Oregon Center for Clinical Investigation

Nephrectomy is the surgical removal of all or part of a kidney. When the aim of nephrectomy is to reduce tumor burden in people with established metastatic disease, the procedure is called cytoreductive nephrectomy (CN). CN is typically combined with systemic anticancer therapy (SACT). SACT can be initiated before or immediately after the operation or deferred until radiological signs of disease progression. The benefits and harms of CN are controversial. To assess the effects of cytoreductive nephrectomy combined with systemic anticancer therapy versus systemic anticancer therapy alone or watchful waiting in newly diagnosed metastatic renal cell carcinoma. We performed a comprehensive search in the Cochrane Library, MEDLINE, Embase, Scopus, two trial registries, and other gray literature sources up to 1 March 2024. We applied no restrictions on publication language or status. We included randomized controlled trials (RCTs) that evaluated SACT and CN versus SACT alone or watchful waiting. Two review authors independently selected studies and extracted data. Primary outcomes were time to death from any cause and quality of life. Secondary outcomes were time to disease progression, treatment response, treatment-related mortality, discontinuation due to adverse events, and serious adverse events. We performed statistical analyses using a random-effects model. We rated the certainty of evidence using the GRADE approach. Our search identified 10 records of four unique RCTs that informed two comparisons. In this abstract, we focus on the results for the two primary outcomes. Cytoreductive nephrectomy plus systemic anticancer therapy versus systemic anticancer therapy alone Three RCTs informed this comparison. Due to the considerable heterogeneity when pooling across these studies, we decided to present the results of the prespecified subgroup analysis by type of systemic agent. Cytoreductive nephrectomy plus interferon immunotherapy versus interferon immunotherapy alone CN plus interferon immunotherapy compared with interferon immunotherapy alone probably increases time to death from any cause (hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.51 to 0.89; I²= 0%; 2 studies, 326 participants; moderate-certainty evidence). Assuming 820 all-cause deaths at two years' follow-up per 1000 people who receive interferon immunotherapy alone, the effect estimate corresponds to 132 fewer all-cause deaths (237 fewer to 37 fewer) per 1000 people who receive CN plus interferon immunotherapy. We found no evidence to assess quality of life. Cytoreductive nephrectomy plus tyrosine kinase inhibitor therapy versus tyrosine kinase inhibitor therapy alone We are very uncertain about the effect of CN plus tyrosine kinase inhibitor (TKI) therapy compared with TKI therapy alone on time to death from any cause (HR 1.11, 95% CI 0.90 to 1.37; 1 study, 450 participants; very low-certainty evidence). Assuming 574 all-cause deaths at two years' follow-up per 1000 people who receive TKI therapy alone, the effect estimate corresponds to 38 more all-cause deaths (38 fewer to 115 more) per 1000 people who receive CN plus TKI therapy. We found no evidence to assess quality of life. Immediate cytoreductive nephrectomy versus deferred cytoreductive nephrectomy One study evaluated CN followed by TKI therapy (immediate CN) versus three cycles of TKI therapy followed by CN (deferred CN). Immediate CN compared with deferred CN may decrease time to death from any cause (HR 1.63, 95% CI 1.05 to 2.53; 1 study, 99 participants; low-certainty evidence). Assuming 620 all-cause deaths at two years' follow-up per 1000 people who receive deferred CN, the effect estimate corresponds to 173 more all-cause deaths (18 more to 294 more) per 1000 people who receive immediate CN. We found no evidence to assess quality of life. CN plus SACT in the form of interferon immunotherapy versus SACT in the form of interferon immunotherapy alone probably increases time to death from any cause. However, we are very uncertain about the effect of CN plus SACT in the form of TKI therapy versus SACT in the form of TKI therapy alone on time to death from any cause. Immediate CN versus deferred CN may decrease time to death from any cause. We found no quality of life data for any of these three comparisons. We also found no evidence to inform any other comparisons, in particular those involving newer immunotherapy agents (programmed death receptor 1 [PD-1]/programmed death ligand 1 [PD-L1] immune checkpoint inhibitors), which have become the backbone of SACT for metastatic renal cell carcinoma. There is an urgent need for RCTs that explore the role of CN in the context of contemporary forms of systemic immunotherapy.

ABSTRACTReported rates of invasive pneumococcal disease were markedly lower than normal during the 2020/2021 winter in the Northern Hemisphere, the first year after the start of the COVID-19 pandemic. However, little is known about rates of carriage of pneumococcus among adults during this period. Between October 2020-August 2021, couples in the Greater New Haven Area, USA, were enrolled if both individuals were aged 60 years and above and did not have any individuals under the age of 60 years living in the household. Saliva samples and questionnaires regarding social activities and contacts and medical history were obtained every 2 weeks for a period of 10 weeks. Following culture-enrichment, extracted DNA was tested using qPCR for pneumococcus-specific sequences piaB and lytA. Individuals were considered positive for pneumococcal carriage when Ct values for piaB were ≤40. Results. We collected 567 saliva samples from 95 individuals (47 household pairs and 1 singleton). Of those, 7.1% of samples tested positive for pneumococcus, representing 22/95 (23.2%) individuals and 16/48 (33.3%) households. Study participants attended few social events during this period. However, many participants continued to have regular contact with children. Individuals who had regular contact with preschool and school-aged children (i.e., 2 to 9 year olds) had a higher prevalence of carriage (15.9% versus 5.4%). Despite COVID-19-related disruptions, a large proportion of older adults continued to carry pneumococcus. Prevalence was particularly high among those who had contact with school-aged children, but carriage was not limited to this group.IMPORTANCE Carriage of Streptococcus pneumoniae (pneumococcus) in the upper respiratory tract is considered a prerequisite to invasive pneumococcal disease. During the first year of the COVID-19 pandemic, markedly lower rates of invasive pneumococcal disease were reported worldwide. Despite this, by testing saliva samples with PCR, we found that older adults continued to carry pneumococcus at pre-pandemic levels. Importantly, this study was conducted during a period when transmission mitigation measures related to the COVID-19 pandemic were in place. However, our observations are in line with reports from Israel and Belgium where carriage was also found to persist in children. In line with this, we observed that carriage prevalence was particularly high among the older adults in our study who maintained contact with school-aged children.

Interventions to prevent smoking uptake or encourage cessation among young persons might help prevent tobacco-related illness. To review the evidence for the efficacy and harms of primary care-relevant interventions that aim to reduce tobacco use among children and adolescents. Three systematic reviews that collectively covered the relevant literature; MEDLINE, PsycINFO, the Cochrane Central Register of Controlled Trials, and the Database of Abstracts of Reviews of Effects through 14 September 2012; and manual searches of reference lists and gray literature. Two investigators independently reviewed 2453 abstracts and 111 full-text articles. English-language trials of behavior-based or medication interventions that were relevant to primary care and reported tobacco use, health outcomes, or harms were included. One investigator abstracted data from good- and fair-quality trials into an evidence table, and a second checked these data. 19 trials (4 good-quality and 15 fair-quality) that were designed to prevent tobacco use initiation or promote cessation (or both) and reported self-reported smoking status or harms were included. Pooled analyses from a random-effects meta-analysis suggested a 19% relative reduction (risk ratio, 0.81 [95% CI, 0.70 to 0.93]; absolute risk difference, -0.02 [CI, -0.03 to 0.00]) in smoking initiation among participants in behavior-based prevention interventions compared with control participants. Neither behavior-based nor bupropion cessation interventions improved cessation rates. Findings about the harms related to bupropion use were mixed. No studies reported health outcomes. Interventions and measures were heterogeneous. Most trials examined only cigarette smoking. The body of evidence was largely published 5 to 15 years ago. Primary care-relevant interventions may prevent smoking initiation over 12 months in children and adolescents.

BackgroundUse of nasal intermittent positive pressure ventilation (NIPPV) in the neonatal intensive care unit (NICU) has shown promise with better clinical outcomes in premature neonates. It is not known if synchronization makes a significant clinical impact when using this technique.ObjectiveTo compare clinical outcomes of premature infants on synchronized NIPPV (SNIPPV) vs. NIPPV in the NICU.Design/MethodsRetrospective data were obtained (1/04 to 12/09) of infants who received NIPPV anytime in the NICU. SNIPPV (Infant Star with StarSync) was utilized from 2004–06, while NIPPV (Bear Cub) was used from 2007–09. BPD was defined using the NIH consensus definition. Unadjusted associations between potential risk factors and BPD/death were assessed using the chi-square or Wilcoxon Rank Sum test. Adjusted analyses were performed using generalized linear mixed models, taking into account correlation among infants of multiple gestation.ResultsThere was no significant difference in the mean gestational age and birth weight in the 2 groups: SNIPPV (n=172; 27.0w; 1016g), NIPPV (n=238; 27.7w; 1117g). There were no significant differences in maternal demographics, use of antenatal steroids, gender, multiple births, SGA, or Apgar scores in the 2 groups. More infants in the NIPPV group were given resuscitation in the delivery room (SNIPPV vs. NIPPV: 44.2% vs. 63%, p<0.001). Surfactant use (84.4% vs. 70.2%; p<0.001) was significantly higher in the SNIPPV group. There were no differences in the rate of PDA, IVH, PVL, ROP, and NEC in the 2 groups. After adjusting for the significant variables, use of NIPPV vs. SNIPPV (OR 0.74; 95%CI: 0.42, 1.30) was not associated with BPD/death.ConclusionsThese data suggest that use of SNIPPV vs. NIPPV is not significantly associated with a differential impact on clinical outcomes.

Background/contextSystematic evidence reviews (SERs) identify knowledge gaps in the literature, a logical starting place for prioritizing future research. Varied methods have been used to elicit diverse stakeholders’ input in such prioritization.ObjectiveTo pilot a simple, easily replicable process for simultaneously soliciting consumer, clinician, and researcher input in the identification of research priorities, based on the results of the 2009 SER on screening adults for depression in primary care.MethodsWe recruited 20 clinicians, clinic staff, researchers, and patient advocates to participate in a half-day event in October 2009. We presented SER research methods, and the results of the 2009 SER. Participants took part in focus groups, organized by profession; broad themes from these groups were then prioritized in a formal exercise. The focus group content was also subsequently analyzed for specific themes.ResultsFocus group themes generally reacted to the evidence presented; few were articulated as research questions. Themes included: the need for resources to respond to positive depression screens; the impact of depression screening on delivery systems; concerns that screening tools do not address comorbid or situational causes of depression; and a perceived ‘disconnect’ between screening and treatment. The two highest-priority themes were: the system effects of screening for depression, and whether depression screening effectively leads to improved treatment.ConclusionWe successfully piloted a simple, half-day, easily replicable multi-stakeholder engagement process based on the results of a recent SER. We recommend a number of potential improvements in future endeavors to replicate this process.

Diabetes outcomes are worse for underserved patients from certain ethnic/racial minority populations. Telephonic disease management is a cost-effective strategy to deliver self-management services and possibly improve diabetes outcomes for such patients. We conducted a trial to test the effectiveness of a supplemental telephonic disease management program compared to usual care alone for patients with diabetes cared for in a community health center. Randomized controlled trial. All patients had type 2 diabetes, and the majority was Hispanic or African American. Most were urban-dwelling with low socioeconomic status, and nearly all had Medicaid or were uninsured. Clinical measures included glycemic control, blood pressure, lipid levels, and body mass index. Validated surveys were used to measure dietary habits and physical activity. A total of 146 patients were randomized to the intervention and 149 to the control group. Depressive symptoms were highly prevalent in both groups. Using an intention to treat analysis, there were no significant differences in the primary outcome (HbA1c) between the intervention and control groups at 12 months. There were also no significant differences for secondary clinical or behavioral outcome measures including BMI, systolic or diastolic blood pressure, LDL cholesterol, smoking, or intake of fruits and vegetables, or physical activity. A clinic-based telephonic disease management support for underserved patients with diabetes did not improve clinical or behavioral outcomes at 1 year as compared to patients receiving usual care alone.

Medications are the most frequently prescribed therapy for low back pain. A challenge in choosing pharmacologic therapy is that each class of medication is associated with a unique balance of risks and benefits. To assess benefits and harms of acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), antidepressants, benzodiazepines, antiepileptic drugs, skeletal muscle relaxants, opioid analgesics, tramadol, and systemic corticosteroids for acute or chronic low back pain (with or without leg pain). English-language studies were identified through searches of MEDLINE (through November 2006) and the Cochrane Database of Systematic Reviews (2006, Issue 4). These electronic searches were supplemented by hand searching reference lists and additional citations suggested by experts. Systematic reviews and randomized trials of dual therapy or monotherapy with 1 or more of the preceding medications for acute or chronic low back pain that reported pain outcomes, back-specific function, general health status, work disability, or patient satisfaction. We abstracted information about study design, population characteristics, interventions, outcomes, and adverse events. To grade methodological quality, we used the Oxman criteria for systematic reviews and the Cochrane Back Review Group criteria for individual trials. We found good evidence that NSAIDs, acetaminophen, skeletal muscle relaxants (for acute low back pain), and tricyclic antidepressants (for chronic low back pain) are effective for pain relief. The magnitude of benefit was moderate (effect size of 0.5 to 0.8, improvement of 10 to 20 points on a 100-point visual analogue pain scale, or relative risk of 1.25 to 2.00 for the proportion of patients experiencing clinically significant pain relief), except in the case of tricyclic antidepressants (for which the benefit was small to moderate). We also found fair evidence that opioids, tramadol, benzodiazepines, and gabapentin (for radiculopathy) are effective for pain relief. We found good evidence that systemic corticosteroids are ineffective. Adverse events, such as sedation, varied by medication, although reliable data on serious and long-term harms are sparse. Most trials were short term (< or =4 weeks). Few data address efficacy of dual-medication therapy compared with monotherapy, or beneficial effects on functional outcomes. Our primary source of data was systematic reviews. We included non-English-language trials only if they were included in English-language systematic reviews. Medications with good evidence of short-term effectiveness for low back pain are NSAIDs, acetaminophen, skeletal muscle relaxants (for acute low back pain), and tricyclic antidepressants (for chronic low back pain). Evidence is insufficient to identify one medication as offering a clear overall net advantage because of complex tradeoffs between benefits and harms. Individual patients are likely to differ in how they weigh potential benefits, harms, and costs of various medications.

Nearly half of adults in the United States use complementary and alternative therapies each year for a variety of reasons. These therapies are increasingly popular among women seeking alternatives to treatment with estrogen for managing menopausal symptoms. The objective of this review was to assess the effectiveness of complementary and alternative therapies in the management of menopausal symptoms. MEDLINE, PsychINFO, Cochrane Library database, MANTIS, and AMED. Full-text, English-language, randomized controlled trials and meta-analyses comparing a complementary or alternative therapy with placebo or control for treatment of menopausal symptoms. All eligible trials were reviewed, abstracted into evidence tables, and rated for quality. Seventy randomized controlled trials met inclusion criteria. Forty-eight studies of phytoestrogens and other biologically based agents showed mixed results. Smaller numbers of studies using mind-body, energy, manipulative, and body-based therapies and whole medical systems showed little benefit in treating menopausal symptoms. Although individual trials suggest benefits from certain therapies, data are insufficient to support the effectiveness of any complementary and alternative therapy in this review for the management of menopausal symptoms. Many of these potential therapies warrant further study in trials with rigorous scientific designs to determine benefit and safety.