JAMA Netw Open. 2022 May 2;5(5):e2211620. doi: 10.1001/jamanetworkopen.2022.11620.
NO ABSTRACT
PMID:35544143 | DOI:10.1001/jamanetworkopen.2022.11620
Category: Nevin Manimala
Lancet Microbe. 2021 Apr;2(4):e141-e150. doi: 10.1016/S2666-5247(21)00009-4. Epub 2021 Mar 2.
ABSTRACT
BACKGROUND: The epidemiology and severity of non-falciparum malaria in endemic settings has garnered little attention. We aimed to characterise the prevalence, interaction, clinical risk factors, and temporal trends of non-falciparum Plasmodium species among symptomatic individuals presenting at health-care facilities in endemic settings of Kenya.
METHODS: We diagnosed and analysed infecting malaria species (Plasmodium falciparum, Plasmodium ovale curtisi, Plasmodium ovale wallikeri, and Plasmodium malariae) via PCR in clinical samples collected between March 1, 2008, and Dec 31, 2016, from six hospitals located in different regions of Kenya. We recruited patients aged 6 months or older who presented at outpatient departments with symptoms of malaria or tested positive for uncomplicated malaria by malaria rapid diagnostic test. Descriptive statistics were used to describe the prevalence and distribution of Plasmodium species. A statistical model was designed and used for estimating the frequency of Plasmodium species and assessing interspecies interactions. Mixed-effect linear regression models with random slopes for each location were used to test for change in prevalence over time.
FINDINGS: Samples from 2027 symptomatic participants presenting at care facilities were successfully analysed for all Plasmodium species. 1469 (72·5%) of the samples were P falciparum single-species infections, 523 (25·8%) were mixed infections, and only 35 (1·7%) were single non-falciparum species infections. 452 (22·3%) were mixed infections containing P ovale spp. A likelihood-based model calculation of the population frequency of each species estimated a significant within-host interference between P falciparum and P ovale curtisi. Mixed-effect logistic regression models identified a significant increase in P ovale wallikeri (2·1% per year; p=0·043) and P ovale curtisi (0·7% per year; p=0·0002) species over time, with a reciprocal decrease in P falciparum single-species infections (2·5% per year; p=0·0065). The frequency of P malariae infections did not significantly change over time. Risk of P falciparum infections presenting with fever was lower if co-infected with P malariae (adjusted odds ratio 0·43, 95% CI 0·25-0·74; p=0·0023).
INTERPRETATION: Our results show a prevalence of non-falciparum species infections of 27·5% among symptomatic individuals presenting at care facilities, which is higher than expected from previous cross-sectional surveys. The proportion of infections with P ovale wallikeri and P ovale curtisi was observed to significantly increase over the period of study, which could be due to attenuated responsiveness of these species to malaria drug treatment. The increase in frequency of P ovale spp could threaten the malaria control efforts in Kenya and pose increased risk of malaria to travellers.
FUNDING: Armed Forces Health Surveillance Branch and its Global Emerging Infections Surveillance Section.
PMID:35544189 | DOI:10.1016/S2666-5247(21)00009-4
JAMA Netw Open. 2022 May 2;5(5):e2211634. doi: 10.1001/jamanetworkopen.2022.11634.
ABSTRACT
IMPORTANCE: Stimulant medication use is common among individuals receiving buprenorphine for opioid use disorder (OUD). Associations between prescription stimulant use and treatment outcomes in this population have been understudied.
OBJECTIVES: To investigate whether use of prescription stimulants was associated with (1) drug-related poisoning and (2) buprenorphine treatment retention.
DESIGN, SETTING, AND PARTICIPANTS: This retrospective, recurrent-event cohort study with a case-crossover design used a secondary analysis of administrative claims data from IBM MarketScan Commercial and Multi-State Medicaid databases from January 1, 2006, to December 31, 2016. Primary analyses were conducted from March 1 through August 31, 2021. Individuals aged 12 to 64 years with an OUD diagnosis and prescribed buprenorphine who experienced at least 1 drug-related poisoning were included in the analysis. Unit of observation was the person-day.
EXPOSURES: Days of active stimulant prescriptions.
MAIN OUTCOMES AND MEASURES: Primary outcomes were drug-related poisoning and buprenorphine treatment retention. Drug-related poisonings were defined using International Classification of Diseases, Ninth Revision, and International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, codes; treatment retention was defined by continuous treatment claims until a 45-day gap was observed.
RESULTS: There were 13 778 567 person-days of observation time among 22 946 individuals (mean [SD] age, 32.8 [11.8] years; 50.3% men) who experienced a drug-related poisoning. Stimulant treatment days were associated with 19% increased odds of drug-related poisoning (odds ratio [OR], 1.19 [95% CI, 1.06-1.34]) compared with nontreatment days; buprenorphine treatment days were associated with 38% decreased odds of poisoning (OR, 0.62 [95% CI, 0.59-0.65]). There were no significant interaction effects between use of stimulants and buprenorphine. Stimulant treatment days were associated with decreased odds of attrition from buprenorphine treatment (OR, 0.64 [95% CI, 0.59-0.70]), indicating that stimulants were associated with 36% longer mean exposure to buprenorphine and its concomitant protection.
CONCLUSIONS AND RELEVANCE: Among persons with OUD, use of prescription stimulants was associated with a modest increase in per-day risk of drug-related poisoning, but this risk was offset by the association between stimulant use and improved retention to buprenorphine treatment, which is associated with protection against overdose.
PMID:35544135 | DOI:10.1001/jamanetworkopen.2022.11634
Lancet Microbe. 2022 May;3(5):e336-e347. doi: 10.1016/S2666-5247(21)00356-6. Epub 2022 Mar 23.
ABSTRACT
BACKGROUND: Tafenoquine was recently approved as a prophylaxis and radical cure for Plasmodium vivax infection, but its Plasmodium falciparum transmission-blocking efficacy is unclear. We aimed to establish the efficacy and safety of three single low doses of tafenoquine in combination with dihydroartemisinin-piperaquine for reducing gametocyte density and transmission to mosquitoes.
METHODS: In this four-arm, single-blind, phase 2, randomised controlled trial, participants were recruited at the Clinical Research Unit of the Malaria Research and Training Centre of the University of Bamako in Mali. Eligible participants were aged 12-50 years, with asymptomatic P falciparum microscopy-detected gametocyte carriage, had a bodyweight of 80 kg or less, and had no clinical signs of malaria defined by fever. Participants were randomly assigned (1:1:1:1) to standard treatment with dihydroartemisinin-piperaquine, or dihydroartemisinin-piperaquine plus a single dose of tafenoquine (in solution) at a final dosage of 0·42 mg/kg, 0·83 mg/kg, or 1·66 mg/kg. Randomisation was done with a computer-generated randomisation list and concealed with sealed, opaque envelopes. Dihydroartemisinin-piperaquine was administered as oral tablets over 3 days (day 0, 1, and 2), as per manufacturer instructions. A single dose of tafenoquine was administered as oral solution on day 0 in parallel with the first dose of dihydroartemisinin-piperaquine. Tafenoquine dosing was based on bodyweight to standardise efficacy and risk variance. The primary endpoint, assessed in the per-protocol population, was median percentage change in mosquito infection rate 7 days after treatment compared with baseline. Safety endpoints included frequency and incidence of adverse events. The final follow-up visit was on Dec 23, 2021; the trial is registered with ClinicalTrials.gov, NCT04609098.
FINDINGS: From Oct 29 to Nov 25, 2020, 1091 individuals were screened for eligibility, 80 of whom were enrolled and randomly assigned (20 per treatment group). Before treatment, 53 (66%) individuals were infectious to mosquitoes, infecting median 12·50% of mosquitoes (IQR 3·64-35·00). Within-group reduction in mosquito infection rate on day 7 was 79·95% (IQR 57·15-100; p=0·0005 for difference from baseline) following dihydroartemisinin-piperaquine only, 100% (98·36-100; p=0·0005) following dihydroartemisinin-piperaquine plus tafenoquine 0·42 mg/kg, 100% (100-100; p=0·0001) following dihydroartemisinin-piperaquine plus tafenoquine 0·83 mg/kg, and 100% (100-100; p=0·0001) following dihydroartemisinin-piperaquine plus tafenoquine 1·66 mg/kg. 55 (69%) of 80 participants had a total of 94 adverse events over the course of the trial; 86 (92%) adverse events were categorised as mild, seven (7%) as moderate, and one (1%) as severe. The most common treatment-related adverse event was mild or moderate headache, which occurred in 15 (19%) participants (dihydroartemisinin-piperaquine n=2; dihydroartemisinin-piperaquine plus tafenoquine 0·42 mg/kg n=6; dihydroartemisinin-piperaquine plus tafenoquine 0·83 mg/kg n=3; and dihydroartemisinin-piperaquine plus tafenoquine 1·66 mg/kg n=4). No serious adverse events occurred. No significant differences in the incidence of all adverse events (p=0·73) or treatment-related adverse events (p=0·62) were observed between treatment groups.
INTERPRETATION: Tafenoquine was well tolerated at all doses and accelerated P falciparum gametocyte clearance. All tafenoquine doses showed improved transmission reduction at day 7 compared with dihydroartemisinin-piperaquine alone. These data support the case for further research on tafenoquine as a transmission-blocking supplement to standard antimalarials.
FUNDING: Bill & Melinda Gates Foundation.
TRANSLATIONS: For the French, Portuguese, Spanish and Swahili translations of the abstract see Supplementary Materials section.
PMID:35544095 | DOI:10.1016/S2666-5247(21)00356-6
Nephrol Dial Transplant. 2022 May 11:gfac174. doi: 10.1093/ndt/gfac174. Online ahead of print.
ABSTRACT
BACKGROUND: In the general population, the seroconversion rate after primary vaccination with two doses of an anti-SARS-CoV-2 mRNA vaccine reaches nearly 100%, with significantly higher antibody titers after mRNA-1273 vaccination compared to BNT162b2 vaccination. Here, we performed a systematic review and meta-analysis to compare the antibody response after two-dose mRNA-1273 versus BNT162b2 vaccination in solid organ transplant (SOT) recipients.
METHODS: A systematic literature research was performed in Pubmed, Web of Science, and the Cochrane library and original research papers were included for a meta-analysis to calculate vaccine-specific seroconversion rates for each of the mRNA vaccines. Next, the pooled relative seroconversion rate was estimated.
RESULTS: Eight studies that described the development of antibodies against receptor-binding domain (RBD) and/or spike protein were eligible for meta-analysis. Two of these studies also reported antibody titers. The meta-analysis revealed lower seroconversion rates in SOT recipients vaccinated with two doses of BNT162b2 (44.3%; 95% confidence interval (CI): [34.1%-54.7%]) as compared to such patients vaccinated with two doses of mRNA-1273 (58.4%; 95% CI: [47.2%-69.2%]). The relative seroconversion rate amounted 0.795 (95% CI: [0.732-0.864]).
CONCLUSIONS: This systematic review and meta-analysis indicates that, in SOT recipients, higher seroconversion rates were observed after vaccination with mRNA-1273 compared to BNT162b2.
PMID:35544087 | DOI:10.1093/ndt/gfac174
Lancet Microbe. 2022 Apr;3(4):e294-e302. doi: 10.1016/S2666-5247(21)00327-X. Epub 2022 Mar 11.
ABSTRACT
BACKGROUND: Pleural infection is a common and severe disease with high morbidity and mortality worldwide. The knowledge of pleural infection bacteriology remains incomplete, as pathogen detection methods based on culture have insufficient sensitivity and are biased to selected microbes. We designed a study with the aim to discover and investigate the total microbiome of pleural infection and assess the correlation between bacterial patterns and 1-year survival of patients.
METHODS: We assessed 243 pleural fluid samples from the PILOT study, a prospective observational study on pleural infection, with 16S rRNA next generation sequencing. 20 pleural fluid samples from patients with pleural effusion due to a non-infectious cause and ten PCR-grade water samples were used as controls. Downstream analysis was done with the DADA2 pipeline. We applied multivariate Cox regression analyses to investigate the association between bacterial patterns and 1-year survival of patients with pleural infection.
FINDINGS: Pleural infection was predominately polymicrobial (192 [79%] of 243 samples), with diverse bacterial frequencies observed in monomicrobial and polymicrobial disease and in both community-acquired and hospital-acquired infection. Mixed anaerobes and other Gram-negative bacteria predominated in community-acquired polymicrobial infection whereas Streptococcus pneumoniae prevailed in monomicrobial cases. The presence of anaerobes (hazard ratio 0·46, 95% CI 0·24-0·86, p=0·015) or bacteria of the Streptococcus anginosus group (0·43, 0·19-0·97, p=0·043) was associated with better patient survival, whereas the presence (5·80, 2·37-14·21, p<0·0001) or dominance (3·97, 1·20-13·08, p=0·024) of Staphylococcus aureus was linked with lower survival. Moreover, dominance of Enterobacteriaceae was associated with higher risk of death (2·26, 1·03-4·93, p=0·041).
INTERPRETATION: Pleural infection is a predominantly polymicrobial infection, explaining the requirement for broad spectrum antibiotic cover in most individuals. High mortality infection associated with S aureus and Enterobacteriaceae favours more aggressive, with a narrower spectrum, antibiotic strategies.
FUNDING: UK Medical Research Council, National Institute for Health Research Oxford Biomedical Research Centre, Wellcome Trust, Oxfordshire Health Services Research Committee, Chinese Academy of Medical Sciences, and John Fell Fund.
PMID:35544066 | DOI:10.1016/S2666-5247(21)00327-X
JAMA Cardiol. 2022 May 11. doi: 10.1001/jamacardio.2022.0901. Online ahead of print.
ABSTRACT
IMPORTANCE: Pathogenic variants associated with inherited cardiomyopathy are recognized as important and clinically actionable when identified, leading some clinicians to recommend population-wide genomic screening.
OBJECTIVE: To determine the prevalence and clinical importance of pathogenic variants associated with inherited cardiomyopathy within the context of contemporary clinical care.
DESIGN, SETTING, AND PARTICIPANTS: This was a genetic association study of participants in Atherosclerosis in Risk Communities (ARIC), recruited from 1987 to 1989, with median follow-up of 27 years, and the UK Biobank, recruited from 2006 to 2010, with median follow-up of 10 years. ARIC participants were recruited from 4 sites across the US. UK Biobank participants were recruited from 22 sites across the UK. Participants in the US were of African and European ancestry; those in the UK were of African, East Asian, South Asian, and European ancestry. Statistical analyses were performed between August 1, 2021, and February 9, 2022.
EXPOSURES: Rare genetic variants predisposing to inherited cardiomyopathy.
MAIN OUTCOMES AND MEASURES: Pathogenicity of observed DNA sequence variants in sequenced exomes of 13 genes (ACTC1, FLNC, GLA, LMNA, MYBPC3, MYH7, MYL2, MYL3, PRKAG2, TNNI3, TNNT2, TPM1, and TTN) associated with inherited cardiomyopathies were classified by a blinded clinical geneticist per American College of Medical Genetics recommendations. Incidence of all-cause mortality, heart failure, and atrial fibrillation were determined. Cardiac magnetic resonance imaging, echocardiography, and electrocardiogram measures were assessed in a subset of participants.
RESULTS: A total of 9667 ARIC participants (mean [SD] age, 54.0 [5.7] years; 4232 women [43.8%]; 2658 African [27.5%] and 7009 European [72.5%] ancestry) and 49 744 UK Biobank participants (mean [SD] age, 57.1 [8.0] years; 27 142 women [54.5%]; 1006 African [2.0%], 173 East Asian [0.3%], 939 South Asian [1.9%], and 46 449 European [93.4%] European ancestry) were included in the study. Of those, 59 participants (0.61%) in ARIC and 364 participants (0.73%) in UK Biobank harbored an actionable pathogenic or likely pathogenic variant associated with dilated or hypertrophic cardiomyopathy. Carriers of these variants were not reliably identifiable by imaging. However, the presence of these variants was associated with increased risk of heart failure (hazard ratio [HR], 1.7; 95% CI, 1.1-2.8), atrial fibrillation (HR, 2.9; 95% CI, 1.9-4.5), and all-cause mortality (HR, 1.5; 95% CI, 1.1-2.2) in ARIC. Similar risk patterns were observed in the UK Biobank.
CONCLUSIONS AND RELEVANCE: Results of this genetic association study suggest that approximately 0.7% of study participants harbored a pathogenic variant associated with inherited cardiomyopathy. These variant carriers would be challenging to identify within clinical practice without genetic testing but are at increased risk for cardiovascular disease and all-cause mortality.
PMID:35544052 | DOI:10.1001/jamacardio.2022.0901
Lancet Microbe. 2022 Feb;3(2):e87-e89. doi: 10.1016/S2666-5247(22)00002-7. Epub 2022 Feb 2.
NO ABSTRACT
PMID:35544046 | DOI:10.1016/S2666-5247(22)00002-7
Biol Trace Elem Res. 2022 May 11. doi: 10.1007/s12011-022-03256-w. Online ahead of print.
ABSTRACT
Increased levels of metal ions in human seminal fluid have a significant correlation with male fertility. Few publications explain the effect of metals in semen and their influence on assisted reproductive treatments. Semen parameters and the levels of twenty-two metals were measured in the seminal fluid of 102 men attended in a Reproductive Unit. Metals were determined by optical emission spectrophotometry. A statistical relationship was found between spermiogram and iron, which was lower than expected in pathological spermiograms (p = 0.032); zinc (p = 0.066), calcium (p = 0.047), and magnesium (p = 0.048) mean levels were higher in normozoospermics. More days of sexual abstinence correlates with higher seminal zinc (p = 0.001) and magnesium levels (p = 0.002). Lower vanadium values were found to be associated with higher fertilization rates (p = 0.039). Higher values of lead (p = 0.052) and vanadium (p = 0.032) were obtained in patients who did not reach 100% embryo cleavage rate. Aluminium (p = 0.042) and sodium (p = 0.002) were found in lower amounts associated with better blastocyst rates. The implantation rate shows an inverse association with women’s age and iron and calcium content, compared to magnesium and sodium which presented a significant direct association with this percentage. A significant direct relationship was found between the positive evolution of pregnancy and the values of zinc (p = 0.004), calcium (p = 0.013), potassium (p = 0.002), and magnesium (p = 0.009). The study confirms that zinc, iron, calcium, sodium, aluminium, magnesium, vanadium, and lead have positive-negative effects on reproduction and support the analysis of metals in semen as a new line of study on male fertility with implications for reproductive outcomes.
PMID:35543968 | DOI:10.1007/s12011-022-03256-w
Zhongguo Zhen Jiu. 2022 May 12;42(5):573-8. doi: 10.13703/j.0255-2930.20210311-0008.
ABSTRACT
OBJECTIVE: To analyze the main factors affecting the positive results of acupuncture for chronic pain in English literature of randomized controlled trial (RCT), in order to provide reference for the design of acupuncture clinical research.
METHODS: The RCTs of acupuncture for chronic pain published before March 26, 2020 were searched in PubMed, EMbase and Cochrane Library by computer. A total of 21 factors were analyzed by single-factor analysis, and the factors with statistically significant difference were selected for multivariate Logistic regression analysis.
RESULTS: A total of 69 RCTs were included, including 47 RCTs (68.12%) with positive results and 22 RCTs (31.88%) with non-positive results. The multivariate Logistic regression analysis was performed with the three screened factors (publication year, treatment frequency and intervention form) selected by single-factor analysis, and the results showed that the positive results were related to the frequency of acupuncture treatment. The positive rate of RCT with frequency≥2 times a week was 3.24 times of that with frequency<2 times a week (OR=3.24, 95%CI =[1.07,9.83], P<0.05).
CONCLUSION: Acupuncture frequency may be the main factor affecting the positive results of RCT in English literature of acupuncture for chronic pain. More researches are needed in the future to explore the influence of acupuncture frequency on the curative effect.
PMID:35543952 | DOI:10.13703/j.0255-2930.20210311-0008