Patterns in Place of Cancer Death in the State of Qatar: A Population-Based Study

Background

International studies show that most people prefer to die at home; however, hospitals remain the most common place of death (PoD). This study aims to investigate the patterns in PoD and the associated factors, which are crucial for end-of-life cancer care enhancement.

Method

This retrospective, population-based study analyzed all registered cancer deaths in Qatar between January 1, 2006 and December 31, 2012 (n = 1,224). The main outcome measures were patient characteristics: age, gender, nationality, cancer diagnosis, year of death, and PoD. Time trends for age-standardized proportions of death in individual PoDs were evaluated using chi-square analysis. Odds ratio (OR) were determined for variables associated with the most preferred (acute palliative care unit [APCU] and hematology/oncology ward) versus least preferred (ICU and general medicine ward) PoDs in Qatar, stratified by nationality.

Results

The hematology/oncology ward was the most common PoD (32.4%; 95% CI 26.7–35.3%) followed by ICU (31.4%; 95% CI 28.7–34.3%), APCU (26.9%; 95% CI 24.3–29.6%), and general medicine ward (9.2%; 95% CI 7.6–11.1%). APCU trended upward (+0.057/year; p<0.001), while the hematology/oncology ward trended downward (−0.055/year; p<0.001). No statistically significant changes occurred in the other PoDs; home deaths remained low (0.4%; 95% Cl 0.38–0.42). Qataris who died from liver cancer (OR 0.23) and aged 65 or older (OR 0.64) were less likely to die in the APCU or hematology/oncology ward (p<0.05). Non-Qataris who died from pancreatic cancer (OR 3.12) and female (OR 2.05) were more likely to die in the APCU or hematology/oncology ward (p<0.05). Both Qataris and non-Qataris who died from hematologic malignancy (OR 0.18 and 0.41, respectively) were more likely to die in the ICU or general medicine ward (p<0.05).

Conclusion

A high percentage of cancer deaths in Qatar occur in hospital. As home was the preferred PoD for most people, effective home care and hospice programs are needed to improve end-of-life cancer care.     

Place and Cause of Death in Centenarians: A Population-Based Observational Study in England, 2001 to 2010

Background

Centenarians are a rapidly growing demographic group worldwide, yet their health and social care needs are seldom considered. This study aims to examine trends in place of death and associations for centenarians in England over 10 years to consider policy implications of extreme longevity.

Methods and Findings

This is a population-based observational study using death registration data linked with area-level indices of multiple deprivations for people aged ≥100 years who died 2001 to 2010 in England, compared with those dying at ages 80-99. We used linear regression to examine the time trends in number of deaths and place of death, and Poisson regression to evaluate factors associated with centenarians’ place of death. The cohort totalled 35,867 people with a median age at death of 101 years (range: 100–115 years). Centenarian deaths increased 56% (95% CI 53.8%–57.4%) in 10 years. Most died in a care home with (26.7%, 95% CI 26.3%–27.2%) or without nursing (34.5%, 95% CI 34.0%–35.0%) or in hospital (27.2%, 95% CI 26.7%–27.6%). The proportion of deaths in nursing homes decreased over 10 years (−0.36% annually, 95% CI −0.63% to −0.09%, p = 0.014), while hospital deaths changed little (0.25% annually, 95% CI −0.06% to 0.57%, p = 0.09). Dying with frailty was common with “old age” stated in 75.6% of death certifications. Centenarians were more likely to die of pneumonia (e.g., 17.7% [95% CI 17.3%–18.1%] versus 6.0% [5.9%–6.0%] for those aged 80–84 years) and old age/frailty (28.1% [27.6%–28.5%] versus 0.9% [0.9%–0.9%] for those aged 80–84 years) and less likely to die of cancer (4.4% [4.2%–4.6%] versus 24.5% [24.6%–25.4%] for those aged 80–84 years) and ischemic heart disease (8.6% [8.3%–8.9%] versus 19.0% [18.9%–19.0%] for those aged 80–84 years) than were younger elderly patients. More care home beds available per 1,000 population were associated with fewer deaths in hospital (PR 0.98, 95% CI 0.98–0.99, p<0.001).

Conclusions

Centenarians are more likely to have causes of death certified as pneumonia and frailty and less likely to have causes of death of cancer or ischemic heart disease, compared with younger elderly patients. To reduce reliance on hospital care at the end of life requires recognition of centenarians’ increased likelihood to “acute” decline, notably from pneumonia, and wider provision of anticipatory care to enable people to remain in their usual residence, and increasing care home bed capacity. Please see later in the article for the Editors'' Summary     

Does Ethnicity Affect Where People with Cancer Die? A Population-Based 10 Year Study

Background

Ageing is a growing issue for people from UK black, Asian and minority ethnic (BAME) groups. The health experiences of these groups are recognised as a ‘tracer’ to measure success in end of life patient-preferred outcomes that includes place of death (PoD).

Aim

To examine patterns in PoD among BAME groups who died of cancer.

Material and Methods

Mortality data for 93,375 cancer deaths of those aged ≥65 years in London from 2001–2010 were obtained from the UK Office for National Statistics (ONS). Decedent''s country of birth was used as a proxy for ethnicity. Linear regression examined trends in place of death across the eight ethnic groups and Poisson regression examined the association between country of birth and place of death.

Results

76% decedents were born in the UK, followed by Ireland (5.9%), Europe(5.4%) and Caribbean(4.3%). Most deaths(52.5%) occurred in hospital, followed by home(18.7%). During the study period, deaths in hospital declined with an increase in home deaths; trend for time analysis for those born in UK(0.50%/yr[0.36–0.64%]p<0.001), Europe (1.00%/yr[0.64–1.30%]p<0.001), Asia(1.09%/yr[0.94–1.20%]p<0.001) and Caribbean(1.03%/yr[0.72–1.30%]p<0.001). However, time consistent gaps across the geographical groups remained. Following adjustment hospital deaths were more likely for those born in Asia(Proportion ratio(PR)1.12[95%CI1.08–1.15]p<0.001) and Africa(PR 1.11[95%CI1.07–1.16]p<0.001). Hospice deaths were less likely for those born in Asia(PR 0.73 [0.68–0.80] p<0.001), Africa (PR 0.83[95%CI0.74–0.93]p<0.001), and ‘other’ geographical regions (PR0.90[95% 0.82–0.98]p<0.001). Home deaths were less likely for those born in the Caribbean(PR0.91[95%CI 0.85–0.98]p<0.001).

Conclusions

Location of death varies by country of birth. BAME groups are more likely to die in a hospital and less likely to die at home or in a hospice. Further investigation is needed to determine whether these differences result from patient-centred preferences, or other environment or service-related factors. This knowledge will enable strategies to be developed to improve access to relevant palliative care and related services, where necessary.     

Risk of Gastric Cancer by Water Source: Evidence from the Golestan Case-Control Study

Background

Gastric cancer (GC) is the world’s fifth most common cancer, and the third leading cause of cancer-related death. Over 70% of incident cases and deaths occur in developing countries. We explored whether disparities in access to improved drinking water sources were associated with GC risk in the Golestan Gastric Cancer Case Control Study.

Methods and Findings

306 cases and 605 controls were matched on age, gender, and place of residence. We conducted unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CI), adjusted for age, gender, ethnicity, marital status, education, head of household education, place of birth and residence, homeownership, home size, wealth score, vegetable consumption, and H. pylori seropositivity. Fully-adjusted ORs were 0.23 (95% CI: 0.05–1.04) for chlorinated well water, 4.58 (95% CI: 2.07–10.16) for unchlorinated well water, 4.26 (95% CI: 1.81–10.04) for surface water, 1.11 (95% CI: 0.61–2.03) for water from cisterns, and 1.79 (95% CI: 1.20–2.69) for all unpiped sources, compared to in-home piped water. Comparing unchlorinated water to chlorinated water, we found over a two-fold increased GC risk (OR 2.37, 95% CI: 1.56–3.61).

Conclusions

Unpiped and unchlorinated drinking water sources, particularly wells and surface water, were significantly associated with the risk of GC.     

Diagnostic accuracy of cervical cancer screening and screening–triage strategies among women living with HIV-1 in Burkina Faso and South Africa: A cohort study

BackgroundCervical cancer screening strategies using visual inspection or cytology may have suboptimal diagnostic accuracy for detection of precancer in women living with HIV (WLHIV). The optimal screen and screen–triage strategy, age to initiate, and frequency of screening for WLHIV remain unclear. This study evaluated the sensitivity, specificity, and positive predictive value of different cervical cancer strategies in WLHIV in Africa.Methods and findingsWLHIV aged 25–50 years attending HIV treatment centres in Burkina Faso (BF) and South Africa (SA) from 5 December 2011 to 30 October 2012 were enrolled in a prospective evaluation study of visual inspection using acetic acid (VIA) or visual inspection using Lugol’s iodine (VILI), high-risk human papillomavirus DNA test (Hybrid Capture 2 [HC2] or careHPV), and cytology for histology-verified high-grade cervical intraepithelial neoplasia (CIN2+/CIN3+) at baseline and endline, a median 16 months later. Among 1,238 women (BF: 615; SA: 623), median age was 36 and 34 years (p < 0.001), 28.6% and 49.6% ever had prior cervical cancer screening (p < 0.001), and 69.9% and 64.2% were taking ART at enrolment (p = 0.045) in BF and SA, respectively. CIN2+ prevalence was 5.8% and 22.4% in BF and SA (p < 0.001), respectively. VIA had low sensitivity for CIN2+ (44.7%, 95% confidence interval [CI] 36.9%–52.7%) and CIN3+ (56.1%, 95% CI 43.3%–68.3%) in both countries, with specificity for ≤CIN1 of 78.7% (95% CI 76.0%–81.3%). HC2 had sensitivity of 88.8% (95% CI 82.9%–93.2%) for CIN2+ and 86.4% (95% CI 75.7%–93.6%) for CIN3+. Specificity for ≤CIN1 was 55.4% (95% CI 52.2%–58.6%), and screen positivity was 51.3%. Specificity was higher with a restricted genotype (HPV16/18/31/33/35/45/52/58) approach (73.5%, 95% CI 70.6%–76.2%), with lower screen positivity (33.7%), although there was lower sensitivity for CIN3+ (77.3%, 95% CI 65.3%–86.7%). In BF, HC2 was more sensitive for CIN2+/CIN3+ compared to VIA/VILI (relative sensitivity for CIN2+ = 1.72, 95% CI 1.28–2.32; CIN3+: 1.18, 95% CI 0.94–1.49). Triage of HC2-positive women with VIA/VILI reduced the number of colposcopy referrals, but with loss in sensitivity for CIN2+ (58.1%) but not for CIN3+ (84.6%). In SA, cytology high-grade squamous intraepithelial lesion or greater (HSIL+) had best combination of sensitivity (CIN2+: 70.1%, 95% CI 61.3%–77.9%; CIN3+: 80.8%, 95% CI 67.5%–90.4%) and specificity (81.6%, 95% CI 77.6%–85.1%). HC2 had similar sensitivity for CIN3+ (83.0%, 95% CI 70.2%–91.9%) but lower specificity compared to HSIL+ (42.7%, 95% CI 38.4%–47.1%; relative specificity = 0.57, 95% CI 0.52–0.63), resulting in almost twice as many referrals. Compared to HC2, triage of HC2-positive women with HSIL+ resulted in a 40% reduction in colposcopy referrals but was associated with some loss in sensitivity. CIN2+ incidence over a median 16 months was highest among VIA baseline screen-negative women (2.2%, 95% CI 1.3%–3.7%) and women who were baseline double-negative with HC2 and VIA (2.1%, 95% CI 1.3%–3.5%) and lowest among HC2 baseline screen-negative women (0.5%, 95% CI 0.1%–1.8%). Limitations of our study are that WLHIV included in the study may not reflect a contemporary cohort of WLHIV initiating ART in the universal ART era and that we did not evaluate HPV tests available in study settings today.ConclusionsIn this cohort study among WLHIV in Africa, a human papillomavirus (HPV) test targeting 14 high-risk (HR) types had higher sensitivity to detect CIN2+ compared to visual inspection but had low specificity, although a restricted genotype approach targeting 8 HR types decreased the number of unnecessary colposcopy referrals. Cytology HSIL+ had optimal performance for CIN2+/CIN3+ detection in SA. Triage of HPV-positive women with HSIL+ maintained high specificity but with some loss in sensitivity compared to HC2 alone.

In this cohort study, Helen Kelly and colleagues explore cervical cancer screening strategies for women living with HIV.     

Increased Childhood Mortality and Arsenic in Drinking Water in Matlab,Bangladesh: A Population-Based Cohort Study

Background

Arsenic in drinking water was associated with increased risk of all-cause, cancer, and cardiovascular death in adults. However, the extent to which exposure is related to all-cause and deaths from cancer and cardiovascular condition in young age is unknown. Therefore, we prospectively assessed whether long-term and recent arsenic exposures are associated with all-cause and cancer and cardiovascular mortalities in Bangladeshi childhood population.

Methods and Findings

We assembled a cohort of 58406 children aged 5–18 years from the Health and Demographic Surveillance System of icddrb in Bangladesh and followed during 2003–2010. There were 185 non-accidental deaths registered in-about 0.4 million person-years of observation. We calculated hazard ratios for cause-specific death in relation to exposure at baseline (µg/L), time-weighted lifetime average (µg/L) and cumulative concentration (µg-years/L). After adjusting covariates, hazard ratios (HRs) for all-cause childhood deaths comparing lifetime average exposure 10–50.0, 50.1–150.0, 150.1–300.0 and ≥300.1µg/L were 1.37 (95% confidence interval [CI], 0.74–2.57), 1.44 (95% CI, 0.88–2.38), 1.22 (95% CI, 0.75–1.98) and 1.88 (95% CI, 1.14–3.10) respectively. Significant increased risk was also observed for baseline (P for trend = 0.023) and cumulative exposure categories (P for trend = 0.036). Girls had higher mortality risk compared to boys (HR for girls 1.79, 1.21, 1.64, 2.31; HR for boys 0.52, 0.53, 1.14, 0.99) in relation to baseline exposure. For all cancers and cardiovascular deaths combined, multivariable adjusted HRs amounted to 1.53 (95% CI 0.51–4.57); 1.29 (95% CI 0.43–3.87); 2.18 (95%CI 1.15–4.16) for 10.0–50.0, 50.1–150.0, and ≥150.1, comparing lowest exposure as reference (P for trend = 0.009). Adolescents had higher mortality risk compared to children (HRs = 1.53, 95% CI 1.03–2.28 vs. HRs = 1.30, 95% CI 0.78–2.17).

Conclusions

Arsenic exposure was associated with substantial increased risk of deaths at young age from all-cause, and cancers and cardiovascular conditions. Girls and adolescents (12–18 years) had higher risk compared to boys and child.     

The Impact of Hospice Care on Survival and Healthcare Costs for Patients with Lung Cancer: A National Longitudinal Population-Based Study in Taiwan

Background

The healthcare costs of cancer care are highest in the last month of life. The effect of hospice care on end-of-life (EOL) healthcare costs is not clearly understood.

Purpose

The purpose of this study was to evaluate the effect of hospice care on survival and healthcare costs for lung cancer patients in their final month of life.

Methods

We adopted Taiwan’s National Health Insurance Research Claims Database to analyze data for 3399 adult lung cancer patients who died in 1997–2011. A logistic regression analysis was performed to determine the predictors of high healthcare cost, defined as costs falling above the 90th percentile. Patients who received hospice cares were assigned to a hospice (H) group and those who did not were assigned to a non-hospice (non-H) group.

Results

The patients in the H group had a longer mean (median) survival time than those in the non-H group did (1.40 ± 1.61 y (0.86) vs. 1.10 ± 1.47 (0.61), p<0.001). The non-H group had a lower mean healthcare cost than the H group (US $1,821 ± 2,441 vs. US $1,839 ± 1,638, p<0.001). And, there were a total of 340 patients (10%) with the healthcare costs exceeding the 90th percentile (US $4,721) as the cutoff value of high cost. The non-H group had a higher risk of high cost than the H group because many more cases in the non-H group had lower costs. Moreover, the risk of high health care costs were predicted for patients who did not receive hospice care (odds ratio [OR]: 3.68, 95% confidence interval [CI]: 2.44–5.79), received chemotherapy (OR: 1.51, 95% CI: 1.18–1.96) and intubation (OR: 2.63, 95% CI: 1.64–4.16), and those who had more emergency department visits (OR: 1.78, 95% CI: 1.24–2.52), longer hospital admission in days (OR: 1.08, 95% CI: 1.07–1.09), and received radiotherapy (OR: 1.33, 95% CI: 1.00–1.78). Lower risks of high health care costs were observed in patients with low socioeconomic status (OR: 0.58, 95% CI: 0.40–0.83), or previous employment (OR: 0.66, 95% CI: 0.47–0.92). After propensity-score matching, the patients of the non-H group had a higher mean cost and a higher risk of high cost. Similar results were obtained from logistic regression analysis in propensity score-matched patients.

Conclusions

The survival of the hospice group was longer than non-H group, and patients in the non-H group were 3.74 times more likely to have high healthcare costs at EOL. The positive predictors for high health care costs were patients who did not receive hospice care, who received chemotherapy and intubation, who had more emergency department visits and longer hospital admission, and who received radiotherapy. Negative predictors were patients who had a low socioeconomic status or previous employment. The issue of how to reduce the high health care costs for patients with lung cancer in the last month of life is a challenge for policy makers and health care providers.     

The Trypanosoma cruzi Satellite DNA OligoC-TesT and Trypanosoma cruzi Kinetoplast DNA OligoC-TesT for Diagnosis of Chagas Disease: A Multi-cohort Comparative Evaluation Study

Background

The Trypanosoma cruzi satellite DNA (satDNA) OligoC-TesT is a standardised PCR format for diagnosis of Chagas disease. The sensitivity of the test is lower for discrete typing unit (DTU) TcI than for TcII-VI and the test has not been evaluated in chronic Chagas disease patients.

Methodology/Principal Findings

We developed a new prototype of the OligoC-TesT based on kinetoplast DNA (kDNA) detection. We evaluated the satDNA and kDNA OligoC-TesTs in a multi-cohort study with 187 chronic Chagas patients and 88 healthy endemic controls recruited in Argentina, Chile and Spain and 26 diseased non-endemic controls from D.R. Congo and Sudan. All specimens were tested in duplicate. The overall specificity in the controls was 99.1% (95% CI 95.2%–99.8%) for the satDNA OligoC-TesT and 97.4% (95% CI 92.6%–99.1%) for the kDNA OligoC-TesT. The overall sensitivity in the patients was 67.9% (95% CI 60.9%–74.2%) for the satDNA OligoC-TesT and 79.1% (95% CI 72.8%–84.4%) for the kDNA OligoC-Test.

Conclusions/Significance

Specificities of the two T. cruzi OligoC-TesT prototypes are high on non-endemic and endemic controls. Sensitivities are moderate but significantly (p = 0.0004) higher for the kDNA OligoC-TesT compared to the satDNA OligoC-TesT.     

Time Series Analysis of Trends in Malaria Cases and Deaths at Hospitals and the Effect of Antimalarial Interventions, 2001–2011, Ethiopia

Background

The Government of Ethiopia and its partners have deployed artemisinin-based combination therapies (ACT) since 2004 and long-lasting insecticidal nets (LLINs) since 2005. Malaria interventions and trends in malaria cases and deaths were assessed at hospitals in malaria transmission areas during 2001–2011.

Methods

Regional LLINs distribution records were used to estimate the proportion of the population-at-risk protected by LLINs. Hospital records were reviewed to estimate ACT availability. Time-series analysis was applied to data from 41 hospitals in malaria risk areas to assess trends of malaria cases and deaths during pre-intervention (2001–2005) and post-interventions (2006–2011) periods.

Findings

The proportion of the population-at-risk potentially protected by LLINs increased to 51% in 2011. The proportion of facilities with ACTs in stock exceeded 87% during 2006–2011. Among all ages, confirmed malaria cases in 2011 declined by 66% (95% confidence interval [CI], 44–79%) and SPR by 37% (CI, 20%–51%) compared to the level predicted by pre-intervention trends. In children under 5 years of age, malaria admissions and deaths fell by 81% (CI, 47%–94%) and 73% (CI, 48%–86%) respectively. Optimal breakpoint of the trendlines occurred between January and June 2006, consistent with the timing of malaria interventions. Over the same period, non-malaria cases and deaths either increased or remained unchanged, the number of malaria diagnostic tests performed reflected the decline in malaria cases, and rainfall remained at levels supportive of malaria transmission.

Conclusions

Malaria cases and deaths in Ethiopian hospitals decreased substantially during 2006–2011 in conjunction with scale-up of malaria interventions. The decrease could not be accounted for by changes in hospital visits, malaria diagnostic testing or rainfall. However, given the history of variable malaria transmission in Ethiopia, more data would be required to exclude the possibility that the decrease is due to other factors.     

Social determinants of mortality from COVID-19: A simulation study using NHANES

BackgroundThe COVID-19 epidemic in the United States is widespread, with more than 200,000 deaths reported as of September 23, 2020. While ecological studies show higher burdens of COVID-19 mortality in areas with higher rates of poverty, little is known about social determinants of COVID-19 mortality at the individual level.Methods and findingsWe estimated the proportions of COVID-19 deaths by age, sex, race/ethnicity, and comorbid conditions using their reported univariate proportions among COVID-19 deaths and correlations among these variables in the general population from the 2017–2018 National Health and Nutrition Examination Survey (NHANES). We used these proportions to randomly sample individuals from NHANES. We analyzed the distributions of COVID-19 deaths by race/ethnicity, income, education level, and veteran status. We analyzed the association of these characteristics with mortality by logistic regression. Summary demographics of deaths include mean age 71.6 years, 45.9% female, and 45.1% non-Hispanic white. We found that disproportionate deaths occurred among individuals with nonwhite race/ethnicity (54.8% of deaths, 95% CI 49.0%–59.6%, p < 0.001), individuals with income below the median (67.5%, 95% CI 63.4%–71.5%, p < 0.001), individuals with less than a high school level of education (25.6%, 95% CI 23.4% –27.9%, p < 0.001), and veterans (19.5%, 95% CI 15.8%–23.4%, p < 0.001). Except for veteran status, these characteristics are significantly associated with COVID-19 mortality in multiple logistic regression. Limitations include the lack of institutionalized people in the sample (e.g., nursing home residents and incarcerated persons), the need to use comorbidity data collected from outside the US, and the assumption of the same correlations among variables for the noninstitutionalized population and COVID-19 decedents.ConclusionsSubstantial inequalities in COVID-19 mortality are likely, with disproportionate burdens falling on those who are of racial/ethnic minorities, are poor, have less education, and are veterans. Healthcare systems must ensure adequate access to these groups. Public health measures should specifically reach these groups, and data on social determinants should be systematically collected from people with COVID-19.

In this simulation study, Benjamin Seligman and colleagues explore socio-demographic factors associated with COVID-19 deaths in the US.     

Effectiveness of a Pre-treatment Snack on the Uptake of Mass Treatment for Schistosomiasis in Uganda: A Cluster Randomized Trial

Background

School-based mass treatment with praziquantel is the cornerstone for schistosomiasis control in school-aged children. However, uptake of treatment among school-age children in Uganda is low in some areas. The objective of the study was to examine the effectiveness of a pre-treatment snack on uptake of mass treatment.

Methods and Findings

In a cluster randomized trial carried out in Jinja district, Uganda, 12 primary schools were randomized into two groups; one received education messages for schistosomiasis prevention for two months prior to mass treatment, while the other, in addition to the education messages, received a pre-treatment snack shortly before mass treatment. Four weeks after mass treatment, uptake of praziquantel was assessed among a random sample of 595 children in the snack schools and 689 children in the non-snack schools as the primary outcome. The occurrence of side effects and the prevalence and mean intensity of Schistosoma mansoni infection were determined as the secondary outcomes. Uptake of praziquantel was higher in the snack schools, 93.9% (95% CI 91.7%–95.7%), compared to that in the non-snack schools, 78.7% (95% CI 75.4%–81.7%) (p = 0.002). The occurrence of side effects was lower in the snack schools, 34.4% (95% CI 31.5%–39.8%), compared to that in the non-snack schools, 46.9% (95% CI 42.2%–50.7%) (p = 0.041). Prevalence and mean intensity of S. mansoni infection was lower in the snack schools, 1.3% (95% CI 0.6%–2.6%) and 38.3 eggs per gram of stool (epg) (95% CI 21.8–67.2), compared to that in the non-snack schools, 14.1% (95% CI 11.6%–16.9%) (p = 0.001) and 78.4 epg (95% CI 60.6–101.5) (p = 0.001), respectively.

Conclusions

Our results suggest that provision of a pre-treatment snack combined with education messages achieves a higher uptake compared to the education messages alone. The use a pre-treatment snack was associated with reduced side effects as well as decreased prevalence and intensity of S. mansoni infection.

Trial registration

www.ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01869465","term_id":"NCT01869465"}}NCT01869465 Please see later in the article for the Editors'' Summary     

Impact on Clinical and Cost Outcomes of a Centralized Approach to Acute Stroke Care in London: A Comparative Effectiveness Before and After Model

Background

In July 2010 a new multiple hub-and-spoke model for acute stroke care was implemented across the whole of London, UK, with continuous specialist care during the first 72 hours provided at 8 hyper-acute stroke units (HASUs) compared to the previous model of 30 local hospitals receiving acute stroke patients. We investigated differences in clinical outcomes and costs between the new and old models.

Methods

We compared outcomes and costs ‘before’ (July 2007–July 2008) vs. ‘after’ (July 2010–June 2011) the introduction of the new model, adjusted for patient characteristics and national time trends in mortality and length of stay. We constructed 90-day and 10-year decision analytic models using data from population based stroke registers, audits and published sources. Mortality and length of stay were modelled using survival analysis.

Findings

In a pooled sample of 307 patients ‘before’ and 3156 patients ‘after’, survival improved in the ‘after’ period (age adjusted hazard ratio 0.54; 95% CI 0.41–0.72). The predicted survival rates at 90 days in the deterministic model adjusted for national trends were 87.2% ‘before’ % (95% CI 86.7%–87.7%) and 88.7% ‘after’ (95% CI 88.6%–88.8%); a relative reduction in deaths of 12% (95% CI 8%–16%). Based on a cohort of 6,438 stroke patients, the model produces a total cost saving of £5.2 million per year at 90 days (95% CI £4.9-£5.5 million; £811 per patient).

Conclusion

A centralized model for acute stroke care across an entire metropolitan city appears to have reduced mortality for a reduced cost per patient, predominately as a result of reduced hospital length of stay.     

The Prognostic Value of p16 Hypermethylation in Cancer: A Meta-Analysis

Background

The prognostic value of p16 promoter hypermethylation in cancers has been evaluated for several years while the results remain controversial. We thus performed a systematic review and meta-analysis of studies assessing the impact of p16 methylation on overall survival (OS) and disease-free survival (DFS) to clarify this issue.

Methods

We searched Pubmed, Embase and ISI web of knowledge to identify studies on the prognostic impact of p16 hypermethylation in cancers. A total of 6589 patients from 45 eligible studies were included in the analysis. Pooled hazard ratios (HRs) with 95% confidence interval (95% CI) were calculated to estimate the effect using random-effects model.

Results

The analysis indicated that p16 hypermethylation had significant association with poor OS of non-small cell lung cancer (NSCLC) (HR 1.74, 95% CI: 1.36–2.22) and colorectal cancer (CRC) (HR 1.80; 95% CI 1.27–2.55). Moreover, the significant correlation was present between p16 hypermethylation and DFS of NSCLC (HR 2.04, 95% CI: 1.19–3.50) and head and neck cancer (HR 2.24, 95% CI: 1.35–3.73). Additionally, in the analysis of the studies following REMARK guidelines more rigorously, p16 hypermethylation had unfavorable impact on OS of NSCLC (HR 1.79, 95% CI: 1.35–2.39) and CRC (HR 1.96, 1.16–3.34), and on DFS of NSCLC (HR 2.12, 95% CI: 1.21–3.72) and head and neck cancer (HR 2.24, 95% CI: 1.35–3.73).

Conclusions

p16 hypermethylation might be a predictive factor of poor prognosis in some surgically treated cancers, particularly in NSCLC.     

Effectiveness of Inactivated Influenza Vaccines in Preventing Influenza-Associated Deaths and Hospitalizations among Ontario Residents Aged ≥65 Years: Estimates with Generalized Linear Models Accounting for Healthy Vaccinee Effects

Background

Estimates of the effectiveness of influenza vaccines in older adults may be biased because of difficulties identifying and adjusting for confounders of the vaccine-outcome association. We estimated vaccine effectiveness for prevention of serious influenza complications among older persons by using methods to account for underlying differences in risk for these complications.

Methods

We conducted a retrospective cohort study among Ontario residents aged ≥65 years from September 1993 through September 2008. We linked weekly vaccination, hospitalization, and death records for 1.4 million community-dwelling persons aged ≥65 years. Vaccine effectiveness was estimated by comparing ratios of outcome rates during weeks of high versus low influenza activity (defined by viral surveillance data) among vaccinated and unvaccinated subjects by using log-linear regression models that accounted for temperature and time trends with natural spline functions. Effectiveness was estimated for three influenza-associated outcomes: all-cause deaths, deaths occurring within 30 days of pneumonia/influenza hospitalizations, and pneumonia/influenza hospitalizations.

Results

During weeks when 5% of respiratory specimens tested positive for influenza A, vaccine effectiveness among persons aged ≥65 years was 22% (95% confidence interval [CI], −6%–42%) for all influenza-associated deaths, 25% (95% CI, 13%–37%) for deaths occurring within 30 days after an influenza-associated pneumonia/influenza hospitalization, and 19% (95% CI, 4%–31%) for influenza-associated pneumonia/influenza hospitalizations. Because small proportions of deaths, deaths after pneumonia/influenza hospitalizations, and pneumonia/influenza hospitalizations were associated with influenza virus circulation, we estimated that vaccination prevented 1.6%, 4.8%, and 4.1% of these outcomes, respectively.

Conclusions

By using confounding-reducing techniques with 15 years of provincial-level data including vaccination and health outcomes, we estimated that influenza vaccination prevented ∼4% of influenza-associated hospitalizations and deaths occurring after hospitalizations among older adults in Ontario.     

Association of Antenatal Depression with Adverse Consequences for the Mother and Newborn in Rural Ghana: Findings from the DON Population-Based Cohort Study

Background

Whilst there is compelling evidence of an almost 2-fold increased risk of still births, and suggestive evidence of increased mortality among offspring of mothers with psychotic disorders, only three studies have addressed the role of antenatal depression (AND) on survival of the baby. We examined these associations in a large cohort of pregnant women in Ghana.

Methods

A Cohort study nested within 4-weekly surveillance of all women of reproductive age to identify pregnancies and collect data on births and deaths in the Kintampo Health Research Centre study area of Ghana. Women were screened for AND using the Patient Health Questionnaire (PHQ-9) to ascertain DSM-IV major or minor depression. Outcomes were adverse birth outcomes, maternal/infant morbidity, and uptake of key newborn care practices, examined using logistic regression; effect sizes reported as relative risks with 95% confidence intervals.

Results

20679 (89.6%) pregnant women completed the PHQ-9. The prevalence of AND was 9.9% (n = 2032) (95% confidence interval 9.4%–10.2%). AND was associated with: prolonged labour (RR 1.25, 95% CI 1.02–1.53); peripartum complications (RR 1.11, 95% CI 1.07–1.15);postpartum complications (RR 1.27, 96% CI 1.21–1.34); non-vaginal delivery (RR 1.19, 95% CI 1.02–1.40); newborn illness (RR 1.52, 95% CI 1.16–1.99); and bed net use during pregnancy (RR 0.93, 95% CI 0.89–0.98), but not neonatal deaths, still births, low birth weight, immediate breast feeding initiation, or exclusive breastfeeding. AND was marginally associated with preterm births (RR 1.32, 95% CI 0.98–1.76).

Conclusion

This paper has contributed important evidence on the role of antenatal depression as a potential contributor to maternal and infant morbidity. Non-pharmacological treatments anchored on primary care delivery structures are recommended as an immediate step. We further recommend that trials are designed to assess if treating antenatal depression in conjunction with improving the quality of obstetric care results in improved maternal and newborn outcomes.     

Evaluating the frequency of English language requirements in clinical trial eligibility criteria: A systematic analysis using ClinicalTrials.gov

BackgroundA number of prior studies have demonstrated that research participants with limited English proficiency in the United States are routinely excluded from clinical trial participation. Systematic exclusion through study eligibility criteria that require trial participants to be able to speak, read, and/or understand English affects access to clinical trials and scientific generalizability. We sought to establish the frequency with which English language proficiency is required and, conversely, when non-English languages are affirmatively accommodated in US interventional clinical trials for adult populations.Methods and findingsWe used the advanced search function on ClinicalTrials.gov specifying interventional studies for adults with at least 1 site in the US. In addition, we used these search criteria to find studies with an available posted protocol. A computer program was written to search for evidence of English or Spanish language requirements, or the posted protocol, when available, was manually read for these language requirements. Of the 14,367 clinical trials registered on ClinicalTrials.gov between 1 January 2019 and 1 December 2020 that met baseline search criteria, 18.98% (95% CI 18.34%–19.62%; n = 2,727) required the ability to read, speak, and/or understand English, and 2.71% (95% CI 2.45%–2.98%; n = 390) specifically mentioned accommodation of translation to another language. The remaining trials in this analysis and the following sub-analyses did not mention English language requirements or accommodation of languages other than English. Of 2,585 federally funded clinical trials, 28.86% (95% CI 27.11%–30.61%; n = 746) required English language proficiency and 4.68% (95% CI 3.87%–5.50%; n = 121) specified accommodation of other languages; of the 5,286 industry-funded trials, 5.30% (95% CI 4.69%–5.90%; n = 280) required English and 0.49% (95% CI 0.30%–0.69%; n = 26) accommodated other languages. Trials related to infectious disease were less likely to specify an English requirement than all registered trials (10.07% versus 18.98%; relative risk [RR] = 0.53; 95% CI 0.44–0.64; p < 0.001). Trials related to COVID-19 were also less likely to specify an English requirement than all registered trials (8.18% versus 18.98%; RR = 0.43; 95% CI 0.33–0.56; p < 0.001). Trials with a posted protocol (n = 366) were more likely than all registered clinical trials to specify an English requirement (36.89% versus 18.98%; RR = 1.94, 95% CI 1.69–2.23; p < 0.001). A separate analysis of studies with posted protocols in 4 therapeutic areas (depression, diabetes, breast cancer, and prostate cancer) demonstrated that clinical trials related to depression were the most likely to require English (52.24%; 95% CI 40.28%–64.20%). One limitation of this study is that the computer program only searched for the terms “English” and “Spanish” and may have missed evidence of other language accommodations. Another limitation is that we did not differentiate between requirements to read English, speak English, understand English, and be a native English speaker; we grouped these requirements together in the category of English language requirements.ConclusionsA meaningful percentage of US interventional clinical trials for adults exclude individuals who cannot read, speak, and/or understand English, or are not native English speakers. To advance more inclusive and generalizable research, funders, sponsors, institutions, investigators, institutional review boards, and others should prioritize translating study materials and eliminate language requirements unless justified either scientifically or ethically.

Akila Muthukumar and coauthors, systematically analyze ClinicalTrials.gov to evaluate the frequency of English language requirements in clinical trial eligibility criteria.     

Functional Promoter -94 ins/del ATTG Polymorphism in NFKB1 Gene Is Associated with Bladder Cancer Risk in a Chinese Population

Background

A functional -94 insertion/deletion polymorphism (rs28362491) in the promoter of the NFKB1 gene was reported to influence NFKB1 expression and confer susceptibility to different types of cancer. This study aims to determine whether the polymorphism is associated with risk of bladder cancer.

Materials and methods

TaqMan assay was used to determine genotype among 609 cases and 640 controls in a Chinese population. Logistic regression was used to assess the association between the polymorphism and bladder cancer risk, and quantitative real-time polymerase chain reaction was used to determine NFKB1 mRNA expression.

Results

Compared with the ins/ins/ins/del genotypes, the del/del genotype was associated with a significantly increased risk of bladder cancer [adjusted odd ratio (OR)  = 1.92, 95% confidence interval (CI)  = 1.42–2.59]. The increased risk was more prominent among subjects over 65 years old (OR  = 2.37, 95% CI  = 1.52–3.70), male subjects (OR  = 1.97, 95% CI = 1.40–2.79) and subjects with self-reported family history of cancer (OR  = 3.59, 95% CI  = 1.19–10.9). Furthermore, the polymorphism was associated with a higher risk of developing non-muscle invasive bladder cancer (OR  = 2.07, 95% CI  = 1.51–2.85), grade 1 bladder cancer (OR  = 2.40, 95% CI  = 1.68–3.43), single tumor bladder cancer (OR  = 2.04, 95% CI  = 1.48–2.82) and smaller tumor size bladder cancer (OR  = 2.10, 95% CI  = 1.51–2.92). The expression of NFKB1 mRNA in bladder cancer tissues with homozygous insertion genotype was higher than that with deletion allele.

Conclusions

In conclusion, the -94 ins/del ATTG polymorphism in NFKB1 promoter may contribute to the etiology of bladder cancer in the Chinese population.     

Pooled Analysis of Non-Union,Re-Operation,Infection, and Approach Related Complications after Anterior Odontoid Screw Fixation

Background

Anterior odontoid screw fixation (AOSF) has been one of the most popular treatments for odontoid fractures. However, the true efficacy of AOSF remains unclear. In this study, we aimed to provide the pooled rates of non-union, reoperation, infection, and approach related complications after AOSF for odontoid fractures.

Methods

We searched studies that discussed complications after AOSF for type II or type III odontoid fractures. A proportion meta-analysis was done and potential sources of heterogeneity were explored by meta-regression analysis.

Results

Of 972 references initially identified, 63 were eligible for inclusion. 54 studies provided data regarding non-union. The pooled non-union rate was 10% (95% CI: 7%–3%). 48 citations provided re-operation information with a pooled proportion of 5% (95% CI: 3%–7%). Infection was described in 20 studies with an overall rate of 0.2% (95% CI: 0%–1.2%). The main approach related complication is postoperative dysphagia with a pooled rate of 10% (95% CI: 4%–17%). Proportions for the other approach related complications such as postoperative hoarseness (1.2%, 95% CI: 0%–3.7%), esophageal/retropharyngeal injury (0%, 95% CI: 0%–1.1%), wound hematomas (0.2%, 95% CI: 0%–1.8%), and spinal cord injury (0%, 95% CI: 0%–0.2%) were very low. Significant heterogeneities were detected when we combined the rates of non-union, re-operation, and dysphagia. Multivariate meta-regression analysis showed that old age was significantly predictive of non-union. Subgroup comparisons showed significant higher non-union rates in age ≥70 than that in age ≤40 and in age 40 to <50. Meta-regression analysis did not reveal any examined variables influencing the re-operation rate. Meta-regression analysis showed age had a significant effect on the dysphagia rate.

Conclusions/Significances

This study summarized the rates of non-union, reoperation, infection, and approach related complications after AOSF for odontoid factures. Elderly patients were more likely to experience non-union and dysphagia.     

Copy Number Variation of GSTT1 and GSTM1 and the Risk of Prostate Cancer in a Caribbean Population of African Descent

Background

Deletions of the glutathione S-transferase genes M1 and T1 (GSTM1 and GSTT1) have been studied as potential risk factors for prostate cancer. Conflicting results have been obtained. Moreover, most such studies could not discriminate heterozygous from homozygous carriers of the non-deleted alleles.

Objective

We investigated whether copy number variation (CNV) of the GSTM1 and/or GSTT1 genes contribute to the risk of prostate cancer in the Caribbean population of African descent of Guadeloupe.

Methods

In a population-based case-control study, we compared 629 prostate cancer patients and 622 control subjects. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). Exact copy numbers of GSTM1 and GSTT1 were determined by real-time PCR.

Results

A higher copy number of GSTM1 was marginally associated with prostate cancer risk. Men with 2 and 3 or more GSTT1 genes were at higher risk of prostate cancer (OR: 1.55, 95% CI: 1.11–2.16 and OR: 4.89, 95% CI: 1.71–13.99, respectively; P_trend<0.001). Men with 3, 4 and 5 or more copies of both GSTM1 and GSTT1 genes were at higher risk of prostate cancer (OR: 2.18, 95% CI: 1.21–3.91, OR: 3.24, 95% CI: 1.63–6.46, and OR: 5.77, 95% CI: 1.40–23.84, respectively; P_trend<0.001).

Conclusions

Copy number of GSTT1 and combined GSTM1/GSTT1 appear to be associated with prostate cancer risk in our population study with gene dose relationship. Our results support the hypothesis that variations in copy number of GSTT1 modulate the risk of prostate cancer.