Delay in diagnosis of pulmonary tuberculosis in low-and middle-income settings: systematic review and meta-analysis

Background

Assessment of delays in seeking care and diagnosis of tuberculosis is essential to evaluate effectiveness of tuberculosis control programs, and identify programmatic impediments. Thus, this review of studies aimed to examine the extent of patient, health system, and total delays in diagnosis of pulmonary tuberculosis in low- and middle- income countries.

Methods

It was done following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Electronic databases were searched to retrieve studies published from 2007 to 2015 including Pubmed central, Springer link, Hinari and Google scholar. Searching terms were pulmonary tuberculosis, health care seeking, health care seeking behavior, patient delay, diagnostic delay, health system delay, provider delay, and doctor delay. Retrieved studies were systematically reviewed and summarized using Comprehensive Meta-analysis software.

Results

Forty studies involving 18,975 patients qualified for systematic review, and 14 of them qualified for meta-analysis. The median diagnostic delay ranged from 30 to 366.5 days [IQR?=?44–77.8], with a 4–199 days [IQR?=?15–50] and 2–128.5 days [IQR?=?12–34] due to patient and health system delays, respectively. The meta-analysis showed 42% of pulmonary tuberculosis patients delayed seeking care by a month or more; uneducated patients [pooled OR?=?1.5, 95%CI?=?1.1–1.9] and those who sought initial care from informal providers [pooled OR?=?3, 95%CI?=?2.3–3.9] had higher odds of patient delay.

Conclusion

Delay in diagnosis is still a major challenge of tuberculosis control and prevention programs in low- and middle- income settings. Efforts to develop new strategies for better case-finding using the existing systems and improving patients’ care seeking behavior need to be intensified.

     

The Biosynthetic Origin of Irregular Monoterpenes in Lavandula: ISOLATION AND BIOCHEMICAL CHARACTERIZATION OF A NOVEL cis-PRENYL DIPHOSPHATE SYNTHASE GENE,LAVANDULYL DIPHOSPHATE SYNTHASE*

Lavender essential oils are constituted predominantly of regular monoterpenes, for example linalool, 1,8-cineole, and camphor. However, they also contain irregular monoterpenes including lavandulol and lavandulyl acetate. Although the majority of genes responsible for the production of regular monoterpenes in lavenders are now known, enzymes (including lavandulyl diphosphate synthase (LPPS)) catalyzing the biosynthesis of irregular monoterpenes in these plants have not been described. Here, we report the isolation and functional characterization of a novel cis-prenyl diphosphate synthase cDNA, termed Lavandula x intermedia lavandulyl diphosphate synthase (LiLPPS), through a homology-based cloning strategy. The LiLPPS ORF, encoding for a 305-amino acid long protein, was expressed in Escherichia coli, and the recombinant protein was purified by nickel-nitrilotriacetic acid affinity chromatography. The approximately 34.5-kDa bacterially produced protein specifically catalyzed the head-to-middle condensation of two dimethylallyl diphosphate units to LPP in vitro with apparent K_m and k_cat values of 208 ± 12 μm and 0.1 s⁻¹, respectively. LiLPPS is a homodimeric enzyme with a sigmoidal saturation curve and Hill coefficient of 2.7, suggesting a positive co-operative interaction among its catalytic sites. LiLPPS could be used to modulate the production of lavandulol and its derivatives in plants through metabolic engineering.     

The distinctness and diversity of Ethiopian barleys

 The relative diversity and distinctness of Ethiopian barleys has been investigated using (1) morphology/isozyme/hordein polymorphisms and (2) RFLP markers. In the former a set of 51 landraces from over the whole of Ethiopia was compared with Iranian landraces based on data from previous studies and new hordein data. The two sets of landraces were found to have a comparable diversity. The Ethiopian ones are more diverse morphologically (5 traits), are similar in numbers of alleles per protein locus (17 loci) and in genetic differentiation, but are less diverse in average heterozygosity per locus and degree of polymorphism. However, on the basis of the hordein data the two sources of germplasm are very distinct. The correlation between morphological and protein diversity is very low. In the RFLP study 28 probes evenly distributed across the genome were used to analyse 43 Ethiopian landraces (represented by one single genotype) and to compare them with modern cultivars from North America, Europe and Japan, as well as 3 landraces from Iran, 1 from Nepal, and 1 accession of H. spontaneum from Afghanistan. The major finding was that the Ethiopian germplasm appears to be significantly less diverse than the modern germplasm but that it is genotypically very distinct. The apparent contradiction between a high diversity of useful genes coming from Ethiopia and an apparently low diversity at the DNA level is discussed. Received: 22 July 1996 / Accepted: 26 July 1996     

Short- and long-term outcomes in infective endocarditis patients: a systematic review and meta-analysis

Background

Despite advances in medical knowledge, technology and antimicrobial therapy, infective endocarditis (IE) is still associated with devastating outcomes. No reviews have yet assessed the outcomes of IE patients undergoing short- and long-term outcome evaluation, such as all-cause mortality and IE-related complications. We conducted a systematic review and meta-analysis to examine the short- and long-term mortality, as well as IE-related complications in patients with definite IE.

Methods

A computerized systematic literature search was carried out in PubMed, Scopus and Google Scholar from 2000 to August, 2016. Included studies were published studies in English that assessed short-and long-term mortality for adult IE patients. Pooled estimations with 95% confidence interval (CI) were calculated with DerSimonian-Laird (DL) random-effects model. Sensitivity and subgroup analyses were also performed. Publication bias was evaluated using inspection of funnel plots and statistical tests.

Results

Twenty five observational studies (retrospective, 14; prospective, 11) including 22,382 patients were identified. The overall pooled mortality estimates for IE patients who underwent short- and long-term follow-up were 20% (95% CI: 18.0–23.0, P?<?0.01) and 37% (95% CI: 27.0–48.0, P?<?0.01), respectively. The pooled prevalence of cardiac complications in patients with IE was found to be 39% (95%CI: 32.0–46.0) while septic embolism and renal complications accounted for 25% (95% CI: 20.0–31) and 19% (95% CI: 14.0–25.0) (all P?<?0.01), respectively.

Conclusion

Irrespective of the follow-up period, a significantly higher mortality rate was reported in IE patients, and the burden of IE-related complications were immense. Further research is needed to assess the determinants of overall mortality in IE patients, as well as well-designed observational studies to conform our results.

     

Aquatic nematodes from Ethiopia III

Six species of the genus Eumonhystera, one of which is new to science, are described from bottom samples of Lake Tana and two associated rivers, River Abbay and R. Gelda, Ethiopia. E. geraerti n.sp. can be identified by being the only species in the genus that combines very posteriorly positioned vulva [V% = 68.2 ± 0.7 (67.3–69.3)] with very anteriorly positioned amphids (Amph-ABE/LRW = 0.8). The other five species encountered, E. dispar (Bastian, 1865) Andrássy, 1981, E. filiformis (Bastian, 1865) Andrássy, 1981, E. pseudobulbosa (von Daday, 1896) Andrássy, 1981, E. mwerazii (Meyl, 1957) Andrássy, 1981, and E. vulgaris (de Man, 1880), Andrássy, 1981, are described in detail. The identities of some of the already described populations of E. dispar, E. filiformis and E. vulgaris are questioned and clearer and better ways of defining each of these three species are suggested. A peritrophic-like membrane on the outer side of the brush-border of the intestine of E. mwerazii, a species reported here for the first time out of its type locality, is reported. Also, scanning electronmicrographs of sectioned and entire specimens of E. mwerazii are presented. All species are reported from Ethiopia for the first time.     

Freshwater nematodes of the Galápagos

Freshwater nematodes of the Galápagos archipelago were studied from four samples collected in 1988. Eighteen species, two of which are new to science, belonging to five orders, Enoplida, Dorylaimida, Mononchida, Monhysterida and Chromadorida, are described. Alaimus wittmeri n.sp. is characterised by having a smooth cuticle, a more posteriorly enlarged pharynx, a posteriorly situated amphidial fusus, obscure but anteriorly situated excretory pore, a mono-opisthodelphic ovary, and by the absence of sexual dimorphism in the lip region, the absence of pre-vulval uterine sac, the presence of males that have few (4–7) and weak ventromedian supplements and absence of mucro on tail tip. Monhystera floreanae n. sp. is distinguished by its females having a small body (L = 492–634 µm) with a narrow lip region, narrow posteriorly located amphidial openings, a small value for the c'-ratio (c' = 6.0–7.5), weak vaginal sphincter, by the absence of post-vaginal gland cells, absence of males and absence of crystalloid bodies. The difficulty in the use of crystalloid bodies as diagnostic character in the genus Monhystera is discussed. Two forms, a big form and a small form, which are similar except in measurements are reported for Achromadora micoletzkyi. SEM photos of ruptured cuticle of A. micoletzkyi and A. semiarmata show unique intra-cuticular structures. Comparison of these structures in the two species is made. Papilliform instead of setiform outer labial sensilla are also observed in A. micoletzkyi. The presence of the male and fine crystalloid bodies in Achromadora semiarmata, dorsal body pore in Prismatolaimus dolichurus and Prismatolaimus kenyensis, forty longitudinal cuticular ridges around the mid-body of Stomachoglossa pachyderma, crystalloid bodies in Ironus dentifurcatus are reported here for the first time. SEM photos of twelve species: Monhystera floreanae n. sp., Monhystera somereni, Alaimus wittmeri n. sp., Monhystrella hastata, Paramphidelus dolichurus, Eutobrilus annetteae, Ironus dentifurcatus, Chronogaster cameroonensis, Rhabdolaimus terrestris, Stomachoglossa pachyderma, Achromadora micoletzkyi and Achromadora semiarmata, are also presented.The richest nematode fauna was found in El Junco (San Cristobal), the only permanent freshwater lake on the archipelago. The nine species recorded from the lake are probably only a fraction of the total nematode fauna. The very recent man made reservoir La Toma has a relatively high diversity, due to its vicinity to El Junco. It is argued that the freshwater nematodes from San Cristobal probably arrived there through passive transport by birds.The freshwater bodies encountered on Floreana are very different from those on San Cristobal and so is their nematode fauna. Part of the species found on these islands may have been transported by land birds, others may have invaded the freshwater from terrestrial habitats.Apart from the two new species, the other ones have a wide to very wide distribution (cosmopolitan, southern hemisphere, ...), so that endemism of freshwater nematodes is very low, if it exists at all. This is due to easy dispersal capacities of nematodes on the one hand and the recent colonization (not more than 10 000, max. 40 000 years) on the other hand.     

A systems approach to improving rural care in Ethiopia

Background

Multiple interventions have been launched to improve the quality, access, and utilization of primary health care in rural, low-income settings; however, the success of these interventions varies substantially, even within single studies where the measured impact of interventions differs across sites, centers, and regions. Accordingly, we sought to examine the variation in impact of a health systems strengthening intervention and understand factors that might explain the variation in impact across primary health care units.

Methodology/Principal Findings

We conducted a mixed methods positive deviance study of 20 Primary Health Care Units (PHCUs) in rural Ethiopia. Using longitudinal data from the Ethiopia Millennium Rural Initiative (EMRI), we identified PHCUs with consistently higher performance (n = 2), most improved performance (n = 3), or consistently lower performance (n = 2) in the provision of antenatal care, HIV testing in antenatal care, and skilled birth attendance rates. Using data from site visits and in-depth interviews (n = 51), we applied the constant comparative method of qualitative data analysis to identify key themes that distinguished PHCUs with different performance trajectories. Key themes that distinguished PHCUs were 1) managerial problem solving capacity, 2) relationship with the woreda (district) health office, and 3) community engagement. In higher performing PHCUs and those with the greatest improvement after the EMRI intervention, health center and health post staff were more able to solve day-to-day problems, staff had better relationships with the woreda health official, and PHCU communities'' leadership, particularly religious leadership, were strongly engaged with the health improvement effort. Distance from the nearest city, quality of roads and transportation, and cultural norms did not differ substantially among PHCUs.

Conclusions/Significance

Effective health strengthening efforts may require intensive development of managerial problem solving skills, strong relationships with government offices that oversee front-line providers, and committed community leadership to succeed.     

Evaluation of the Performance Characteristics of Bilayer Tablets: Part I. Impact of Material Properties and Process Parameters on the Strength of Bilayer Tablets

Bilayer tableting technology has gained popularity in recent times, as bilayer tablets offer several advantages over conventional tablets. There is a dearth of knowledge on the impact of material properties and process conditions on the performance of bilayer tablets. This paper takes a statistical approach to develop a model that will determine the effect of the material properties and bilayer compression process parameters on the bonding strength and mode of breakage of bilayer tablets. Experiments were carried out at pilot scale to simulate the commercial manufacturing conditions. As part of this endeavor, a seven-factor half-fraction factorial (2⁷⁻¹) design was executed to study the effect of bilayer tablet compression process factors on the bonding strength of bilayer tablets. Factors studied in this work include: material properties (plastic and brittle), layer ratio, dwell time, layer sequence, first- and second-layer forces, and lubricant concentration. Bilayer tablets manufactured in this study were tested using the axial tester, as it considers both the interfacial and individual layer bonding strengths. Responses of the experiments were analyzed using PROC GLM of SAS (SAS Institute Inc, Cary, North Carolina). A model was fit using all the responses to determine the significant interactions (p < 0.05). The results of this study indicated that nature of materials played a critical role on the strength of bilayer compacts and also on mode of fracture. Bilayer tablets made with brittle materials in both the layers are strongest, and fracture occurred in the first layer indicating that interface is stronger than layers. Significant interactions were observed between the selected factors and these results will provide an insight into the interplay of material properties, process parameters, and lubricant concentration on the bonding strength and mode of breakage of bilayer tablets.

Electronic supplementary material

The online version of this article (doi:10.1208/s12249-012-9845-9) contains supplementary material, which is available to authorized users.KEY WORDS: axial tester, bilayer tablets, DOE, interfacial strength, process parameters     

Suitability of nutrients removal from brewery wastewater using a hydroponic technology with <Emphasis Type="Italic">Typha latifolia</Emphasis>

Background

This study aims to assess suitability of hydroponic technology for treatment of brewery wastewater in a hydroponic bioreactor using Typha latifolia. Triplicated hydroponic bioreactor treatment units were designed, constructed and operated at a hydraulic retention time of 5?days with different surface loadings and mean hydraulic loading rate 0.023?m³ m^?2d^??1. Young T. latifolia shoots were collected in the vicinity of study site. Wastewater characteristics, plant growth and nutrient accumulation during experiment were analyzed as per APHA standard methods and nutrient removal efficiency was evaluated based on inlet and outlet values.

Results

T. latifolia established and grew well in the hydroponics under fluctuations of wastewater loads and showed a good phytoremedial capacity to remove nutrients. Significant removal efficiencies (p?<?0.05) varied between 54 and 80% for Total Kjeldahl Nitrogen, 42 and 65% for NH₄⁺ -N, 47 and 58% for NO₃^? -N, and 51 and 70% for PO₄^3?-P. The system improved the removal up to 29% compared to control and produced biomass of 0.61–0.86?kg dry weight (DW) m^??2. Nutrients retained were up to 21.17?g?N?kg^??1 DW and 2.87?g P kg^??1 DW.

Conclusion

The significant nutrients reduction obtained and production of biomass led us to conclude that hydroponics technology using T. latifolia has suitability potential for treatment of brewery wastewater and similar agro-industrial wastewaters. Thus it could be considered as a promising eco-friendly option for wastewater treatment to mitigate water pollution. Integration of treatment and production of biomass needs further improvement.