Hysterectomy for heavy menstrual bleeding: rapid health technology assessment

Source at https://www.fhi.no/publ/2021/hysterektomi-ved-kraftige-menstruasjonsblodninger/Vi har på oppdrag fra Bestillerforum for nye metoder utarbeidet en forenklet metodevurdering om hysterektomi (kirurgisk fjerning av livmor) ved kraftige menstruasjonsblødninger. Dette er en pilot i et prosjekt innen revurdering som ledes av Helse Midt-Norge RHF. Vi har hentet ut resultater for effekt og sikkerhet og vurderinger av tillit til resultatene for effekt fra en rapport av The National Institute of Health and Care Excellence, og utført en kostnadsanalyse. Resultatene må ses i sammenheng med andre faktorer som påvirker valg av behandling, og at vanlig praksis bør være å forsøke mindre invasive alternativer først

Global, regional, and national burden of stroke and its risk factors, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries.publishedVersio

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings In 2019, there were 12.2 million (95% UI 11.0-13.6) incident cases of stroke, 101 million (93.2-111) prevalent cases of stroke, 143 million (133-153) DALYs due to stroke, and 6.55 million (6.00-7.02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11.6% 10.8-12.2] of total deaths) and the third-leading cause of death and disability combined (5.7% 5.1-6.2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70.0% (67.0-73.0), prevalent strokes increased by 85.0% (83.0-88.0), deaths from stroke increased by 43.0% (31.0-55.0), and DALYs due to stroke increased by 32.0% (22.0-42.0). During the same period, age-standardised rates of stroke incidence decreased by 17.0% (15.0-18.0), mortality decreased by 36.0% (31.0-42.0), prevalence decreased by 6.0% (5.0-7.0), and DALYs decreased by 36.0% (31.0-42.0). However, among people younger than 70 years, prevalence rates increased by 22.0% (21.0-24.0) and incidence rates increased by 15.0% (12.0-18.0). In 2019, the age-standardised stroke-related mortality rate was 3.6 (3.5-3.8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3.7 (3.5-3.9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62.4% of all incident strokes in 2019 (7.63 million 6.57-8.96]), while intracerebral haemorrhage constituted 27.9% (3.41 million 2.97-3.91]) and subarachnoid haemorrhage constituted 9.7% (1.18 million 1.01-1.39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79.6 million 67.7-90.8] DALYs or 55.5% 48.2-62.0] of total stroke DALYs), high body-mass index (34.9 million 22.3-48.6] DALYs or 24.3% 15.7-33.2]), high fasting plasma glucose (28.9 million 19.8-41.5] DALYs or 20.2% 13.8-29.1]), ambient particulate matter pollution (28.7 million 23.4-33.4] DALYs or 20.1% 16.6-23.0]), and smoking (25.3 million 22.6-28.2] DALYs or 17.6% 16.4-19.0]). Interpretation The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Natalizumab subkutant til behandling av relapserende remitterende multippel sklerose: forenklet metodevurdering– helseøkonomisk evaluering

Hovedbudskap Folkehelseinstituttet (FHI) har på oppdrag fra Bestillerforum for nye metoder utarbeidet en forenklet metodevurdering hvor den helseøkonomiske modellen i den fullstendige metodevurderingen om legemidler til behandling av relapserende-remitterende mul-tiple sklerose (RRMS) gjennomført av FHI ble oppdatert med data for natalizumab subkutant til behandling av pasienter med RRMS. Natalizumab subkutant er en ny administrasjonsform av virkestof-fet natalizumab. Resultater fra en fase II-studie viste at effekt (årlig attakkrate og nye MR lesjoner) av natalizumab subkutant er sammenlignbar med natalizumab intravenøst. Vi vurderte nytte og ressursbruk ved behandling med natalizumab subkutant sammenlignet med rituksimab, det mest kostnads-effektive behandlingsalternativet, og kladribin som også brukes for behandling av høyaktiv RRMS. Våre resultater viste at: En reduksjon på xxxxx i legemiddelkostnader for natalizumab subkutant medører at behandlingen koster NOK xxxxxxxx per vunnet kvalitetsjustert leveår (QALY) sammenlignet med rituksimab, gitt samme nytte som natalizumab intravenøst. Gitt samme nytte som natalizumab intravenøst, er natalizumab subkutant marginalt mer effektivt (0,017 vunne QALY) enn rituksimab. Et pristilbud på NOK xxxxxxxx (inkl. mva.) per 300 mg natalizumab subkutant gir en merkostnad på ca. xxxxxxxx NOK per vunnet QALY sammenlignet med rituksimab. En reduksjon på ca. xxxxx i legemiddelkostnader for natalizumab subkutant fører til at behandlingen koster NOK xxxxxxxx per vunnet QALY sammenlignet med kladribin, gitt samme nytte som natalizumab intravenøst. Gitt samme nytte som natalizumab intravenøst, er natalizumab subkutant mer effektivt (0,238 vunne QALY) enn kladribin. Et pristilbud på NOK xxxxxxxx (inkl. mva.) per 300 mg natalizumab subkutant gir en merkostnad på ca. xxxxxxxx NOK per vunnet QALY sammenlignet med kladribin. Relapserende remitterende multippel sklerose er en svært alvorlig sykdom som kan gi alvorlig funksjonssvikt og tap av gode leveår. Priser er ikke oppgitt på grunn av konfidensialitetshensyn (xxxxx)

Ofatumumab til behandling av relapserende remitterende multippel sklerose: forenklet metodevurdering– helseøkonomisk evaluering

Hovedbudskap Folkehelseinstituttet (FHI) har på oppdrag fra Bestillerforum for nye metoder utarbeidet en forenklet metodevurdering hvor den helseøkonomiske modellen i den fullstendige metodevurderingen om legemidler til behandling av relapserende-remitterende multippel sklerose (RRMS) gjennomført av FHI ble oppdatert med data for ofatumumab til behandling av voksne pasienter med RRMS. Ofatumumab er et fullstendig humant anti-CD20-antistoff og administreres som subkutan injeksjon. Resultater fra denne forenklede metodevurderingen viste at: Rituksimab er det klart mest kostnadseffektive behandlings-alternativet blant anti-CD20 medikamenter, basert på gjeldende anbudspriser. Okrelizumab (maksimalpris) er både dyrere og mer effektivt enn rituksimab og kladribin (gjeldende anbudspriser). Okrelizumab koster NOK xxxxxxxxxx per vunnet kvalitetsjustert leveår (QALY) sammenlignet med rituksimab og kladribin med en pakningspis på henholdvis NOK xxxxxxxxxx (xxxxx reduksjon i legemiddelkostnader) og NOK xxxxxxxxxx (xxxxx reduksjon i legemiddelkostnader). Ofatumumab er enda ikke markedsført i Norge. Gitt same nytte og gjennomsnittlig årlig legemiddelkostnad (maksimal- pris) som okrelizumab, er ofatumumab både dyrere og mer effektivt sammenlignet med rituksimab og kladribin. Gitt same nytte og årlig legemiddelkostnad (maksimalpris) som okrelizumab, koster ofatumumab NOK xxxxxxxx per vunnet QALY sammenlignet med rituksimab og kladribin med en prisreduksjon på henholdvis xxxxx og xxxxx. Et pristilbud på NOK xxxxxxxxx (inkl. mva.) per 20 mg ofatumumab gir en merkostnad på NOK xxxxxxxxx per vunnet QALY sammenlignet med rituksimab. Et pristilbud på NOK xxxxxxxxxx (inkl. mva.) per 20 mg ofatumumab gir mer helsegevinst og er samtidig mindre kostbar enn kladribin. Relapserende remitterende multippel sklerose er en svært alvorlig sykdom som kan gi alvorlig funksjonssvikt og tap av gode leveår. Prisene er fjernet pga krav til konfidensialitet (xxxxxx)

Tests for detection of ROS1 gene alterations in people with non-small cell lung cancer (NSCLC): A Health Technology Assessment.

Key messages: The Norwegian Institute of Public Health has been commissioned to evaluate molecular tests for the identification of somatic ROS1 gene alterations in people with locally advanced or metastatic non-small cell lung cancer (NSCLC). People with tumours harbouring ROS1 gene alterations probably make up 1-2% of NSCLC cases. Accurate and reliable detection of ROS1 gene alterations is important for identification of people who may benefit from treatment, as well as ROS1 negative patients, to avoid provision of unnecessary and costly treatment. We included one systematic review, six narrative reviews, a survey of Norwegian Hospital trusts, and two reviews on the preferences of patients related to molecular testing. Experts were contacted for cost information. The results of this HTA show that: • There is scarce, incomplete and low-quality evidence on the sensitivity and specificity of tests for the detection of ROS1 gene alterations in people with advanced or metastasised NSCLC • Positive IHC ROS1 results needs confirmation with FISH or other methods, due to a tendency for false positive staining. • While the different tests had different pros and cons, single gene testing may be unfeasible, since people with NSCLC typically are tested for more than one type of actionable gene alteration. • NGS due to its capacity to analyse multiple genes simultaneously, may have the potential to reduce the risk of repeat biopsies. • The cost for ROS1 using IHC as pre-test with FISH confirmation, is possibly less than for the other methods. • The cost associated with NGS testing will significantly decrease when parallel tests are to be performed for several biomarkers (i.e. gene panels) from multiple patients. However, at present, the capital and infrastructure as well as maintenance costs are higher for NGS than the other diagnostic methods. • Future research should focus on conducting larger cohort studies with welldefined patient populations, that follows the patients from testing (or no testing), through treatment and final outcomes

Estimating QUALY gains in applied studies: A review of cost-utility analyses published in 2010

Reimbursement agencies in several countries now require health outcomes to be measured in terms of quality-adjusted life-years (QALYs), leading to an immense increase in publications reporting QALY gains. However, there is a growing concern that the various ‘multi-attribute utility’ (MAU) instruments designed to measure the Q in the QALY yield disparate values, implying that results from different instruments are incommensurable. By reviewing cost-utility analyses published in 2010, we aim to contribute to improved knowledge on how QALYs are currently calculated in applied analyses; how transparently QALY measurement is presented; and how large the expected incremental QALY gains are. We searched Embase, MEDLINE and NHS EED for all cost-utility analyses published in 2010. All analyses that had estimated QALYs gained from health interventions were included. Of the 370 studies included in this review, 48 % were pharmacoeconomic evaluations. Active comparators were used in 71 % of studies. The median incremental QALY gain was 0.06, which translates to 3 weeks in best imaginable health. The EQ-5D-3L is the dominant instrument used. However, reporting of how QALY gains are estimated is generally inadequate. In 55 % of the studies there was no reference to which MAU instrument or direct valuation method QALY data came from. The methods used for estimating expected QALY gains are not transparently reported in published papers. Given the wide variation in utility scores that different methodologies may assign to an identical health state, it is important for journal editors to require a more transparent way of reporting the estimation of incremental QALY gains. This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited