Nevin Manimala

Int J Colorectal Dis. 2022 Jul 2. doi: 10.1007/s00384-022-04206-7. Online ahead of print.

ABSTRACT

PURPOSE: To determine the results after rectovaginal fistula (RVF) repair and find predictors of outcome. Primary objective was fistula healing. Secondary outcomes were morbidity and patient health-related quality of life (HRQoL).

METHOD: An observational study of 55 women who underwent RVF repair including both local procedures and tissue transposition 2003-2018 was performed. Baseline patient and fistula characteristics were registered, combined with a prospective HRQoL follow-up and a general questionnaire describing fistula symptoms.

RESULTS: Healing rate after index surgery was 25.5% (n = 14) but the final healing rate was 67.3% (n = 37). Comparing the etiologies, traumatic fistulas (iatrogenic and obstetric) had the highest healing rates after index surgery (n = 11, 45.9%) and after repeated operations at final follow-up (n = 22, 91.7%) compared with fistulas of inflammatory fistulas (Crohn’s disease, cryptoglandular infection, and anastomotic leakage) that had inferior healing rates after both index surgery (n = 7, 7.1%) and at final follow-up (n = 13, 46.4%). Fistulas of the category others (radiation damage and unknown etiology) included a small amount of patients with intermediate results at both index surgery (n = 1, 33.3%) and healing rate at last follow-up (n = 2, 66.7%). The differences were statistically significant for both index surgery (p = 0.004) and at final follow-up (p = 0.001). Unhealed patients scored lower than both healed patients and the normal population in 6/8 Rand-36 domains, but the differences were not statistically significant.

CONCLUSIONS: Most traumatic rectovaginal fistulas closed after repeated surgery whereas inflammatory fistulas had a poor prognosis. Low healing rates after local repairs suggest that tissue transfer might be indicated more early in the treatment process. Unhealed fistulas were associated with reduced quality of life. Trial registration Clinicaltrials.gov No. NCT05006586.

PMID:35779081 | DOI:10.1007/s00384-022-04206-7

J Med Philos. 2022 Jul 2:jhac001. doi: 10.1093/jmp/jhac001. Online ahead of print.

ABSTRACT

The status of risk factors and disease remains a disputed question in the theory and practice of medicine and healthcare, and so does the related question of delineating disease boundaries. I present a framework based on Bernard Lonergan’s account of emergent probability for differentiating (1) generically distinct levels of systematic function within organisms and between organisms and their environments and (2) the methods of functional, genetic, and statistical investigation. I then argue on this basis that it is possible to understand disease in terms of biological or higher intra-level dysfunction, risk factors-including genetic risk factors-in terms of statistical inter-level conditioning of a given stage or developmental sequence of systematic functioning, and the empirical boundaries of disease in terms of the limits of both functional categorization (from an epistemic standpoint) and upper-level integration of lower-level processes and events (from an ontological standpoint).

PMID:35779075 | DOI:10.1093/jmp/jhac001

ANZ J Surg. 2022 Jul 2. doi: 10.1111/ans.17896. Online ahead of print.

ABSTRACT

BACKGROUND: Stage III colorectal cancer (CRC), which accounts for approximately one third of all CRC cases, is associated with worsened prognosis. The aim of this study was to compare the preoperatively measured systemic inflammatory markers and to define the most significant marker in terms of its prognostic value in stage III CRC.

METHODS: Surgically treated stage III CRC patients were included. Demographics, preoperatively measured Glasgow prognostic score (GPS), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/C-reactive protein ratio (LCR) and C-reactive protein/albumin ratio (CAR) values, clinicopathological features, surgical, oncological and survival outcomes were recorded and statistically analysed.

RESULTS: The study group of 102 patients consisted of 65 (63.7%) men and 37 (36.3%) women with a median age of 64 (range: 26-89). The mean follow-up period was 42.8 ± 30.5 (range: 6-107) months. Overall survival (OS) and disease-free survival (DFS) rates were 71.6%, and 67.7%, respectively. Elevated CRP, GPS 2, LCR ≤ 0.530, CAR ≥ 0.080, higher numbers of metastatic lymph nodes and N2b nodal status were detected to impair DFS (P = 0.001, P = 0.015, P = 0.001, P = 0.001, P = 0.001 and P = 0.043, respectively). Variables including GPS 2, PLR≥190.83, CAR≥0.045, LCR≤0.684, surgical site infection and longer hospital stay decreased OS (P = 0.004, P = 0.002, P = 0.005, P = 0.001, P = 0.001 and P = 0.001, respectively). According to multivariate analysis; PLR ≥ 190.83 was associated with three times [HR: 2.892 (95% CI: 1.100-7.602), P = 0.031], and LCR ≤ 0.684 was associated with four times [HR: 3.919 (95% CI: 1.130-13.592), P = 0.031] greater risk of cancer-related mortality.

CONCLUSION: As an independent prognostic factor, LCR had the highest impact on predicting survival after curative resection for stage III CRC.

PMID:35779019 | DOI:10.1111/ans.17896

J Obstet Gynaecol Res. 2022 Jul 2. doi: 10.1111/jog.15344. Online ahead of print.

ABSTRACT

AIM: This study aimed to present the contribution of prenatal magnetic resonance imaging (MRI) in the diagnosis of fetuses that were previously identified as isolated mild and moderate cerebral ventriculomegaly (VM) by ultrasound (US).

METHODS: The data between February 2013 and August 2020 were collected for women who were diagnosed with isolated mild or moderate fetal VM by US and subsequently underwent a fetal MRI.

RESULTS: Among 321 women, 21 (6.5%) had a clinically important additional finding after MRI. Twelve of 276 (4.3%) fetuses with mild VM and 9 of 45 (20%) with moderate VM had turned out to have additional central nervous system abnormalities. Additional findings were detected more in fetuses with moderate VM, mothers with an anterior-located placenta, and mothers with higher body mass indexes (BMIs) with statistical significance (p = 0.001, p = 0.013, p = 0.036, respectively). The most common additional MRI finding was grade 3 or 4 germinal matrix hemorrhage, which was detected in 11 of 21 fetuses (52.3%).

CONCLUSIONS: Considering the countries’ health policies, prenatal MRI would contribute mostly to the diagnosis of fetuses with moderate VM, pregnancies with anterior-located placenta, and mothers with high BMIs. According to our data, we believe that MRI will be valuable, especially in the diagnosis of grade 3 and 4 intracranial hemorrhage group.

PMID:35778980 | DOI:10.1111/jog.15344

Clin Pharmacol Drug Dev. 2022 Jul 2. doi: 10.1002/cpdd.1135. Online ahead of print.

ABSTRACT

This study aimed to evaluate the pharmacokinetics (PK), safety, and immunogenicity of the infliximab biosimilar CMAB008 compared to the reference product (Remicade) in healthy Chinese male subjects to provide the basis for the similarity evaluation of the 2 drugs. In this phase I randomized, double-blind, parallel-controlled, single-dose study, a total of 90 subjects were randomized 1:1 to receive CMAB008 or infliximab reference product with single intravenous injections (5 mg/kg). Blood samples were collected at designed time points for PK and immunogenicity assessment. If the 90%CI of the geometric mean ratio of area under the plasma concentration-time curve from 0 to the time of the last observation, maximum observed plasma concentration, area under the plasma concentration-time curve from 0 to infinity was completely within the range of 80% to 125%, the PK bioequivalence was established. Other PK parameters including time to maximum plasma concentration_, half-life time, clearance, apparent volume of distribution, and last measurable concentration time point were also assessed. Adverse events (AEs) were recorded. Serum concentration-time profiles were similar across the 2 groups, and PK parameters were comparable in the 2 groups. The 90%CI of the geometric mean ratio of test to reference was within the predefined bioequivalence range of 80% to 125%. The AEs occurred similarly in 2 groups. One serious AE (rhabdomyolysis, grade 3) occurred in the test group. The total positive rates of antidrug antibody and neutralizing antibodies in the test group (85.7% and 5.6%, respectively) were numerically lower than infliximab reference product group (90.9% and 15%, respectively). The PK profile of the 2 groups is statistically equivalent. The preliminary safety and immunogenicity evaluation of the 2 drugs are comparable.

PMID:35778977 | DOI:10.1002/cpdd.1135

Clin Chem Lab Med. 2022 Jul 4. doi: 10.1515/cclm-2022-0415. Online ahead of print.

ABSTRACT

OBJECTIVES: Automated machine learning (AutoML) tools can help clinical laboratory professionals to develop machine learning models. The objective of this study was to develop a novel formula for the estimation of urine osmolality using an AutoML tool and to determine the efficiency of AutoML tools in a clinical laboratory setting.

METHODS: Three hundred routine urinalysis samples were used for reference osmolality and urine clinical chemistry analysis. The H2O AutoML engine completed the machine learning development steps with minimum human intervention. Four feature groups were created, which include different urinalysis measurements according to the Boruta feature selection algorithm. Method comparison statistics including Spearman correlation, Passing-Bablok regression analysis were performed, and Bland Altman plots were created to compare model predictions with the reference method. The minimum allowable bias (24.17%) from biological variation data was used as the limit of agreement.

RESULTS: The AutoML engine developed a total of 183 ML models. Conductivity and specific gravity had the highest variable importance. Models that include conductivity, specific gravity, and other urinalysis parameters had the highest R² (0.70-0.83), and 70-84% of results were within the limit of agreement.

CONCLUSIONS: Combining urinary conductivity with other urinalysis parameters using validated machine learning models can yield a promising surrogate. Additionally, AutoML tools facilitate the machine learning development cycle and should be considered for developing ML models in clinical laboratories.

PMID:35778953 | DOI:10.1515/cclm-2022-0415

Phys Ther. 2022 Jun 29:pzac051. doi: 10.1093/ptj/pzac051. Online ahead of print.

ABSTRACT

OBJECTIVE: Guidelines recommend supervised exercise therapy and lifestyle counseling by a physical therapist as initial treatment of patients with intermittent claudication. However, guidelines provide only a crude estimate of the outcomes that therapists and patients might expect from treatment. The purpose of this study was to explore the impact of personalized outcomes forecasts (POFs) on the decision-making process of physical therapists and to learn lessons on facilitating the use of forecasts in daily practice.

METHODS: A vignette-based, think-aloud interview study design was used. The participants were physical therapists trained in treating patients with intermittent claudication. Vignettes described fictitious patients diagnosed with intermittent claudication and included POFs. A directed approach was used to code, organize, and describe the data. Transcripts were analyzed using a thematic approach.

RESULTS: Sixteen therapists participated in the study. Three themes were identified: (1) setting and contextualizing treatment expectations; (2) setting (shared) goals and (de)motivating the patient, and (3) establishing and monitoring the treatment plan. Therapists mentioned that POFs could be useful for setting expectations and realistic treatment goals, contextualizing expected treatment response, stimulating patients to achieve their goals, and deciding on treatment frequency and treatment timing. Therapists thought POFs would be of less use for changing treatment goals during follow-up visits or for establishing intensity or type of training.

CONCLUSION: To overcome challenges that may arise when adopting POFs in daily practice, adequate training of physical therapists should be conducted. Potential areas to address with training include statistical and data literacy as well as guidance on integrating POFs with existing treatment protocols.

IMPACT: The use of POFs by physical therapists might contribute to a more person-centered care approach. The insights provided by this study on the first use of POFs by physical therapists can serve as an example and lesson on how to optimally implement such supporting tools into daily practice.

PMID:35778937 | DOI:10.1093/ptj/pzac051

Acta Paediatr. 2022 Jul 2. doi: 10.1111/apa.16472. Online ahead of print.

ABSTRACT

AIM: The aim of this review was to compile existing evidence on the role of platelets in the development of severe retinopathy of prematurity (ROP), highlight the strengths and weaknesses of the available studies and critically discuss the reported data.

METHODS: A comprehensive literature search was conducted on PubMed from January 2000 to January 2022, and the reference lists of the included studies were screened manually.

RESULTS: There were 19 primary studies that fulfilled the eligibility criteria. Experimental research indicated lower platelet count in mice oxygen-induced retinopathy model compared with normoxia controls, while platelet transfusions suppressed neovascularisation. The latter finding was not consistently confirmed in clinical research, where a low platelet count, an increased number of thrombopenic episodes and of platelet transfusions have all been implicated in the development of ROP requiring treatment, either type I or aggressive posterior or both. However, existing studies exhibit significant clinical heterogeneity and present methodological limitations that imperil their reliability and validity.

CONCLUSION: Platelet deficiency has been associated with severe ROP. However, critical thresholds of platelet parameters are still unrecognised. Future research is required to determine whether platelet parameters can be predictive biomarkers for ROP requiring treatment and at what thresholds.

PMID:35778901 | DOI:10.1111/apa.16472

Eur J Clin Invest. 2022 Jul 1:e13830. doi: 10.1111/eci.13830. Online ahead of print.

ABSTRACT

BACKGROUND: The CHA₂ DS₂ -VASc score, widely used to estimate cardioembolic risk in patients with atrial fibrillation (AF), appears to be useful also in predicting vascular adverse events and death in different sets of patients without AF. The R₂ CHA₂ DS₂ -VASc score, which includes renal impairment, allows a better prediction of death and thromboembolism in patients without AF. The aims of our study were to assess, in a large sample of patients at high cardiovascular (CV) risk, i) the correlation between CHA₂ DS₂ -VASc and R₂ CHA₂ DS₂ -VASc with all-cause mortality, and ii) to compare the performances of CHA₂ DS₂ -VASc and R₂ CHA₂ DS₂ -VASc in predicting all-cause mortality.

METHODS: In this single-center prospective observational study, conducted at the Research Hospital “Casa Sollievo della Sofferenza” between June 2016 and December 2018, 1017 CV patients at high risk of undergoing coronary angiography were enrolled.

RESULTS: CHA₂DS₂-VASc and R₂ CHA₂ DS₂ -VASc scores significantly associated with all-cause mortality. For each one-point increase in CHA₂ DS₂ -VASc or R₂ CHA₂ DS₂ -VASc scores, mortality increased by almost 1.5-fold. The R₂ CHA₂ DS₂ -VASc score (C-statistic=0.71; 95%CI=0.65-76) outperformed the CHA₂ DS₂ -VASc score (C-statistic=0.66; 95%CI=0.61-0.71) in predicting 4-year mortality (delta C-statistic =0.05; 95%CI=0.02-0.07). The better predictive ability of the R-CHA₂ DS₂ -VASc score was also demonstrated by an IDI=0.027 (95CI=0.021-0.034, p<0.00001) and a relative IDI=62.8% (95%CI=47.9%-81.3%, p<0.00001). The R₂ CHA₂ DS₂ -VASc score correctly reclassified the patients with a NRI=0.715 (95%=0.544-0.940, p<0.00001).

CONCLUSIONS: The CHA₂DS₂-VASc and R₂ CHA₂ DS₂ -VASc scores are useful predictors of all-cause mortality in subjects at high CV risk, with the R₂ CHA₂ DS₂ -VASc score being the best performer.

PMID:35778894 | DOI:10.1111/eci.13830

Health Promot Pract. 2022 Jul 1:15248399221102919. doi: 10.1177/15248399221102919. Online ahead of print.

ABSTRACT

Gardening is associated with a wide array of health benefits. We describe the dissemination of a low-cost social media-based campaign (Grow This!), an intervention intended to reach novice gardeners and which combined elements of old (seeds) and new (Facebook) technology. Grow This! was implemented before (2018, 2019) and during (2020) the COVID pandemic, providing an interesting framework for understanding participants’ motivations for gardening. Pre- and post-surveys assessed a variety of topics, including participants’ motivations for participating in Grow This!, how they planned to participate, previous gardening experience, the main benefits attributed to participation, and intentions to garden in the future. Descriptive statistics and qualitative analysis were used to analyze the survey data. More than 25,000 people participated in Grow This! over the 3 years, with the majority (77%) participating as a family. Participation in the project spiked during COVID. Primary motivations for participating in Grow This! pre-COVID were education, enjoyment, family engagement, and self-sufficiency; during COVID, motivations remained the same, but shifted in rank. Just over a third of participants were novice gardeners. Participants attributed numerous benefits to their participation, including stress reduction/relaxation, more outdoor time, reduced grocery bills, and eating more fruits and vegetables than normal. A total of 83% of respondents reported being highly likely to have a garden in the future. Home gardening as an intervention is ripe for dissemination, particularly in the aftermath of COVID. Public health professionals can benefit from this understanding of people’s motivations to garden and the perceived benefits associated with gardening.

PMID:35778887 | DOI:10.1177/15248399221102919