Causes of Childhood Cancer: A Review of the Recent Literature: Part I-Childhood Factors.

PURPOSE: To review the childhood risk factors for pediatric cancer (diagnosis before age 20). METHODS: We conducted literature searches using Ovid Medline and Scopus to find primary research studies, review articles, and meta-analyses published from 2014 to 3 March 2021. RESULTS: Strong evidence indicates that an array of genetic and epigenetic phenomena, structural birth defects, and chromosomal anomalies are associated with an increased risk of various childhood cancers. Increased risk is also associated with prior cancer, likely due to previous treatment agents and therapeutic ionizing radiation. Convincing evidence supports associations between several pediatric cancers and ionizing radiation, immunosuppression, and carcinogenic virus infection both in healthy children and in association with immune suppression following organ transplantation. Breastfeeding and a childhood diet rich in fruits and vegetables appears to reduce the risk of pediatric leukemia but the evidence is less strong. Childhood vaccination against carcinogenic viruses is associated with a lower risk of several cancers; there is less strong evidence that other childhood vaccinations more broadly may also lower risk. Ultraviolet (UV) radiation is associated with increased melanoma risk, although most melanomas following childhood UV exposure occur later, in adulthood. Evidence is weak or conflicting for the role of body mass index, other childhood infections, allergies, and certain treatments, including immunomodulator medications and human growth therapy.

Safety of Single High-Dose Liposomal Amphotericin B for Induction Treatment of Cryptococcal Meningitis and Histoplasmosis in People With HIV: A Systematic Review and Meta-analysis.

Background: Evidence for efficacy of single, high-dose liposomal amphotericin B (LAmB) in HIV-associated cryptococcal meningitis and histoplasmosis is growing. No systematic review has examined the safety of this regimen across multiple studies. Methods: We systematically searched Medline, Scopus, and the Cochrane Library from inception to April 2023 for studies reporting grade 3 and 4 adverse events (AEs) with single high-dose LAmB vs traditional amphotericin regimens for HIV-associated fungal infections. Results: Three trials (n = 946) were included. Compared with traditional regimens, single high-dose LAmB was associated with equivalent risk of grade 3 and 4 AEs (risk ratio [RR], 0.75; 95% CI, 0.53-1.06) and lower overall risk of grade 4 AEs (RR, 0.68; 95% CI, 0.55-0.86), grade 4 renal (RR, 0.43; 95% CI, 0.20-0.94) and grade 4 hematological AEs (RR, 0.46; 95% CI, 0.32-0.65). Conclusions: Single, high-dose LAmB is associated with a lower risk of life-threatening AEs compared with other World Health Organization-endorsed amphotericin B-based regimens in invasive HIV-related fungal infection.

The submissive silence of others: Examining definitions of shared decision making.

OBJECTIVE: Our aim was to use critical discourse analysis (CDA) to examine the most widely cited definitions of shared decision making so that we can evaluate how language is used to position participants. Based on our conceptual understanding, we presumed that shared decision making involves acts of communication where processes are collaborative. METHODS: We used a CDA lens to closely examine the phrases, semantics, syntax, implied functions, and the social actions proposed in SDM definition texts. We conducted a systematic search guided by the PRISMA guidelines, to identify the most widely cited definitions of SDM. RESULTS: A total of 72 studies met our inclusion criteria. While SDM is not consistently defined, it was striking to find that clinicians are constructed as active whereas patients were viewed to be passive participants. The definitions construct SDM to be a gift that the clinician has the power to offer, and the relationship in the definitions appears asymmetric, in which only one party seems to speak. CONCLUSIONS: The SDM definitions examined convey a process characterized by a clinician who speaks, while a patient mostly listens, and is invited to contribute. An alternative definition might be constructed through references to joint activity via sentences in active voice. PRACTICE IMPLICATIONS: Clinicians may be influenced by definitions of SDM that reinforce the positionality of active speaker versus passive recipient. Clearer definitions that address the constructs of power and roles may help support the implementation of SDM.

Urethral outcomes in metoidioplasty and phalloplasty gender affirming surgery (MaPGAS) and vaginectomy: a systematic review.

Background: There is currently a paucity of data on urethral-related outcomes in metoidioplasty and phalloplasty gender affirming surgery (MaPGAS) with urethral lengthening (UL)and vaginectomy. Methods: A systematic review was performed utilizing MEDLINE, Web of Science, Cochrane Library, Europe PMC, OSF Preprints, and EMBASE. Methodologic quality was scored using Methodological Index for Non-Randomized Studies (MINORS) criteria. Four independent reviewers performed the article evaluation, data extraction, and methodologic quality assessment. Primary outcomes included standing to urinate/pee (STP), penile length, glanular meatus, urethral stricture, fistula, and flap necrosis. Results were summarized qualitatively with descriptive statistics. Results: A total of 2,881 articles of which 11 retrospective reviews of 13 cohorts met criteria; 4.3/16 average (avg) MINORS score. Six metoidioplasty cohorts had an average penile length of 6 cm, 74% reported successful STP, and a quarter developed stricture or fistula. Phalloplasty cohorts included radial forearm flap (RF) and Anterolateral Thigh flap (ALT). Of the 4 RF studies nearly a third developed a stricture or fistula and only one study reported 99% STP with a glanular meatus. Three ALT studies reported no length but had 80-90% STP with a glanular meatus and a quarter with stricture or fistula. Conclusions: Urethral complications in MaPGAS-UL in a cohort with prior vaginectomy are common and variably reported. Patient centered outcome measures as well as clearly defined outcome metrics created in partnership with community members are needed.

A systematic review of decision aids for gender affirming therapy.

BACKGROUND: Transgender and gender diverse (TGD) persons considering gender affirming therapy have to make many complex medical decisions, potentially without understanding the associated harms or benefits of hormonal and surgical interventions. Further, clinicians are often unaware of how best to communicate information to persons seeking gender affirming therapy. Patient decision aids have been developed to provide evidence-based information as a way to help people make decisions in collaboration with their clinicians. It is unclear whether such tools exist for persons seeking gender affirming therapy. The objective of our systematic review is to search for and determine the quality of any existing patient decision aids developed for TGD persons considering gender affirming therapy, and the outcomes associated with their use. METHODS: We adapted a search strategy for databases using two key concepts "decision support intervention/patient decision aid" and "transgender". We also conducted a brief online search of Google and abstracts from relevant conferences to identify any tools not published in the academic literature. Following study selection and data extraction, we used the International Patient Decision Aid Standards instrument (IPDASi) to assess the quality of patient decision aids, and the Standards for UNiversal reporting of patient Decision Aid Evaluations (SUNDAE) checklist to assess the quality of evaluations. RESULTS: We identified 762 studies; none were identified from Google or conference content. One tool met our inclusion criteria: an online, pre-encounter patient decision aid for transmasculine genital gender-affirming surgery developed in Amsterdam, translated in English and Dutch. The tool met all the IPDASi qualifying criteria, and scored a 17/28 on the certification criteria, and 57/112 on the quality criteria. The efficacy of the patient decision aid has not been evaluated. CONCLUSIONS: Despite multiple decisions required for gender affirming therapies, only one patient decision aid has been developed for transmasculine genital reconstruction. Further research is required to develop patient decision aids for the multiple decision points along the gender affirming journey.

A Systematic Review of Dietary Supplements and Alternative Therapies for Weight Loss.

OBJECTIVE: Dietary supplements and alternative therapies are commercialized as a panacea for obesity/weight gain as a result of the minimal regulatory requirements in demonstrating efficacy. These products may indirectly undermine the value of guideline-driven obesity treatments. Included in this study is a systematic review of the literature of purported dietary supplements and alternative therapies for weight loss. METHODS: A systematic review was conducted to evaluate the efficacy of dietary supplements and alternative therapies for weight loss in participants aged ≥18 years. Searches of Medline (PubMed), Cochrane Library, Web of Science, CINAHL, and Embase (Ovid) were conducted. Risk of bias and results were summarized qualitatively. RESULTS: Of the 20,504 citations retrieved in the database search, 1,743 full-text articles were reviewed, 315 of which were randomized controlled trials evaluating the efficacy of 14 purported dietary supplements, therapies, or a combination thereof. Risk of bias and sufficiency of data varied widely. Few studies (n = 52 [16.5%]) were classified as low risk and sufficient to support efficacy. Of these, only 16 (31%) noted significant pre/post intergroup differences in weight (range: 0.3-4.93 kg). CONCLUSIONS: Dietary supplements and alternative therapies for weight loss have a limited high-quality evidence base of efficacy. Practitioners and patients should be aware of the scientific evidence of claims before recommending use.

Community health worker interventions for older adults with complex health needs: A systematic review.

BACKGROUND/OBJECTIVES: The number of older adults with complex health needs is growing, and this population experiences disproportionate morbidity and mortality. Interventions led by community health workers (CHWs) can improve clinical outcomes in the general adult population with multimorbidity, but few studies have investigated CHW-delivered interventions in older adults. DESIGN: We systematically reviewed the impact of CHW interventions on health outcomes among older adults with complex health needs. We searched for English-language articles from database inception through April 2020 using seven databases. PROSPERO protocol registration CRD42019118761. SETTING: Any U.S. or international setting, including clinical and community-based settings. PARTICIPANTS: Adults aged 60 years or older with complex health needs, defined in this review as multimorbidity, frailty, disability, or high-utilization. INTERVENTIONS: Interventions led by a CHW or similar role consistent with the American Public Health Association's definition of CHWs. MEASUREMENTS: Pre-defined health outcomes (chronic disease measures, general health measures, treatment adherence, quality of life, or functional measures) as well as qualitative findings. RESULTS: Of 5671 unique records, nine studies met eligibility criteria, including four randomized controlled trials, three quasi-experimental studies, and two qualitative studies. Target population and intervention characteristics were variable, and studies were generally of low-to-moderate methodological quality. Outcomes included mood, functional status and disability, social support, well-being and quality of life, medication knowledge, and certain health conditions (e.g., falls, cognition). Results were mixed with several studies demonstrating significant effects on mood and function, including one high-quality RCT, while others noted no significant intervention effects on outcomes. CONCLUSION: CHW-led interventions may have benefit for older adults with complex health needs, but additional high-quality studies are needed to definitively determine the effectiveness of CHW interventions in this population. Integration of CHWs into geriatric clinical settings may be a strategy to deliver evidence-based interventions and improve clinical outcomes in complex older adults.

Does the use of patient decision aids lead to cost savings? a systematic review.

OBJECTIVES: To update a previous systematic review to determine if patient decision aid (PDA) interventions generate savings in healthcare settings, and if so, from which perspective (ie, patient, organisation providing care, society). DESIGN: Systematic review. DATA SOURCES: MEDLINE, CINAHL, PsycINFO, Web of Science, Cochrane Library, Embase, Campbell Collaboration Library, EconLit, Business Source Complete, Centre for Reviews and Dissemination: NHS Economic Evaluations Database (NHS EED), Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA) from 15 March 2013 to 25 January 2019. The references of studies that met the eligibility criteria and any publications related to conference abstracts or registered clinical trials were reviewed to increase the sensitivity of the search. ELIGIBILITY CRITERIA: Full and partial economic evaluations with an experimental, quasi-experimental or randomised controlled design were included. The intervention had to satisfy the pre-determined minimum conditions necessary to be defined as a PDA, and (for full evaluations) provide details on the comparator used. DATA EXTRACTION AND SYNTHESIS: All study outcomes and economic data were extracted. The reporting and quality of the economic analyses were independently assessed by two health economists. RESULTS: Of 5066 studies, 22 studies were included, including the 8 studies from the previous review. Twelve studies reported cost-savings (range=US$10 to US$81 156; US dollars in 2020), primarily from the organisational or health system perspective, and 10 studies did not. However, due to the quality of the economic analyses, and the related issues with the interpretative validity of results it would be inappropriate to say that PDAs will generate savings, from any perspective. CONCLUSIONS: It is unclear whether PDAs will generate savings. Greater consensus on what constitutes a PDA and the need to compare them against usual care over a sufficient time horizon to allow valid assessment of costs and outcomes is required. PROSPERO REGISTRATION NUMBER: CRD42019118457.

Neonatal early onset sepsis in Middle Eastern countries: a systematic review.

BACKGROUND: Early onset neonatal sepsis (EOS) accounts for a significant portion of neonatal mortality, which accounts for 46% of global under five child mortality. OBJECTIVE: This systematic review studies the bacterial aetiology of EOS in the Middle East, susceptibility patterns to recommended empirical antibiotic therapy and whether this differs between high-income and middle-income countries in the region. METHODS: Articles were collected from Medline, Web of Science, the Cochrane Library and Index Medicus for the Eastern Mediterranean Region. The articles included in our systematic review met the following criteria: published after January 2000, data relevant to the Middle East, data specific for early onset sepsis, no language restriction. Data on aetiology and susceptibility were extracted from prospective and retrospective studies. Risk of bias was assessed using the Newcastle-Ottawa Scale. This study focused on EOS but does include data regarding neonatal late-onset sepsis antibiotic susceptibility. The data regarding coagulase-negative Staphylococcus species were excluded from final analysis, as possible contaminants. The protocol for this systematic review was registered on PROSPERO: CRD42017060662. RESULTS: 33 articles from 10 countries were included in the analysis. There were 2215 cases of culture-positive EOS, excluding coagulase-negative Staphylococcus. In middle-income countries, Klebsiella species (26%), Staphylococcus aureus (17%) and Escherichia coli (16%) were the most common pathogens, in contrast to group B Streptococcus (26%), E. coli (24%) and Klebsiella (9%) in high-income countries. Overall susceptibility to ampicillin/gentamicin and third-generation cephalosporin were 40% and 37%, respectively, in middle-income countries versus 93% and 91%, respectively, in high-income countries. CONCLUSIONS: EOS in middle-income countries was more likely to be due to Gram-negative pathogens and less likely to be susceptible to empirical antibiotic therapy. This has important public health implications regarding neonatal mortality in the Middle East region.

Effectiveness of Ambulatory Telemedicine Care in Older Adults: A Systematic Review.

BACKGROUND: Disparities in healthcare access and delivery, caused by transportation and health workforce difficulties, negatively impact individuals living in rural areas. These challenges are especially prominent in older adults. DESIGN: We systematically evaluated the feasibility, acceptability, and effectiveness in providing telemedicine (TMed), searching the English-language literature for studies (January 2012 to July 2018) in the following databases: Medline (PubMed); Cochrane Library (Wiley); Web of Science; CINAHL; EMBASE (Ovid); and PsycINFO (EBSCO). PARTICIPANTS: Older adults (mean age = 65 years or older, and none were younger than 60 years). INTERVENTIONS: Interventions consisted of live, synchronous, two-way videoconferencing communication in nonhospital settings. All medical interventions were included. MEASUREMENTS: Quality assessment, using the Cochrane Collaboration's Risk-of-Bias Tool, was applied on all included articles, including a qualitative summary of all articles. RESULTS: Of 6616 citations, we reviewed the full text of 1173 articles, excluding 1047 that did not meet criteria. Of the 17 randomized controlled trials, the United States was the country with the most trials (6 [35%]), with cohort sizes ranging from 3 to 844 (median = 35) participants. Risk of bias among included studies varied from low to high. Our qualitative analysis suggests that TMed can improve health outcomes in older adults and that it could be used in this population. CONCLUSIONS: TMed is feasible and acceptable in delivering care to older adults. Research should focus on well-designed randomized trials to overcome the high degree of bias observed in our synthesis. Clinicians should consider using TMed in routine practice to overcome barriers of distance and access to care. J Am Geriatr Soc 67:1737-1749, 2019.

Weight Loss Interventions in Older Adults with Obesity: A Systematic Review of Randomized Controlled Trials Since 2005.

OBJECTIVES: To identify geriatric obesity interventions that can guide clinical recommendations. DESIGN: Systematic review using Medline (PubMed), Cochrane Central Register of Controlled Trials, Web of Science, CINAHL, EMBASE (Ovid), and PsycINFO (Proquest) from January 1, 2005, to October 12, 2015, to identify English-language randomized controlled trials. PARTICIPANTS: Individuals aged 60 and older (mean age ≥65) and classified as having obesity (body mass index ≥30 kg/m2 ). INTERVENTIONS: Behavioral weight loss interventions not involving pharmacological or procedural therapies lasting 6 months or longer. MEASUREMENTS: Two investigators performed the systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria and achieved a high concordance rate (97.3%) in summarizing the primary outcomes. The three primary outcomes were weight loss, physical performance, and quality of life. RESULTS: Of 5,741 citations, 19 were included. (Six studies were unique, and the remaining 13 were based on the same study population.) Duration ranged from 6 to 18 months (n = 405 participants, age range 66.7-71.1). Weight loss in the intervention groups ranged from 0.5 to 10.7 kg (0.1-9.3%). Five studies had a resistance exercise program accompanying a dietary component. Greater weight loss was observed in groups with a dietary component than those with exercise alone. Exercise alone led to better physical function but no significant weight loss. Combined dietary and exercise components led to the greatest improvement in physical performance measures and quality of life and mitigated reductions in muscle and bone mass observed in diet-only study arms. Heterogeneous outcomes were observed, which limited the ability to synthesize the data quantitatively. CONCLUSIONS: The evidence supporting geriatric obesity interventions to improve physical function and quality of life is of low to moderate quality. Well-designed trials are needed in this population.

Treating tobacco use disorder in pregnant women in medication-assisted treatment for an opioid use disorder: a systematic review.

Smoking is associated with adverse effects on pregnancy and fetal development, yet 88-95% of pregnant women in medication-assisted treatment for an opioid use disorder smoke cigarettes. This review summarizes existing knowledge about smoking cessation treatments for pregnant women on buprenorphine or methadone, the two forms of medication-assisted treatment for opioid use disorder indicated for prenatal use. We performed a systematic review of the literature using indexed terms and key words to capture the concepts of smoking, pregnancy, and opioid substitution and found that only three studies met search criteria. Contingency management, an incentive based treatment, was the most promising intervention: 31% of participants achieved abstinence within the 12-week study period, compared to 0% in a non-contingent behavior incentive group and a group receiving usual care. Two studies of brief behavioral interventions resulted in reductions in smoking but not cessation. Given the growing number of pregnant women in medication-assisted treatment for an opioid use disorder and the negative consequences of smoking on pregnancy, further research is needed to develop and test effective cessation strategies for this group.

Risks of serious infection or lymphoma with anti-tumor necrosis factor therapy for pediatric inflammatory bowel disease: a systematic review.

BACKGROUND & AIMS: Many physicians hesitate to recommend anti-tumor necrosis factor (TNF) therapy for pediatric patients with inflammatory bowel disease (IBD) because of concerns about risk of infection and cancer. We performed a systematic review to quantify the incidence of serious infection, lymphoma, and death among pediatric patients with IBD who received anti-TNF therapy. These values were compared with those expected from other treatments, from adults with IBD, and from the general pediatric population. METHODS: We searched MEDLINE, EMBASE, the Cochrane Collaboration, and Web of Knowledge for studies of infliximab therapy for children with ulcerative colitis or Crohn's disease, or adalimumab therapy for children with Crohn's disease. Standardized incidence ratios (SIRs) were calculated, comparing rates of infection and cancer among pediatric patients exposed to anti-TNF agents vs expected rates from pediatric patients not exposed to anti-TNF therapies or adult patients exposed to anti-TNF agents. Our analysis included 5528 patients with 9516 patient-years of follow-up evaluation (PYF). RESULTS: The rate of serious infections among pediatric patients treated with anti-TNF agents (352/10,000 PYF) was similar to that of pediatric patients who received immunomodulator monotherapy (333/10,000 PYF; SIR, 1.06; 95% confidence interval [CI], 0.83-1.36), but significantly lower than the expected rate for pediatric patients treated with steroids (730/10,000 PYF; SIR, 0.48; 95% CI, 0.40-0.58) or adults treated with anti-TNF agents (654/10,000 PYF; SIR, 0.54; 95% CI, 0.43-0.67). Five treatment-related deaths occurred (4 from sepsis and 1 from arrhythmia). Two patients developed lymphoma (2.1/10,000 PYF). This value was similar to the expected rate of lymphoid neoplasia in the entire pediatric population (5.8/100,000 PYF; SIR, 3.5; 95% CI, 0.35-19.6), and lower than the population of pediatric patients receiving thiopurine monotherapy (4.5/10,000 PYF; SIR, 0.47; 95% CI, 0.03-6.44), and among adults treated with anti-TNF agents (6.1/10,000 PYF; SIR, 0.34; 95% CI, 0.04-1.51). CONCLUSIONS: Based on a systematic review, the risk of lymphoma was no greater among children with IBD who received anti-TNF therapy than those treated with other IBD therapies or adults treated with anti-TNF agents. The rate of serious infection was significantly lower among pediatric patients with IBD treated with anti-TNF agents than those treated with steroids, or adults with IBD who received anti-TNF therapy.