98 research outputs found

    Are we doing enough? Improved breastfeeding practices at 14 weeks but challenges of non-initiation and early cessation of breastfeeding remain: Findings of two consecutive cross-sectional surveys in KwaZulu-Natal, South Africa

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    Background KwaZulu-Natal (KZN) Initiative for breastfeeding support (KIBS) was a multipronged intervention to support the initiation and sustaining of breastfeeding, implemented between 2014 and 2017. We present results of two surveys conducted before and after KIBS implementation to assess changes in infant feeding practices in KZN over this time period. Methods Two cross-sectional surveys were conducted in primary health care clinics. Multistage stratified random sampling was used to select clinics and participants. Sample size was calculated to provide district estimates of 14-week exclusive breastfeeding (EBF) rates at baseline (KIBS1), and provincial estimates at endpoint (KIBS2). At KIBS1 the sample required was nine participating clinics in each of 11 districts (99 clinics) with 369 participants per district (N = 4059), and at KIBS2 was 30 clinics in KZN with 30 participants per clinic (N = 900). All caregivers aged ≥15 years attending the clinic with infants aged 13- < 16 weeks were eligible to participate. Data was collected using structured interviews on android devices. Multi-variable logistic regression was used to adjust odds ratios for differences between time points. Results At KIBS1 (May2014- March2015), 4172 interviews were conducted with carers, of whom 3659 (87.6%) were mothers. At KIBS2 (January–August 2017), 929 interviews were conducted which included 788 (84.8%) mothers. Among all carers the proportion exclusively breastfeeding was 44.6 and 50.5% (p = 0.1) at KIBS1 and KIBS2 respectively, but greater improvements in EBF were shown among mothers (49.9 vs 59.1: p = 0.02). There were reductions in mixed breastfeeding among all infants (23.2% vs 16.3%; p = 0.016). Although there was no change in the proportion of carers who reported not breastfeeding (31.9% vs 32.8%; p = 0.2), the duration of breastfeeding among mothers who had stopped breastfeeding was longer at KIBS2 compared to KIBS1 (p = 0.0015). Mothers who had returned to work or school were less likely to be breastfeeding (adjusted odds ratio [AOR] 3.76; 95% CI 3.1–4.6), as were HIV positive mothers (AOR 2.1; 95% CI 1.7–2.6). Conclusion Despite improvements to exclusive breastfeeding, failure to initiate and sustain breastfeeding is a challenge to achieving optimal breastfeeding practices. Interventions are required to address these challenges and support breastfeeding particularly among working mothers and HIV positive mothers.publishedVersio

    Spread of Extensively Drug-Resistant Tuberculosis in KwaZulu-Natal Province, South Africa

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    Background In 2005 a cluster of 53 HIV-infected patients with extensively drug-resistant tuberculosis (XDR-TB) was detected in the Msinga sub-district, the catchment area for the Church of Scotland Hospital (CoSH) in Tugela Ferry, in KwaZulu-Natal province (KZN), South Africa. KZN is divided into 11 healthcare districts. We sought to determine the distribution of XDR TB cases in the province in relation to population density. Methods In this cross-sectional study, the KZN tuberculosis laboratory database was analysed. Results of all patients with a sputum culture positive for Mycobacterium tuberculosis from January 2006 to June 2007 were included. Drug-susceptibility test results for isoniazid, rifampicin, ethambutol, streptomycin, kanamycin and ofloxacin were available for all patients as well as the location of the hospital where their clinical diagnosis was made. Findings In total, 20858 patients attending one of 73 hospitals or their adjacent clinics had cultures positive for M. tuberculosis. Of these, 4170 (20%) were MDR-TB cases. Four hundred and forty three (11%) of the MDR tuberculosis cases displayed the XDR tuberculosis susceptibility profile. Only 1429 (34%) of the MDR-TB patients were seen at the provincial referral hospital for treatment. The proportion of XDR-TB amongst culture-confirmed cases was highest in the Msinga sub-district (19.6%), followed by the remaining part of the Umzinyati district (5.9%) and the other 10 districts (1.1%). The number of hospitals with at least one XDR-TB case increased from 18 (25%) to 58 (80%) during the study period. Interpretation XDR-TB is present throughout KZN. More than 65% of all diagnosed MDR-TB cases, including XDR-TB patients, were left untreated and likely remained in the community as a source of infection

    Diagnostic accuracy of quantitative PCR (Xpert MTB/RIF) for tuberculous meningitis in a high burden setting: a prospective study

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    Background: Tuberculous meningitis (TBM) is difficult to diagnose promptly. The utility of the Xpert MTB/RIF test for the diagnosis of TBM remains unclear, and the effect of host- and sample-related factors on test performance is unknown. This study sought to evaluate the sensitivity and specificity of Xpert MTB/RIF for the diagnosis of TBM. Methods and Findings: 235 South-African patients with a meningeal-like illness were categorised as having definite (culture or Amplicor PCR positive), probable (anti-TBM treatment initiated but microbiological confirmation lacking), or non-TBM. Xpert MTB/RIF accuracy was evaluated using 1 ml of uncentrifuged and, when available, 3 ml of centrifuged cerebrospinal fluid (CSF). To evaluate the incremental value of MTB/RIF over a clinically based diagnosis, test accuracy was compared to a clinical score (CS) derived using basic clinical and laboratory information. Of 204 evaluable patients (of whom 87% were HIV-infected), 59 had definite TBM, 64 probable TBM, and 81 non-TBM. Overall sensitivity and specificity (95% CI) were 62% (48%–75%) and 95% (87%–99%), respectively. The sensitivity of Xpert MTB/RIF was significantly better than that of smear microscopy (62% versus 12%; p = 0.001) and significantly better than that of the CS (62% versus 30%; p = 0.001; C statistic 85% [79%–92%]). Xpert MTB/RIF sensitivity was higher when centrifuged versus uncentrifuged samples were used (82% [62%–94%] versus 47% [31%–61%]; p = 0.004). The combination of CS and Xpert MTB/RIF (Xpert MTB/RIF performed if CS<8) performed as well as Xpert MTB/RIF alone but with a ∼10% reduction in test usage. This overall pattern of results remained unchanged when the definite and probable TBM groups were combined. Xpert MTB/RIF was not useful in identifying TBM among HIV-uninfected individuals, although the sample was small. There was no evidence of PCR inhibition, and the limit of detection was ∼80 colony forming units per millilitre. Study limitations included a predominantly HIV-infected cohort and the limited number of culture-positive CSF samples. Conclusions: Xpert MTB/RIF may be a good rule-in test for the diagnosis of TBM in HIV-infected individuals from a tuberculosis-endemic setting, particularly when a centrifuged CSF pellet is used. Further studies are required to confirm these findings in different settings

    Utility of a novel lipoarabinomannan assay for the diagnosis of tuberculous meningitis in a resource-poor high-HIV prevalence setting

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    <p>Abstract</p> <p>Background</p> <p>In Africa, tuberculous meningitis (TBM) is an important opportunistic infection in HIV-positive patients. Current diagnostic tools for TBM perform sub-optimally. In particular, the rapid diagnosis of TBM is challenging because smear microscopy has a low yield and PCR is not widely available in resource-poor settings.</p> <p>Methods</p> <p>We evaluated the performance outcome of a novel standardized lipoarabinomannan (LAM) antigen-detection assay, using archived cerebrospinal fluid samples, in 50 African TBM suspects of whom 68% were HIV-positive.</p> <p>Results</p> <p>Of the 50 participants 14, 23 and 13 patients had definite, probable and non-TBM, respectively. In the non-TB group there were 5 HIV positive patients who were lost to follow-up and in whom concomitant infection with <it>Mycobacterium tuberculosis </it>could not be definitively excluded. The test sensitivities and specificities were as follows: LAM assay 64% and 69% (cut-point 0.22), smear microscopy 0% and 100% and PCR 93% and 77%, respectively.</p> <p>Conclusion</p> <p>In this preliminary proof-of-concept study, a rapid diagnosis of TBM could be achieved using LAM antigen detection. Although specificity was sub-optimal, the estimates provided here may be unreliable because of a classification bias inherent in the study design where it was not possible to exclude TBM in the presumed non-TBM cases owing to a lack of clinical follow-up. As PCR is largely unavailable, the LAM assay may well prove to be a useful adjunct for the rapid diagnosis of TBM in high HIV-incidence settings. These preliminary results justify further enquiry and prospective studies are now required to definitively establish the place of this technology for the diagnosis of TBM.</p

    Origin and evolution of formation waters, Alberta Basin, Western Canada sedimentary Basin. I. Chemistry

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    Inorganic chemical analyses and short-chain aliphatic acid content are used to interpret the origin and compositional evolution of formation waters in the Alberta portion of the Western Canada Sedimentary Basin. Forty-three formation water samples were obtained covering a stratigraphic interval from Devonian to Cretaceous. The data show that: (1) there is a subaerially evaporated brine component that shows no apparent contribution of waters derived from evaporite dissolution; and (2) formation waters have maintained characteristics indicative of subaerially evaporated waters, despite subsequent flushing by gravity-driven meteoric waters in the basin.Formation waters are predominantly Na---Cl brines that contain 4-235g/l total dissolved solids (TDS). Short-chain aliphatic acids (SCA) range up to 932 mg/l, with the following abundance: acetate &gt;&gt; propionate &gt; butyrate. Their number varies randomly with subsurface temperature, depth, geological age and salinity. Instead, SCA distributions appear related to proximity to Jurassic and Mississippian source rocks and to zones of active bacterial SO4 reduction.Based on chemical composition, the formation waters can be divided into three groups. Group I waters are from dominantly carbonate reservoirs and Group II from clastics. Groups I and II are differentiated from Group III in that they are composed of a brine end member, formed by evaporation of sea water beyond the point of halite saturation, that has been subsequently diluted 50-80% by a meteoric water end member. Group III waters are from clastic reservoirs and are dilute, meteoric waters that are decoupled from the more saline, stratigraphically lower, waters of Groups I and II.Group I waters have been influenced by clay mineral transformations in shales surrounding the carbonate reservoirs, ankeritization reactions of reservoir dolomites and calcites, and possible decarboxylation reactions. Group II waters indicate significant leaching reactions, particularly of feldspar and clay minerals. Group I and Group II waters both indicate ion exchange reactions were also possible. The waters are near equilibrium with respect to quartz, calcite, dolomite and barite, but are undersaturated with respect to evaporite minerals (halite, anhydrite). Occurrence of feldspar (predominantly albite) and kaolinite seems to control the population of the water cations. Post-Laramide invasion of meteoric waters provided an impetus for many of the diagenetic reactions in both carbonate, but especially in clastic reservoirs. Subsequent hydrochemical isolation of Group I and II waters from further meteoric influences occurred, resulting in pronounced mixing relations and cross-formational fluid flow replacing the once dominant lateral flow.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28507/1/0000304.pd

    Origin and evolution of formation waters, Alberta Basin, Western Canada Sedimentary Basin. II. Isotope systematics and water mixing

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    Isotopic measurements (Sr, O, D) on formation waters from the Alberta Basin have been made, covering a stratigraphic range from Devonian to Upper Cretaceous. These measurements, combined with chemical compositional trends, give evidence for two distinct water regimes. One hydrological regime is composed of waters hosted in Devonian-Lower Cretaceous reservoirs, the other waters from Upper Cretaceous and younger sedimentary rocks. The two regimes are separated by a regional transgressive shale in the Colorado Group, the Second White Speckled Shale Formation.The waters within the Devonian-Lower Cretaceous regime exhibit a large range in 87Sr/86Sr values (0.7076-0.7129), but have similar Sr concentrations, regardless of host lithology. Bulk rock and late-stage diagenetic cements are less radiogenic than present brines. Importantly, brines from Devonian carbonates possess the most radiogenic Sr isotopic signatures of the waters examined. Devonian shales and/or Cambrian shales may be sources of high 87Sr/86Sr ratios in the carbonate-hosted waters. Waters from the Upper Cretaceous clastic units, which have ratios as low as 0.7058, and diagenetic cements from Upper Cretaceous clastic units appear to have precipitated from fluids similar in Sr isotopic value to modern brines. High Sr concentrations in the Cretaceous clastic waters and sedimentary rocks and correspondingly low 87Sr/86Sr ratios suggest that volcanism in Montana during the Cretaceous may have provided a source of sediments to the study area.Cross-formational upward water migration, superimposed on lateral fluid flow, is required to explain the geochemistry and isotopic systematics in the brines from Devonian-Lower Cretaceous reservoirs. Strontium isotope ratios and Sr contents suggest a two component mixing relation for these waters. This system of waters also exhibits [delta]D values characteristic of meteoric values in the Neogene, reflecting post-Laramide flushing of Tertiary waters throughout the basin, with subsequent hydrochemical isolation from more modern waters. In contrast, waters in Upper Cretaceous reservoirs have O and D isotopic compositions similar to those of present day rainfall; these, in conjunction with very dilute Sr concentrations and low Sr ratios, suggest hydrological isolation from the stratigraphically lower system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/28509/1/0000306.pd

    N-Acetyltransferase 2 Genotypes among Zulu-Speaking South Africans and Isoniazid and N-Acetyl-Isoniazid Pharmacokinetics during Antituberculosis Treatment.

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    The distribution of N-acetyltransferase 2 gene (NAT2) polymorphisms varies considerably among different ethnic groups. Information on NAT2 single-nucleotide polymorphisms in the South African population is limited. We investigated NAT2 polymorphisms and their effect on isoniazid pharmacokinetics (PK) in Zulu black HIV-infected South Africans in Durban, South Africa. HIV-infected participants with culture-confirmed pulmonary tuberculosis (TB) were enrolled from two unrelated studies. Participants with culture-confirmed pulmonary TB were genotyped for the NAT2 polymorphisms 282C>T, 341T>C, 481C>T, 857G>A, 590G>A, and 803A>G using Life Technologies prevalidated TaqMan assays (Life Technologies, Paisley, UK). Participants underwent sampling for determination of plasma isoniazid and N-acetyl-isoniazid concentrations. Among the 120 patients, 63/120 (52.5%) were slow metabolizers (NAT2*5/*5), 43/120 (35.8%) had an intermediate metabolism genotype (NAT2*5/12), and 12/120 (11.7%) had a rapid metabolism genotype (NAT2*4/*11, NAT2*11/12, and NAT2*12/12). The NAT2 alleles evaluated in this study were *4, *5C, *5D, *5E, *5J, *5K, *5KA, *5T, *11A, *12A/12C, and *12M. NAT2*5 was the most frequent allele (70.4%), followed by NAT2*12 (27.9%). Fifty-eight of 60 participants in study 1 had PK results. The median area under the concentration-time curve from 0 to infinity (AUC0-∞) was 5.53 (interquartile range [IQR], 3.63 to 9.12 μg h/ml), and the maximum concentration (Cmax) was 1.47 μg/ml (IQR, 1.14 to 1.89 μg/ml). Thirty-four of 40 participants in study 2 had both PK results and NAT2 genotyping results. The median AUC0-∞ was 10.76 μg·h/ml (IQR, 8.24 to 28.96 μg·h/ml), and the Cmax was 3.14 μg/ml (IQR, 2.39 to 4.34 μg/ml). Individual polymorphisms were not equally distributed, with some being represented in small numbers. The genotype did not correlate with the phenotype, with those with a rapid acetylator genotype showing higher AUC0-∞ values than those with a slow acetylator genotype, but the difference was not significant (P = 0.43). There was a high prevalence of slow acetylator genotypes, followed by intermediate and then rapid acetylator genotypes. The poor concordance between genotype and phenotype suggests that other factors or genetic loci influence isoniazid metabolism, and these warrant further investigation in this population

    Early Clinical and Subclinical Visual Evoked Potential and Humphrey's Visual Field Defects in Cryptococcal Meningitis.

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    Cryptococcal induced visual loss is a devastating complication in survivors of cryptococcal meningitis (CM). Early detection is paramount in prevention and treatment. Subclinical optic nerve dysfunction in CM has not hitherto been investigated by electrophysiological means. We undertook a prospective study on 90 HIV sero-positive patients with culture confirmed CM. Seventy-four patients underwent visual evoked potential (VEP) testing and 47 patients underwent Humphrey's visual field (HVF) testing. Decreased best corrected visual acuity (BCVA) was detected in 46.5% of patients. VEP was abnormal in 51/74 (68.9%) right eyes and 50/74 (67.6%) left eyes. VEP P100 latency was the main abnormality with mean latency values of 118.9 (±16.5) ms and 119.8 (±15.7) ms for the right and left eyes respectively, mildly prolonged when compared to our laboratory references of 104 (±10) ms (p<0.001). Subclinical VEP abnormality was detected in 56.5% of normal eyes and constituted mostly latency abnormality. VEP amplitude was also significantly reduced in this cohort but minimally so in the visually unimpaired. HVF was abnormal in 36/47 (76.6%) right eyes and 32/45 (71.1%) left eyes. The predominant field defect was peripheral constriction with an enlarged blind spot suggesting the greater impact by raised intracranial pressure over that of optic neuritis. Whether this was due to papilloedema or a compartment syndrome is open to further investigation. Subclinical HVF abnormalities were minimal and therefore a poor screening test for early optic nerve dysfunction. However, early optic nerve dysfunction can be detected by testing of VEP P100 latency, which may precede the onset of visual loss in CM

    Moving beyond the 2018 minimum international care considerations for osteoporosis management in duchenne muscular dystrophy (DMD): Meeting report from the 3rd International Muscle-Bone Interactions Meeting 7th and 14th November 2022

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    This current manuscript summarizes the proceedings of the “Third Muscle-bone interactions in Duchenne Muscular Dystrophy Symposium: Moving Beyond the 2018 Minimum International Standards of Care for Osteoporosis Management”, an event co-organized by the World Duchenne Organization (www.worldduchenne.org) and the International Conference on Children’s Bone Health (www.theiscbh.org). This virtual symposium, held on November 7th and 14th 2022, brought together a total of 385 delegates representing 55 countries registered for the symposium, which included 239 clinicians, 70 researchers, 40 patient representatives and others from pharmaceutical companies and regulators. This symposium aimed to review the evidence base that informed the 2018 international minimum Care Considerations, best practices for implementation of these Care Considerations, and emerging knowledge that has arisen from research since the 2018 Care Considerations that shines light on the path forward. The online symposium and this report cover the following areas: 1. Current understanding of the bone morbidity in DMD, especially in relation to conventional glucocorticoid therapy. 2. The published, 2018 minimum international Care Considerations for osteoporosis monitoring and management in DMD. 3. Real world initiatives and challenges in the implementation of the 2018 minimum international Care Considerations for osteoporosis monitoring and management in DMD. 4. The need to consider strategies to move beyond the 2018 minimum international Care Considerations to prevent first fractures in DMD. 5. New therapies in DMD with potential impact on skeletal outcomes
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