Epilation for minor trachomatous trichiasis: four-year results of a randomised controlled trial.

BACKGROUND: Trachomatous trichiasis (TT) needs to be managed to reduce the risk of vision loss. The long-term impact of epilation (a common traditional practice of repeated plucking of lashes touching the eye) in preventing visual impairment and corneal opacity from TT is unknown. We conducted a randomized controlled trial of epilation versus surgery for the management of minor TT (fewer than six lashes touching the eye) in Ethiopia. Here we report the four-year outcome and the effect on vision and corneal opacity. METHODOLOGY/ PRINCIPAL FINDINGS: 1300 individuals with minor TT were recruited and randomly assigned to quality trichiasis surgery or repeated epilation using high quality epilation forceps by a trained person with good near vision. Participants were examined six-monthly for two-years, and then at four-years after randomisation. At two-years all epilation arm participants were offered free surgery. At four-years 1151 (88.5%) were re-examined: 572 (88%) and 579 (89%) from epilation and surgery arms, respectively. At that time, 21.1% of the surgery arm participants had recurrent TT; 189/572 (33%) of the epilation arm had received surgery, while 383 (67%) declined surgery and had continued epilating ("epilation-only"). Among the epilation-only group, 207 (54.1%) fully controlled their TT, 166 (43.3%) had minor TT and 10 (2.6%) had major TT (>5 lashes). There were no differences between participants in the epilation-only, epilation-to-surgery and surgery arm participants in changes in visual acuity and corneal opacity between baseline and four-years. CONCLUSIONS/ SIGNIFICANCE: Most minor TT participants randomised to the epilation arm continued epilating and controlled their TT. Change in vision and corneal opacity was comparable between surgery and epilation-only participants. This suggests that good quality epilation with regular follow-up is a reasonable second-line alternative to surgery for minor TT for individuals who either decline surgery or do not have immediate access to surgical treatment

The Impact of Trachomatous Trichiasis on Quality of Life: A Case Control Study.

BACKGROUND: Trachomatous trichiasis is thought to have a profound effect on quality of life (QoL), however, there is little research in this area. We measured vision and health-related QoL in a case-control study in Amhara Region, Ethiopia. METHODOLOGY/PRINCIPAL FINDINGS: We recruited 1000 adult trichiasis cases and 200 trichiasis-free controls, matched to every fifth trichiasis case on age (+/- two years), sex and location. Vision-related quality of life (VRQoL) and health-related quality of life (HRQoL) were measured using the WHO/PBD-VF20 and WHOQOL-BREF questionnaires. Comparisons were made using linear regression adjusted for age, sex and socioeconomic status. Trichiasis cases had substantially lower VRQoL than controls on all subscales (overall eyesight, visual symptom, general functioning and psychosocial, p<0.0001), even in the sub-group with normal vision (p<0.0001). Lower VRQoL scores in cases were associated with longer trichiasis duration, central corneal opacity, visual impairment and poor contrast sensitivity. Trichiasis cases had lower HRQoL in all domains (Physical-health, Psychological, Social, Environment, p<0.0001), lower overall QoL (mean, 34.5 v 64.6; p<0.0001) and overall health satisfaction (mean, 38.2 v 71.7; p<0.0001). This association persisted in a sub-group analysis of cases and controls with normal vision. Not having a marriage partner (p<0.0001), visual impairment (p = 0.0068), daily labouring (p<0.0001), presence of other health problems (p = 0.0018) and low self-rated wealth (p<0.0001) were independently associated with lower overall QoL scores in cases. Among cases, trichiasis caused 596 (59%) to feel embarrassed, 913 (91.3%) to worry they may lose their remaining eyesight and 681 (68.1%) to have sleep disturbance. CONCLUSIONS/SIGNIFICANCE: Trachomatous trichiasis substantially reduces vision and health related QoL and is disabling, even without visual impairment. Prompt trichiasis intervention is needed both to prevent vision loss and to alleviate physical and psychological suffering, social exclusion and improve overall well-being. Implementation of the full SAFE strategy is needed to prevent the development of trachomatous trichiasis

Impact of Trichiasis Surgery on Quality of Life: A Longitudinal Study in Ethiopia.

BACKGROUND: Trachomatous trichiasis significantly reduces vision and health related quality of life (QoL). Although trichiasis surgery is widely performed to treat trichiasis, there is little data on the effect of surgery on QoL. We measured the impact of trichiasis surgery on vision and health related QoL in a longitudinal study from Amhara Region, Ethiopia. METHODOLOGY/PRINCIPAL FINDINGS: We recruited 1000 adult participants with trichiasis (cases) and 200 comparison participants, matched to every fifth trichiasis case on age (+/- two years), sex and location. Vision-related quality of life (VRQoL) and health-related quality of life (HRQoL) were measured using the WHO/PBD-VF20 and WHOQOL-BREF questionnaires respectively, at enrolment and 12 months after enrolment. All trichiasis cases received free standard trichiasis surgery immediately after enrolment. The mean difference in QoL scores between enrolment and follow-up for cases and comparison participants, and the difference-in-differences by baseline trichiasis status was analysed using random effects linear regression, the later adjusted for age, sex and socioeconomic status. At 12-months follow-up, data was collected from 980 (98%) and 198 (98%) trichiasis cases and comparison participants respectively. At this follow-up visit, VRQoL and HRQoL scores of trichiasis cases improved substantially in all subscales and domains by 19.1-42.0 points (p<0.0001) and 4.7-17.2 points (p<0.0001), respectively. In contrast, among the comparison participants, there was no evidence of improvement in VRQoL and HRQoL domain scores during follow-up. The improvement in VRQoL and HRQoL in cases was independent of the presence of visual acuity improvement at 12 months. CONCLUSIONS/SIGNIFICANCE: Trichiasis surgery substantially improves both VRQoL and HRQoL regardless of visual acuity change. Unprecedented effort is needed to scale-up trichiasis surgical programmes not only to prevent the risk of sight loss but also to improve overall wellbeing and health perception of affected individuals

Posterior lamellar versus bilamellar tarsal rotation surgery for trachomatous trichiasis in Ethiopia: a randomised controlled trial

Background Eyelid surgery is done to correct trachomatous trichiasis to prevent blindness. However, recurrent trichiasis is frequent. Two procedures are recommended by WHO and are in routine practice: bilamellar tarsal rotation (BLTR) and posterior lamellar tarsal rotation (PLTR). This study was done to identify which procedure gives the better results. Methods A randomised, controlled, single masked clinical trial was done in Ethiopia. Participants had upper lid trachomatous trichiasis with one or more eyelashes touching the eye or evidence of epilation, in association with tarsal conjunctival scarring. Exclusion criteria were age less than 18 years, recurrent trichiasis after previous surgery, hypertension, and pregnancy. Participants were randomly assigned (1:1) to either BLTR or PLTR surgery, stratifi ed by surgeon. The sequences were computer-generated by an independent statistician. Surgery was done in a community setting following WHO guidelines. Participants were examined at 6 months and 12 months by assessors masked to allocation. The primary outcome was the cumulative proportion of individuals who developed recurrent trichiasis by 12 months. Primary analyses were by modifi ed intention to treat. The intervention eff ect was estimated by logistic regression, controlled for surgeon as a fi xed eff ect in the model. The trial is registered with the Pan African Clinical Trials Registry (number PACTR201401000743135). Findings 1000 participants with trichiasis were recruited, randomly assigned, and treated (501 in the BLTR group and 499 in the PLTR group) between Feb 13, 2014, and May 31, 2014. Eight participants were not seen at either 6 month or 12 month follow-up visits and were excluded from the analysis: three from the PLTR group and fi ve from the BLTR group. The follow-up rate at 12 months was 98%. Cumulative recurrent trichiasis by 12 months was more frequent in the BLTR group than in the PLTR group (110/496 [22%] vs 63/496 [13%]; adjusted odds ratio [OR] 1·96 [95% CI 1·40–2·75]; p=0·0001), with a risk diff erence of 9·50% (95% CI 4·79–14·16). Interpretation PLTR surgery was superior to BLTR surgery for management of trachomatous trichiasis, and could be the preferred procedure for the programmatic management of trachomatous trichiasis

Oral doxycycline for the prevention of postoperative trachomatous trichiasis in Ethiopia: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Trachomatous trichiasis is treated surgically to prevent sight loss. Unfavourable surgical outcomes remain a major challenge. We investigated the hypothesis that doxycycline might reduce the risk of postoperative trichiasis following surgery in patients with trachomatous trichiasis through anti-matrix metalloproteinase and anti-inflammatory activity. METHODS: In this randomised, double-blind, placebo-controlled trial, adults (aged >18 years) with upper lid trachomatous trichiasis in association with tarsal conjunctive scarring were recruited through community-based screening and surgical outreach campaigns in Ethiopia. Individuals who had previously had eyelid surgery were excluded. Participants were randomly assigned (1:1), with random block sizes of four or six, to receive oral doxycycline (100 mg once a day) or placebo for 28 days immediately after trichiasis surgery. Randomisation was stratified by surgeon. Patients, investigators, surgeons, and all other study team members were masked to study group allocation and treatment. Participants were examined at 10 days, and 1, 6, and 12 months after surgery. The primary outcome was the cumulative proportion of individuals who developed postoperative trichiasis by 12 months. Primary analyses were done in all participants who attended at least one of the four follow-up assessments. Safety analyses were done in all participants who attended either the 10 day or 1 month follow-up assessments. This trial is registered with the Pan African Clinical Trials Registry, number PACTR201512001370307. FINDINGS: Between Dec 21, 2015, and April 6, 2016, 1000 patients with trichiasis were enrolled and randomly assigned to treatment (499 patients to doxycycline, 501 patients to placebo). All but one participant attended at least one follow-up assessment. Thus, 999 participants were assessed for the primary outcome: 498 in the doxycycline group and 501 in the placebo group. By month 12, 58 (12%) of 498 patients in the doxycycline group and 62 (12%) of 501 patients in the placebo group had developed postoperative trichiasis (adjusted odds ratio 0·91, 95% CI 0·61 to 1·34, p=0·63), with a risk difference of -0·5% (-4·5% to 3·5%). Significantly more patients in the doxycycline group had an adverse event than in the placebo group (18 [4%] of 498 vs six [1%] of 501; odds ratio 3·09, 95% CI 1·21-7·84; p=0·02). The most frequent adverse events in the doxycycline group were gastritis symptoms (n=9), constipation (n=4), and diarrhoea (n=4). INTERPRETATION: Doxycycline did not reduce the risk of postoperative trichiasis and is therefore not indicated for the improvement of outcomes following trachomatous trichiasis surgery. Surgical programmes should continue to make efforts to strengthen surgical training and supervision to improve outcomes. FUNDING: The Wellcome Trust

Re-evaluation of mammary stem cell biology based on in vivo transplantation

Over nearly half a century, transplantation methods have been employed to regenerate the mammary gland in vivo. Recent highly cited reports claim to have demonstrated the regeneration of an entire functional mammary gland from a single mammary epithelial cell. Nevertheless, re-examination of the literature on the transplantation biology of mammary gland regeneration reveals that a complex, combinatorial interaction between variously differentiated mammary epithelial cells and the mammary fat pad stroma is indispensable to this process. In the present article, these issues are reviewed and discussed to provide a greater understanding of the complexity of these multiplex interactions

The conjunctival transcriptome in Ethiopians after trichiasis surgery: associations with the development of eyelid contour abnormalities and the effect of oral doxycycline treatment

Background: Surgery to correct trichiasis is a key component of the World Health Organisation trachoma control strategy, however unfavourable outcomes such as eyelid contour abnormalities (ECA) following surgery are relatively common. This study aimed to understand the transcriptional changes associated with the early development of ECA and the impact of doxycycline, which has anti-inflammatory and anti-fibrotic properties, upon these transcription patterns. Methods: One thousand Ethiopians undergoing trichiasis surgery were enrolled in a randomised controlled trial following informed consent. Equal groups of randomly assigned individuals were orally administered with 100mg/day of doxycycline (n=499) or placebo (n=501) for 28 days. Conjunctival swabs were collected immediately prior to surgery and at one- and six-months post-surgery. 3’ mRNA sequencing was performed on paired baseline and one-month samples from 48 individuals; 12 in each treatment/ECA outcome group. qPCR validation was then performed for 46 genes of interest in 145 individuals who developed ECA at one month and 145 matched controls, using samples from baseline, one and six months. Results: All treatment/outcome groups upregulated genes associated with wound healing pathways at one month relative to baseline, however no individual differences were detected between groups. The summed expression of a highly coexpressed cluster of pro-fibrotic genes was higher in patients that developed ECA in the placebo group relative to controls. qPCR validation revealed that all genes in this cluster and a number of other pro-inflammatory genes were strongly associated with ECA, however these associations were not modulated by trial arm. Conclusions: The development of post-operative ECA is associated with overexpression of pro-inflammatory and pro-fibrotic genes including growth factors, matrix metalloproteinases, collagens and extracellular matrix proteins. There was no evidence that doxycycline modulated the association between gene expression and ECA.</ns4:p

The conjunctival transcriptome in Ethiopians after trichiasis surgery: associations with the development of eyelid contour abnormalities and the effect of oral doxycycline treatment

Background: Surgery to correct trichiasis is a key component of the World Health Organisation trachoma control strategy, however unfavourable outcomes such as eyelid contour abnormalities (ECA) following surgery are relatively common. This study aimed to understand the transcriptional changes associated with the early development of ECA and the impact of doxycycline, which has anti-inflammatory and anti-fibrotic properties, upon these transcription patterns. Methods: One thousand Ethiopians undergoing trichiasis surgery were enrolled in a randomised controlled trial following informed consent. Equal groups of randomly assigned individuals were orally administered with 100mg/day of doxycycline (n=499) or placebo (n=501) for 28 days. Conjunctival swabs were collected immediately prior to surgery and at one- and six-months post-surgery. 3’ mRNA sequencing was performed on paired baseline and one-month samples from 48 individuals; 12 in each treatment/outcome group (Placebo-Good outcome, Placebo-Poor outcome, Doxycycline-Good outcome, Doxycycline-Poor outcome). qPCR validation was then performed for 46 genes of interest in 145 individuals who developed ECA at one month and 145 matched controls, using samples from baseline, one and six months. Results: All treatment/outcome groups upregulated genes associated with wound healing pathways at one month relative to baseline, however no individual differences were detected between groups. The summed expression of a highly coexpressed cluster of pro-fibrotic genes was higher in patients that developed ECA in the placebo group relative to controls. qPCR validation revealed that all genes in this cluster and a number of other pro-inflammatory genes were strongly associated with ECA, however these associations were not modulated by trial arm. Conclusions: The development of post-operative ECA is associated with overexpression of pro-inflammatory and pro-fibrotic genes including growth factors, matrix metalloproteinases, collagens and extracellular matrix proteins. There was no evidence that doxycycline modulated the association between gene expression and ECA.</ns4:p

Downregulation of metastasis suppressor 1(MTSS1) is associated with nodal metastasis and poor outcome in Chinese patients with gastric cancer

<p>Abstract</p> <p>Background</p> <p>The putative tumor metastasis suppressor 1(MTSS1) is an actin-binding scaffold protein that has been implicated to play an important role in carcinogenesis and cancer metastasis, yet its role in the development of gastric cancer has not been well illustrated. In this study, we detected MTSS1 expression and explored its clinical significance in gastric cancer.</p> <p>Methods</p> <p>Immunohistochemistry was performed using tissue microarrays containing gastric adenocarcinoma specimens from 1,072 Chinese patients with normal adjacent mucosa, primary gastric cancer and lymph node (LN) metastasis and specific antibody against MTSS1. MTSS1 mRNA and protein expression were detected by reverse transcription-polymerase chain reaction and Western blotting. The clinical follow-up was done in the 669 patients living in Shanghai that was chose from the 1072 cases.</p> <p>Results</p> <p>Complete loss of MTSS1 expression was observed in 751 cases (70.1%) of the 1,072 primary tumors and 103 (88%) of 117 nodal metastases; and loss of MTSS1 expression was significantly associated with poorly differentiated tumors, large tumor size, deep invasion level, the presence of nodal metastases and advanced disease stage. Moreover, multivariate analysis demonstrated that loss of MTSS1 expression correlated significantly with poor survival rates (RR = 0.194, 95% CI = 0.144-0.261, P < 0.001).</p> <p>Conclusions</p> <p>MTSS1 expression decreased significantly as gastric cancer progressed and metastasized, suggesting MTSS1 may serve as a useful biomarker for the prediction of outcome of gastric cancer.</p

Ethnicity and gender related differences in extended intraesophageal pH monitoring parameters in infants: a retrospective study

BACKGROUND: Gastroesophageal reflux disease (GERD) is believed to be more common in adult males as compared to females. It also has been shown in adults to be more common in Caucasians. We wanted to determine ethnicity and gender related differences for extended pH monitoring parameters in infancy. METHODS: Extended pH monitoring data (EPM) from infants <1 year of age were reviewed. Results were classified in two groups, as control and Gastroesophageal reflux disease (GERD) group based on the reflux index (RI). The GERD group had RI of equal to or more than 5% of total monitoring period. The parameters of RI, total number of episodes of pH < 4, and the number of episodes with pH < 4 lasting more than 5 minutes were compared by genders and by ethnic groups, Caucasians and African American (AA). RESULTS: There were 569 infants, 388 controls, 181 with GERD (320 males, 249 females; 165 Caucasians, 375 AA). No statistical difference in EPM parameters was detected between genders in both groups. However, Caucasian infants had a significantly higher incidence of GERD than AA infants (p = 0.036). On stratifying by gender, Caucasian females had a significantly higher number of reflux episodes >5 minutes as compared to AA females in the control group (p = 0.05). Furthermore, Caucasian females with GERD showed an overall higher trend for all parameters. Caucasian males had a trend for higher mean number of reflux episodes as compared to AA males in the control group (p = 0.09). CONCLUSION: Although gender specific control data do not appear warranted in infants undergoing EPM, ethnic differences related to an overall increased incidence of pathologic GERD in Caucasian infants should be noted