bluuebunny/crossref_metadata_2025 huggingface dataset:
Indications for a genetic basis for big bacteria and description of the giant cable bacterium
Candidatus
Electrothrix gigas sp. nov.
Authors: Geelhoed Jeanine S. , Thorup Casper A. , Bjerg Jesper J. , Schreiber Lars , Nielsen Lars Peter , Schramm Andreas , Meysman Filip J. R. , Marshall Ian P. G.
Published: September 2023

Bacterial cells can vary greatly in size, from a few hundred nanometers to hundreds of micrometers in diameter. Filamentous cable bacteria also display substantial size differences, with filament diameters ranging from 0.4 to 8 µm. We analyzed the genomes of cable bacterium filaments from 11 coastal environments of which the resulting 23 new genomes represent 10 novel species-level clades of
Candidatus
Electrothrix and two clades that putatively represent novel genus-level diversity. Fluorescence
in situ
hybridization with a species-level probe showed that large-sized cable bacteria belong to a novel species with the proposed name
Ca
. Electrothrix gigas. Comparative genome analysis suggests genes that play a role in the construction or functioning of large cable bacteria cells: the genomes of
Ca
. Electrothrix gigas encode a novel actin-like protein as well as a species-specific gene cluster encoding four putative pilin proteins and a putative type II secretion platform protein, which are not present in other cable bacteria. The novel actin-like protein was also found in a number of other giant bacteria, suggesting there could be a genetic basis for large cell size. This actin-like protein (denoted big bacteria protein, Bbp) may have a function analogous to other actin proteins in cell structure or intracellular transport. We contend that Bbp may help overcome the challenges of diffusion limitation and/or morphological complexity presented by the large cells of
Ca
. Electrothrix gigas and other giant bacteria.

IMPORTANCE

In this study, we substantially expand the known diversity of marine cable bacteria and describe cable bacteria with a large diameter as a novel species with the proposed name
Candidatus
Electrothrix gigas. In the genomes of this species, we identified a gene that encodes a novel actin-like protein [denoted big bacteria protein (Bbp)]. The
bbp
gene was also found in a number of other giant bacteria, predominantly affiliated to Desulfobacterota and Gammaproteobacteria, indicating that there may be a genetic basis for large cell size. Thus far, mostly structural adaptations of giant bacteria, vacuoles, and other inclusions or organelles have been observed, which are employed to overcome nutrient diffusion limitation in their environment. In analogy to other actin proteins, Bbp could fulfill a structural role in the cell or potentially facilitate intracellular transport.
Phenotype and genotype analysis for
Helicobacter pylori
antibiotic resistance in outpatients: a retrospective study
Authors: Xiong Mengqiu , Mohammed Aljaberi Hend Sadeq , Khalid Ansari Nida , Sun Yalan , Yin Sijie , Nasifu Lubanga , Sun Huiling , Xu Tao , Pan Yuqin , Nie Zhenlin , Liu Caidong , Zhang Zhenyu , Jiang Zongdan , Wang Shukui , He Bangshun
Published: September 2023

To investigate the antibiotic resistance of
Helicobacter pylori
(
H. pylori
) in outpatients and to explore the consistency between genotype and phenotype of
H. pylori
antibiotic resistance. A retrospective study on outpatients screened with urea breath test for
H. pylori
infection in Nanjing First Hospital from April 2018 to January 2022. Patients who tested positive underwent a consented upper endoscopy, and the
H. pylori
infection was confirmed by rapid urease test (RUT) and
H. pylori
culture. For antibiotic resistance phenotype analysis, the
H. pylori
strains isolated from gastric biopsy were tested for antibiotic resistance phenotype by the Kirby-Bauer disk diffusion test. In addition, the antibiotic resistance genotype of isolated
H. pylori
was tested with a real-time polymerase chain reaction. A total of 4,399 patients underwent
H. pylori
infection screening, and 3,306
H. pylori
strains were isolated. The antibiotic resistance phenotype test revealed that the resistance rates of metronidazole (MTZ), clarithromycin (CLR), levofloxacin (LEV), amoxicillin (AMX), furazolidone (FR), and tetracycline (TE) were 74.58%, 48.61%, 34.83%, 0.76%, 0.27%, and 0.09%, respectively. Additionally, the antibiotic resistance genotype test revealed that rdxA gene mutation A610G (92.96%), A91G (92.95%), C92A (93.00%), and G392A (95.07%) were predominant in
H. pylori
with MTZ resistance; 23S rRNA gene mutation A2143G (86.47%) occurred in most
H. pylori
with CLR resistance; and gyrA gene mutation 87Ile/Lys/Tyr/Arg (97.32%) and 91Asn/Gly/Tyr (90.61%) were the most popular mutations in strains with LEV resistance. The phenotypic resistance and genotypic resistance to CLR (kappa value = 0.824) and LEV (kappa value = 0.895) were in good agreement. The history of eradication with MTZ, CLR, LEV, and AMX was correlated with
H. pylori
resistance. In short, this study demonstrated that drug resistance of
H. pylori
was mainly to MTZ, CLR, and LEV in local outpatients. Three drugs can be selected for increased MICs (Minimum Inhibitory Concentration) via single chromosomal mutations. In addition, the genotype could be used to predict the phenotypic
H. pylori
resistance to CLR and LEV.

IMPORTANCE

Helicobacter pylori
is a key bacterium that causes stomach diseases. There was a high prevalence of
H. pylori
in the Chinese population. We analyzed the resistance phenotype and genotype characteristics of
H. pylori
in 4,399 outpatients at the First Hospital of Nanjing, China. We found a higher resistance rate to metronidazole (MTZ) , clarithromycin (CLR), and levofloxacin (LEV), and the genotype could be used to predict the phenotypic
H. pylori
resistance to CLR and LEV. This study provides information on
H. pylori
infection and also provides guidance for clinical doctors' drug treatment.
A novel coli myophage and antibiotics synergistically inhibit the growth of the uropathogenic
E. coli
strain CFT073 in stoichiometric niches
Authors: Khunti Patiphan , Chantakorn Kittapart , Tantibhadrasapa Arishabhas , Htoo Htut Htut , Thiennimitr Parameth , Nonejuie Poochit , Chaikeeratisak Vorrapon
Published: September 2023

Urinary tract infections are widespread bacterial infections affecting millions of people annually, with
Escherichia coli
being the most prevalent. Although phage therapy has recently gained interest as a promising alternative therapy for antibiotic-resistant bacteria, several studies have raised concerns regarding the evolution of phage resistance, making the therapy ineffective. In this study, we discover a novel coli myophage designated as Killian that targets
E. coli
strains, including the uropathogenic
E. coli
(UPEC) strain CFT073. It requires at least 20 minutes for 90% of its particles to adsorb to the host cells, undergoes subcellular activities for replication for 30 minutes, and eventually lyses the cells with a burst size of about 139 particles per cell. Additionally, Killian can withstand a wide variety of temperatures (4–50°C) and pHs (
4
–
10
). Genome analysis reveals that Killian’s genome consists of 169,905 base pairs with 35.5% GC content, encoding 276 open reading frames; of these, 209 are functionally annotated with no undesirable genes detected, highlighting its potential as an antibiotic alternative against UPEC. However, after an 8-hour phage treatment at high multiplicities of infection, bacterial density continuously increases, indicating an onset of bacterial growth revival. Thus, the combination study between the phage and three different antibiotics, including amikacin, ciprofloxacin, and piperacillin, was performed and showed that certain pairs of phage and antibiotics exhibited synergistic interactions in suppressing the bacterial growth revival. These findings suggest that Killian-antibiotic combinations are effective in inhibiting the growth of UPEC.

IMPORTANCE

Phage therapy has recently been in the spotlight as a viable alternative therapy for bacterial infections. However, several studies have raised concerns about the emergence of phage resistance that occurs during treatment, making the therapy not much effective. Here, we present the discovery of a novel
E. coli
myophage that, by itself, can effectively kill the uropathogenic
E. coli
, but the emergence of bacterial growth revival was detected during the treatment. Phage and antibiotics are then combined to improve the efficiency of the phage in suppressing the bacterial re-growth. This research would pave the way for the future development of phage-antibiotic cocktails for the sustainable use of phages for therapeutic purposes.
Lugdunin production and activity in
Staphylococcus lugdunensis
isolates are associated with its genotypes
Authors: Chang Shih-Cheng , Kao Cheng-Yen , Lin Lee-Chung , Hidrosollo Jazon Harl , Lu Jang-Jih
Published: September 2023

Lugdunin produced by
Staphylococcus lugdunensis
has been shown to have broad inhibitory activity against Gram-positive bacteria; however, lugdunin activity among
S. lugdunensis
isolates and its association with different
agr
, SCC
mec
, and sequence types remain unclear. We used matrix-assisted laser desorption ionization-time-of-flight mass spectrometry to identify
S. lugdunensis
and collected 202
S
.
lugdunensis
samples for further assays. Agar spot tests were performed to characterize
S. lugdunensis
lugdunin production and activity. Multilocus sequence typing, SCC
mec,
and
agr
genotyping were performed on
S. lugdunensis
. In all, 91 S
taphylococcus aureus
strains with varying vancomycin susceptibilities were used to examine lugdunin activity in
S. lugdunensis
. In total, 48
S
.
lugdunensis
strains (23.8%) were found to be oxacillin-resistant
S. lugdunensis
(ORSL), whereas 154 (76.2%) were classified as oxacillin-sensitive
S. lugdunensis
(OSSL). Moreover, 16 (33.3%) ORSL and 35 (22.7%) OSSL strains showed antibacterial activity against
S. aureus
. Our data showed that most lugdunin-producing ORSL strains (14/48, 29.2%) were of ST3-SCC
mec
V-
agr
II genotypes, whereas most lugdunin-producing OSSL strains (15/154, 9.7%) were of ST3-
agr
II, followed by ST1-
agr
I (10/154, 6.5%). Our data also revealed that lugdunin exhibited weak inhibitory activity against the VISA ST239 isolate. In addition, we observed that ST239 VSSA was more resistant to lugdunin than ST5, ST59, and ST45 VSSA. Taken together, our data pioneered the epidemiology of lugdunin production in
S. lugdunensis
isolates and revealed its association with genotypes. However, further molecular and bioinformatics investigations are needed to elucidate the regulatory mechanisms of lugdunin production and activity.

IMPORTANCE

Lugdunin is active against both methicillin-resistant
Staphylococcus aureus
and vancomycin-resistant enterococci by dissipating their membrane potential. However, the association of lugdunin activity with the genotypes of
Staphylococcus lugdunensis
has not been addressed. Here, we show the high prevalence of lugdunin-producing strains among ST1 (83.3%), ST2 (66.7%), and ST3 (53.3%)
S. lugdunensis
. Moreover, we identified the antibacterial activity of lugdunin-producing strains against VISA and hVISA. These results shed light on the potential application of lugdunin for the treatment of drug-resistant pathogens.
Insight into the drug-resistant characteristics and genetic diversity of multidrug-resistant
Mycobacterium tuberculosis
in China
Authors: Song Zexuan , Liu Chunfa , He Wencong , Pei Shaojun , Liu Dongxin , Cao Xiaolong , Wang Yiting , He Ping , Zhao Bing , Ou Xichao , Xia Hui , Wang Shengfen , Zhao Yanlin
Published: September 2023

Multidrug-resistant tuberculosis (MDR-TB) has a severe impact on public health. To investigate the drug-resistant profile, compensatory mutations and genetic variations among MDR-TB isolates, a total of 546 MDR-TB isolates from China underwent drug-susceptibility testing and whole genome sequencing for further analysis. The results showed that our isolates have a high rate of fluoroquinolone resistance (45.60%, 249/546) and a low proportion of conferring resistance to bedaquiline, clofazimine, linezolid, and delamanid. The majority of MDR-TB isolates (77.66%, 424/546) belong to Lineage 2.2.1, followed by Lineage 4.5 (6.41%, 35/546), and the Lineage 2 isolates have a strong association with pre-XDR/XDR-TB (
P
< 0.05) in our study. Epidemic success analysis using time-scaled haplotypic density (THD) showed that clustered isolates outperformed non-clustered isolates. Compensatory mutations happened in
rpoA
,
rpoC,
and non-RRDR of
rpoB
genes, which were found more frequently in clusters and were associated with the increase of THD index, suggesting that increased bacterial fitness was associated with MDR-TB transmission. In addition, the variants in resistance associated genes in MDR isolates are mainly focused on single nucleotide polymorphism mutations, and only a few genes have indel variants, such as
katG
,
ethA
. We also found some genes underwent indel variation correlated with the lineage and sub-lineage of isolates, suggesting the selective evolution of different lineage isolates. Thus, this analysis of the characterization and genetic diversity of MDR isolates would be helpful in developing effective strategies for treatment regimens and tailoring public interventions.

IMPORTANCE

Multidrug-resistant tuberculosis (MDR-TB) is a serious obstacle to tuberculosis prevention and control in China. This study provides insight into the drug-resistant characteristics of MDR combined with phenotypic drug-susceptibility testing and whole genome sequencing. The compensatory mutations and epidemic success analysis were analyzed by time-scaled haplotypic density (THD) method, suggesting clustered isolates and compensatory mutations are associated with MDR-TB transmission. In addition, the insertion and deletion variants happened in some genes, which are associated with the lineage and sub-lineage of isolates, such as the
mpt64
gene. This study offered a valuable reference and increased understanding of MDR-TB in China, which could be crucial for achieving the objective of precision medicine in the prevention and treatment of MDR-TB.
Nifuratel reduces
Salmonella
survival in macrophages by extracellular and intracellular antibacterial activity
Authors: Xie Tian , Liu Guifeng , Ma Jiayi , Wang Yaonan , Gao Ran , Geng Shizhong , Jiao Xinan , Barrow Paul
Published: September 2023

Salmonella
are intracellular bacterial pathogens for which, as with many of the other
Enterobacteriaceae
, antibiotic resistance is becoming an increasing problem. New antibiotics are being sought as recommended by the World Health Organization and other international institutions. These must be able to penetrate macrophages, and infect the major host cells and the
Salmonella
-containing vacuole. This study reports screening a small library of Food and Drug Administration (FDA)-approved drugs for their antibacterial effect in macrophages infected with a rapid-multiplying mutant of
Salmonella
Enteritidis. The most effective drug that was least toxic for macrophages was Nifuratel, a nitrofuran antibiotic already in use for parasitic infections. In mice, it provided 60% protection after oral infection with a lethal
S
. Enteritidis dose with reduced bacterial numbers in the tissues. It was effective against different serovars, including multidrug-resistant strains of
Salmonella
Typhimurium, and in macrophages from different host species and against
Listeria monocytogenes
and
Shigella flexneri
. It reduced IL-10 and STAT3 production in infected macrophages which should increase the inflammatory response against
Salmonella
.

IMPORTANCE

Salmonella
can keep long-term persistence in host's macrophages to evade cellular immune defense and antibiotic attack and exit in some condition and reinfect to cause salmonellosis again. In addition to multidrug resistance, this infection circle causes
Salmonella
clearance difficult in the host, and so there is a great need for new antibacterial agents that reduce intramacrophage
Salmonella
survival to block endogenous
Salmonella
reinfection.
First Data on Vertical Particle Fluxes and Environmental Conditions in the Northern Segment of the Mohns Ridge, Norwegian Sea
Authors: Klyuvitkin A. A. , Kravchishina M. D. , Novigatsky A. N. , Politova N. V. , Bulokhov A. V. , Gulev S. K.
Published: September 2023

Continuous two-year studies of particle fluxes and associated environmental parameters in the axial zone of the Arctic segment of the Mid-Atlantic Ridge at the junction of the Mohns and Knipovich ridges (Norwegian Sea) have been carried out for the first time. Sediment traps were deployed from the R/VAkademik Mstislav Keldyshin June 2019 in the northeastern part of the Mohns Ridge with revision in August 2020 and lifting in July 2021. It is shown that the sedimentation of particles in the study area was affected by the global transport of water masses in the northeasterly direction, with Atlantic waters in the subsurface layer and water masses of Arctic origin recirculating deeper in the subsurface. A weak positive temperature trend at a depth of more than 2500 m (0.02°C over two years) is detected. The bimodal vertical distribution of fluxes and changes in the composition of sinking particles corresponded to the pattern of sediment recycling in the ocean. The annual course of fluxes in the subsurface layer is determined by the activity of Si-concentrating and calcifying plankton, while the maximum bloom period is also manifested in the deep layer. At the same time, the main significant source of the flux deeper than 2000 m is the supply of lithogenic matter from the near-bottom nepheloid layer.
Prognostic significance of melanogenesis pathway and its association with the ultrastructural characterisation of melanosomes in uveal melanoma
Authors: Jha Jayanti , Singh Mithalesh Kumar , Singh Lata , Pushker Neelam , Meel Rachna , Lomi Neiwete , Bakhshi Sameer , Nag Tapas Chandra , Chosdol Kunzang , Sen Seema , Kashyap Seema
Published: September 2023

Background

Pigmentation could be a relevant prognostic factor in uveal melanoma (UM) development. Microphthalmia-associated transcription factor (MITF) regulates melanin synthesis by activating tyrosinase-related protein 2 (TYRP2) and silver protein (SILV) that induce the melanogenesis pathway. Although their oncogenic potential has been observed in various malignancies but has not been investigated in UM Asian population. Our aim is to study the ultrastructure of melanosomes and the prognostic significance of pigmentation markers such as TYRP2, MITF and SILV in UM.

Methods

Transmission electron microscopy was performed to compare the ultrastructure of melanosomes in the normal choroid and UM cases. Immunoexpression of TYRP2, SILV and MITF was analysed in 82 UM samples. The mRNA expression level of all genes was measured in 70 UM cases. A statistical correlation was performed to determine the prognostic significance of all markers.

Results

Premelanosomes and mature melanosomes undergoing dedifferentiation were observed in high-pigmented UM cases as compared with low-pigmented UM cases. Seventy per cent of UM cases showed high SILV expression while TYRP2 and MITF expression was present in 58% and 56% of cases, respectively. At the mRNA level, upregulation of TYRP2, SILV and MITF markers was seen in around 50% of UM cases, which was statistically significant with high pigmentation. Reduced metastatic-free survival was statistically significant with the MITF protein expression.

Conclusion

Our results demonstrated that ultrastructural changes in melanosomes and high expression of TYRP2, MITF and SILV could dysregulate the melanogenesis pathway and might be responsible for the aggressive behaviour of UM.
Suboptimal gestational weight gain and neonatal outcomes in low and middle income countries: individual participant data meta-analysis
Authors: Perumal Nandita , Wang Dongqing , Darling Anne Marie , Liu Enju , Wang Molin , Ahmed Tahmeed , Christian Parul , Dewey Kathryn G , Kac Gilberto , Kennedy Stephen H , Subramoney Vishak , Briggs Brittany , Fawzi Wafaie W
Published: September 2023

Objective

To estimate the associations between gestational weight gain (GWG) during pregnancy and neonatal outcomes in low and middle income countries.

Design

Individual participant data meta-analysis.

Setting

Prospective pregnancy studies from 24 low and middle income countries.

Main outcome measures

Nine neonatal outcomes related to timing (preterm birth) and anthropometry (weight, length, and head circumference) at birth, stillbirths, and neonatal death.

Analysis methods

A systematic search was conducted in PubMed, Embase, and Web of Science which identified 53 prospective pregnancy studies published after the year 2000 with data on GWG, timing and anthropometry at birth, and neonatal mortality. GWG adequacy was defined as the ratio of the observed maternal weight gain over the recommended weight gain based on the Institute of Medicine body mass index specific guidelines, which are derived from data in high income settings, and the INTERGROWTH-21st GWG standards. Study specific estimates, adjusted for confounders, were generated and then pooled using random effects meta-analysis models. Maternal age and body mass index before pregnancy were examined as potential modifiers of the associations between GWG adequacy and neonatal outcomes.

Results

Overall, 55% of participants had severely inadequate (<70%) or moderately inadequate (70% to <90%) GWG, 22% had adequate GWG (90-125%), and 23% had excessive GWG (≥125%). Severely inadequate GWG was associated with a higher risk of low birthweight (adjusted relative risk 1.62, 95% confidence interval 1.51 to 1.72; 48 studies, 93 337 participants; τ
2
=0.006), small for gestational age (1.44, 1.36 to 1.54; 51 studies, 93 191 participants; τ
2
=0.016), short for gestational age (1.47, 1.29 to 1.69; 40 studies, 83 827 participants; τ
2
=0.074), and microcephaly (1.57, 1.31 to 1.88; 31 studies, 80 046 participants; τ
2
=0.145) compared with adequate GWG. Excessive GWG was associated with a higher risk of preterm birth (1.22, 1.13 to 1.31; 48 studies, 103 762 participants; τ
2
=0.008), large for gestational age (1.44, 1.33 to 1.57; 47 studies, 90 044 participants; τ
2
=0.009), and macrosomia (1.52, 1.33 to 1.73; 29 studies, 68 138 participants; τ
2
=0) compared with adequate GWG. The direction and magnitude of the associations between GWG adequacy and several neonatal outcomes were modified by maternal age and body mass index before pregnancy.

Conclusions

Inadequate and excessive GWG are associated with a higher risk of adverse neonatal outcomes across settings. Interventions to promote optimal GWG during pregnancy are likely to reduce the burden of adverse neonatal outcomes, however further research is needed to assess optimal ranges of GWG based on data from low and middle income countries.
Efficacy and safety of an inactivated virus-particle vaccine for SARS-CoV-2, BIV1-CovIran: randomised, placebo controlled, double blind, multicentre, phase 3 clinical trial
Authors: Mohraz Minoo , Vahdat Katayoun , Ghamari Seyyed-Hadi , Abbasi-Kangevari Mohsen , Ghasemi Erfan , Ghabdian Yasaman , Rezaei Negar , Pouya Maryam Amini , Abdoli Asghar , Malekpour Mohammad-Reza , Koohgir Keyvan , Saeedi Moghaddam Sahar , Tabarsi Payam , Moghadami Mohsen , Khorvash Farzin , Khodashahi Rozita , Salehi Mohammadreza , Hosseini Hamed
Published: September 2023

Objective

To report the efficacy, safety, and exploratory immunogenicity findings of two 5 µg doses of the BIV1-CovIran vaccine.

Design

Randomised, placebo controlled, double blind, multicentre, phase 3 clinical trial.

Setting

In six cities of Iran, including Bushehr, Isfahan, Karaj, Mashhad, Shiraz, and Tehran. The first vaccine or placebo injection of the first participant was on 16 May 2021 in Tehran. The last vaccine or placebo injection of the last participant occurred on 15 July 2021 in Isfahan.

Participants

20 000 participants aged 18-75 years were randomly assigned to the intervention or placebo groups with a ratio of 2:1.

Intervention

5 µg vaccine or placebo with the interval of 28 days.

Main outcome measures

Vaccine efficacy for a 90 day follow-up period, safety and explanatory immunogenicity assessment, and variant detection during the trial.

Results

20 000 participants were recruited and randomly assigned to receive BIV1-CovIran (n=13 335 (66.7%)) or placebo (n=6665 (33.3%)). Participants' mean age was 38.3 (standard deviation 11.2) years, and 6913 (34.6%) were female. Among vaccinated participants that had covid-19 reported during the follow-up (median 83 days), 758 (5.9%) had symptoms, 144 (1.1%) had severe infection, and seven (0.1%) were critical. Among participants who received placebo during the follow-up, 688 (10.7%) had symptoms, 221 (3.4%) had severe infection, and 19 (0.3%) were critical. Overall efficacy was 50.2% (95% confidence interval 44.7% to 55.0%) against symptomatic covid-19, 70.5% (63.7% to 76.1%) against severe disease, and 83.1% (61.2% to 93.5%) against critical cases. Two deaths were reported in the efficacy population in the placebo group, no deaths were from the intervention group. During follow-up, 41 922 adverse events were reported: 28 782 (68.7%) were adverse reactions, of which 19 363 (67.3%) were in the intervention group. Most adverse reactions were mild or moderate in severity (grade 1 or 2) and self-limiting. No serious adverse events were related to the injections. For variant investigation, of 119 participants positive for the SARS-CoV-2 variant, 106 (89.1%) were positive for the delta variant.

Conclusions

A two dose regimen of the BIV1-CovIran vaccine conferred efficacy of 50.2% against symptomatic covid-19, 70.5% against severe disease, and 83.1% against critical disease. Vaccination was well tolerated, with no safety concerns raised.

Trial registration

Iranian Registry of Clinical Trials, IRCT20201202049567N3.

Funding

Shifa-Pharmed Industrial Group.
Antimalarial stocking decisions among medicine retailers in Ghana: implications for quality management and control of malaria
Authors: Osman Adams , Amoako Johnson Fiifi , Mariwah Simon , Amoako-Sakyi Daniel , Asiedu Owusu Samuel , Ekor Martins , Hamill Heather , Hampshire Kate
Published: September 2023

Global health efforts such as malarial control require efficient pharmaceutical supply chains to ensure effective delivery of quality-assured medicines to those who need them. However, very little is currently known about decision-making processes within antimalarial supply chains and potential vulnerabilities to substandard and falsified medicines. Addressing this gap, we report on a study that investigated decision-making around the stocking of antimalarial products among private-sector medicine retailers in Ghana. Licensed retail pharmacies and over-the-counter (OTC) medicine retail outlets were sampled across six regions of Ghana using a two-stage stratified sampling procedure, with antimalarial medicines categorised as ‘expensive,’ ‘mid-range,’ and ‘cheaper,’ relative to other products in the shop. Retailers were asked about their motivations for choosing to stock particular products over others. The reasons were grouped into three categories: financial, reputation/experience and professional recommendation. Reputation/experience (76%, 95% CI 72.0% to 80.7%) were the drivers of antimalarial stocking decisions, followed by financial reasons (53.2%, 95% CI 48.1% to 58.3%) and recommendation by certified health professionals (24.7%, 95% CI 20.3% to 29.1%). Financial considerations were particularly influential in stocking decisions of cheaper medicines. Moreover, pharmacies and OTCs without a qualified pharmacist were significantly more likely to indicate financial reasons as a motivation for stocking decisions. No significant differences in stocking decisions were found by geographical location (zone and urban/rural) or outlet (pharmacy/OTC). These findings have implications for the management of antimalarial quality across supply chains in Ghana, with potentially important consequences for malaria control, particularly in lower-income areas where people rely on low-cost medication.
Association between urban–rural location and prevalence of type 2 diabetes and impaired fasting glucose in West Africa: a cross–sectional population–based epidemiological study
Authors: Issaka Ayuba , Stevenson Christopher , Paradies Yin , Houehanou Yessito Corine N , Bosu William K , Kiwallo Jean Baptiste , Wesseh Chea Sanford , Houinato Dismand Stephan , Nazoum Diarra J P , Cameron Adrian J
Published: September 2023

Objectives

We investigated the association between urban/rural location and both type 2 diabetes mellitus (T2DM) and pre-diabetes among populations of five West African countries.

Design

Cross-sectional studies, using the WHO Stepwise (STEPs) survey data.

Setting

National representative data of both urban and rural areas from Benin, Burkina Faso, Ghana, Liberia and Mali.

Participants

Adults comprising 15 468 participants (6774 men and 8746 women; 7663 urban and 7805 rural residents) aged between 25 and 64 years.

Results

The age and sex-adjusted prevalence of T2DM was 6.2% for urban areas and 2.5% for rural areas. The prevalence of impaired fasting glucose (IFG) was 6.6% for urban areas, and 3.0% for rural areas. No differences by sex were observed. The crude relative risk (RR) and 95% CI of T2DM and IFG in urban compared with rural areas were 2.69 (1.85 to 3.91) and 2.37 (1.53 to 3.66), respectively. This reduced to RR: 2.03, 95% CI (1.34 to 3.08) and RR: 2.04, 95% CI (1.27 to 3.28), respectively, after adjusting for covariables.

Conclusion

The prevalence of both T2DM and IFG was more than two times as high in urban areas compared with rural areas in West Africa. Behavioural risk factors are common among urban populations, with ongoing urbanisation expected to drive increases in the prevalence of T2DM. These results could guide planning for T2DM screening, preventive strategies and resource allocation in West Africa.
Quantifying the impact of taking medicines for primary prevention: a time-trade off study to elicit direct treatment disutility in the UK
Authors: Thompson Alexander , Youn Ji-Hee , Guthrie Bruce , Hainsworth Robert , Donnan Peter , Rogers Gabriel , Morales Daniel , Payne Katherine
Published: September 2023

Background

Direct treatment disutility (DTD) represents an individual’s disutility associated with the inconvenience of taking medicine over a long period of time.

Objectives

The main aim of this study was to elicit DTD values for taking a statin or a bisphosphonate for primary prevention. A secondary aim was to understand factors which influence DTD values.

Methods

Design:We used a cross-sectional study consisting of time-trade off exercises embedded within online surveys. Respondents were asked to compare a one-off pill (‘Medicine A’) assumed to have no inconvenience and a daily pill (‘Medicine B’) over 10 years (statins) or 5 years (bisphosphonates).

Setting:Individuals from National Health Service (NHS) primary care and the general population were surveyed using an online panel company.

Participants:Two types of participants were recruited. First, a purposive sample of patients with experience of taking a statin (n=260) or bisphosphonate (n=100) were recruited from an NHS sampling frame. Patients needed to be aged over 30, have experience of taking the medicine of interest and have no diagnosis of dementia or of using dementia drugs. Second, a demographically balanced sample of members of the public were recruited for statins (n=376) and bisphosphonates (n=359).

Primary and secondary outcome measures:Primary outcome was mean DTD. Regression analysis explored factors which could influence DTD values.

Results

A total of 879 respondents were included for analysis (514 for statins and 365 for bisphosphonates). The majority of respondents reported a disutility associated with medicine use. Mean DTD for statins was 0.034 and for bisphosphonates 0.067, respectively. Respondent characteristics including age and sex did not influence DTD. Experience of bisphosphonate-use reduced reported disutilities.

Conclusions

Statins and bisphosphonates have a quantifiable DTD. The size of estimated disutilities suggest they are likely to be important for cost-effectiveness, particularly in individuals at low-risk when treated for primary prevention.
Game-supported cognitive strategy training for slowed information processing speed after acquired brain injury: study protocol for a randomised controlled trial
Authors: Abelmann Amy C , Kessels Roy P C , Brazil Inti A , Fasotti Luciano , Bertens Dirk
Published: September 2023

Introduction

Many individuals with acquired brain injury tend to experience problems with slowed information processing speed (IPS). A potentially beneficial and cost-effective supplement for cognitive rehabilitation of impaired IPS may be the implementation of serious gaming that focuses on compensatory learning as part of cognitive training. However, most digital platforms used during cognitive rehabilitation focus on restoring cognitive function and evidence for skill transfer from digital practice to everyday life is lacking. This study aims to investigate the efficacy of a game-supported cognitive strategy training. The training combines a well-validated time pressure management cognitive strategy training, targeting slowed IPS, with a novel game and a mobile application. The game-supported training focuses on the generalisation of strategy-use to untrained tasks in everyday life.

Methods and analysis

The study is designed as a randomised controlled trial in which the experimental group (Karman Line — Tempo module: an 8-week game-supported cognitive strategy training) will be compared with an active control group (CogniPlus training: an 8-week computerised cognitive function training). Data from 60 individuals with acquired brain injury (30 per group, ages between 16 and 75) will be collected at baseline (T0), post-treatment (T1) and at 3-month follow-up (T2). The primary outcome measure is an objective assessment of compensatory strategy use in an untrained experimental task. The secondary outcome is the attainment of trained and untrained treatment goals assessed by goal attainment scaling. Pre-training and post-training data will be analysed using a 2×2 repeated measure analysis of variance.

Ethics and dissemination

This study has been approved by the medical review ethics committee CMO Region Arnhem and Nijmegen (NL74818.091.20) and is registered in the Netherlands Trial Register. Research findings will be published in peer-reviewed journals and presented at conferences.

Trial registration number

NL9437; The Netherlands Trial Register.
Can the date of last menstrual period be trusted in the first trimester? Comparisons of gestational age measures from a prospective cohort study in six low-income to middle-income countries
Authors: Patel Archana , Bann Carla M , Thorsten Vanessa R , Rao Sowmya R , Lokangaka Adrien , Tshefu Kitoto Antoinette , Bauserman Melissa , Figueroa Lester , Krebs Nancy F , Esamai Fabian , Bucher Sherri , Saleem Sarah , Goldenberg Robert L , Chomba Elwyn , Carlo Waldemar A , Goudar Shivaprasad , Derman Richard , Koso-Thomas Marion , McClure Elizabeth , Hibberd Patricia L
Published: September 2023

Objectives

We examined gestational age (GA) estimates for live and still births, and prematurity rates based on last menstrual period (LMP) compared with ultrasonography (USG) among pregnant women at seven sites in six low-resource countries.

Design

Prospective cohort study

Setting and participants

This study included data from the Global Network’s population-based Maternal and Newborn Health Registry which follows pregnant women in six low-income and middle-income countries (Democratic Republic of the Congo, Guatemala, India, Kenya, Pakistan and Zambia). Participants in this analysis were 42 803 women, including their 43 230 babies, who registered for the study in their first trimester based on GA estimated either by LMP or USG and had a live or stillbirth with an estimated GA of 20–42 weeks.

Outcome measures

GA was estimated in weeks and days based on LMP and/or USG. Prematurity was defined as GA of 20 weeks+0 days through 36 weeks+6 days, calculated by both USG and LMP.

Results

Overall, average GA varied ≤1 week between LMP and USG. Mean GA for live births by LMP was lower than by USG (adjusted mean difference (95% CI) = −0.23 (–0.29 to –0.17) weeks). Among stillbirths, a higher GA was estimated by LMP than USG (adjusted mean difference (95% CI)= 0.42 (0.11 to 0.72) weeks). Preterm birth rates for live births were significantly higher when dated by LMP (adjusted rate difference (95% CI)= 4.20 (3.56 to 4.85)). There was no significant difference in preterm birth rates for stillbirths.

Conclusion

The small differences in GA for LMP versus USG in the Guatemalan and Indian sites suggest that LMP may be a useful alternative to USG for GA dating during the first trimester until availability of USG improves in those areas. Further research is needed to assess LMP for first-trimester GA dating in other regions with limited access to USG.

Trial registration number

NCT01073475.
Safety and efficacy of steerable versus non-steerable sheaths for catheter ablation of atrial fibrillation systematic review and meta-analysis
Authors: Jin Xinyao , Zhou Yuqing , Wu Yuanhong , Xie Mingbin
Published: September 2023

Objectives

With the development of radiofrequency (RF) ablation technology. In recent years, more and more patients with atrial fibrillation (AF) have been treated with RF ablation. Steerable sheaths (SS) have been widely used in RF ablation of AF. The aim of this meta-analysis was to compare the efficacy and safety of AF ablation using SS and non-steerable sheaths (NSS).

Methods

From the beginning to March 2022, we conducted a comprehensive, systematic search of the databases PubMed, MEDLINE, EMBASE, Web of Science and the Cochrane Library to finish the study. For categorical and continuous data, we used ORs and mean difference to calculate the effect. We also estimated the 95% CI.

Results

Five studies of RF ablation of AF were selected, three prospective and two retrospective, involving 282 SS and 236 NSS ablation patients. The rate of recurrence of AF or atrial arrhythmias was 27.3% versus 42.8% (OR: 0.52, 95% CI 0.36, 0.76, z=3.41, p=0.0006) and acute pulmonary vein (PV) reconnection (8.7% vs 17.4%, OR: 0.47, 95% CI 0.23, 0.95, z=2.10, p=0.04). In the SS group and the NSS group, the total ablation time (p=0.25), fluoroscopy time (p=0.26) and total operative time (p=0.35) were not significantly different.

Conclusions

Compared with the use of NSS, the use of SS for RF ablation of AF can effectively reduce the recurrence rate of AF and the occurrence of acute PVs reconnection events. However, there is no advantage in shortening the total RF time, fluoroscopy time, total surgical time and reducing complications.
Qualitative process evaluation of the EmpaTeach intervention to reduce teacher violence in schools in Nyarugusu Refugee Camp, Tanzania
Authors: Bakari Mtumwa , Shayo Elizabeth H , Barongo Vivien , Kiwale Zenais , Fabbri Camilla , Turner Ellen , Eldred Emily , Mubyazi Godfrey M , Rodrigues Katherine , Devries Karen
Published: September 2023

Objective

We explored the experiences and perceptions of school staff and students with the EmpaTeach intervention to prevent teachers’ violence against school students.

Design

This qualitative study involved in-depth interviews with 58 and 39 participants at midline and endline, respectively, with Burundian and Congolese intervention schools in Nyarugusu refugee camp. They comprised three education coordinators of primary and secondary schools, 29 EmpaTeach intervention coordinators, 14 stakeholders including headteachers and discipline teachers, 25 classroom teachers and 26 students. Thematic analysis was used to develop codes by examining the content of quotes to capture key themes in line with the key elements of the programme theory.

Results

Coordinators and teachers widely reported positive experiences with the EmpaTeach programme. The intervention sessions enabled teachers to reflect on their own values and experiences of corporal punishment and equipped them with useful and acceptable classroom management and alternative discipline strategies. Teachers adopted the use of counselling, praise and reward, and joint discussions with students and parents. On the other hand, several teachers reported persistent use of corporal punishment which they attributed to children’s (mis)behaviours and strong beliefs that beating was a positive approach to disciplining students.

Conclusion

The majority of coordinators and teachers widely accepted the EmpaTeach intervention as it offered useful and relevant knowledge and skills on alternative disciplinary methods. Students noticed some positive changes on the way they were being disciplined by teachers, where non-violent methods were used. Further research is needed to understand how violence prevention interventions can successfully lead to reductions in violence in fragile settings.

Trial registration number

NCT03745573.
Parents’ experiences and need for social support after pregnancy termination for fetal anomaly: a qualitative study in China
Authors: Sun Shiwen , Sun Yaping , Qian Jialu , Tian Yanping , Wang Fang , Yu Qing , Yu Xiaoyan
Published: September 2023

Objective

The aim of this study was to explore the experiences and need for social support of Chinese parents after termination of pregnancy for fetal anomalies.

Design

A qualitative study using semistructured, in-depth interviews combined with observations. Data were analysed by Claizzi’s phenomenological procedure.

Setting

A large, tertiary obstetrics and gynaecology hospital in China.

Participants

Using purposive sampling approach, we interviewed 12 couples and three additional women (whose spouses were not present).

Results

Four themes were identified from the experiences of parents: the shock of facing reality, concerns surrounding termination of pregnancy, the embarrassment of the two-child policy and the urgent need for social support.

Conclusion

Parents experienced complicated and intense emotional reactions, had concerns surrounding the termination of pregnancy and an urgent need for social support. Paternal psychological reactions were often neglected by healthcare providers and the fathers, themselves. These findings suggest that both mothers and fathers should receive appropriate support from family, medical staff and peers to promote their physical and psychological rehabilitation.
Distinctive model for HIV index testing (IT) in Eastern Europe: results of Ukraine’s physician-led, integrated IT programme
Authors: Ihnatiuk Alyona P , Shapoval Anna Y , Kazanzhy Anna P , Kuzin Igor V , Riabokon Sergii V , Shotorbani Solmaz , McDowell Misti R , Golden Matthew R , Puttkammer Nancy H
Published: September 2023

Objectives

The effectiveness of HIV index testing (IT) in Eastern Europe has not been described. This study reports the performance of a scaled IT programme in Ukraine.

Design

This observational study included clients enrolled in IT services in 2020, and used routinely collected data from programme registers and the national electronic health record system.

Setting

The study covered 39 public-sector health facilities where IT services were integrated into medical visits for persons living with HIV (PLHIV) already enrolled in HIV care.

Participants

Participants included PLHIV with both recent (<6 months) and previously established (≥6 months) HIV diagnoses.

Intervention

Ukraine’s physician-led IT model involves a cascade of steps including voluntary informed consent, partner elicitation, selection of partner notification method and follow-up with clients to ensure partners are notified, tested for HIV and linked to HIV prevention and treatment services, as needed.

Primary and secondary outcome measures

Outcomes included contact index, testing, index and HIV case-finding index disaggregated by index client (IC) subgroups, including people with current or past injection drug use (PWID) and men who have sex with men (MSM).

Results

Of 14 525 ICs offered index testing, 51.9% accepted, of whom 98.3% named at least one sexual, injection or biological child partner. In total, 14.9% of ICs were PWID and 3.5% were MSM. Clients named 8448 unique partners (contact index=1.14). HIV case finding averaged 0.14 cases per client, and was highest among clients with recent HIV diagnosis (0.29) and among PWID (0.23), and lower among clients with established HIV diagnosis (0.07). More than 90% of all partners with new HIV diagnoses were linked to care.

Conclusions

There was a high case-finding index among ICs with recent HIV and high linkage to care for all partners, demonstrating the effectiveness of this integrated, physician-led model implemented in 39 health facilities in Ukraine.
Health data ecosystem in Pakistan: a multisectoral qualitative assessment of needs and opportunities
Authors: Mahmood Sana , Noorali Ali Aahil , Manji Afshan , Afzal Noreen , Abbas Saadia , Qamar Javeria Bilal , Siddiqi Sameen , Hoodbhoy Zahra , Virani Salim S , Bhutta Zulfiqar A , Samad Zainab
Published: September 2023

Objective

Data are essential for tracking and monitoring of progress on health-related sustainable development goals (SDGs). But the capacity to analyse subnational and granular data is limited in low and middle-income countries. Although Pakistan lags behind on achieving several health-related SDGs, its health information capacity is nascent. Through an exploratory qualitative approach, we aimed to understand the current landscape and perceptions on data in decision-making among stakeholders of the health data ecosystem in Pakistan.

Design

We used an exploratory qualitative study design.

Setting

This study was conducted at the Aga Khan University, Karachi, Pakistan.

Participants

We conducted semistructured, in-depth interviews with multidisciplinary and multisectoral stakeholders from academia, hospital management, government, Non-governmental organisations and other relevant private entities till thematic saturation was achieved. Interviews were recorded and transcribed, followed by thematic analysis using NVivo.

Results

Thematic analysis of 15 in-depth interviews revealed three major themes: (1) institutions are collecting data but face barriers to its effective utilisation for decision-making. These include lack of collection of needs-responsive data, lack of a gender/equity in data collection efforts, inadequate digitisation, data reliability and limited analytical ability; (2) there is openness and enthusiasm for sharing data for advancing health; however, multiple barriers hinder this including appropriate regulatory frameworks, platforms for sharing data, interoperability and defined win-win scenarios; (3) there is limited capacity in the area of both human capital and infrastructure, for being able to use data to advance health, but there is appetite to improve and invest in capacity in this area.

Conclusions

Our study identified key areas of focus that can contribute to orient a national health data roadmap and ecosystem in Pakistan.