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The Journal of Clinical Endocrinology... Oct 2023Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) affecting mineral and bone metabolism and characterized by excessive parathyroid... (Meta-Analysis)
Meta-Analysis
CONTEXT
Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) affecting mineral and bone metabolism and characterized by excessive parathyroid hormone (PTH) production and parathyroid hyperplasia.
OBJECTIVE
The objective of this analysis was to compare the efficacy and adverse effects of extended-release calcifediol (ERC) and paricalcitol (PCT) by assessing their effect on the biomarkers PTH, calcium, and phosphate in patients with non-dialysis CKD (ND-CKD).
METHODS
A systematic literature research was performed in PubMed to identify randomized control trials (RCTs). Quality assessment was done with the GRADE method. The effects of ERC vs PCT were compared using random effects in a frequentist setting.
RESULTS
Nine RCTs comprising 1426 patients were included in the analyses. The analyses were performed on 2 overlapping networks, due to nonreporting of outcomes in some of the included studies. No head-to-head trials were identified. No statistically significant differences in PTH reduction were found between PCT and ERC. Treatment with PCT showed statistically significant increases in calcium compared with ERC (0.2 mg/dL increase; 95% CI, -0.37 to -0.05 mg/dL). No differences in effects on phosphate were observed.
CONCLUSION
This network meta-analysis showed that ERC is comparable in lowering PTH levels vs PCT. ERC displayed avoidance of potentially clinically relevant increases in serum calcium, offering an effective and well-tolerated treatment option for the management of SHPT in patients with ND-CKD.
Topics: Humans; Calcifediol; Calcium; Ergocalciferols; Hyperparathyroidism, Secondary; Network Meta-Analysis; Parathyroid Hormone; Phosphates; Renal Insufficiency, Chronic; Randomized Controlled Trials as Topic
PubMed: 37235771
DOI: 10.1210/clinem/dgad289 -
Frontiers in Pharmacology 2023According to the 2023 guidelines for treating non-small-cell lung cancer (NSCLC), first-line treatment and recently developed agents for the treatment of epidermal...
Comparison of the efficacy and safety of first-line treatments for of advanced EGFR mutation-positive non-small-cell lung cancer in Asian populations: a systematic review and network meta-analysis.
According to the 2023 guidelines for treating non-small-cell lung cancer (NSCLC), first-line treatment and recently developed agents for the treatment of epidermal growth factor (EGFR) mutation-positive locally advanced or metastatic NSCLC were compared in this meta-analysis. Treatment regimens involved in the included studies included first, second, and third-generation tyrosine kinase inhibitors (TKIs), TKIs plus chemotherapy, TKIs plus angiogenesis inhibitors, and platinum-containing doublet chemotherapy with or without bevacizumab. Considering the varying efficacy and safety of drugs in people of different ethnic origins, the optimal regimen should be determined, and the safety of first-line treatments should be assessed in the Asian population specifically. PubMed, Embase, the Cochrane Library, Web of Science, and the China National Knowledge Infrastructure (CNKI) were systematically searched to retrieve reports on randomized controlled trials (RCTs) with research data published from inception to 1 February 2023. Adopting Asian patient populations as the target (including studies in which Asian patients accounted for more than 50% of the sample), a network meta-analysis (NMA) was conducted for comparison of treatment regimens and treatments were ranked based on the surface under the cumulative ranking curve (SUCRA). A total of 19 RCTs involving 5,824 patients and covering 14 treatment regimens were included. The primary outcome measure examined in this study was progression-free survival (PFS); other outcome measures examined were overall survival (OS), disease control rate (DCR), objective response rate (ORR), occurrence of any adverse events (AE), occurrence of adverse events of grade 3 or above (≥3AE), and occurrence of serious adverse events (SAE). In terms of PFS, all regimens including TKIs (as a monotherapy or in combination with other therapies), as well as bevacizumab (Bev) plus chemotherapy (Ch) were found to be significantly superior to basic chemotherapy (HRs: 0.09-0.61, < 0.05 in all cases compared with Ch alone). The highest-ranking therapies were erlotinib (Erl) plus Bev (SUCRA: 0.94) and Erl plus ramucirumab (Ram) (SUCRA: 0.93). Regarding OS, no significant differences was observed between first-line treatment strategies; the top four treatments based on SUCRA, in rank order, were Bev + Ch (0.87), gefitinib (Gef) plus Ch (0.81), dacomitinib (Dac) (0.79), and osimertinib (Osi) (0.69). Additionally, there were no significant differences between first-line treatment strategies in terms of DCR. Regarding ORR, the top three treatments based on SUCRA were Erl + Bev (0.85), Erl + Ram (0.76), and Gef + Ch (0.74). No significant difference between first-line treatment strategies was observed in terms of the risk of AE. However, based on SUCRA, Erl ranked highest on avoidance of ≥ 3AE (0.97), and Osi ranked highest on avoidance of SAE (0.91). Based on these analyses of survival benefits, tumor burden response, and safety, furmonertinib (Fur), Osi, and aumolertinib (Aum) may represent the best treatment regimen options for Asian patients, significantly prolonging survival (as measured by median PFS/OS), eliciting a greater tumor burden response, and exposing patients to a lower risk of adverse events. Although Erl + Bev and Erl + Ram are associated with the best survival benefits in terms of PFS, further clinical studies are still needed to identify ways to reduce the risk of adverse events. https://www.crd.york.ac.uk/prospero/display_record.php? ID=CRD42023407994, identifier CRD42023407994.
PubMed: 37484016
DOI: 10.3389/fphar.2023.1212313 -
Medicine Nov 2023Major depressive disorder is often resistant to first-line treatment, with around 30% failing to respond to traditional therapy. Treatment-resistant depression results... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Major depressive disorder is often resistant to first-line treatment, with around 30% failing to respond to traditional therapy. Treatment-resistant depression results in prolonged hospitalization and healthcare costs. Anti-inflammatory drugs have shown promising results in depression not responding to initial therapy. Minocycline has anti-inflammatory properties and crosses the blood-brain barrier. It has demonstrated varied results in several randomized controlled trials (RCTs).
METHODS
We assessed the efficacy of minocycline compared to placebo in depression not responding to one first-line antidepressant via a systematic review and meta-analysis. We performed a comprehensive literature search across PubMed, Cochrane, and Scopus for RCTs. We visualized the results using forest plots and drapery plots. We assessed and explored heterogeneity using I2, prediction interval, and meta-regression. Then, we rated the certainty of the evidence.
RESULTS
Four RCTs revealed a non-significant difference in depression severity [-3.93; 95% CI: -16.14 to 8.28], rate of response [1.15; 0.33-4.01], and rate of remission [0.94; 0.44-2.01]. However, the reduction in depression severity is significant at a trend of P < .1. The high between-study heterogeneity (I2 = 78%) for depression severity could be answered by meta-regression (P = .02) for the duration of therapy.
CONCLUSION
There is no significant difference with minocycline compared to placebo for depression not responding to first-line antidepressant therapy. However, the treatment response varies with treatment duration and patients' neuroinflammatory state. Thus, larger and longer RCTs, especially in diverse disease subgroups, are needed for further insight. This is needed to allow greater precision medicine in depression and avoid elevated healthcare expenditure associated with hit-and-trial regimens.
REGISTRATION
CRD42023398476 (PROSPERO).
Topics: Humans; Depression; Minocycline; Antidepressive Agents; Depressive Disorder, Major; Anti-Inflammatory Agents
PubMed: 37960804
DOI: 10.1097/MD.0000000000035937 -
Prehospital and Disaster Medicine Aug 2023An under-developed and fragmented prehospital Emergency Medical Services (EMS) system is a major obstacle to the timely care of emergency patients. Insufficient emphasis... (Review)
Review
BACKGROUND
An under-developed and fragmented prehospital Emergency Medical Services (EMS) system is a major obstacle to the timely care of emergency patients. Insufficient emphasis on prehospital emergency systems in low- and middle-income countries (LMICs) currently causes a substantial number of avoidable deaths from time-sensitive illnesses, highlighting a critical need for improved prehospital emergency care systems. Therefore, this systematic review aimed to assess the prehospital emergency care services across LMICs.
METHODS
This systematic review used four electronic databases, namely: PubMed/MEDLINE, CINAHL, EMBASE, and SCOPUS, to search for published reports on prehospital emergency medical care in LMICs. Only peer-reviewed studies published in English language from January 1, 2010 through November 1, 2022 were included in the review. The Newcastle-Ottawa Scale (NOS) and Critical Appraisal Skills Programme (CASP) checklist were used to assess the methodological quality of the included studies. Further, the protocol of this systematic review has been registered on the International Prospective Register of Systematic Reviews (PROSPERO) database (Ref: CRD42022371936) and has been conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Of the 4,909 identified studies, a total of 87 studies met the inclusion criteria and were therefore included in the review. Prehospital emergency care structure, transport care, prehospital times, health outcomes, quality of information exchange, and patient satisfaction were the most reported outcomes in the considered studies.
CONCLUSIONS
The prehospital care system in LMICs is fragmented and uncoordinated, lacking trained medical personnel and first responders, inadequate basic materials, and substandard infrastructure.
Topics: Humans; Developing Countries; Emergency Medical Services
PubMed: 37492946
DOI: 10.1017/S1049023X23006088 -
PLoS Neglected Tropical Diseases Dec 2023Cutaneous (CL) and mucocutaneous leishmaniasis (MCL) are parasitic diseases caused by parasites of the genus leishmania leading to stigma caused by disfigurations. This...
BACKGROUND
Cutaneous (CL) and mucocutaneous leishmaniasis (MCL) are parasitic diseases caused by parasites of the genus leishmania leading to stigma caused by disfigurations. This study aimed to systematically review the dimensions, measurement methods, implications, and potential interventions done to reduce the CL- and MCL- associated stigma, synthesising the current evidence according to an accepted stigma framework.
METHODS
This systematic review followed the PRISMA guidelines and was registered in PROSPERO (ID- CRD42021274925). The eligibility criteria included primary articles discussing stigma associated with CL and MCL published in English, Spanish, or Portuguese up to January 2023. An electronic search was conducted in Medline, Embase, Scopus, PubMed, EBSCO, Web of Science, Global Index Medicus, Trip, and Cochrane Library. The mixed methods appraisal tool (MMAT) was used for quality checking. A narrative synthesis was conducted to summarise the findings.
RESULTS
A total of 16 studies were included. The studies report the cognitive, affective, and behavioural reactions associated with public stigma. Cognitive reactions included misbeliefs about the disease transmission and treatment, and death. Affective reactions encompass emotions like disgust and shame, often triggered by the presence of scars. Behavioural reactions included avoidance, discrimination, rejection, mockery, and disruptions of interpersonal relationships. The review also highlights self-stigma manifestations, including enacted, internalised, and felt stigma. Enacted stigma manifested as barriers to forming proper interpersonal relationships, avoidance, isolation, and perceiving CL lesions/scars as marks of shame. Felt stigma led to experiences of marginalisation, rejection, mockery, disruptions of interpersonal relationships, the anticipation of discrimination, fear of social stigmatisation, and facing disgust. Internalised stigma affected self-identity and caused psychological distress.
CONCLUSIONS
There are various manifestations of stigma associated with CL and MCL. This review highlights the lack of knowledge on the structural stigma associated with CL, the lack of stigma interventions and the need for a unique stigma tool to measure stigma associated with CL and MCL.
Topics: Humans; Leishmaniasis, Mucocutaneous; Cicatrix; Social Stigma; Stereotyping; Fear; Leishmaniasis, Cutaneous
PubMed: 38153950
DOI: 10.1371/journal.pntd.0011818 -
Frontiers in Oncology 2023The role of cranial radiation therapy with hippocampus avoidance (HA-CRT) in neurocognitive function (NCF), brain metastasis (BM), and overall survival (OS) in lung...
BACKGROUND
The role of cranial radiation therapy with hippocampus avoidance (HA-CRT) in neurocognitive function (NCF), brain metastasis (BM), and overall survival (OS) in lung cancer remains unclear.
METHODS
A meta-analysis was conducted to evaluate the impact of HA-CRT in lung cancer. Data from studies on hippocampal-avoidance prophylactic cranial irradiation (HA-PCI) and whole brain radiotherapy (HA-WBRT) were pooled.
RESULTS
A total of 14 studies, including 5 randomized controlled trials, were included. The focus of NCF was mainly the Hopkins Verbal Learning Test-Revised or the Free and Cued Selective Reminding Test. At 6 months post-radiotherapy, the pooled proportion of participants with decline in the performance of total recall, delayed recall, and discrimination in neurocognitive tests were 0.22 (95% CI 0.15, 0.29), 0.20 (95% CI 0.13, 0.27), and 0.14 (95% CI 0.05, 0.24) respectively. After 12 months, the proportion were 0.16 (95% CI 0.08, 0.23), 0.10 (95% CI 0.04, 0.16), and 0.04 (95% CI 0, 0.09) respectively. For HA zone relapse, the RR of HA-CRT versus CRT was 2.72 (95% CI 0.53, 13.87), and for 2-year BM, it was 1.20 (95% CI 0.82, 1.75). Regarding HA-PCI in SCLC, the 1-year BM rate was 0.12 (95% CI 0.07, 0.17), and the 2-year BM rate was 0.20 (95% CI 0.16, 0.25). For HA-WBRT in NSCLC with BM, the 2-year intracranial progression rate was 0.38 (95% CI 0.13, 0.62). There was no significant difference in OS between HA-CRT and CRT.
CONCLUSIONS
HA-CRT appears to be safe in lung cancer, but it may not outperform conventional CRT. Larger RCTs comparing HA-CRT and CRT are warranted.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022360890, identifier CRD42022360890.
PubMed: 37936606
DOI: 10.3389/fonc.2023.1268754 -
Human Reproduction Update Mar 2024Pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to experience preterm birth and their neonates are more likely... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pregnant women infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are more likely to experience preterm birth and their neonates are more likely to be stillborn or admitted to a neonatal unit. The World Health Organization declared in May 2023 an end to the coronavirus disease 2019 (COVID-19) pandemic as a global health emergency. However, pregnant women are still becoming infected with SARS-CoV-2 and there is limited information available regarding the effect of SARS-CoV-2 infection in early pregnancy on pregnancy outcomes.
OBJECTIVE AND RATIONALE
We conducted this systematic review to determine the prevalence of early pregnancy loss in women with SARS-Cov-2 infection and compare the risk to pregnant women without SARS-CoV-2 infection.
SEARCH METHODS
Our systematic review is based on a prospectively registered protocol. The search of PregCov19 consortium was supplemented with an extra electronic search specifically on pregnancy loss in pregnant women infected with SARS-CoV-2 up to 10 March 2023 in PubMed, Google Scholar, and LitCovid. We included retrospective and prospective studies of pregnant women with SARS-CoV-2 infection, provided that they contained information on pregnancy losses in the first and/or second trimester. Primary outcome was miscarriage defined as a pregnancy loss before 20 weeks of gestation, however, studies that reported loss up to 22 or 24 weeks were also included. Additionally, we report on studies that defined the pregnancy loss to occur at the first and/or second trimester of pregnancy without specifying gestational age, and for second trimester miscarriage only when the study presented stillbirths and/or foetal losses separately from miscarriages. Data were stratified into first and second trimester. Secondary outcomes were ectopic pregnancy (any extra-uterine pregnancy), and termination of pregnancy. At least three researchers independently extracted the data and assessed study quality. We calculated odds ratios (OR) and risk differences (RDs) with corresponding 95% CI and pooled the data using random effects meta-analysis. To estimate risk prevalence, we performed meta-analysis on proportions. Heterogeneity was assessed by I2.
OUTCOMES
We included 120 studies comprising a total of 168 444 pregnant women with SARS-CoV-2 infection; of which 18 233 women were in their first or second trimester of pregnancy. Evidence level was considered to be of low to moderate certainty, mostly owing to selection bias. We did not find evidence of an association between SARS-CoV-2 infection and miscarriage (OR 1.10, 95% CI 0.81-1.48; I2 = 0.0%; RD 0.0012, 95% CI -0.0103 to 0.0127; I2 = 0%; 9 studies, 4439 women). Miscarriage occurred in 9.9% (95% CI 6.2-14.0%; I2 = 68%; 46 studies, 1797 women) of the women with SARS CoV-2 infection in their first trimester and in 1.2% (95% CI 0.3-2.4%; I2 = 34%; 33 studies; 3159 women) in the second trimester. The proportion of ectopic pregnancies in women with SARS-CoV-2 infection was 1.4% (95% CI 0.02-4.2%; I2 = 66%; 14 studies, 950 women). Termination of pregnancy occurred in 0.6% of the women (95% CI 0.01-1.6%; I2 = 79%; 39 studies; 1166 women).
WIDER IMPLICATIONS
Our study found no indication that SARS-CoV-2 infection in the first or second trimester increases the risk of miscarriages. To provide better risk estimates, well-designed studies are needed that include pregnant women with and without SARS-CoV-2 infection at conception and early pregnancy and consider the association of clinical manifestation and severity of SARS-CoV-2 infection with pregnancy loss, as well as potential confounding factors such as previous pregnancy loss. For clinical practice, pregnant women should still be advised to take precautions to avoid risk of SARS-CoV-2 exposure and receive SARS-CoV-2 vaccination.
Topics: Female; Humans; Pregnancy; Abortion, Spontaneous; COVID-19; Premature Birth; Prevalence
PubMed: 38016805
DOI: 10.1093/humupd/dmad030 -
Transplantation Reviews (Orlando, Fla.) Dec 2023Opting for a preemptive kidney transplant (PKT) can help avoid costs and morbidity associated with dialysis. However, while multiple studies have shown clinical benefits... (Meta-Analysis)
Meta-Analysis Review
Opting for a preemptive kidney transplant (PKT) can help avoid costs and morbidity associated with dialysis. However, while multiple studies have shown clinical benefits of PKT, other studies have not demonstrated this, leading to controversy in the literature regarding the exact benefits of PKT. Therefore, this study aimed to determine the clinical outcomes of PKT versus non-preemptive kidney transplantation (nPKT) in adult patients. Multiple databases were searched up to May 4, 2022. Independent reviewers selected studies for inclusion and extracted relevant data. Risk of bias was assessed using the Downs and Black checklist. Eighty-seven studies including 859,715 adult kidney transplant patients were included the review. The risk of patient death (relative risk [95% confidence interval] 0.74 [0.60-0.91]) was significantly lower in PKT versus nPKT patients for living donor (LD) transplants, whereas the risk of overall graft loss was significantly lower in PKT compared to nPKT patients for both LD (0.72 [0.62-0.83]) as well as deceased donor (DD) transplants (0.80 [0.69-0.92]). The evidence suggests that LD PKT patients have a lower risk of patient death and graft loss compared to nPKT patients, and DD PKT patients have a lower risk of graft loss than nPKT patients.
Topics: Adult; Humans; Kidney Transplantation; Renal Dialysis; Living Donors; Risk; Graft Survival
PubMed: 37801855
DOI: 10.1016/j.trre.2023.100798 -
Journal of Endovascular Therapy : An... Feb 2024Comparative effectiveness of fenestrated endovascular aneurysm repair (FEVAR) and chimney graft endovascular aneurysm repair (ChEVAR) for juxtarenal aortic aneurysms... (Review)
Review
OBJECTIVES
Comparative effectiveness of fenestrated endovascular aneurysm repair (FEVAR) and chimney graft endovascular aneurysm repair (ChEVAR) for juxtarenal aortic aneurysms (JAAs) remains unclear. Our objective was to identify and analyze the current body of evidence comparing the effectiveness of both techniques for JAA.
METHODS
We performed a systematic review and meta-analysis comparing the effectiveness of FEVAR and ChEVAR for JAA repair. We searched MEDLINE, EMBASE, and Cochrane Register for Controlled Trials from January 1, 1990, for randomized and non-randomized studies assessing outcomes of FEVAR and ChEVAR for JAA repair. Screening, data extraction, risk of bias assessment, and GRADE (Grading of Recommendations, Assessments, Development, and Evaluations) certainty of evidence were performed in duplicate. Data were pooled statistically where possible.
RESULTS
Nine retrospective cohort studies comparing the use of FEVAR and ChEVAR for juxtarenal aneurysm were included for meta-analysis. The FEVAR and ChEVAR arms of the meta-analysis consisted of 726 participants and 518 participants, respectively. There were 598 (86.8%) and 332 (81.6%) men in each arm. The mean diameter was larger in the ChEVAR arm (59 mm vs 52.5 mm). Both techniques had similar rates of postoperative 30-day mortality, 3.38% (8/237) versus 3.52% (8/227), acute kidney injury, 16.76% (31/185) versus 17.31% (18/104), and major adverse cardiac events, 7.30% (46/630) versus 6.60% (22/333). The meta-analysis supported the use of FEVAR for most outcomes, with significant advantage for technical success (odds ratio [OR]: 3.24, 95% CI: 1.24-8.42) and avoidance of type 1 endoleak (OR: 5.76, 95% CI: 1.94-17.08), but a disadvantage for spinal cord ischemia (OR: 10.21, 95% CI: 1.21-86.11), which had a very low number of events. The quality of evidence was "moderate" for most outcomes.
CONCLUSION
Both endovascular techniques had good safety profiles. The evidence does not support superiority of either FEVAR or ChEVAR for JAA.
CLINICAL IMPACT
While lack of equipoise has hampered the design of randomised trials of open versus endovascular repair of juxtarenal aortic aneurysms, concern about the durability of endovascular repair highlights the need for stronger evidence of the comparative efficacy of endovascular techniques. This review performed meta-analysis and evidence appraisal of recent data from large observational studies comparing fenestrated and chimney techniques, using a comprehensive outcome set. Superiority of either intervention could not be established due to differences in participants' baseline risk in each study arm. However, data suggests that both techniques are safe and suitable for use when indicated.
PubMed: 38388373
DOI: 10.1177/15266028241231171 -
The Knee Dec 2023In recent years, kinematic alignment (KA) is becoming a valid alternative to mechanical alignment (MA) in total knee arthroplasty (TKA). However, to avoid early... (Review)
Review
BACKGROUND
In recent years, kinematic alignment (KA) is becoming a valid alternative to mechanical alignment (MA) in total knee arthroplasty (TKA). However, to avoid early failures, the restricted kinematic alignment (rKA) approach has been developed to restore native knee kinematics without reproducing extreme knee phenotype. This systematic review aims to evaluate clinical and radiological outcomes between rKA and MA for TKA.
METHODS
A systematic literature search was conducted following PRISMA guidelines on Pubmed, Scopus and Cochrane Library. The following search string was adopted: (((restricted kinematic) AND (mechanical)) AND (alignment)) AND (knee). We included studies that analyzed rKA versus MA in terms of clinical outcomes and complications with a minimum of 6 months of follow up. The following rKA- and MA-related data were evaluated: patient-reported outcome scores (PROMs), radiographic analysis of lower limb alignment, and complications. Criteria from the Methodological Index for Non-Randomized Studies were used to assess the methodological quality of the articles.
RESULTS
This systematic review included seven clinical studies with a total of 892 knees (471 for MA group and 421 for rKA group, respectively). Overall, post-operative PROMs were similar between rKA and MA. Moreover, rKA reached better results regarding Forgotten Joint Score and post-operative patient satisfaction. Finally, no higher complication rate was observed with the rKA approach.
CONCLUSION
The rKA aims to restore native knee kinematics, avoiding extreme deformities. Clinical outcomes are not inferior or even better for rKA compared with MA, without increasing the risk of short-middle-term implant failure. However, there is a high heterogeneity regarding the 'restricted' protocols used.
Topics: Humans; Biomechanical Phenomena; Arthroplasty, Replacement, Knee; Knee Joint; Lower Extremity; Radiography; Osteoarthritis, Knee; Knee Prosthesis
PubMed: 37925804
DOI: 10.1016/j.knee.2023.10.003