Juvenile Otosclerosis (JO) and Congenital Stapes Footplate Fixation (CSFF) are rare ossicular chain disorders seen in the paediatric population and present with conductive hearing loss. Ongoing controversy exists regarding the role of surgical intervention in JO and CSFF given the poorer hearing outcomes and complications when compared with surgical intervention for adult otosclerosis. The objective of this study is to assess the published data on the surgical outcomes of JO and CSFF in order to guide clinicians and counsel patients on the various medical options for these disease entities.
A systematic review of MEDLINE, EMBASE and Cochrane was performed with inclusion criteria of children with JO or CSFF and hearing outcomes following stapes surgery. Studies identified by the search were reviewed and assessed by two independent reviewers in line with the PRISMA guidelines.
464 articles were initially reviewed and 28 articles met inclusion in the systematic review and meta-analysis. A total of 810 ears (473 and 337 cases of JO and CSFF respectively) underwent stapes surgery. Average age at time of surgery for JO and CSFF was 14.3 and 10.2 years old respectively. The mean pre-operative Air-Bone-Gap (ABG) for JO and CSFF was 31.8 ± 5.2 dB and 39.4 ± 10 dB respectively. Following stapes surgery, the mean post-operative ABG for JO and CSFF was 9.6 ± 6 dB and 19.2 ± 12.5 dB respectively. Surgical success rate (defined as ABG <10 dB) was 81% for JO and 41% for CSFF. Mean ABG gain for JO and CSFF was 24.8 dB (95% CI: 18.6-33.1) and 22.6 dB (95% CI: 18.4-27.8) respectively. The reported number of dead ears was 4/473 (0.8%) for JO and 2/337 (0.6%) for CSFF. 23 cases (2.8%) reported sensorineural hearing loss (SNHL) >10 dB.
CSFF was associated with poorer hearing outcomes compared to JO, however both entities showed similar improvement in ABG post operatively. Counselling patients and their families on the surgical success rates and complications of JO or CSFF is an important part of the decision making process when deciding between a surgical option or conservative measures such as hearing aids.

Juvenile otosclerosis and congenital stapes footplate fixation. A systematic review and meta-analysis of surgical outcomes and management.

Malaria in pregnancy affects both the mother and the fetus. However, evidence supporting treatment guidelines for uncomplicated (including asymptomatic) falciparum malaria in pregnant women is scarce and assessed in varied ways. We did a systematic literature review and individual patient data (IPD) meta-analysis to compare the efficacy and tolerability of different artemisinin-based or quinine-based treatments for malaria in pregnant women.
We did a systematic review of interventional or observational cohort studies assessing the efficacy of artemisinin-based or quinine-based treatments in pregnancy. Seven databases (MEDLINE, Embase, Global Health, Cochrane Library, Scopus, Web of Science, and Literatura Latino Americana em Ciencias da Saude) and two clinical trial registries (International Clinical Trials Registry Platform and ClinicalTrials.gov) were searched. The final search was done on April 26, 2019. Studies that assessed PCR-corrected treatment efficacy in pregnancy with follow-up of 28 days or more were included. Investigators of identified studies were invited to share data from individual patients. The outcomes assessed included PCR-corrected efficacy, PCR-uncorrected efficacy, parasite clearance, fever clearance, gametocyte development, and acute adverse events. One-stage IPD meta-analysis using Cox and logistic regression with random-effects was done to estimate the risk factors associated with PCR-corrected treatment failure, using artemether-lumefantrine as the reference. This study is registered with PROSPERO, CRD42018104013.
Of the 30 studies assessed, 19 were included, representing 92% of patients in the literature (4968 of 5360 episodes). Risk of PCR-corrected treatment failure was higher for the quinine monotherapy (n=244, adjusted hazard ratio [aHR] 6·11, 95% CI 2·57-14·54, p<0·0001) but lower for artesunate-amodiaquine (n=840, 0·27, 95% 0·14-0·52, p<0·0001), artesunate-mefloquine (n=1028, 0·56, 95% 0·34-0·94, p=0·03), and dihydroartemisinin-piperaquine (n=872, 0·35, 95% CI 0·18-0·68, p=0·002) than artemether-lumefantrine (n=1278) after adjustment for baseline asexual parasitaemia and parity. The risk of gametocyte carriage on day 7 was higher after quinine-based therapy than artemisinin-based treatment (adjusted odds ratio [OR] 7·38, 95% CI 2·29-23·82).
Efficacy and tolerability of artemisinin-based combination therapies (ACTs) in pregnant women are better than quinine. The lower efficacy of artemether-lumefantrine compared with other ACTs might require dose optimisation.
The Bill & Melinda Gates Foundation, ExxonMobil Foundation, and the University of Oxford Clarendon Fund.

Efficacy and tolerability of artemisinin-based and quinine-based treatments for uncomplicated falciparum malaria in pregnancy: a systematic review and individual patient data meta-analysis.

Understanding the level and characteristics of protection from past SARS-CoV-2 infection against subsequent re-infection, symptomatic COVID-19 disease, and severe disease is essential for predicting future potential disease burden, for designing policies that restrict travel or access to venues where there is a high risk of transmission, and for informing choices about when to receive vaccine doses. We aimed to systematically synthesise studies to estimate protection from past infection by variant, and where data allow, by time since infection.
In this systematic review and meta-analysis, we identified, reviewed, and extracted from the scientific literature retrospective and prospective cohort studies and test-negative case-control studies published from inception up to Sept 31, 2022, that estimated the reduction in risk of COVID-19 among individuals with a past SARS-CoV-2 infection in comparison to those without a previous infection. We meta-analysed the effectiveness of past infection by outcome (infection, symptomatic disease, and severe disease), variant, and time since infection. We ran a Bayesian meta-regression to estimate the pooled estimates of protection. Risk-of-bias assessment was evaluated using the National Institutes of Health quality-assessment tools. The systematic review was PRISMA compliant and was registered with PROSPERO (number CRD42022303850).
We identified a total of 65 studies from 19 different countries. Our meta-analyses showed that protection from past infection and any symptomatic disease was high for ancestral, alpha, beta, and delta variants, but was substantially lower for the omicron BA.1 variant. Pooled effectiveness against re-infection by the omicron BA.1 variant was 45·3% (95% uncertainty interval [UI] 17·3-76·1) and 44·0% (26·5-65·0) against omicron BA.1 symptomatic disease. Mean pooled effectiveness was greater than 78% against severe disease (hospitalisation and death) for all variants, including omicron BA.1. Protection from re-infection from ancestral, alpha, and delta variants declined over time but remained at 78·6% (49·8-93·6) at 40 weeks. Protection against re-infection by the omicron BA.1 variant declined more rapidly and was estimated at 36·1% (24·4-51·3) at 40 weeks. On the other hand, protection against severe disease remained high for all variants, with 90·2% (69·7-97·5) for ancestral, alpha, and delta variants, and 88·9% (84·7-90·9) for omicron BA.1 at 40 weeks.
Protection from past infection against re-infection from pre-omicron variants was very high and remained high even after 40 weeks. Protection was substantially lower for the omicron BA.1 variant and declined more rapidly over time than protection against previous variants. Protection from severe disease was high for all variants. The immunity conferred by past infection should be weighed alongside protection from vaccination when assessing future disease burden from COVID-19, providing guidance on when individuals should be vaccinated, and designing policies that mandate vaccination for workers or restrict access, on the basis of immune status, to settings where the risk of transmission is high, such as travel and high-occupancy indoor settings.
Bill & Melinda Gates Foundation, J Stanton, T Gillespie, and J and E Nordstrom.

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