The association between an energy-adjusted dietary inflammatory index and inflammation in rural and urban Black South Africans.

OBJECTIVE: To quantify the inflammatory potential of the diet of rural and urban Black South Africans using an adapted energy-adjusted dietary inflammatory index (AE-DII) and to investigate its relationship with inflammatory and cardio-metabolic disease risk markers. Dietary inflammatory potential has not been investigated in African populations. DESIGN: Cross-sectional investigation. SETTING: Rural and urban sites in the North West province of South Africa. PARTICIPANTS: 1885 randomly selected, apparently healthy Black South Africans older than 30 years. RESULTS: AE-DII scores ranged from -3·71 to +5·08 with a mean of +0·37. AE-DII scores were significantly higher in men (0·47 ± 1·19) than in women (0·32 ± 1·29), and in rural (0·55 ± 1·29) than urban participants (0·21 ± 1·19). Apart from its dietary constituents, AE-DII scores are primarily associated with age, rural-urban status and education. Contrary to the literature, alcohol consumption was positively associated with AE-DII scores. Of the four tested inflammatory and thirteen cardio-metabolic biomarkers, the AE-DII was only significantly negatively associated with albumin and HDL cholesterol, and positively with waist circumference and fasting glucose, upon full adjustment. CONCLUSION: Rural men consumed the most pro-inflammatory diet, and urban women the least pro-inflammatory diet. The diet of the participants was not overtly pro- or anti-inflammatory and was not associated with measured inflammatory markers. The inflammatory potential of alcohol at different levels of intake requires further research. Understanding dietary inflammatory potential in the context of food insecurity, unhealthy lifestyle practices and lack of dietary variety remains limited.

Epigenetic age acceleration in the emerging burden of cardiometabolic diseases among migrant and non-migrant African populations: the population based cross-sectional RODAM study.

BACKGROUND: African populations are experiencing health transitions due to rapid urbanization and international migration. However, the role of biological aging in this emerging burden of cardiometabolic diseases (CMD) among migrant and non-migrant Africans is unknown. We aimed to examine differences in epigenetic age acceleration (EAA) as measured by four clocks (Horvath, Hannum, PhenoAge and GrimAge) and their associations with cardiometabolic factors among migrant Ghanaians in Europe and non-migrant Ghanaians. METHODS: Genome-wide DNA methylation (DNAm) data of 712 Ghanaians from cross-sectional RODAM study were used to quantify EAA. We assessed correlation of DNAmAge measures with chronological age, and then performed linear regressions to determine associations of body mass index (BMI), fasting blood glucose (FBG), blood pressure, alcohol consumption, smoking, physical activity, and one-carbon metabolism nutrients with EAA among migrant and non-migrants. We replicated our findings among 172 rural-urban sibling pairs from India migration study and among 120 native South Africans from PURE-SA-NW study. FINDINGS: We found that Ghanaian migrants have lower EAA than non-migrants. Within migrants, higher FBG was positively associated with EAA measures. Within non-migrants, higher BMI, and Vitamin B9 (folate) intake were negatively associated with EAA measures. Our findings on FBG, BMI and folate were replicated in the independent cohorts. INTERPRETATION: Our study shows that migration is negatively associated with EAA among Ghanaians. Moreover, cardiometabolic factors are differentially associated with EAA within migrant and non-migrant subgroups. Our results call for context-based interventions for CMD among transitioning populations that account for effects of biological aging. FUNDING: European Commission.

Replication and expansion of epigenome-wide association literature in a black South African population.

BACKGROUND: DNA methylation is associated with non-communicable diseases (NCDs) and related traits. Methylation data on continental African ancestries are currently scarce, even though there are known genetic and epigenetic differences between ancestral groups and a high burden of NCDs in Africans. Furthermore, the degree to which current literature can be extrapolated to the understudied African populations, who have limited resources to conduct independent large-scale analysis, is not yet known. To this end, this study examines the reproducibility of previously published epigenome-wide association studies of DNA methylation conducted in different ethinicities, on factors related to NCDs, by replicating findings in 120 South African Batswana men aged 45 to 88 years. In addition, novel associations between methylation and NCD-related factors are investigated using the Illumina EPIC BeadChip. RESULTS: Up to 86% of previously identified epigenome-wide associations with NCD-related traits (alcohol consumption, smoking, body mass index, waist circumference, C-reactive protein, blood lipids and age) overlapped with those observed here and a further 13% were directionally consistent. Only 1% of the replicated associations presented with effects opposite to findings in other ancestral groups. The majority of these inconcistencies were associated with population-specific genomic variance. In addition, we identified eight new 450K array CpG associations not previously reported in other ancestries, and 11 novel EPIC CpG associations with alcohol consumption. CONCLUSIONS: The successful replication of existing EWAS findings in this African population demonstrates that blood-based 450K EWAS findings from commonly investigated ancestries can largely be extrapolated to ethnicities for which epigenetic data are not yet available. Possible population-specific differences in 14% of the tested associations do, however, motivate the need to include a diversity of ethnic groups in future epigenetic research. The novel associations found with the enhanced coverage of the Illumina EPIC array support its usefulness to expand epigenetic literature.

Fibrinogen and clot-related phenotypes determined by fibrinogen polymorphisms: Independent and IL-6-interactive associations.

Interleukin-6 (IL-6) induces the expression of fibrinogen, and polymorphic variation within the fibrinogen genes is believed to alter the magnitude of this expression. The identification of the functional relevance of individual fibrinogen single nucleotide polymorphisms (SNPs) has been hindered by the high linkage disequilibrium (LD) reported in the European fibrinogen gene locus. This study investigated two novel and 12 known fibrinogen SNPs of potential functional relevance, in 2010 Tswana individuals known to have low LD. We aimed to identify functional polymorphisms that contribute to clot-related phenotypes and total and γ' fibrinogen concentrations independently and through their interaction with IL-6, by taking advantage of the high fibrinogen and IL-6 concentrations and the low LD reported in black South Africans. Fibrinogen was significantly associated with IL-6, thereby mediating associations of IL-6 with clot formation and structure, although attenuating the association of IL-6 with clot lysis time. None of the common European fibrinogen haplotypes was present in this study population. Putative functional fibrinogen SNPs FGB-rs7439150, rs1800789 (-1420G/A) and rs1800787 (-148C/T) were significantly associated with fibrinogen concentration and altered clot properties, with several associations significantly influenced by IL-6 concentrations. The impact of harbouring several minor fibrinogen SNP alleles on the association of IL-6 and fibrinogen concentration was cumulative, with possession of each additional minor allele showing a stronger relationship of IL-6 with fibrinogen. This was also reflected in differences in clot properties, suggesting potential clinical relevance. Therefore, when investigating the effect of fibrinogen genetics on fibrinogen concentrations and CVD outcome, the possible interactions with modulating factors and the fact that SNP effects seem to be additive should be taken into account.

Candidate gene analysis of the fibrinogen phenotype reveals the importance of polygenic co-regulation.

Fibrinogen and its functional aspects have been linked to cardiovascular disease. There is vast discrepancy between the heritability of fibrinogen concentrations observed in twin studies and the heritability uncovered by genome wide association studies. We postulate that some of the missing heritability might be explained by the pleiotropic and polygenic co-regulation of fibrinogen through multiple targeted genes, apart from the fibrinogen genes themselves. To this end we investigated single nucleotide polymorphisms (SNPs) in genes coding for phenotypes associated with total and γ' fibrinogen concentrations and clot properties. Their individual and accumulative associations with the fibrinogen variables were explored together with possible co-regulatory processes as a result of the gain and loss of transcription factor binding sites (TFBS). Seventy-eight SNPs spanning the APOB, APOE, CBS, CRP, F13A1, FGA, FGB, FGG, LDL-R, MTHFR, MTR, PCSK-9 and SERPINE-1 genes were included in the final analysis. A novel PCSK-9 SNP (rs369066144) was identified in this population, which associated significantly (p=0.04) with clot lysis time (CLT). Apart from SNPs in the fibrinogen (FGA, FGB and FGG) and FXIII (F13A1) genes, the fibrinogen phenotypes were also associated with SNPs in genes playing a role in lipid homeostasis (LDL-R, PCSK-9) together with CBS and CRP polymorphisms (particularly, CRP-rs3093068). The genetic risk scores, presenting accumulative genetic risk, were significantly associated (p≤0.007) with total and γ' fibrinogen concentrations, lag time, slope and CLT, highlighting the importance of a polygenetic approach in determining complex phenotypes. SNPs significantly associated with the fibrinogen phenotypes, resulted in a total of 75 TFBS changes, of which 35 resulted in a loss and 40 in a gain of TFBS. In terms of co-regulation, V$IRF4.02, V$E2FF and V$HIFF were of particular importance. The investigation into TFBS provided valuable insight as to how sequence divergences in seemingly unrelated genes can result in transcriptional co-regulation of the fibrinogen phenotypes. The observed associations between the identified SNPs and the fibrinogen phenotypes therefore do not imply direct effects on cardiovascular disease outcomes, but may prove useful in explaining more of the genetic regulation of the investigated fibrinogen phenotypes.

Cervical screening strategies in resourced and resource-constrained countries.

Screening for cervical cancer is well established in resourced countries, but in resource-constrained countries, it is almost non-existent at national level. In resourced countries, the Pap test forms the hallmark of screening, with the human papillomavirus DNA test a recent adjunct. In many resourced countries, however, screening for cervical cancer is still far from ideal. A coverage around 50% prevails in some countries, and few have reached the target of 80% or more. Furthermore, the human papillomavirus test and newly developed biomarkers may lead to the development of a 'super test', which could be applied less frequently compared with present-day cytological screening. In resource-constrained countries, the movement is towards a 'screen and treat' approach. The main screening methods under investigation are the visual inspection after diluted acetic acid application test and the human papillomavirus test. Cryotherapy and large loop excision of the transformation zone have been used most often as treatment methods. The ideal seems to be the human papillomavirus test with large loop excision of the transformation zone, provided a low-cost human papillomavirus test becomes available. Coverage is even a greater problem in resource-constrained countries, a problem in need of urgent attention. Resource-constrained countries, however, must curtail the high incidence of cervical cancer, which is often a lower priority than other pressing healthcare needs.

Culdocele repair in female pelvic organ prolapse.

OBJECTIVES: To review patients with a culdocele, a wide and deep cul-de-sac, and to report the results of treatment by sacrocolpopexy. METHODS: A retrospective review of 117 patients with a culdocele identified by clinical examination and intraoperatively. RESULTS: The mean age and parity of the patients were 61.4 years and 3.1, respectively. Bladder complaints occurred in 46% of patients and bowel problems in 74% (mainly obstructed defecation). Something protruded through the vaginal introitus in 84% of patients. All patients were treated with a sacrocolpopexy: 96% with mobilization and elevation of the rectum (rectopexy), and 79% with Burch colposuspension. Follow-up results were obtained for 98% of the patients (mean, 14.7 months). Recurrent prolapse occurred in 10% of patients. CONCLUSIONS: A culdocele differs from an enterocele because it a distended and deep cul-de-sac without a true hernia between the distal vagina and rectum. Sacrocolpopexy resulted in a 10% recurrence rate of prolapse.

Screening for cervical cancer in an African setting.

OBJECTIVE: To estimate the proportion of women who were screened for cervical neoplasia with Papanicolaou (Pap) smears in 2002 in the Free State province of South Africa, and determine whether progress had been made since 1985. METHODS: A cross-sectional survey was done using 1887 smears, which represented 5% of the 37,749 smears examined at the 7 laboratories serving the province in 2002. RESULTS: Extrapolating the results to the census data for 2002, Pap smears were taken in 4.1% of the female population aged 15 to 65 years during that year. The rates were 18.8% for white women, most of whom use private medical services, and 2.6% for black women, almost all of whom use public medical services. In 1985, in a similar study found that 7.1% of the female population was screened with Pap smears, which means that cervical screening decreased by 42% over the 17 years (P< or =0.0001; 95% confidence interval, -3.1% to -2.9%). CONCLUSION: In view of the deterioration of cervical screening services documented in this study, it seems unlikely that Pap smear screening will succeed in Africa.

Vault Prolapse Treated by Sacrocolpopexy

Objective. To evaluate the success rate of sacrocolpopexy in 153 patients with stage 3 and 4 vault prolapse. Methods. A retrospective review was done on 153 patient records from a database in a urogynaecological unit. For the sacrocolpopexy procedure; semi-absorbable mesh was placed along the anterior and posterior vaginal walls; and attached to the anterior longitudinal ligament of the sacrum. Results. The median age was 65 years and parity 3.0; 94of the patients were white. Previous surgery for prolapse was reported by 48of the patients and 25were on thyroid hormone treatment. The vault prolapse was stage 3 in 81 patients (52.9) and stage 4 in 72 (47.1). At surgery; the mesh extended from the vaginal vault to the sacrum in 7 patients (4.6). In the remaining 146 patients (95.4) the mesh was attached to the posterior vaginal wall and in 133 (86.9) a second strip of mesh was fixed to the anterior vaginal wall. Follow-up was possiblein 149 patients (97.4); with a median of 29 months. Recurrent prolapse (any type) occurred in 22 patients (14.4)and 12 had repeat surgery for recurrent prolapse (7.8). In total; 25 patients (16.3) had repeat surgery for anyindication. Conclusions. Vault prolapse is difficult to treat owing to absence of support of the upper vagina; but sacrocolpopexy delivered acceptable results

Combined Abdominal Sacrocolpopexy and Burch Colposuspension for the Treatment of Stage 3 and 4 Anterior Compartment Prolapse

Objective. To review our experience with sacrocolpopexy and Burch colposuspension for stage 3 and 4 anterior compartment prolapse. Methods. Review of 154 patient records drawn from a urogynaecological database; with stage 3 and 4 anterior compartment prolapse treated by sacrocolpopexy and Burch colposuspension. Results. The median age of the patients was 60 years and a third of them had had previous prolapse surgery. Patients presented with bladder (41) and bowel (55) symptoms; and most complained of prolapse protruding through the vaginal introitus (86). Recurrent prolapse; stage 2 - 4; occurred in 24 patients (15.6); 9.7were anterior compartment prolapses. Where mesh was omitted from the anterior vaginal wall but placed on the posterior vaginal wall; significantly more recurrent anterior compartment prolapses occurred (95confidence interval (CI) 0.2; 34.8) compared with cases where mesh was placed both anteriorly and posteriorly to the vagina. Perioperative complications occurred in 13of patients. A tension-free vaginal tape (TVT) procedure for urinary stress incontinence was done at a later stage in 8of the patients. Conclusion. Sacrocolpopexy effectively treated anterior compartment prolapse where mesh was attached to the anterior vaginal wall as well. A Burch colposuspension probably did not make a difference

Moxifloxacin versus ofloxacin plus metronidazole in uncomplicated pelvic inflammatory disease: results of a multicentre, double blind, randomised trial.

OBJECTIVE: This multinational, multicentre, prospective, randomised, double blind, parallel group, non-inferiority study compared the efficacy and safety of moxifloxacin monotherapy with ofloxacin plus metronidazole in women with uncomplicated pelvic inflammatory disease. METHODS: Women from hospitals throughout 13 countries received a 14 day course of either oral moxifloxacin, 400 mg once daily (n = 384), or oral ofloxacin, 400 mg twice daily plus oral metronidazole, 500 mg twice daily (n = 365). RESULTS: Of the 741 patients in the intent to treat (ITT) population, 564 (74.2%) were valid for the per protocol (PP) analyses; 112 (19.9%) of these were included in the microbiologically valid population (MBV). Clinical resolution rates in the PP population at the test of cure visit (TOC, 5-24 days post-therapy, primary efficacy end point) were 90.2% (248/275) for moxifloxacin and 90.7% (262/289) for ofloxacin plus metronidazole (95% CI: -5.7% to 4.0%). At follow up (28-42 days post-therapy), resolution rates in the PP population were 85.8% (236/275) and 87.9% (254/289) for moxifloxacin and comparator, respectively (95% CI: -8.0% to 3.1%). Bacteriological success rates in the MBV population at TOC were 87.5% (49/56) for moxifloxacin and 82.1% (46/56) for comparator (95% CI: -8.3% to 18.8%). Against Chlamydia trachomatis and Neisseria gonorrhoeae, bacteriological success rates with moxifloxacin were 88.5% (23/26) and 100% (13/13) and for comparator 85.7% (18/21) and 81.8% (18/22), respectively. Drug related adverse events occurred less frequently with moxifloxacin (22.5% (85/378)) versus the comparator (30.9% (112/363)) (p = 0.01). CONCLUSION: In uncomplicated PID, once daily moxifloxacin monotherapy was clinically and bacteriologically as efficacious as twice daily ofloxacin plus metronidazole therapy and was associated with fewer drug related adverse events.

Posterior intravaginal slingplasty for vaginal prolapse.

OBJECTIVE: To evaluate the results of the posterior intravaginal slingplasty (IVS). PATIENTS AND METHODS: From a urogynecology database, 42 patients who had undergone posterior IVS procedures were analyzed. All the selected patients had also had a posterior colporrhaphy (88% with mesh inserted into the rectovaginal space). RESULTS: Intraoperatively, there was one complication, a rectum perforation. All patients were followed-up, with a median of 13 months. Recurrent prolapse, grade 3 or 4, developed in 12 patients (29%) which included ten cystoenteroceles (24%), four rectoenteroceles (10%), and three cases of utero/vault prolapse (7%). Repeat surgery was performed in six patients (14%). For utero/vault prolapse, eight patients presented preoperatively with grades 3 and 4 prolapse. On follow-up, three patients had utero/vault prolapse, one of whom did not have utero/vault prolapse on presentation. Therefore, of the eight patients presenting with utero/vault prolapse, only two had repeat prolapse on follow-up, which reflected an improvement of 75%. CONCLUSION: The posterior IVS delivered satisfactory results for vault and posterior compartment prolapse, with a 75% improvement in vault prolapse. It was not possible, however, to separate the effect of posterior IVS and posterior colporrhaphy on the prevention of recurrent prolapse nor on the improvement of difficulty in defecation. Due to the utilization of the now-abandoned vaginal anterior colposuspension procedure for the treatment of anterior compartment prolapse, no conclusions regarding the impact of the posterior IVS on the anterior compartment can be made.

Electrosurgical bipolar vessel sealing during vaginal hysterectomy.

OBJECTIVE: To compare electrosurgical bipolar vessel sealing (EBVS) with traditional suturing during vaginal hysterectomy. METHODS: In a randomized controlled trial involving 68 women undergoing vaginal hysterectomy for benign disease, 37 procedures were performed using EBVS and 31 using traditional suturing. The end points were procedure time, blood loss, number of ligatures used, postoperative pain score, and number of days in hospital. RESULTS: The procedure duration was shorter using EBVS (median duration, 32 vs. 40 min; P=.0003), with fewer ligatures (1 vs. 7; P<.0001) and less pain (median score, 4 vs. 6; P<.0001). There were no significant differences regarding blood loss (median, 100 vs. 160 mL; P=.36) and days in hospital (median, 2 vs. 2; P=.03). CONCLUSION: The EBVS system provided advantages over traditional suturing with regard to procedure time, number of ligatures used, and postoperative pain score.

Screening for cervical cancer in the developing world.

Cervical cancer remains the most common malignancy amongst females in countries of low income, mainly due to a lack of screening. Responsible factors are centred around inadequacies of the Pap smear: high cost; low sensitivity; the need of a laboratory with high human expertise; and a demanding logistic system for mass screening. No alternative screening method seems to be clearly advantageous. Although combinations of tests have higher sensitivities, they are complex, costly and associated with low specificities. Adding the problem of effective treatment, it seems that mass screening with adequate coverage of the population is an unreachable goal for many developing countries. The most promising development in the control of cervical cancer seems to be vaccination against the human papillomavirus, either as a preventative measure or for stimulating immunity in infected women.

Abdominal hysterectomy and Burch colposuspension for uterovaginal prolapse.

The recurrence rate for prolapse in patients who underwent abdominal hysterectomy and sacrocolposuspension for genital prolapse were determined. Patient records were reviewed and 58 patients who had undergone abdominal hysterectomy for genital prolapse and sacrocolposuspension with mesh were included. The patients' median age was 47.0 years and parity 3. Preoperatively, 25 patients (43%) presented with bladder symptoms, 17 (29%) with bowel symptoms and 45 (78%) with something protruding through the vagina. All patients underwent hysterectomy, of which 51 (88%) were subtotal. Colposuspension was performed by inserting a mesh from the mid-vagina to the sacrum (S1). A Burch colposuspension was performed in 50 patients (87%). The median follow-up was 20 months. Six patients (10%) developed recurrent prolapse, of which five (9%) underwent repeat surgery. There were no mesh erosions. The recurrence rate for prolapse was low, indicating that abdominal hysterectomy with sacrocolposuspension is an excellent option for uterovaginal prolapse.