. They were older, more likely to be women, smokers and with lower education. 10 of the 11 'unease' items were significantly related to the development of multimorbidity. The items 'poor self-rated health' and 'feeling dissatisfied with life' exhibited the highest RR, 1.55 and 1.44, respectively (95% CI 1.44 to 1.66 and 1.21 to 1.71). The prevalence of multimorbidity increased with the number of 'unease' factors, from 26.7% for no factor to 49.2% for 6 or more. CONCLUSIONS: In this prospective study, 'existential unease' was associated with the development of multimorbidity in a dose-response manner. The finding indicates that existential unease increases people's vulnerability to disease, concordant with current literature regarding increased allostatic load.

Self Reported Childhood Difficulties, Adult Multimorbidity and Allostatic Load. A Cross-Sectional Analysis of the Norwegian HUNT Study.

BACKGROUND: Multimorbidity receives increasing scientific attention. So does the detrimental health impact of adverse childhood experiences (ACE). Aetiological pathways from ACE to complex disease burdens are under investigation. In this context, the concept of allostatic overload is relevant, denoting the link between chronic detrimental stress, widespread biological perturbations and disease development. This study aimed to explore associations between self-reported childhood quality, biological perturbations and multimorbidity in adulthood. MATERIALS AND METHODS: We included 37 612 participants, 30-69 years, from the Nord-Trøndelag Health Study, HUNT3 (2006-8). Twenty one chronic diseases, twelve biological parameters associated with allostatic load and four behavioural factors were analysed. Participants were categorised according to the self-reported quality of their childhood, as reflected in one question, alternatives ranging from 'very good' to 'very difficult'. The association between childhood quality, behavioural patterns, allostatic load and multimorbidity was compared between groups. RESULTS: Overall, 85.4% of participants reported a 'good' or 'very good' childhood; 10.6% average, 3.3% 'difficult' and 0.8% 'very difficult'. Childhood difficulties were reported more often among women, smokers, individuals with sleep problems, less physical activity and lower education. In total, 44.8% of participants with a very good childhood had multimorbidity compared to 77.1% of those with a very difficult childhood (Odds ratio: 5.08; 95% CI: 3.63-7.11). Prevalences of individual diseases also differed significantly according to childhood quality; all but two (cancer and hypertension) showed a significantly higher prevalence (p<0.05) as childhood was categorised as more difficult. Eight of the 12 allostatic parameters differed significantly between childhood groups. CONCLUSIONS: We found a general, graded association between self-reported childhood difficulties on the one hand and multimorbidity, individual disease burden and biological perturbations on the other. The finding is in accordance with previous research which conceptualises allostatic overload as an important route by which childhood adversities become biologically embodied.

Immediate surge in female visits to the cardiac emergency department following the economic collapse in Iceland: an observational study.

OBJECTIVE: To study potential changes in attendance at emergency departments (ED) in Reykjavík immediately following the swift economic meltdown in Iceland in October 2008. METHODS: Using electronic medical records of the National University Hospital in Reykjavík, a population-based register study was conducted contrasting weekly attendance rates at Reykjavík ED (cardiac and general ED) during 10-week periods in 2006, 2007 and 2008. The weekly number of all ED visits (major track), with discharge diagnoses, per total population at risk were used to estimate RR and 95% CI of ED attendance in weeks 41-46 (after the 2008 economic collapse) with the weekly average number of visits during weeks 37-40 (before the collapse) as reference. RESULTS: Compared with the preceding weeks (37-40), the economic collapse in week 41 2008 was associated with a distinct increase in the total number of visits to the cardiac ED (RR 1.26; 95% CI 1.07 to 1.49), particularly among women (RR 1.41; 95% CI 1.17 to 1.69) and marginally among men (RR 1.15; 95% CI 0.96 to 1.37). A similar increase was not observed in week 41 at the general ED in 2008 or in either ED in 2007 or 2006. In week 41 2008, visits with ischaemic heart disease as discharge diagnoses (ICD-10: I20-25) were increased among women (RR 1.79; 95% CI 1.01 to 3.17) but not among men (RR 1.07; 95% CI 0.71 to 1.62). CONCLUSION: The dramatic economic collapse in Iceland in October 2008 was associated with an immediate short-term increase in female attendance at the cardiac ED.

[The use of embryonic stem cells for medical-therapeutical purposes: a study of attitudes among Icelandic physicians, lawyers and clergymen.].

OBJECTIVE: To study the bioethical standpoints among three groups of Icelandic professionals in relation to the use of embryonic stem cells for medical-therapeutical purposes. MATERIAL AND METHODS: In June 2002, a questionnaire was sent by mail to a random sample of 284 doctors and 293 lawyers, as well as all 168 practicing clergymen in Iceland. The participants' position in relation to the use of embryonic stem cells for therapeutical purposes was elicited through general questions as well as case examples. 290 questionnaires (39%) were returned. RESULTS: 62% of participants believed the embryo to have an ethical status superior to that of biologically comparable life forms. 20% of respondents considered its status as equal to that of a grown human being, whilst 18% considered it equal to biologically comparable primitive life forms. There was a difference between the respondent groups (p<0,05). A vast majority believed the use of embryonic stem cells for therapeutical purposes to be justifiable, although the origin of the stem cells appeared to make a difference to many respondents. 8% of participants took an unconditional position against the use of embryonic stem cells. Among those who considered the use of embryonic stem cells with a therapeutic aim to be justifiable, 71% believed that embryonic stem cells should only be utilized to treat diseases of a severe nature. 64% of participants defended the idea of therapeutic cloning with the intention to treat a patient with Parkinson's disease, but the case history elicited considerable difference between professional groups. Clergymen and lawyers tended to hold firmer attitudes, clergymen against and lawyers for the use of stem cells, whilst medical doctors as a group positioned themselves more towards the middle. Female respondents generally took a more modest stand whilst males were more likely to take a firmer stand in both directions. A vast majority (87%) of the participants believed there to be a need for public debate in relation to the use of embryonic stem cells for therapeutical purposes. CONCLUSION: Overall, participants views in relation to the use of embryonic stem cells for medical purposes were rather liberal. There were however significant differences between professional groups. The relatively high tolerance in regard to therapeutic cloning is interesting in view of the considerable controversy over this topic in many countries. There appears to be fertile ground for a public debate about the use of embryonic stem cells for medical purposes in Iceland.