Health Outcomes and Cost-effectiveness of Monoclonal SARS-CoV-2 Antibodies as Pre-exposure Prophylaxis

Importance: Pre-exposure prophylaxis with neutralizing SARS-CoV-2 monoclonal antibodies (mAbs PrEP) prevents infection and reduces hospitalizations and the duration thereof for COVID-19 and death among high-risk individuals. However, reduced effectiveness due to a changing SARS-CoV-2 viral landscape and high drug prices remain substantial implementation barriers. Objective: To assess the cost-effectiveness of mAbs PrEP as COVID-19 PrEP. Design, Setting, and Participants: For this economic evaluation, a decision analytic model was developed and parameterized with health care outcome and utilization data from individuals with high risk for COVID-19. The SARS-CoV-2 infection probability, mAbs PrEP effectiveness, and drug pricing were varied. All costs were collected from a third-party payer perspective. Data were analyzed from September 2021 to December 2022. Main Outcomes and Measures: Health care outcomes including new SARS-CoV-2 infections, hospitalization, and deaths. The cost per death averted and cost-effectiveness ratios using a threshold for prevention interventions of $22000 or less per quality-adjusted life year (QALY) gained. Results: The clinical cohort consisted of 636 individuals with COVID-19 (mean [SD] age 63 [18] years; 341 [54$275 and 75% or higher effectiveness. With a 100% effectiveness mAbs PrEP can reduce ward admissions by 70%, ICU admissions by 97%, and deaths by 92%. Drug prices, however, need to reduce to $550 for cost-effectiveness ratios less than$22000 per QALY gained per death averted and to $2200 for ratios between$22000 and $88000. Conclusions and Relevance: In this study, use of mAbs PrEP for preventing SARS-CoV-2 infections was cost-saving at the beginning of an epidemic wave (high infection probability) with 75$275. These results are timely and relevant for decision-makers involved in mAbs PrEP implementation. When newer mAbs PrEP combinations become available, guidance on implementation should be formulated ensuring a fast rollout. Nevertheless, advocacy for mAbs PrEP use and critical discussion on drug prices are necessary to ensuring cost-effectiveness for different epidemic settings.</p

Long-Term Outcome of Patients With a Hematologic Malignancy and Multiple Organ Failure Admitted at the Intensive Care

Objectives: Historically, patients with a hematologic malignancy have one of the highest mortality rates among cancer patients admitted to the ICU. Therefore, physicians are often reluctant to admit these patients to the ICU. The aim of our study was to examine the survival of patients who have a hematologic malignancy and multiple organ failure admitted to the ICU. Design: This retrospective cohort study, part of the HEMA-ICU study group, was designed to study the survival of patients with a hematologic malignancy and organ failure after admission to the ICU. Patients were followed for at least 1 year. Setting: Five university hospitals in the Netherlands. Patients: One-thousand ninety-seven patients with a hematologic malignancy who were admitted at the ICU. Interventions: None. Measurements and Main Results: Primary outcome was 1-year survival. Organ failure was categorized as acute kidney injury, respiratory failure, hepatic failure, and hemodynamic failure; multiple organ failure was defined as failure of two or more organs. The World Health Organization performance score measured 3 months after discharge from the ICU was used as a measure of functional outcome. The 1-year survival rate among these patients was 38%. Multiple organ failure was inversely associated with long-term survival, and an absence of respiratory failure was the strongest predictor of 1-year survival. The survival rate among patients with 2, 3, and 4 failing organs was 27%, 22%, and 8%, respectively. Among all surviving patients for which World Health Organization scores were available, 39% had a World Health Organization performance score of 0-1 3 months after ICU discharge. Functional outcome was not associated with the number of failing organs. Conclusions: Our results suggest that multiple organ failure should not be used as a criterion for excluding a patient with a hematologic malignancy from admission to the ICU.</p

Gall-bladder dysmotility - A risk factor for gall-stone formation in hypertriglyceridaemia and reversal on triglyceride-lowering therapy with bezafibrate and fish oil

Doel: Onderzoeken van de pathofysiologische mechanismen die de kans op galstenen verhogen bij hypertriglyceridemie (HTG) en het vergelijken van de effecten van triglycerideverlagende therapie met bezafibraat en visolie op determinanten van cholelithiasis (biliaire lipidesamenstelling en galblaasmotoriek) bij HTG-patiënten.Opzet: Gekruiste opzet met ‘random’-volgorde.Patiënten en methoden: De galblaasmotoriek werd postprandiaal en tijdens cholecystokinine(CCK)-infusie echografisch onderzocht. De determinanten van cholelithiasis en de serumlipiden werden vergeleken tussen 9 HTG-patiënten en 10 normolipidemische controlepersonen van hetzelfde geslacht, dezelfde leeftijd en ‘body mass’-index. Bij de HTG-patiënten werden de effecten van bezafibraat en gezuiverde omega-3-olie (‘visolie’) bepaald.Resultaten: De serumtriglyceride(TG)-spiegel van de HTG-patiënten was 14-voudig verhoogd, vergeleken met de controlepersonen. De lipidesamenstelling van de gal, de nuchtere galblaasvolumen en de serum-CCK-spiegels verschilden niet tussen HTG-patiënten en controlepersonen. De galblaaslediging was verminderd bij HTG-patiënten versus controlepersonen tijdens CCK-infusie (–22) en ook na een maaltijd (–37; beide p &lt; 0,001). De postprandiale serum-CCK-spiegels waren significant hoger bij HTG-patiënten. Zowel bezafibraat als visolie verlaagde de serum-TG-spiegel (–68 en –51 ten opzichte van de uitgangswaarde; beide: p &lt; 0,01). Nuchtere CCK-spiegels verschilden niet, terwijl de CCK-geïnduceerde galblaaslediging onder bezafibraat toenam met 29 (p &lt; 0,001) en met visolie met 13 (p = 0,07). De postprandiale galblaasmotoriek verbeterde tijdens zowel bezafibraat- (+47) als visoliebehandeling (+25; beide: p &lt; 0,02), waarschijnlijk gedeeltelijk door een toegenomen gevoeligheid van de galblaas voor CCK (voor beide: p &lt; 0,05 vergeleken met de uitgangsfase). Bezafibraat, in tegenstelling tot visolie, verhoogde de molaire cholesterol-galzuurratio (+40; p ≤ 0,05), terwijl beide behandelingen geen effect hadden op de cholesterolsaturatie-index.Conclusies: De verminderde galblaasmotoriek bij HTG-patiënten lijkt het gevolg te zijn van verminderde gevoeligheid voor CCK, wat kan bijdragen aan het verhoogde risico op galsteenvorming. Bij HTG-patiënten verbetert triglycerideverlagende therapie met visolie of bezafibraat de verminderde galblaasmotoriek zonder nadelig effect op de biliaire cholesterolverzadiging.Objective. To unravel the mechanisms responsible for the increased risk of gall-stone disease in hypertriglyceridaemia (HTG) and to compare the effects of triglyceride-lowering therapy with bezafibrate and fish oil on determinants of cholelithiasis (biliary-lipid composition and gall-bladder motility) in HTG patients. Design. Randomised cross over. Patients and methods. Gall-bladder motility (ultrasonography) was studied postprandially and during infusion of cholecystokinin (CCK). Determinants of cholelithiasis and serum lipids were compared between 9 HTG patients and 10 age, sex and body-mass index matched normolipidaemic controls. The effects of bezafibrate and purified omega-3-oil ('fish oil') in HTG patients were studied. Results. HTG patients showed 14-fold higher serum-triglyceride (TG) levels than controls. Biliary-lipid composition, fasting gall-bladder volumes, and CCK levels did not differ between HTG patients and controls. Gall-bladder emptying was reduced in HTG patients compared with controls during CCK infusion (-22%) as well as in response to a meal (-37%; both p &lt; 0.001). Postprandial CCK levels were significantly higher in HTG patients. Both bezafibrate and fish oil reduced serum TG levels (-68 and -51% versus baseline, respectively; both p &lt; 0.01). Fasting CCK levels were not affected whereas CCK-induced gall-bladder emptying increased during bezafibrate (+29%; p &lt; 0.001) and tended to increase upon fish-oil therapy (+13%; p = 0.07). Postprandial gall-bladder motility improved at least partly with bezafibrate and fish oil (+47 and +25% versus baseline, respectively; both p &lt; 0.02) due to increased gallbladder sensitivity to CCK (both p &lt; 0.05 versus baseline). Bezafibrate but not fish oil increased the molar ratio of cholesterol to bile acids (+40%; p ≤ 0.05), but no effects on the cholesterol-saturation index were seen with either treatment. Conclusions. We suggest that impaired gall-bladder motility occurs in HTG patients due to decreased sensitivity to CCK, which may add to the enhanced risk of gall-stone disease in HTG patients. Triglyceride-lowering therapy by both fish oil and bezafibrate improves gall-bladder dysmotility without adversely affecting biliary-cholesterol saturation.</p

Gall-bladder dysmotility - A risk factor for gall-stone formation in hypertriglyceridaemia and reversal on triglyceride-lowering therapy with bezafibrate and fish oil

Doel: Onderzoeken van de pathofysiologische mechanismen die de kans op galstenen verhogen bij hypertriglyceridemie (HTG) en het vergelijken van de effecten van triglycerideverlagende therapie met bezafibraat en visolie op determinanten van cholelithiasis (biliaire lipidesamenstelling en galblaasmotoriek) bij HTG-patiënten.Opzet: Gekruiste opzet met ‘random’-volgorde.Patiënten en methoden: De galblaasmotoriek werd postprandiaal en tijdens cholecystokinine(CCK)-infusie echografisch onderzocht. De determinanten van cholelithiasis en de serumlipiden werden vergeleken tussen 9 HTG-patiënten en 10 normolipidemische controlepersonen van hetzelfde geslacht, dezelfde leeftijd en ‘body mass’-index. Bij de HTG-patiënten werden de effecten van bezafibraat en gezuiverde omega-3-olie (‘visolie’) bepaald.Resultaten: De serumtriglyceride(TG)-spiegel van de HTG-patiënten was 14-voudig verhoogd, vergeleken met de controlepersonen. De lipidesamenstelling van de gal, de nuchtere galblaasvolumen en de serum-CCK-spiegels verschilden niet tussen HTG-patiënten en controlepersonen. De galblaaslediging was verminderd bij HTG-patiënten versus controlepersonen tijdens CCK-infusie (–22) en ook na een maaltijd (–37; beide p &lt; 0,001). De postprandiale serum-CCK-spiegels waren significant hoger bij HTG-patiënten. Zowel bezafibraat als visolie verlaagde de serum-TG-spiegel (–68 en –51 ten opzichte van de uitgangswaarde; beide: p &lt; 0,01). Nuchtere CCK-spiegels verschilden niet, terwijl de CCK-geïnduceerde galblaaslediging onder bezafibraat toenam met 29 (p &lt; 0,001) en met visolie met 13 (p = 0,07). De postprandiale galblaasmotoriek verbeterde tijdens zowel bezafibraat- (+47) als visoliebehandeling (+25; beide: p &lt; 0,02), waarschijnlijk gedeeltelijk door een toegenomen gevoeligheid van de galblaas voor CCK (voor beide: p &lt; 0,05 vergeleken met de uitgangsfase). Bezafibraat, in tegenstelling tot visolie, verhoogde de molaire cholesterol-galzuurratio (+40; p ≤ 0,05), terwijl beide behandelingen geen effect hadden op de cholesterolsaturatie-index.Conclusies: De verminderde galblaasmotoriek bij HTG-patiënten lijkt het gevolg te zijn van verminderde gevoeligheid voor CCK, wat kan bijdragen aan het verhoogde risico op galsteenvorming. Bij HTG-patiënten verbetert triglycerideverlagende therapie met visolie of bezafibraat de verminderde galblaasmotoriek zonder nadelig effect op de biliaire cholesterolverzadiging.Objective. To unravel the mechanisms responsible for the increased risk of gall-stone disease in hypertriglyceridaemia (HTG) and to compare the effects of triglyceride-lowering therapy with bezafibrate and fish oil on determinants of cholelithiasis (biliary-lipid composition and gall-bladder motility) in HTG patients. Design. Randomised cross over. Patients and methods. Gall-bladder motility (ultrasonography) was studied postprandially and during infusion of cholecystokinin (CCK). Determinants of cholelithiasis and serum lipids were compared between 9 HTG patients and 10 age, sex and body-mass index matched normolipidaemic controls. The effects of bezafibrate and purified omega-3-oil ('fish oil') in HTG patients were studied. Results. HTG patients showed 14-fold higher serum-triglyceride (TG) levels than controls. Biliary-lipid composition, fasting gall-bladder volumes, and CCK levels did not differ between HTG patients and controls. Gall-bladder emptying was reduced in HTG patients compared with controls during CCK infusion (-22%) as well as in response to a meal (-37%; both p &lt; 0.001). Postprandial CCK levels were significantly higher in HTG patients. Both bezafibrate and fish oil reduced serum TG levels (-68 and -51% versus baseline, respectively; both p &lt; 0.01). Fasting CCK levels were not affected whereas CCK-induced gall-bladder emptying increased during bezafibrate (+29%; p &lt; 0.001) and tended to increase upon fish-oil therapy (+13%; p = 0.07). Postprandial gall-bladder motility improved at least partly with bezafibrate and fish oil (+47 and +25% versus baseline, respectively; both p &lt; 0.02) due to increased gallbladder sensitivity to CCK (both p &lt; 0.05 versus baseline). Bezafibrate but not fish oil increased the molar ratio of cholesterol to bile acids (+40%; p ≤ 0.05), but no effects on the cholesterol-saturation index were seen with either treatment. Conclusions. We suggest that impaired gall-bladder motility occurs in HTG patients due to decreased sensitivity to CCK, which may add to the enhanced risk of gall-stone disease in HTG patients. Triglyceride-lowering therapy by both fish oil and bezafibrate improves gall-bladder dysmotility without adversely affecting biliary-cholesterol saturation.</p