Assessing the impact of Australia's mass vaccination campaigns over the Delta and Omicron outbreaks.

BACKGROUND: The Australian Government implemented a national vaccination campaign against COVID-19 beginning February 22, 2021. The roll-out was criticised for being delayed relative to many high-income countries, but high levels of vaccination coverage were belatedly achieved. The large-scale Omicron outbreak in January 2022 resulted in a massive number of cases and deaths, although mortality would have been far higher if not for vigorous efforts to rapidly vaccinate the entire population. The impact of the vaccination coverage was assessed over this extended period. METHODS: We considered NSW, as the Australian jurisdiction with the highest quality data for our purposes and which still reflected the national experience. Weekly death rates were derived among individuals aged 50+ with respect to vaccine status between August 8, 2021 and July 9, 2022. We evaluated deaths averted by the vaccination campaign by modelling alternative counterfactual scenarios based on a simple data-driven modelling methodology presented by Jia et al. (2023). FINDINGS: Unvaccinated individuals had a 7.7-fold greater mortality rate than those who were fully vaccinated among people aged 50+, which rose to 11.2-fold in those who had received a booster dose. If NSW had fully vaccinated its ~2.9 million 50+ residents earlier (by July 28, 2021), only 440 of the total 3,495 observed 50+ deaths would have been averted. Up to July 9, 2022, the booster campaign prevented 1,860 deaths. In the absence of a vaccination campaign, ~21,250 COVID-19 50+ deaths (conservative estimate) could have been expected in NSW i.e., some 6 times the actual total. We also find the methodology of Jia et al. (2023) can sometimes significantly underestimate that actual number. INTERPRETATION: The Australian vaccination campaign was successful in reducing mortality over 2022, relative to alternative hypothetical vaccination scenarios. The success was attributable to the Australian public's high levels of engagement with vaccination in the face of new SARS-COV-2 variants, and because high levels of vaccination coverage (full and booster) were achieved in the period shortly before the major Omicron outbreak of 2022.

Interstitial nephritis secondary to bevacizumab treatment in metastatic leiomyosarcoma.

OBJECTIVE: To report a case of interstitial nephritis associated with the administration of bevacizumab. CASE SUMMARY: A 26-year-old man diagnosed with metastatic rectal leiomyosarcoma was treated with intravenous bevacizumab 5 mg/kg and received a total of 3 doses at 2 week intervals. His creatinine had increased from 1.0 mg/dL at baseline to 1.6 mg/dL after 2 doses of bevacizumab and to 4.7 mg/dL after the third dose, prompting admission. Acute renal failure was diagnosed, and hemodialysis was initiated. A renal biopsy revealed interstitial nephritis. Renal failure resolved with cessation of the drug, and the patient did not require further hemodialysis. DISCUSSION: Bevacizumab is a recombinant humanized monoclonal immunoglobulin G antibody to vascular endothelial growth factor. Bevacizumab has shown efficacy in treatment of patients with renal cell carcinoma and colorectal cancer and has been approved by the Food and Drug Administration as a first-line treatment for metastatic colorectal cancer. Our patient had no other confounding factors that might have caused renal failure. The presence of primary glomerular disease was excluded by biopsy. According to the Naranjo probability scale, bevacizumab was the probable cause of acute renal failure in this patient. CONCLUSIONS: Bevacizumab can cause acute renal failure by inducing interstitial nephritis. Renal function should be monitored during bevacizumab therapy.

Acute amphotericin B overdose.

OBJECTIVE: To report the clinical course of a woman with cryptococcal meningitis and no previous cardiac disease who developed a fatal cardiac arrhythmia after an acute overdose of amphotericin B and to review its toxicity. CASE SUMMARY: A 41-year-old woman with a history of proliferative glomerulonephritis from systemic lupus erythematosus was admitted with a diagnosis of cryptococcal meningitis. Liposomal amphotericin B was prescribed at the standard dose of 5 mg/kg/day; however, amphotericin B deoxycholate 5 mg/kg was inadvertently administered (usual dose of the deoxycholate formulation is 0.5-0.8 mg/kg/day). The patient developed cardiac arrhythmias, acute renal failure, and anemia. The medication error was noticed after she had received 2 doses of amphotericin B deoxycholate, and it was then discontinued. Despite treatment in the intensive care unit, the woman died on the sixth day after admission. DISCUSSION: Amphotericin B deoxycholate has been reported to produce significant cardiac toxicity, with ventricular arrhythmias and bradycardia reported in overdoses in children and in adults with preexisting cardiac disease, even when administered in conventional dosages and infusion rates. Use of the Naranjo probability scale indicated a highly probable relationship between the observed cardiac toxicity and amphotericin B deoxycholate therapy in this patient. CONCLUSIONS: Given the fulminant course of amphotericin B deoxycholate overdosage and lack of effective therapy, stringent safeguards against its improper administration should be in place.

Use of continuous venovenous hemodiafiltration in a case of severe phenobarbital poisoning.

Conventional hemodialysis and hemoperfusion have been used for life-threatening phenobarbital poisoning. We report the successful use of continuous renal replacement therapy in a case of severe phenobarbital poisoning associated with severe coma and hypotension. Use of this modality led to clearance of phenobarbital with improvement in the clinical status of the patient.