Delay in continuous renal replacement therapy initiation linked to worse major adverse kidney events among adolescents and adults

The early or accelerated CRRT initiation strategy among adults with a history of acute kidney injury or volume overload has not demonstrated a survival benefit. There needs to be more data on the association of the timing of CRRT initiation with outcomes among children and young adults.

An Original Investigation on Nephrology published in JAMA Network Open has concluded that delaying the initiation of continuous renal replacement therapy (CRRT) in critically ill children increases the risk of adverse events. This includes death, dialysis dependence, and persistent kidney dysfunction at 90 days.

In this cohort study of 969 patients with data for the primary outcome of MAKE-90, a propensity score–weighted analysis found that each 1-day delay in CRRT initiation was associated with 3% higher odds of MAKE-90.

This retrospective cohort study utilized data from the Worldwide Exploration of Renal Replacement Outcome Collaborative in Kidney Disease (WE-ROCK) registry, collected between 2015 and 2021 across 32 centres in 7 countries. The participants included children and young adults (birth to 25 years) diagnosed with acute kidney injury or VO. The primary exposure was the time from intensive care unit admission to CRRT initiation, and the primary outcome was MAKE-90 (death, dialysis dependence, or persistent kidney dysfunction).

Critical points in the study are:

A total of 996 patients were enrolled.

· MAKE-90 occurred in 65 % of patients (n=630).

· 368 patients, constituting 58.4 %, died.

· Out of 601 patients who survived, 262 patients had persistent kidney dysfunction. Out of these patients, 91 patients were dependent on dialysis.

· The time taken to initiate CRRT was about a day longer for those with MAKE-90 (three days vs two days.

· In the generalized propensity score-weighted regression, there were approximately 3% higher odds of MAKE-90 for every 1-day delay in CRRT initiation, with an odds ratio of 1.03.

In this study of children and young adults receiving CRRT, it was observed that a longer time in initiating CRRT is associated with a greater risk of MAKE-90 outcomes, particularly death. These results imply further research to determine the optimal time to initiate CRRT and its interaction with other factors like VO to improve survival rates and reduce complications in this category of patients.

Reference:

Gist KM, et al. Time to Continuous Renal Replacement Therapy Initiation and 90-Day Major Adverse Kidney Events in Children and Young Adults. JAMA Netw Open. 2024;7(1):e2349871. doi:10.1001/jamanetworkopen.2023.49871

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Peri operative antibiotic prophylaxis not necessary for patients undergoing orthopaedic surgery using K-wire fixation

Kirschner (K) wires are commonly used in orthopaedic surgery for fixation of unstable fractures such as supracondylar humerus fractures in paediatric patients, distal radius fractures in paediatric and adult patients and elective surgery of the foot. They can be inserted percutaneously with minimal damage to soft tissues such as tendons and neurovascular structures, followed by cutting and bending of the wires. The wires are then either left protruding outside the skin or buried.

Overall, there is no consensus or clear guidance on the administration of antibiotics for K-wire. Reducing the incidence of SSI needs to be balanced with potential risks of the unnecessary use of antibiotics, such as antibiotic resistance and allergic reaction. Currently, there are no systematic reviews or meta-analyses that investigate the use of prophylactic antibiotics for orthopaedic surgery using K-wire.

Ahmad Abul et al conducted a study to investigate incidence of SSI using prophylactic antibiotics compared to no antibiotics in the context of percutaneous fixation of fractures with K-wire.

Two authors independently searched the following electronic databases: MEDLINE, EMBASE, EMCARE, CINAHL, and the Cochrane Central Register of Controlled Trials (CENTRAL). The last search was run on 10th January 2022.

A systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Guidelines and a search of electronic information was conducted to identify all randomised controlled trials (RCTs) and non-randomised studies comparing the outcomes of antibiotic prophylaxis group versus those without antibiotic in patients undergoing orthopaedic surgery in which K-wire fixation was used. Incidence of surgical site infection (SSI) was the primary outcome. Random effects modelling was used for the analysis. The study has been published in “Indian Journal of Orthopaedics.”

Key findings of the study were:

• Four retrospective cohort studies and one RCT were identified with a total of 2316 patients.

• There was no significant difference between the prophylactic antibiotic and no antibiotic groups in terms of incidence of SSI (odds ratio [OR] =0.72, P=0.18).

“In conclusion, based on the current available evidence there is no significant difference in administering perioperative antibiotics for patients undergoing fracture fixation with K-wire. Further high quality, prospective studies are required to improve the evidence base to influence guidelines” the authors commented.

Further reading:

Peri operative Antibiotic Prophylaxis in K Wire Fixation: A Systematic Review and Meta analysis Ahmad Abul, Mohammad Karam et al Indian Journal of Orthopaedics (2023) 57:1000–1007 https://doi.org/10.1007/s43465-023-00879-6

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Unsupervised home-use of transcranial direct current fails to improve major depression: JAMA

Transcranial direct current stimulation (tDCS) is moderately effective in treating depression when administered by trained professionals. However, it remains unclear whether self-administered tDCS, either alone or in combination with a digital psychological intervention, is also effective in treating depression. 

According to an Original Investigation published in JAMA Psychiatry, Unsupervised home-use transcranial direct current stimulation (tDCS) along with a digital psychological intervention or a digital placebo demonstrates no superiority compared to sham treating individuals with major depressive episodes.

In this randomized clinical trial involving 210 adults with a major depressive episode, no significant differences were found between home-use tDCS combined with either a digital psychological intervention or digital placebo and sham in reducing depressive symptoms after six weeks. The aim was to determine whether fully unsupervised home-use tDCS, combined with a digital psychological intervention or digital placebo, is effective for treating major depressive episodes.

The intervention involved 2-mA, 30-minute prefrontal tDCS sessions for 15 consecutive weekdays and twice-weekly sessions for three weeks. The digital intervention had 46 sessions based on behavioral therapy. Digital placebo included internet browsing. The main outcome measure was the change in HDRS-17 score at week 6.

Key findings from the study are:

  • Among the 210 participants, aged 38.9 years on average, 30 were men, and 180 were women. All of them had major depression, at least eight years of education, and access to a smartphone and home internet.
  • 64 participants were allocated to double active, 73 to tDCS only, or 73 to double sham. One hundred ninety-nine participants finished the trial.
  • No statistically significant differences were found in HDRS-17 scores between groups.
  • Skin redness and heat or burning sensations were more common in the double active and tDCS-only groups, and one nonfatal suicide attempt occurred in the tDCS-only group.

According to the results, it is not advisable to recommend unsupervised home use of tDCS for clinical practice.

Reference:

Borrione L et al. Home-Use Transcranial Direct Current Stimulation for the Treatment of a Major Depressive Episode: A Randomized Clinical Trial. JAMA Psychiatry.

doi:10.1001/jamapsychiatry.2023.4948

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Lung Biopsy Crucial in Diagnosing diffuse developmental disorder of lung in Pediatric Intensive Care

In a recent study published in the Pediatric Pulmonology found the critical role of lung biopsy in diagnosing critical lung conditions in pediatric intensive care units (ICUs). This investigation was conducted between 1995 and 2022 and majorly focused on the diagnostic yield of lung biopsies in 31 critically ill children. This provides valuable insights into the delicate balance between diagnostic necessity and the invasive nature of the procedure.

This study spanned over two decades involved children ranging from newborns to 10.8 years old who underwent lung biopsy in the ICU were examined thoroughly. The criteria for inclusion excluded biopsies conducted in operating rooms and post-mortem cases. Out of the 31 patients, majority (67.7%) were newborns who required invasive mechanical ventilation. Also, 70.9% were placed under extracorporeal membrane oxygenation (ECMO) and 89.7% had pulmonary hypertension.

The lung biopsy proved to be a diagnostic success in 81% of cases with reliability seemingly decreasing with age. The study identified diffuse developmental disorders of the lung as a primary diagnostic outcomes with alveolar capillary dysplasia and surfactant disorders. but, complications were observed in 29% of cases, with a significant association with ECMO usage, particularly showcasing a higher risk in cases extending beyond 10 days and in children over 2 years old.

The study underscores the significance of lung biopsy as a reliable diagnostic tool, specially in neonates who undergo critical situations with suspected diffuse developmental lung disorders. As the findings also highlight the complications linked to ECMO, this study calls paves way for a prospective evaluation of biopsy-related risks under ECMO, specially in prolonged cases and older children.

This research deepens the understanding of the diagnostic efficacy of lung biopsies in critical pediatric cases and also highlights the need for a nuanced approach that considers both diagnostic benefits and potential complications to optimize patient outcomes in intensive care settings.

Reference:

Levy, Y., Bitton, L., Sileo, C., Rambaud, J., Soreze, Y., Louvrier, C., Ducou le Pointe, H., Corvol, H., Hervieux, E., Irtan, S., Leger, P., Prévost, B., Coulomb L’Herminé, A., & Nathan, N. (2024). Lung biopsies in infants and children in critical care situation. In Pediatric Pulmonology. Wiley. https://doi.org/10.1002/ppul.26845

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Choroidal Microvasculature Changes Linked to Smoking in Glaucoma Patients

A recent study published by BMJ Open Ophthalmology clarified the effect of smoking on choroidal microvasculature dropout (MvD) in glaucoma patients. Based on a cross-sectional investigation, the results indicate that higher smoking intensity is linked to larger MvD regions, specially in individuals with more severe forms of the disease.

Undertaken at a tertiary glaucoma center, 223 eyes from 163 patients with primary open-angle glaucoma were included in this study. As part of the Diagnostic Innovations in Glaucoma Study, researchers used optical coherence tomography angiography and sent out smoking questionnaires to collect data.

The study revealed that smoking history was associated with MvD in 51.4% of eyes, while non-smokers exhibited MvD in 44.4% of cases. Though the overall prevalence of MvD didn’t significantly differ between the two groups (p=0.389), some important distinctions were observed.

Compared to non-smokers, smokers displayed larger MvD areas (p=0.068) and wider angular circumferences (p=0.046). Importantly, a multivariable model showed that smoking intensity had a significant link to MvD area (0.30; 95% CI 0.01 to 0.60) for each 0.01 mm² per 10 pack-years (p=0.044).

However, the impact of smoking on MvD wasn’t uniform across glaucoma severity levels. In individuals with moderate to severe glaucoma (MD < −6), smoking intensity was significantly associated with larger MvD areas (0.47; 95% CI 0.11 to 0.83) for each 0.01 mm² per 10 pack-years (p=0.011). This effect was not observed in individuals with early glaucoma (MD ≥ −6), where the association was not significant (−0.08; 95% CI −0.26 to 0.11, p=0.401).

These findings raise concerns about the potential impact of smoking on the eye health of glaucoma patients. The study suggests that smoking, particularly its intensity, may contribute to larger MvD areas, especially in individuals with moderate to severe forms of the condition. The study highlights the importance of addressing smoking cessation in glaucoma management and underscores the need for further research into the relationship between smoking and eye health. Understanding these connections can aid in the development of targeted interventions to improve the eye health and overall well-being of glaucoma patients, especially those who smoke.

Reference:

Nishida, T., Micheletti, E., Latif, K., Du, K. H., Weinreb, R. N., & Moghimi, S. (2023). Impact of smoking on choroidal microvasculature dropout in glaucoma: a cross-sectional study. In BMJ Open Ophthalmology (Vol. 8, Issue 1, p. e001421). BMJ. https://doi.org/10.1136/bmjophth-2023-001421

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Novel antibiotic class promising against invasive infections caused by carbapenem-resistant Acinetobacter: Study

Switzerland: A team of researchers from Swiss drugmaker Roche have identified a novel class of antibiotics that target a highly drug-resistant and deadly bacterial pathogen.

In the research published in Nature, Claudia Zampaloni, Roche Innovation Center Basel, F. Hoffmann-La Roche, Basel, Switzerland, and colleagues described the identification and optimization of tethered macrocyclic peptide (MCP) antibiotics. These antibiotics target carbapenem-resistant Acinetobacter baumannii (CRAB) by inhibiting one of the building blocks of the bacterium’s hard-to-penetrate outer wall.

They further found the high effectiveness of a clinical candidate from this class called zosurabalpin (RG6006) at treating CRAB isolates both in vitro and in mouse models of infection.

“This chemical class is a promising treatment paradigm for patients with invasive infections due to CRAB, for whom current treatment options are inadequate,” the researchers wrote. They additionally identified LptB2FGC as a tractable target for antimicrobial drug development.

Carbapenem-resistant Acinetobacter baumannii has emerged as a major global pathogen having limited treatment options. In patients over 50 years old, no new antibiotic chemical class with activity against A. baumannii has been reached. Dr. Zampaloni and colleagues report the identification and optimization of tethered macrocyclic peptide antibiotics with potent antibacterial activity against CRAB.

CRAB is considered one of the leading antibiotic resistance threats by both the Centers for Disease Control and Prevention and the World Health Organization and a priority for antibiotic development, with mortality estimates for invasive infections ranging from 40% to 60% and limited treatment options.

Beyond carbapenems, CRAB infections are often resistant to multiple other antibiotics, leaving patients with limited treatment options. However, A baumannii has a tough outer membrane (like other gram-negative bacterial pathogens) blocking the entry of most antibiotics, making it a difficult target for antibiotic developers.

Collectively, these data support the hypothesis that antibacterial activity is mediated through a new target.

“MCP displayed a highly similar phenotypic profile across several tested compounds while differentiating from other known antibiotic classes,” they wrote. “Taken together, these data support the hypothesis that antibacterial activity is mediated through a new target.”

According to the researchers, tethered MCPs, identified through the screening of about 45,000 compounds, solve the problem by blocking the transport of lipopolysaccharide (LPS) from the inner membrane to the outer membrane, which is requisite for the formation of an outer membrane and antibiotic resistance.

A process called bacterial phenotypic fingerprint profiling revealed that a cluster of the identified MCP shared this mode of action.

“Collectively, these data demonstrate the zosurabalpin’s potential as an antibiotic and human clinical trials have been initiated to further develop this compound to provide a treatment option for invasive infections caused by CRAB,” the researchers wrote.

Reference:

Zampaloni, C., Mattei, P., Bleicher, K., Winther, L., Thäte, C., Bucher, C., Adam, J., Alanine, A., Amrein, K. E., Baidin, V., Bieniossek, C., Bissantz, C., Boess, F., Cantrill, C., Clairfeuille, T., Dey, F., Di Giorgio, P., Du Castel, P., Dylus, D., . . . Bradley, K. A. (2024). A novel antibiotic class targeting the lipopolysaccharide transporter. Nature, 1-6. https://doi.org/10.1038/s41586-023-06873-0

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18F-FDG-PET/CT helps in prediction of brain metastasis in melanoma patients

Malignant melanoma is known for its aggressive nature and disproportionately high mortality rate among skin-related malignancies and is the third most common cancer to metastasize to the brain. A recent retrospective study published in the Journal of Cancers unveiled the potential breakthrough in prediction of brain metastases in melanoma patients.

18F-FDG PET/CT is a powerful imaging modality for detecting melanoma metastases, this study evaluated its prognostic value in the context of brain metastases. The limitation of 18F-FDG PET/CT, an unfavorable tumor-to-background uptake ratio in the brain, prompted researchers to explore its potential as a prognostic tool.

This retrospective analysis included a total of 201 melanoma patients with pathology-proven cases between 2008 and 2021. The baseline assessments included histopathology, 18F-FDG PET/CT, and brain MRI. A median follow-up of six years was conducted that revealed intriguing associations.

Among the clinical variables, the initial M-stage and TNM-stage were significantly associated to the occurrence of brain metastasis.18F-FDG PET/CT parameters, specially regional metastatic lymph node uptake values, prominent SULmax (pSULmax) and prominent SUVmean (pSUVmean), demonstrated significant links with the outcome.

The cumulative incidences observed following 1, 5, and 10 years were 10%, 31%, and 35.2%, respectively. The notable significance were the correlations between pSULmax and pSUVmean and the occurrence of brain metastases, where higher values corresponded to a swifter development of brain metastases.

This outcomes not only highlight the potential of baseline 18F-FDG PET/CT in predicting brain metastasis but also emphasize the importance of follow-up and complementary evaluations, like the MRI brain for melanoma patients with high total metabolic activity.

This study deepens the understanding of melanoma progression and also improves possibilities of targeted and timely interventions by potentially transforming the melanoma management.

Source:

Kalantari, F., Mirshahvalad, S. A., Hoellwerth, M., Schweighofer-Zwink, G., Huber-Schönauer, U., Hitzl, W., Rendl, G., Koelblinger, P., Pirich, C., & Beheshti, M. (2023). Prognostic Value of Baseline 18F-FDG PET/CT to Predict Brain Metastasis Development in Melanoma Patients. In Cancers (Vol. 16, Issue 1, p. 127). MDPI AG. https://doi.org/10.3390/cancers16010127

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Obeticholic Acid may Improve outcomes in NASH-Related Liver Fibrosis

A new study published in Journal of Hepatology confirms the efficacy of Obeticholic Acid (OCA), a novel farnesoid X receptor agonist and antifibrotic agent against non-alcoholic steatohepatitis (NASH).

The Phase III REGENERATE trial originally reported results from an 18-month liver biopsy analysis involving OCA. The treatment demonstrated its efficacy, prompting further investigation. In this study, the potential of OCA was reaffirmed, providing hope for those battling this debilitating liver condition.

The study aimed to validate the previous findings and gather additional data to support OCA’s effectiveness. A diverse panel of three pathologists independently evaluated digitized whole-slide images using the NASH Clinical Research Network scoring system. The primary endpoints were either an improvement of at least one stage in fibrosis without worsening of NASH or NASH resolution without worsening of fibrosis.

Among 931 participants, OCA demonstrated its potential with 22.4% achieving an improvement in fibrosis without NASH worsening, compared to only 9.6% on a placebo. Furthermore, 6.5% of those on OCA achieved NASH resolution without fibrosis progression, compared to 3.5% on the placebo.

Not only did OCA showcase its efficacy, but it also demonstrated a high degree of safety and tolerability. The study included data from 2,477 participants, and the incidence of treatment-emergent adverse events (TEAEs) and serious TEAEs was not substantially different across treatment groups. The most common TEAE reported was pruritus. Moreover, rates of hepatic, renal, and cardiovascular events were low and comparable across treatment groups.

These findings highlight OCA’s potential to significantly impact the lives of patients with NASH-related liver fibrosis. Preventing fibrosis from progressing to cirrhosis or even reversing it is a critical goal in NASH treatment. OCA’s antifibrotic effects, proven effectiveness, and favorable safety profile offer hope for patients dealing with this challenging condition.

Source:

Sanyal, A. J., Ratziu, V., Loomba, R., Anstee, Q. M., Kowdley, K. V., Rinella, M. E., Knapple, W., Lawitz, E. J., Abdelmalek, M. F., Shiff, S. J., Sawhney, S., Capozza, T., … Younossi, Z. M. (2023). Results from a new efficacy and safety analysis of the REGENERATE trial of obeticholic acid for treatment of pre-cirrhotic fibrosis due to non-alcoholic steatohepatitis. Journal of Hepatology, 79(5), 1110–1120. https://doi.org/10.1016/j.jhep.2023.07.014

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Higher ambient temperature tied to increased hypoglycemia risk in older insulin users

USA: A recent study published in Diabetes Care has revealed an increased hypoglycemia risk in extreme heat among older adults (aged ≥ 65 years) with diabetes who received insulin.

“Higher ambient temperature was associated with increased risk of serious hypoglycemic events in two national samples of older insulin users,” the researchers reported.

The thermoregulatory response is often compromised in older adults with diabetes, making them vulnerable to extreme heat. Soko Setoguchi, Department of Medicine, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, and colleagues aimed to measure the association between ambient heat and hypoglycemia-related emergency department visits or hospitalization in insulin users.

For this purpose, the researchers evaluated the association between ambient heat and hypoglycemia in about 2 million and 283,000 patients (aged 65-100 years) with diabetes from the United States and Taiwan, respectively, who received insulin.

A serious hypoglycemic event was defined as a primary visit to the emergency department (ED) or an unplanned inpatient admission for hypoglycemia from June 1 to September 30. Medication use was determined by at least one prescription dispensing insulin within 90 days of the index event.

Cases of serious hypoglycemia were identified among adults using insulin aged ≥65 in Taiwan (via the National Health Insurance Database) and the US (via Medicare Part A/B/D-eligible beneficiaries) from 2016 to 2019. The odds of hypoglycemia were estimated by heat index (HI) percentile categories using conditional logistic regression with a time-stratified case-crossover design.

The study led to the following findings:

  • Among insulin users overall, 32,461 and 10,162 older adults from the United States and Taiwan, respectively, experienced a hypoglycemic event.
  • The risk for a serious hypoglycemic event was about 40% higher among insulin users on days with an HI ≥ 99th percentile than 25-74th percentile (unadjusted odds ratio, 1.38)
  • On days with a low HI (< 25th percentile), the risk for hypoglycemia among insulin users decreased.
  • No substantial differences were observed in the risk for hypoglycemic events and HI by climate region in either country, such as between the US Northeast and Southwest.

“Our finding of increased risk of hypoglycemia-related ED visits in older adults using insulin and exposed to extreme heat emphasizes the need for patients and providers to be aware and cautious that extreme heat may raise the risk of hypoglycemia,” the authors wrote.

The study limitations include individuals with hypoglycemia who were older and had more comorbidities, so the authors suggest using caution before the results can be generalized to broader populations. The authors were also unable to capture variables that can modify the risk for serious hypoglycemia, such as exercise, outdoor activity and diet.

Reference:

Aayush Visaria, Shu-Ping Huang, Chien-Chou Su, David Robinson, John Read, Chuan-Yao Lin, Rachel Nethery, Kevin Josey, Poonam Gandhi, Benjamin Bates, Melanie Rua, Ashwagosha Parthasarathi, Arnab K. Ghosh, Yea-Huei Kao Yang, Soko Setoguchi; Ambient Heat and Risk of Serious Hypoglycemia in Older Adults With Diabetes Using Insulin in the U.S. and Taiwan: A Cross-National Case-Crossover Study. Diabetes Care 2023; dc231189. https://doi.org/10.2337/dc23-1189

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Frequent Self-monitoring of Blood sugar improves glycemic control in Non-insulin-Treated diabetes Patients

Frequent Self-monitoring of Blood sugar improves glycemic control in Non-insulin-Treated diabetes Patients suggests a new study published in the Journal of General Internal Medicine

Self-monitoring of blood glucose (SMBG) is a useful tool in diabetes management, but its efficacy and optimal application in type 2 diabetes (T2D) patients treated without insulin have been controversial. We aimed to evaluate the efficacy of SMBG in controlling blood glucose levels in non-insulin-treated T2D patients and to determine the optimal frequency and the most appropriate population to benefit from SMBG.

Eligible publications from January 2000 to April 2022 were retrieved from PubMed, Embase, Cochrane Library, and ClinicalTrials.gov databases. Randomized controlled trials comparing SMBG with no SMBG or structured SMBG (S-SMBG, SMBG with defined timing and frequency of glucose measurements) were included. Meta-analyses and sub-analyses were performed to assess the efficacy, optimal frequency, and most appropriate population for SMBG. Risk of bias was assessed regarding randomization, allocation sequence concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases.

Results:

Twenty-two studies involving 6204 participants were identified, including 17 comparing SMBG with no SMBG and 4 comparing SMBG with S-SMBG. SMBG reduced HbA1c (MD -0.30%, 95% CI -0.42 to -0.17) compared with no SMBG, and S-SMBG performed better than SMBG (MD -0.23%, 95% CI -0.38 to -0.07). Subgroup analyses showed that HbA1c control was better with SMBG at 8-11 times weekly (MD -0.35%, 95% CI -0.51 to -0.20) compared with other frequencies and with lifestyle adjustments (MD -0.37%, 95% CI -0.50 to -0.23) than with no adjustments. No significant differences in HbA1c were observed between baseline HbA1c subgroups (≤ 8% and > 8%, P = 0.63) and between diabetes duration subgroups (≤ 6 years and > 6 years, P = 0.72), respectively.

SMBG was effective for controlling HbA1c in non-insulin-treated T2D patients, although lacking detailed monitoring design. Better outcomes were seen with SMBG at 8-11 times weekly and lifestyle adjustment based on SMBG results.

Reference:

Zou Y, Zhao S, Li G, Zhang C. The Efficacy and Frequency of Self-monitoring of Blood Glucose in Non-insulin-Treated T2D Patients: a Systematic Review and Meta-analysis. J Gen Intern Med. 2023 Feb;38(3):755-764. doi: 10.1007/s11606-022-07864-z. Epub 2022 Nov 20. PMID: 36403159; PMCID: PMC9971532.

Keywords:

Frequent, Self-monitoring, Blood sugar, improves, glycemic, control, Non-insulin-Treated, diabetes, Patients, Zou Y, Zhao S, Li G, Zhang C, frequency; glycemic control; non-insulin; self-monitoring of blood glucose; type 2 diabetes, Journal of General Internal Medicine

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