The efficacy and safety of adding bevacizumab in neoadjuvant therapy for locally advanced rectal cancer patients: A systematic review and meta-analysis

BackgroundPatients with locally advanced rectal cancer (LARC) are more likely to suffer local recurrence and distant metastases, contributing to worse prognoses. Considering the provided dramatic reduction of local recurrences, neoadjuvant CRT (nCRT) followed by curative resection with total mesorectal excision (TME) and adjuvant chemotherapy has been established as standard therapy for LARC patients. However, the efficacy of adding bevacizumab in neoadjuvant therapy, especially in induction therapy-containing nCRT for LARC patients remains uncertain.MaterialsPubMed, Embase, and Web of Science were searched to retrieve records on the application of bevacizumab in a neoadjuvant setting for LARC patients. The endpoints of interest were pCR and the rates of patients suffering Grade 3/4 bevacizumab-specific adverse events, namely bleeding, wound healing complications, and gastrointestinal perforation.Results29 cohorts covering 1134 subjects were included in this systematic review. The pooled pCR rate for bevacizumab-relevant cohorts was 21% (95% confidence interval (95% CI), 17–25%; I² = 61.8%), the pooled estimates of Grade 3/4 bleeding, Grade 3/4 wound healing complication, Grade 3/4 gastrointestinal perforation were 1% (95% CI, 0–3%; I² = 0%), 2% (95% CI, 1–5%; I² = 4.7%), and 2% (95% CI, 0–5%; I² = 0%), respectively.ConclusionThe addition of bevacizumab in the nCRT, especially in the TNT, for LARC patients provides promising efficacy and acceptable safety. However, the results should be interpreted cautiously due to the small amount of relevant data and need further confirmation by future studies.     

The Safety of Artemisinin Derivatives for the Treatment of Malaria in the 2nd or 3rd Trimester of Pregnancy: A Systematic Review and Meta-Analysis

Given the high morbidity for mother and fetus associated with malaria in pregnancy, safe and efficacious drugs are needed for treatment. Artemisinin derivatives are the most effective antimalarials, but are associated with teratogenic and embryotoxic effects in animal models when used in early pregnancy. However, several organ systems are still under development later in pregnancy. We conducted a systematic review and meta-analysis of the occurrence of adverse pregnancy outcomes among women treated with artemisinins monotherapy or as artemisinin-based combination therapy during the 2nd or 3rd trimesters relative to pregnant women who received non-artemisinin antimalarials or none at all. Pooled odds ratio (POR) were calculated using Mantel-Haenszel fixed effects model with a 0.5 continuity correction for zero events. Eligible studies were identified through Medline, Embase, and the Malaria in Pregnancy Consortium Library. Twenty studies (11 cohort studies and 9 randomized controlled trials) contributed to the analysis, with 3,707 women receiving an artemisinin, 1,951 a non-artemisinin antimalarial, and 13,714 no antimalarial. The PORs (95% confidence interval (CI)) for stillbirth, fetal loss, and congenital anomalies when comparing artemisinin versus quinine were 0.49 (95% CI 0.24–0.97, I² = 0%, 3 studies); 0.58 (95% CI 0.31–1.16, I² = 0%, 6 studies); and 1.00 (95% CI 0.27–3.75, I² = 0%, 3 studies), respectively. The PORs comparing artemisinin users to pregnant women who received no antimalarial were 1.13 (95% CI 0.77–1.66, I² = 86.7%, 3 studies); 1.10 (95% CI 0.79–1.54, I² = 0%, 4 studies); and 0.79 (95% CI 0.37–1.67, I² = 0%, 3 studies) for miscarriage, stillbirth and congenital anomalies respectively. Treatment with artemisinin in 2^nd and 3^rd trimester was not associated with increased risks of congenital malformations or miscarriage and may be was associated with a reduced risk of stillbirths compared to quinine. This study updates the reviews conducted by the WHO in 2002 and 2006 and supports the current WHO malaria treatment guidelines malaria in pregnancy.     

Does the Chemotherapy Backbone Impact on the Efficacy of Targeted Agents in Metastatic Colorectal Cancer? A Systematic Review and Meta-Analysis of the Literature

ImportanceThe EGFR inhibitors (EGFR-I) cetuximab and panitumumab and the angiogenesis inhibitors (AIs) bevacizumab and aflibercept have demonstrated varying efficacy in mCRC.ObjectiveTo document the overall impact of specific chemotherapy regimens on the efficacy of targeted agents in treating patients with mCRC. Data sources: MEDLINE, EMBASE and Cochrane databases were searched to 2014, supplemented by hand-searching ASCO/ESMO conference abstracts.ResultsEGFR-I added to irinotecan-based chemotherapy modestly improved OS with HR 0.90 (95% CI 0.81–1.00, p = 0.04), but more so PFS with HR 0.77 (95% CI 0.69–0.86, p<0.00001). No benefit was evident for EGFR-I added to oxaliplatin-based chemotherapy (OS HR 0.97 (95% CI 0.87–1.09) and PFS HR 0.92 (95% CI 0.83–1.02)). Significant oxaliplatin-irinotecan subgroup interactions were present for PFS with I² = 82%, p = 0.02. Further analyses of oxaliplatin+EGFR-I trials showed greater efficacy with infusional 5FU regimens (PFS HR 0.82, 95% CI 0.72–0.94) compared to capecitabine (HR 1.09; 95% CI 0.91–1.30) and bolus 5FU (HR 1.07; 95% CI 0.79–1.45); subgroup interaction was present with I² = 72%, p = 0.03. The oxaliplatin-irinotecan interaction was not evident for infusional 5FU regimens. For AIs, OS benefit was observed with both oxaliplatin-based (HR 0.83) and irinotecan-based (HR 0.77) regimens without significant subgroup interactions. Oxaliplatin+AI trials showed no subgroup interactions by type of FP, whilst an interaction was present for irinotecan+AI trials although aflibercept was only used with infusional FP (I² = 89.7%, p = 0.002).

Conclusion and Relevance

The addition of EGFR-I to irinotecan-based chemotherapy has consistent efficacy, regardless of FP regimen, whereas EGFR-I and oxaliplatin-based regimens were most active with infusional 5FU. No such differential activity was observed with the varying chemotherapy schedules when combined with AIs.     

Serious adverse events following treatment of visceral leishmaniasis: A systematic review and meta-analysis

BackgroundDespite a historical association with poor tolerability, a comprehensive review on safety of antileishmanial chemotherapies is lacking. We carried out an update of a previous systematic review of all published clinical trials in visceral leishmaniasis (VL) from 1980 to 2019 to document any reported serious adverse events (SAEs).MethodsFor this updated systematic review, we searched the following databases from 1^st Jan 2016 through 2^nd of May 2019: PUBMED, Embase, Scopus, Web of Science, Cochrane, clinicaltrials.gov, WHO ICTRP, and the Global Index Medicus. We included randomised and non-randomised interventional studies aimed at assessing therapeutic efficacy and extracted the number of SAEs reported within the first 30 days of treatment initiation. The incidence rate of death (IRD) from individual treatment arms were combined in a meta-analysis using random effects Poisson regression.ResultsWe identified 157 published studies enrolling 35,376 patients in 347 treatment arms. Pentavalent antimony was administered in 74 (21.3%), multiple-dose liposomal amphotericin B (L-AmB) in 52 (15.0%), amphotericin b deoxycholate in 51 (14.7%), miltefosine in 33 (9.5%), amphotericin b fat/lipid/colloid/cholesterol in 31 (8.9%), and single-dose L-AmB in 17 (4.9%) arms. There was a total of 804 SAEs reported of which 793 (including 428 deaths) were extracted at study arm level (11 SAEs were reported at study level only). During the first 30 days, there were 285 (66.6%) deaths with the overall IRD estimated at 0.068 [95% confidence interval (CI): 0.041–0.114; I² = 81.4%; 95% prediction interval (PI): 0.001–2.779] per 1,000 person-days at risk; the rate was 0.628 [95% CI: 0.368–1.021; I² = 82.5%] in Eastern Africa, and 0.041 [95% CI: 0.021–0.081; I² = 68.1%] in the Indian Subcontinent. In 21 study arms which clearly indicated allowing the inclusion of patients with HIV co-infections the IRD was 0.575 [95% CI: 0.244–1.355; I² = 91.9%] compared to 0.043 [95% CI: 0.020–0.090; I² = 62.5%] in 160 arms which excluded HIV co-infections.ConclusionMortality within the first 30 days of VL treatment initiation was a rarely reported event in clinical trials with an overall estimated rate of 0.068 deaths per 1,000 person-days at risk, though it varied across regions and patient populations. These estimates may serve as a benchmark for future trials against which mortality data from prospective and pharmacovigilance studies can be compared. The methodological limitations exposed by our review support the need to assemble individual patient data (IPD) to conduct robust IPD meta-analyses and generate stronger evidence from existing trials to support treatment guidelines and guide future research.     

Is Plasmodium vivax Malaria a Severe Malaria?: A Systematic Review and Meta-Analysis

Background

Plasmodium vivax is one of the major species of malaria infecting humans. Although emphasis on P. falciparum is appropriate, the burden of vivax malaria should be given due attention. This study aimed to synthesize the evidence on severe malaria in P. vivax infection compared with that in P. falciparum infection.

Methods/Principal Findings

We searched relevant studies in electronic databases. The main outcomes required for inclusion in the review were mortality, severe malaria (SM) and severe anaemia (SA). The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Overall, 26 studies were included. The main meta-analysis was restricted to the high quality studies. Eight studies (n = 27490) compared the incidence of SM between P. vivax infection and P. falciparum mono-infection; a comparable incidence was found in infants (OR: 0.45, 95% CI:0.04–5.68, I ²:98%), under 5 year age group (OR: 2.06, 95% CI: 0.83–5.1, I ²:83%), the 5–15 year-age group (OR: 0.6, 95% CI: 0.31–1.16, I ²:81%) and adults (OR: 0.83, 95% CI: 0.67–1.03, I ²:25%). Six studies reported the incidences of SA in P. vivax infection and P. falciparum mono-infection; a comparable incidence of SA was found among infants (OR: 3.47, 95%:0.64–18.94, I ²: 92%), the 5–15 year-age group (OR:0.71, 95% CI: 0.06–8.57, I ²:82%). This was significantly lower in adults (OR:0.75, 95% CI: 0.62–0.92, I ²:0%). Five studies (n = 71079) compared the mortality rate between vivax malaria and falciparum malaria. A lower rate of mortality was found in infants with vivax malaria (OR:0.61, 95% CI:0.5–0.76, I ²:0%), while this was comparable in the 5–15 year- age group (OR: 0.43, 95% CI:0.06–2.91, I ²:84%) and the children of unspecified-age group (OR: 0.77, 95% CI:0.59–1.01, I ²:0%).

Conclusion

Overall, the present analysis identified that the incidence of SM in patients infected with P. vivax was considerable, indicating that P. vivax is a major cause of SM. Awareness of the clinical manifestations of vivax malaria should prompt early detection. Subsequent treatment and monitoring of complications can be life-saving.     

Dietary Fat Intake and Risk of Gastric Cancer: A Meta-Analysis of Observational Studies

Background and Objectives

Consumption of dietary fat has been reported to be associated with gastric cancer risk, but the results of epidemiologic studies remain inconsistent. We conducted a meta-analysis to summarize the evidence regarding the association between dietary fat intake and gastric cancer risk.

Methods

A comprehensive search of PubMed and EMBASE was performed to identify observational studies providing quantitative estimates between dietary fat and gastric cancer risk. Random effects model was used to calculate the summary relative risk(SRR) in the highest versus lowest analysis. Categorical dose-response analysis was conducted to quantify the association between dietary fat intake and gastric cancer risk. Heterogeneity among studies was evaluated using I² and tau2(between study variance)statistics. Subgroup analysis and publication bias analysis were also performed.

Results

Twenty-two articles were included in the meta-analysis. The SRR for gastric cancer was 1.18 for individuals with highest intake versus lowest intake of total fat (95% confidence interval [CI]: 0.999–1.39; n = 28; P< 0.001; tau² = 0.12; I² = 69.5%, 95% CI: 55%-79%) and 1.08 with a daily increase in total fat intake (20 g/d) (95%CI: 1.02–1.14; n = 6; P = 0.09; tau² = 0.002; I² = 46.8%, 95% CI: 0%-79%). Positive association between saturated fat intake (SRR = 1.31; 95%CI: 1.09–1.58;n = 18;P<0.001; tau² = 0.08; I² = 60.6%, 95% CI: 34%-76%), inverse association between polyunsaturated fat intake (SRR = 0.77; 95%CI: 0.65–0.92; n = 16; P = 0.003; tau² = 0.06; I² = 56.2%, 95% CI: 23%-75%) and vegetable fat intake (SRR = 0.55; 95%CI: 0.41–0.74; n = 4;P = 0.12; tau² = 0.04; I² = 48.6%, 95% CI: 0%-83%), and no association between monounsaturated fat intake (SRR = 1.00; 95%CI: 0.79–1.25; n = 14; P< 0.001; tau² = 0.10; I² = 63.0%, 95% CI: 34%-79%) and animal fat intake (SRR = 1.10; 95%CI: 0.90–1.33; n = 6; P = 0.13;tau² = 0.02; I² = 42.0%, 95% CI: 0%-70%) and gastric cancer risk were observed.

Conclusions

Our results suggest that intake of total fat is potentially positively associated with gastric cancer risk, and specific subtypes of fats account for different effects. However, these findings should be confirmed by further well-designed cohort studieswith detailed dietary assessments and strict control of confounders.     

Covered versus Uncovered Self-Expandable Metal Stents for Managing Malignant Distal Biliary Obstruction: A Meta-Analysis

Aim

To compare the efficacy of using covered self-expandable metal stents (CSEMSs) and uncovered self-expandable metal stents (UCSEMSs) to treat objective jaundice caused by an unresectable malignant tumor.

Methods

We performed a comprehensive electronic search from 1980 to May 2015. All randomized controlled trials comparing the use of CSEMSs and UCSEMSs to treat malignant distal biliary obstruction were included.

Results

The analysis included 1417 patients enrolled in 14 trials. We did not detect significant differences between the UCSEMS group and the CSEMS group in terms of cumulative stent patency (hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.19–4.53; p = 0.93, I² = 0%), patient survival (HR 0.77, 95% CI 0.05–10.87; p = 0.85, I² = 0%), overall stent dysfunction (relative ratio (RR) 0.85, M-H, random, 95% CI 0.57–1.25; p = 0.83, I² = 63%), the overall complication rate (RR 1.26, M-H, fixed, 95% CI 0.94–1.68; p = 0.12, I² = 0%) or the change in serum bilirubin (weighted mean difference (WMD) -0.13, IV fixed, 95% CI 0.56–0.3; p = 0.55, I² = 0%). However, we did detect a significant difference in the main causes of stent dysfunction between the two groups. In particular, the CSEMS group exhibited a lower rate of tumor ingrowth (RR 0.25, M-H, random, 95% CI 0.12–0.52; p = 0.002, I² = 40%) but a higher rate of tumor overgrowth (RR 1.76, M-H, fixed, 95% CI 1.03–3.02; p = 0.04, I² = 0%). Patients with CSEMSs also exhibited a higher migration rate (RR 9.33, M-H, fixed, 95% CI 2.54–34.24; p = 0.008, I² = 0%) and a higher rate of sludge formation (RR 2.47, M-H, fixed, 95% CI 1.36–4.50; p = 0.003, I² = 0%).

Conclusions

Our meta-analysis indicates that there is no significant difference in primary stent patency and stent dysfunction between CSEMSs and UCSEMSs during the period from primary stent insertion to primary stent dysfunction or patient death. However, when taking further management for occluded stents into consideration, CSEMSs is a better choice for patients with malignant biliary obstruction due to their removability.     

Antiretroviral Therapy Uptake,Attrition, Adherence and Outcomes among HIV-Infected Female Sex Workers: A Systematic Review and Meta-Analysis

Purpose

We aimed to characterize the antiretroviral therapy (ART) cascade among female sex workers (FSWs) globally.

Methods

We systematically searched PubMed, Embase and MEDLINE in March 2014 to identify studies reporting on ART uptake, attrition, adherence, and outcomes (viral suppression or CD4 count improvements) among HIV-infected FSWs globally. When possible, available estimates were pooled using random effects meta-analyses (with heterogeneity assessed using Cochran''s Q test and I² statistic).

Results

39 studies, reporting on 21 different FSW study populations in Asia, Africa, North America, South America, and Central America and the Caribbean, were included. Current ART use among HIV-infected FSWs was 38% (95% CI: 29%–48%, I² = 96%, 15 studies), and estimates were similar between high-, and low- and middle-income countries. Ever ART use among HIV-infected FSWs was greater in high-income countries (80%; 95% CI: 48%–94%, I² = 70%, 2 studies) compared to low- and middle-income countries (36%; 95% CI: 7%–81%, I² = 99%, 3 studies). Loss to follow-up after ART initiation was 6% (95% CI: 3%–11%, I² = 0%, 3 studies) and death after ART initiation was 6% (95% CI: 3%–11%, I² = 0%, 3 studies). The fraction adherent to ≥95% of prescribed pills was 76% (95% CI: 68%–83%, I² = 36%, 4 studies), and 57% (95% CI: 46%–68%, I² = 82%, 4 studies) of FSWs on ART were virally suppressed. Median gains in CD4 count after 6 to 36 months on ART, ranged between 103 and 241 cells/mm³ (4 studies).

Conclusions

Despite global increases in ART coverage, there is a concerning lack of published data on HIV treatment for FSWs. Available data suggest that FSWs can achieve levels of ART uptake, retention, adherence, and treatment response comparable to that seen among women in the general population, but these data are from only a few research settings. More routine programme data on HIV treatment among FSWs across settings should be collected and disseminated.     

Prognostic Value of Procalcitonin in Adult Patients with Sepsis: A Systematic Review and Meta-Analysis

Procalcitonin (PCT) has been widely investigated for its prognostic value in septic patients. However, studies have produced conflicting results. The purpose of the present meta-analysis is to explore the diagnostic accuracy of a single PCT concentration and PCT non-clearance in predicting all-cause sepsis mortality. We searched PubMed, Embase, Web of Knowledge and the Cochrane Library. Articles written in English were included. A 2 × 2 contingency table was constructed based on all-cause mortality and PCT level or PCT non-clearance in septic patients. Two authors independently evaluated study eligibility and extracted data. The diagnostic value of PCT in predicting prognosis was determined using a bivariate meta-analysis model. We used the Q-test and I ² index to test heterogeneity. Twenty-three studies with 3,994 patients were included. An elevated PCT level was associated with a higher risk of death. The pooled relative risk (RR) was 2.60 (95% confidence interval (CI), 2.05–3.30) using a random-effects model (I ² = 63.5%). The overall area under the summary receiver operator characteristic (SROC) curve was 0.77 (95% CI, 0.73–0.80), with a sensitivity and specificity of 0.76 (95% CI, 0.67–0.82) and 0.64 (95% CI, 0.52–0.74), respectively. There was significant evidence of heterogeneity for the PCT testing time (P = 0.020). Initial PCT values were of limited prognostic value in patients with sepsis. PCT non-clearance was a prognostic factor of death in patients with sepsis. The pooled RR was 3.05 (95% CI, 2.35–3.95) using a fixed-effects model (I ² = 37.9%). The overall area under the SROC curve was 0.79 (95% CI, 0.75–0.83), with a sensitivity and specificity of 0.72 (95% CI, 0.58–0.82) and 0.77 (95% CI, 0.55–0.90), respectively. Elevated PCT concentrations and PCT non-clearance are strongly associated with all-cause mortality in septic patients. Further studies are needed to define the optimal cut-off point and the optimal definition of PCT non-clearance for accurate risk assessment.     

Comparisons of Adherence to Antiretroviral Therapy in a High- Risk Population in China: A Systematic Review and Meta-Analysis

Background

Reports on antiretroviral therapy (ART) adherence are scare in China; we performed this meta-analysis to estimate ART adherence rates in different populations at high risk for HIV transmission in China.

Methods

We searched PubMed, Chinese Biomedical Literature Database (Chinese), China National Knowledge Infrastructure (Chinese), and Wanfang (Chinese) to identify studies published from January 1985 to May 2015. We used random-effects meta-analysis to calculate weighted mean estimates across studies and 95% CIs. Data were pooled with proportions transformed prior to pooling using the Freeman–Tukey double arcsine transformation and then back transformed to the original scale. We calculated the I² (and its 95% confidence intervals) and tau² to assess between-study heterogeneity.

Results

We identified 36 eligible articles, including 6885 HIV-positive individuals, reporting ART adherence. Pooled analysis produced an estimate of 77.61% (95% CI = 71.63–83.08) of patients with HIV with adequate adherence; however, high heterogeneity was observed between studies (I² = 96.60%, 95%CI = 96.00%-97.20%; tau² = 0.16). Three studies, which included 149 old HIV-infected patients, reported the highest ART adequate adherence rate (89.39%, 95% CI = 72.01–99.26) with high heterogeneity between the studies (I² = 86.20%, 95%CI = 60.00–95.20%; tau² = 0.13). While, only two studies, which included 143 heterosexual transmission group (HTG) patients, reported the lowest ART adequate adherence rate (51.55%, 95% CI = 41.33–61.71) with low heterogeneity between the studies (I² = 31.3%, tau² = 0.007). In the multivariable meta-regression model, high-risk populations was the main factor explaining heterogeneity (variance explained 28.14%).

Conclusions

ART adherence in some high-risk populations (e.g., heterosexual transmission group) is below the recommended levels for maintaining virologic suppression. It is crucial to develop comprehensive intervention strategies to promote ART adherence in high-risk populations and effectively prevent the spread of HIV/AIDS in China.     

Interferon Gamma +874T/A Polymorphism Increases the Risk of Hepatitis Virus-Related Diseases: Evidence from a Meta-Analysis

BackgroundInterferon gamma (IFN-γ) is a key regulatory cytokine, which plays an important role in antiviral defense of an infected host. However, the association between the IFN-γ +874T/A gene polymorphism and hepatitis virus-related diseases is heterogeneous.MethodsBased on the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement, a comprehensive literature search of eligible studies in Embase, Pubmed, and the Cochrane Library was undertaken through November 2014. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were used to measure the strength of the models.ResultsSeventeen case-control articles, including 24 studies with 5503 individuals, met the inclusion criteria. The results indicated a statistically significant association between the IFN-γ +874T/A polymorphism and hepatitis virus—related diseases in a recessive gene model (AA vs. TT+TA: OR=1.350, 95% CI=1.101-1.657, P=0.004, I²%=54.3, and P_Q=0.001 for heterogeneity), especially in Asians (OR=1.407, 95% CI=1.035-1.911, P=0.029, I²%=61.9, and P_Q=0.005 for heterogeneity) and hepatitis B virus (HBV)–related disease (OR=1.486, 95% CI=1.195–1.849, P=0.000, I²%=40.4, and P_Q=0.053 for heterogeneity).ConclusionsThe evidence suggests that the IFN-γ +874T/A polymorphism increases the risk of hepatitis virus—related diseases, especially in Asians and HBV—related diseases. Further studies on this topic in different ethnicities, especially genome-wide association studies, should be conducted to strengthen our results.     

Socio-Economic Disparities in Use of Family Planning Methods among Pakistani Women: Findings from Pakistan Demographic and Health Surveys

BackgroundSeveral developing countries like Pakistan step into Sustainable Development Goals period with crucial maternal and child health needs that need to be addressed for improving health outcomes among people. We aim to explore existent socio-economic disparities in use of family planning methods (FPM) among Pakistani women, and compare any such inequalities between the years 2006 and 2013.SettingPakistan Demographic and Health Surveys (PDHS) 2006–7 (n = 9177) and the most recent 2012–13(n = 13558) data were used to conduct secondary analysis. Participants were ever married women aged between 15 and 49 years. Socio-economic status was assessed by the education level and wealth index. Inequalities were measured through Odds Ratio (OR), Relative Index of inequality (RII), and Slope index of inequality (SII) on non-use of FPM.ResultsAlthough the prevalence of FPM use has increased over time (28% in 2006 versus 54% in 2013), the socio-economic inequalities persistently exist. Comparing results of PDHS 2006 with PDHS 2013, education related absolute inequalities among urban dwellers increased from -0.41 (95% CI -0.67, -0.13, p-value < 0.01) to -0.83 (95% CI -1.02, -0.63, p-value < 0.01); and increased from -0.93 (95% CI -1.21, -0.64, p-value < 0.01) to -0.98 (95% CI -1.20, -0.76, p-value < 0.01) among rural dwellers. Similarly wealth related absolute inequalities are also existent.ConclusionsAlthough the FPM use has increased over time, but it is important to note that socio-economic gap in use of FPM persists. Such differences have disadvantaged the poor and the illiterate. Family planning programs may target the disadvantaged subgroups for ensuring well-being of women and children in Pakistan.     

Complications after breast reconstruction with alloplastic material in breast cancer patients submitted or not to post mastectomy radiotherapy

Background and purposeBreast reconstruction following mastectomy is a relevant element of breast cancer treatment. The purpose of this study was to evaluate the influence of radiotherapy (RT) on local complications in patients with breast cancer that had undergone breast reconstruction with alloplastic material.Materials and methodsRetrospective study of breast cancer patients submitted to mastectomy and breast reconstruction from 2009 to 2013. Clinical and treatment variables were correlated with early and late complications.Results251 patients were included; mean age was 49.7 (25 to 78) years. Reconstruction was immediate in 94% of the patients, with 88% performed with a temporary tissue expander. Postoperative radiotherapy (RT) was delivered to 167 patients (66.5%). Early complications were present in 26.3% of the patients. Irradiated patients presented 5.4% incidence of late complications versus 2.4% for non-irradiated patients (p = 0.327). Diabetes (OR = 3.41 95% CI: 1.23–9.45, p = 0.018) and high body mass index (BMI) (OR = 2.65; 95% CI: 1.60–4.37, p < 0.0001) were the main risk factors. The overall incidence of late complications was 4.4%, with predominance of severe capsular contracture (8/11). Arterial hypertension (OR = 4.78; 95% CI: 1.97–11.63, p = 0.001), BMI (OR = 0.170; 95% CI: 0.048–0.607, p = 0.006) and implant placement (OR = 3.55; 95% CI: 1.26–9.99, p = 0.016) were related to late complications.ConclusionsThe overall rate of complications was low in this population. Radiotherapy delivery translated into a higher but not statistically significant risk of late complications when compared with the non-irradiated patients. Already well-known clinical risk factors for complications after breast reconstruction were identified.     

Infection with Blastocystis spp. and its association with enteric infections and environmental enteric dysfunction among slum-dwelling malnourished adults in Bangladesh

BackgroundBlastocystis spp. (Blastocystis) is a widely distributed gastrointestinal protist frequently reported in countries with tropical and sub-tropical climate. We sought to determine the factors associated with Blastocystis infection and investigate its role on biomarkers of intestinal health among slum-dwelling malnourished adults in Bangladesh.MethodologyTotal 524 malnourished adults with a body mass index ≤18.5 kg/m² were included in this analysis. Presence of Blastocystis in feces was evaluated by TaqMan Array Card assays.Principal findingsBlastocystis was tested positive in 78.6% of the participants. Prevalence of infection with atypical strains of enteropathogenic Escherichia coli (aEPEC) (56% vs. 38%, p<0.001), and Trichuris trichiura (28% vs. 15%, p-value = 0.02) was significantly greater in adults with Blastocystis, while Giardia intestinalis was significantly lower (8% vs. 14%, p-value = 0.04) in Blastocystis positive adults. Malnourished adults who were living in households with high crowding index (aOR = 2.18; 95% CI = 1.11, 4.65; p-value = 0.03), and infected with aEPEC (aOR = 2.14; 95% CI = 1.35, 3.44; p-value = 0.001) and Trichuris trichiura (aOR = 1.97; 95% CI = 1.08, 3.77; p = 0.03) were more likely to be infected with Blastocystis. A significant negative relationship was observed between Blastocystis and fecal concentrations of alpha-1 antitrypsin (β = -0.1; 95% CI = -1.7, -0.1; p-value<0.001) and Reg1B (β = -3.6; 95% CI = -6.9, -3.0; p-value = 0.03).ConclusionsThe study findings suggest that the presence of Blastocystis in human intestine influences gut health and may have potential pathogenic role in presence of other pathogens.     

The Prognostic Value of Epigenetic Silencing of p16 Gene in NSCLC Patients: A Systematic Review and Meta-Analysis

Background

The prognostic significance of p16 promoter hypermethylation in patients with non-small cell lung cancer (NSCLC) is still controversial. This analysis presents pooled estimates of the association to better elucidate whether p16 methylation has a prognostic role in NSCLC.

Methods

Relevant studies were identified by searching PubMed, Embase and Web of Science databases until June 2012. The association of p16 methylation with both overall survival (OS) and disease-free survival (DFS) was preformed. Studies were pooled and summary hazard ratios (HR) were calculated. Subgroup analyses, sensitivity analysis and publication bias were also conducted.

Results

A total of 18 studies containing 2432 patients met the inclusion criteria and had sufficient survival data for quantitative aggregation. The results showed that p16 methylation was an indicator of poor prognosis in NSCLC. The HR was 1.36 (95% CI: 1.08–1.73, I² = 56.7%) and 1.68 (95% CI: 1.12–2.52, I² = 38.7%) for OS and DFS, respectively. Subgroup analyses were carried out. The HRs of fresh and paraffin tissue were 1.50 (95% CI: 1.11–2.01) and 1.10 (95% CI: 0.77–1.57). The pooled HR was 1.40 (95% CI: 1.02–1.92) for methylation-specific PCR (MSP) and 1.26 (95% CI: 0.87–1.82) for quantitative MSP (Q-MSP). The combined HR of the 16 studies reporting NSCLC as a whole indicated that patients with p16 hypermethylation had poor prognosis. No significant association was found when adenocarcinoma subtype pooled. When seven studies on DFS were aggregated, the HR was 1.68 (95% CI: 1.12–2.52) without significant heterogeneity. Moreover, no obvious publication bias was detected on both OS and DFS.

Conclusion

The meta-analysis findings support the hypothesis that p16 methylation is associated with OS and DFS in NSCLC patients. Large well-designed prospective studies are now needed to confirm the clinical utility of p16 methylation as an independent prognostic marker.     

Diagnosis-wide analysis of COVID-19 complications: an exposure-crossover study

BACKGROUND:Many studies reporting coronavirus disease 2019 (COVID-19) complications have involved case series or small cohorts that could not establish a causal association with COVID-19 or provide risk estimates in different care settings. We sought to study all possible complications of COVID-19 to confirm previously reported complications and to identify potential complications not yet known.METHODS:Using United States health claims data, we compared the frequency of all International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10-CM) diagnosis codes occurring before and after the onset of the COVID-19 pandemic in an exposure-crossover design. We included patients who received a diagnosis of COVID-19 between Mar. 1, 2020, and Apr. 30, 2020, and computed risk estimates and odds ratios (ORs) of association with COVID-19 for every ICD-10-CM diagnosis code.RESULTS:Among 70 288 patients with COVID-19, 69 of 1724 analyzed ICD-10-CM diagnosis codes were significantly associated with COVID-19. Disorders showing both strong association with COVID-19 and high absolute risk included viral pneumonia (OR 177.63, 95% confidence interval [CI] 147.19–214.37, absolute risk 27.6%), respiratory failure (OR 11.36, 95% CI 10.74–12.02, absolute risk 22.6%), acute kidney failure (OR 3.50, 95% CI 3.34–3.68, absolute risk 11.8%) and sepsis (OR 4.23, 95% CI 4.01–4.46, absolute risk 10.4%). Disorders showing strong associations with COVID-19 but low absolute risk included myocarditis (OR 8.17, 95% CI 3.58–18.62, absolute risk 0.1%), disseminated intravascular coagulation (OR 11.83, 95% CI 5.26–26.62, absolute risk 0.1%) and pneumothorax (OR 3.38, 95% CI 2.68–4.26, absolute risk 0.4%).INTERPRETATION:We confirmed and provided risk estimates for numerous complications of COVID-19. These results may guide prognosis, treatment decisions and patient counselling.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel strain of coronavirus that has been identified as the cause of the coronavirus disease 2019 (COVID-19) pandemic. As of Nov. 20, 2020, more than 50 million people have received a diagnosis of COVID-19 globally.¹ The clinical spectrum of disease is wide and can range from symptoms typical of the common cold to respiratory failure and death.² Most patients have mild symptoms and can be managed as outpatients, but as many as 20% have a severe form of the disease requiring admission to hospital, commonly presenting with hypoxia secondary to pneumonia.³Studies also show that COVID-19 is associated with a wide variety of nonrespiratory sequelae, including endothelial, thrombotic, cardiac, inflammatory, neurologic and other complications. ^4–9 Whether these associations are causal is not well established, as many of these findings originate from case reports, which are prone to publication bias and cannot provide risk estimates, or from cohort studies that often do not provide relative risk estimates.An alternative strategy for identifying potential complications of COVID-19 is studying all possible complications as captured in International Classification of Diseases, 10th Revision, Clinical Modification (ICD-10 CM) diagnosis codes, which allows for the discovery of unreported complications and can confirm previously identified ones. The objective of our study was to analyze all diagnoses associated with COVID-19, to identify those that could be complications of the disease and to present both the absolute risk and relative odds of any complications identified.     

Effects and interaction of meteorological factors on hemorrhagic fever with renal syndrome incidence in Huludao City,northeastern China, 2007–2018

BackgroundHemorrhagic fever with renal syndrome (HFRS), a rodent-borne disease, is a severe public health threat. Previous studies have discovered the influence of meteorological factors on HFRS incidence, while few studies have concentrated on the stratified analysis of delayed effects and interaction effects of meteorological factors on HFRS.ObjectiveHuludao City is a representative area in north China that suffers from HFRS with primary transmission by Rattus norvegicus. This study aimed to evaluate the climate factors of lag, interaction, and stratified effects of meteorological factors on HFRS incidence in Huludao City.MethodsOur researchers collected meteorological data and epidemiological data of HFRS cases in Huludao City during 2007–2018. First, a distributed lag nonlinear model (DLNM) for a maximum lag of 16 weeks was developed to assess the respective lag effect of temperature, precipitation, and humidity on HFRS incidence. We then constructed a generalized additive model (GAM) to explore the interaction effect between temperature and the other two meteorological factors on HFRS incidence and the stratified effect of meteorological factors.ResultsDuring the study period, 2751 cases of HFRS were reported in Huludao City. The incidence of HFRS showed a seasonal trend and peak times from February to May. Using the median WAT, median WTP, and median WARH as the reference, the results of DLNM showed that extremely high temperature (97.5^th percentile of WAT) had significant associations with HFRS at lag week 15 (RR = 1.68, 95% CI: 1.04–2.74) and lag week 16 (RR = 2.80, 95% CI: 1.31–5.95). Under the extremely low temperature (2.5^th percentile of WAT), the RRs of HFRS infection were significant at lag week 5 (RR = 1.28, 95% CI: 1.01–1.67) and lag 6 weeks (RR = 1.24, 95% CI: 1.01–1.57). The RRs of relative humidity were statistically significant at lag week 10 (RR = 1.19, 95% CI: 1.00–1.43) and lag week 11 (RR = 1.24, 95% CI: 1.02–1.50) under extremely high relative humidity (97.5^th percentile of WARH); however, no statistically significance was observed under extremely low relative humidity (2.5^th percentile of WARH). The RRs were significantly high when WAT was -10 degrees Celsius (RR = 1.34, 95% CI: 1.02–1.76), -9 degrees Celsius (1.37, 95% CI: 1.04–1.79), and -8 degrees Celsius (RR = 1.34, 95% CI: 1.03–1.75) at lag week 5 and more than 23 degrees Celsius after 15 weeks. Interaction and stratified analyses showed that the risk of HFRS infection reached its highest when both temperature and precipitation were at a high level.ConclusionsOur study indicates that meteorological factors, including temperature and humidity, have delayed effects on the occurrence of HFRS in the study area, and the effect of temperature can be modified by humidity and precipitation. Public health professionals should pay more attention to HFRS control when the weather conditions of high temperature with more substantial precipitation and 15 weeks after the temperature is higher than 23 degrees Celsius.     

Stereotactic radiosurgery for patients with breast cancer brain oligometastases — molecular subtypes and clinical outcomes

BackgroundWe sought to determine the clinical outcomes of patients with breast cancer (BC) who had undergone stereotactic radiosurgery (SRS) for a limited number of brain metastases (BM) and to identify factors influencing overall survival (OS) and local control.Materials and methodsThe records of 45 patients who underwent SRS for 72 brain lesions were retrospectively evaluated. Statistics included the chi-squared test, Kaplan-Meier method, and the multivariate Cox model.ResultsThe median number of treated BM was 2 (range 1–10). Median OS from BM diagnosis and post-SRS were 27.6 [95% confidence interval (CI): 14.8–40.5) and 18.5 months (95% CI: 11.1–25.8), respectively. One-year and two-year survival rates after BM diagnosis were 55% and 41%, respectively. In a univariate analysis, the Luminal-B-human-epidermal-growth-receptor-positive (HER2+) subtype had the longest median OS at 39.1 months (95% CI: 34.1–44.1, p = 0.004). In an adjusted analysis, grade 2 [hazard ratio (HR): 0.1; 95% CI: 0.1–0.6, p = 0.005), craniotomy (HR: 0.3; 95% CI: 0.1–0.7; p = 0.006), and ≥ 2 systemic therapies received (HR: 0.3; 95% CI: 0.1–0.9, p = 0.028) were associated with improved OS. One-year and two-year intracranial progression-free survival rates were 85% and 63%, respectively. Four factors for a higher risk of any intracranial recurrence remained significant in the adjusted analysis, as follows: age < 50 years (HR: 4.2; 95% CI: 1.3–36.3; p = 0.014), grade 3 (HR: 3.7; 95% CI: 1.1–13.2; p = 0.038), HER2+ (HR: 6.9; 95% CI: 1.3–36.3; p = 0.023), and whether the brain was the first metastatic site (HR: 4.7; 95% CI: 1.6–14.5; p = 0.006).ConclusionIntrinsic BC characteristics are important determinants for both survival and intracranial control for patients undergoing SRS for oligometastatic brain disease.     

Ferrous Sulfate Supplementation Causes Significant Gastrointestinal Side-Effects in Adults: A Systematic Review and Meta-Analysis

BackgroundThe tolerability of oral iron supplementation for the treatment of iron deficiency anemia is disputed.ObjectiveOur aim was to quantify the odds of GI side-effects in adults related to current gold standard oral iron therapy, namely ferrous sulfate.MethodsSystematic review and meta-analysis of randomized controlled trials (RCTs) evaluating GI side-effects that included ferrous sulfate and a comparator that was either placebo or intravenous (IV) iron. Random effects meta-analysis modelling was undertaken and study heterogeneity was summarised using I² statistics.ResultsForty three trials comprising 6831 adult participants were included. Twenty trials (n = 3168) had a placebo arm and twenty three trials (n = 3663) had an active comparator arm of IV iron. Ferrous sulfate supplementation significantly increased risk of GI side-effects versus placebo with an odds ratio (OR) of 2.32 [95% CI 1.74–3.08, p<0.0001, I² = 53.6%] and versus IV iron with an OR of 3.05 [95% CI 2.07-4.48, p<0.0001, I² = 41.6%]. Subgroup analysis in IBD patients showed a similar effect versus IV iron (OR = 3.14, 95% CI 1.34-7.36, p = 0.008, I² = 0%). Likewise, subgroup analysis of pooled data from 7 RCTs in pregnant women (n = 1028) showed a statistically significant increased risk of GI side-effects for ferrous sulfate although there was marked heterogeneity in the data (OR = 3.33, 95% CI 1.19-9.28, p = 0.02, I² = 66.1%). Meta-regression did not provide significant evidence of an association between the study OR and the iron dose.ConclusionsOur meta-analysis confirms that ferrous sulfate is associated with a significant increase in gastrointestinal-specific side-effects but does not find a relationship with dose.     

Prevalence,Awareness, Treatment and Control of Diabetes Mellitus in a Chinese Population

ObjectiveThe purpose of this study is to evaluate the prevalence, awareness, treatment and glycemic control of diabetes mellitus (DM) in a Chinese population. The findings from this study are expected to offer scientific evidence to better prevent and control the growing number of reported and untreated cases.MethodsA cross-sectional survey was conducted in Jiangsu, China. We recruited permanent residents over 18 years of age from eight towns in Jintan (JT) and six towns in Yangzhong (YZ) using a three-stage stratified cluster sampling method. The rates of DM prevalence, awareness, treatment and control as well as their related factors were analyzed.ResultsA total number of 15404 people were entered into the analysis. The DM prevalence, awareness, treatment and control rates were 7.31%, 58.35%, 51.87% and 14.12%, respectively. Multivariable logistic regression analysis showed that being female was positively related to prevalence (OR = 1.21, 95% CI: 1.07–1.37), awareness (OR = 1.52, 95% CI: 1.19–1.93), treatment (OR = 1.48, 95% CI: 1.17–1.88) and control (OR = 1.87, 95% CI: 1.30–2.67) of DM. Having a family history of diabetes was significantly correlated with DM risk (OR = 1.86, 95% CI: 1.37–2.54) and increased awareness (OR = 3.12, 95% CI: 2.19–4.47), treatment (OR = 3.47, 95% CI: 2.45–4.90) and control (OR = 1.81, 95% CI: 1.22–2.68) of DM. Former smoking status (OR = 1.82, 95% CI: 1.23–2.71), overweight (OR = 2.11, 95% CI: 1.72–2.60) and obesity (OR = 3.46, 95% CI: 2.67–4.50) were related to the risk of DM. Additionally, we found current drinking status to be positively correlated with DM risk (OR = 1.30, 95% CI: 1.01–1.66) and negatively correlated with DM awareness (OR = 0.41, 95% CI: 0.29–0.59) and treatment (OR = 0.41, 95% CI: 0.29–0.59). Our study highlights the high prevalence and inadequate awareness, treatment and control of DM in the Chinese population.ConclusionsManagement and prevention of DM-related complications should be considered an essential strategy by governments and society. This study assessed the reasons why DM has been increasing and established the first step in determining where to start regarding preventative methods.